title
stringlengths 2
235
| text
stringlengths 100
102k
|
|---|---|
Pristinamycin | Pristinamycin (INN), also spelled pristinamycine, is an antibiotic used primarily in the treatment of staphylococcal infections, and to a lesser extent streptococcal infections. It is a streptogramin group antibiotic, similar to virginiamycin, derived from the bacterium Streptomyces pristina spiralis. It is marketed in Europe by Sanofi-Aventis under the trade name Pyostacine.
Pristinamycin is a mixture of two components that have a synergistic antibacterial action. Pristinamycin I is a macro |
Promoter_region | ology,emt synthesizes the RNA from the coding region of the gene.
In prokaryotes, the promoter is recognized by RNA polymerase and an associated sigma factor, which in turn are brought to the promoter DNA by an activator protein binding to its own DNA sequence nearby.
In eukaryotes, the process is more complicated, and at least seven different factors ah noting that promoters are not DNA specific, and can in fact locate upstream towards the 3' end of an RNA genome, e.g. Respiratory Syncytial Virus (RSV).
As promoters are typically immediately adjacent to the gene in question, positions in the promoter are designated relative to the transcriptional start site, where transcription of RNA begins for a particular gene (i.e., positions upstream are negative numbers counting back from -1, for example -100 is a position 100 base pairs upstream).
Core promoter - the minimal portion of the promoter required to properly initiate transcription, Transcription Start Site (TSS), Approximately -34, A binding site for RNA polymerase, RNA polymerase I: transcribes genes encoding ribosomal RNA, RNA polymerase II: transcribes genes encoding messenger RNA and certain small nuclear RNAs, RNA polymerase III: transcribes genes encoding tRNAs and other small RNAs, General transcription factor binding sites
Proximal promoter - the proximal sequence upstream of the gene that tends to contain primary regulatory elements, Approximately -250, Specific transcription factor binding sites, nhancing RNAP binding to the promoter but helps RNAP target which genes to transcribe.
The sequence at -10 is called the Pribnow box, or the -10 element, and usually consistter. No promoter has been identified to date that has intact consensus sequences at both the -10 and -35; it is thought that this would lead to such tight binding by the sigma factor that the polymerase would be unable to initiate productive transcription.
Some promoters contain a UP element (consensus sequence 5’-TGNTATAAT-3')upstream of the -35 element; the presence of the -35 element appears to be unimportant for transcription from the UP element-containing promoters.
It should be noted that the above promoter sequences are only recognized by the sigma-70 protein that interacts with the prokaryotic RNA polymerase. Complexes of prokaryotic RNA polymerase with other sigma factors recognize totally dGGGGGGGGGGGGGGGGGGGGGGGGGGGGGXXXX-3'
-35 -10 Gene to be transcribed
(note that the optimal spacing between the -35 and -10 sequences is 17 nt)
for -10 sequence
T A T A A T
77% 76% 60% 61% 56% 82%
for -35 sequence
T T G A C A
69% 79% 61% 56% 54% 54%
Eukaryotic promoters are extremely diverse and are difficult to characterize. They typically lie upstream of the gene and can have regulatory elements several kilobases away from the transcriptional start site. In eukaryotes, the transcriptional complex can cause the DNA to bend back on itself, which allows for placement of regulatory sequences far from the actual site of transcription. Many eukaryotic promoters, but by no means all, contain a TATA box (sequence TATAAA), which in turn binds a TATA binding protein which assists in the formation of the RNA polymerase transcriptional complex. The TATA box typically lies very close to the transcriptional start site (often within 50 bases).
Eukaryotic promoter regulatory sequences typically bind proteins called transcription factors which are involved in the formation of the transcriptional complex. An example is the E-box (sequence CACGTG), which binds transcription factors in the basic-helix-loop-helix (bHLH) family (e.g. BMAL1-Clock, cMyc).
A wide variety of algorithms have been developed to facilitate detection of promoters in genomic sequence, and promoter prediction is a common element of many gene prediction methods.
A major question in evolutionary biology is how important tinkering with promoter sequences is to evolutionary change, for example, the changes that have occurred in the human lineage after separating from chimps.
Some evolutionary biologists, for example Allan Wilson, have proposed that evolution in promoter or regulatory regions may be more important than changes in coding sequences over such time frames.
The binding of a promoter sequence (P) to a sigma factor-RNAP complex (R) is a two-step process:
R+P ↔ RP(closed). K = 107
RP(closed) → RP(open). K = 10−2
Though OMIM is a major resource for gathering information on the relationship between mutations and natural variation in gene sequence and susceptibility to hundreds of diseases, it requires a sophisticated search strategy to extract those diseases that are associated with defects in transcriptional control where the promoter is believed to have direct involvement.
This is a list of diseases that evidence suggests have some involvement of promoter malfunction, either through direct mutation of a promoter sequence or mutation in a transcription factor or transcriptional co-activator.
Keep in mind that most diseases are heterogeneous in etiology, meaning that one "disease" is often many different diseases at the molecular level, though the symptoms exhibited and the response to treatment might be identical. How diseases respond differently to treatment as a result of differences in the underlying molecular origins is partially addressed by the discipline of pharmacogenomics.
Not listed here are the many kinds of cancers that involve aberrant changes in transcriptional regulation owing to the creation of chimeric genes through pathological chromosomal translocation.
The usage of canonical sequence for a promoter is often problematic, and can lead to misunderstandings about promoter sequences. Canonical implies perfect, in some sense.
In the case of a transcription factor binding site, then there may be a single sequence which binds the protein most strongly under specified cellular conditions. This might be called canonical.
However, natural selection may favor less energetic binding as a way of regulating transcriptional output. In this case, we may call the most common sequence in a population, the wild-type sequence. It may not even be the most advantageous sequence to have under prevailing conditions.
Recent evidence also indicates that several genes (including the proto-oncogene c-myc) have G-quadruplex motifs as potential regulatory signals.
Asthma
Beta thalassemia
Rubinstein-Taybi syndrome |
Basic_taste | Taste Bud
Taste (or, more formally, gustation) is a form of direct chemoreception and is one of the traditional five senses. It refers to the ability to detect the flavor of substances such as food and poisons. In humans and many other vertebrate animals the sense of taste partners with the less direct sense of smell, in the brain's perception of flavor. In the West, experts traditionally identified four taste sensations: sweet, salty, sour, and bitter. Eastern experts traditionally identified a fifth, called umami. More recently, psychophysicists and neuroscientists have suggested other taste categories (umami and fatty acid taste most prominently, as well as the sensation of metallic and water tastes, although the latter is commonly disregarded due to the phenomenon of taste adaptation.)
Taste is a sensory function of the central nervous system. The receptor cells for taste in humans are found on the surface of the tongue, along the soft palate, and in the epithelium of the pharynx and epiglottis.
Psychophysicists have long suggested the existence of four taste 'primaries', referred to as the basic tastes: sweetness, bitterness, sourness, and saltiness. Umami is now accepted as the fifth basic taste, exemplified by the non-salty sensations evoked by some free amino acids such as monosodium glutamate.
Other possible categories have been suggested, such as a taste exemplified by certain fatty acids such as linoleic acid. Some researchers still argue against the notion of primaries at all and instead favor a continuum of percepts , similar to color vision.
All of these taste sensations arise from all regions of the oral cavity, despite the common misconception of a "taste map" of sensitivity to different tastes thought to correspond to specific areas of the tongue. This myth is generally attributed to the mis-translation of a German text, and perpetuated in North American schools since the early twentieth century . Very slight regional differences in sensitivity to compounds exist, though these regional differences are subtle and do not conform exactly to the mythical tongue map. Individual taste buds (which contain approximately 100 taste receptor cells), in fact, typically respond to compounds evoking each of the five basic tastes.
The basic tastes are those commonly recognized types of taste sensed by humans. Humans receive tastes through sensory organs called taste buds or gustatory calyculi, concentrated on the upper surface of the tongue, but a few are also found on the roof of ones mouth furthering the taste sensations we can receive. Scientists describe five basic tastes: bitter, salty, sour, sweet, and umami (described as savory, meaty, or brothy). The basic tastes are only one component that contributes to the sensation of food in the mouth—other factors include the food's smell, detected by the olfactory epithelium of the nose, its texture, detected by mechanoreceptors, and its temperature, detected by thermoreceptors. Taste and smell are subsumed under the term flavor.
In Western culture, the concept of basic tastes can be traced back at least to Aristotle, who cited "sweet" and "bitter", with "succulent", "salt", "pungent", "harsh", "puckery", and "sour" as elaborations of those two basics. The ancient Chinese Five Elements philosophy lists slightly different five basic tastes: bitter, salty, sour, sweet, and spicy. Japanese and Indian cultures each add their own sixth taste to the basic five.
For many years, books on the physiology of human taste contained diagrams of the tongue showing levels of sensitivity to different tastes in different regions. In fact, taste qualities are found in all areas of the tongue, in contrast with the popular view that different tastes map to different areas of the tongue.
The receptors for all known basic tastes have been identified. The receptors for sour and salty are ion channels while the receptors for sweet, bitter, and umami belong to the class of G protein coupled receptors.
In November 2005, a team of French researchers experimenting on rodents claimed to have evidence for a sixth taste, for fatty substances. It is speculated that humans may also have the same receptors. Fat has occasionally been raised as a possible basic taste in the past (Bravo 1592, Linnaeus 1751) but later classifications abandoned fat as a separate taste (Haller 1751 and 1763).
Meanwhile, scientists from the Monell Chemical Senses Center continue to research the five basic tastes, especially Umami.
For a long period, it has been commonly accepted that there are a finite number of "basic tastes" by which all foods and tastes can be grouped. Just like with primary colors, these "basic tastes" only apply to the human perception, ie. the different sorts of tastes our tongue can identify. Up until the 2000s, this was considered to be a group of four basic tastes. More recently, a fifth taste, Umami, was added by a wide number of authorities in this field.
The bitter taste is perceived by many to be unpleasant, sharp, or disagreeable. Common bitter foods and beverages include coffee, unsweetened chocolate, bitter melon, beer, uncured olives, citrus peel, many plants in the Brassicaceae family, dandelion greens and escarole. Quinine is also known for its bitter taste and is found in tonic water.
The most bitter substance known is the synthetic chemical denatonium. It is used as an aversive agent that is added to toxic substances to prevent accidental ingestion. This was discovered in 1958 during research on lignocaine, a local anesthetic, by Macfarlan Smith of Edinburgh, Scotland.
Research has shown that TAS2Rs (taste receptors, type 2, also known as T2Rs) such as TAS2R38 coupled to the G protein gustducin are responsible for the human ability to taste bitter substances. They are identified not only by their ability to taste for certain "bitter" ligands, but also by the morphology of the receptor itself (surface bound, monomeric). Researchers use two synthetic substances, phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) to study the genetics of bitter perception. These two substances taste bitter to some people, but are virtually tasteless to others. Among the tasters, some are so-called "supertasters" to whom PTC and PROP are extremely bitter. This genetic variation in the ability to taste a substance has been a source of great interest to those who study genetics. In addition, it is of interest to those who study evolution since PTC-tasting is associated with the ability to taste numerous natural bitter compounds, a large number of which are known to be toxic.
Saltiness is a taste produced primarily by the presence of sodium ions. Other ions of the alkali metals group also taste salty. However the further from sodium the less salty is the sensation. The size of lithium and potassium ions most closely resemble those of sodium and thus the saltiness is most similar. In contrast rubidium and cesium ions are far larger so their salty taste differs accordingly. Potassium, as potassium chloride - KCl, is the principle ingredient in salt subshanism for detecting sour taste is similar to that which detects salt taste. Hydrogen ion channels detect the concentration of hydronium ions (H3O+ ions) that are formed from acids and water.
Hydrogen ions are capable of permeating the amiloride-sensitive channels, but this is not the only mechanism involved in detel, which normally functions to hyperpolarize the cell. By a combination of direct intake of hydrogen ions (which itself depolarizes the cell) and the inhibition of the hyperpolarizing channel, sourness causes the taste cell to fire in this specific manner. In addition, it has also been suggested that weak acids, such ak acid transport.Template:Unclear
Main article: Sweetness
Sweetness is produced by the presence of sugars, some proteins and a few other substances. Sweetness is often connected to aldehydes and ketones, which contain a carbonyl group. Sweetness is detected by a variety of G protein coupled receptors coupled to the G protes 30 millimoles per litre, and 5-Nitro-2-propoxyaniline 0.002 millimoles per litre.
Template:Seealso
Main article: Umami
Template:Nihongo is the name for the taste sensation produced by compounds such as glutamate, and are commonly found in fermented and aged foods. In English, it is also described as "meatiness", "relish", or "savoriness". The Japanese word comes from Template:Nihongo for yummy, red a fundamental taste in Chinese and Japanese cooking, but i Asia. There is a synergistic effect between MSG, IMP, and GMP which together in certain ratios produce a strong umami.
Some umami taste buds respond specifically to glutamate in the same way that sweet ones respond to sugar. Glutamate binds to a variant of G protein coupled glutamate receptors.
Recent research has revealed a potential taste receptor called the CD36 receptor to be reacting to fat, more specifically, fatty acids. This receptor was found in mice, but probably exists among other m same urge to consume fatty acids as normal mice, and failed to prepare gastric juices in their digestive tracts to digest fat. This discovery may lead to a better understanding of the biochemical reasons behind this behaviour, although more research is still necessary to confirm the relationship between CD36 and the perception of fat.
The tongue can also feel other sensations, not generally called tastes per se or included in the five human tastes. These are largely detected by the somatosensory system.
Some foods, such as unripe fruits, contain tannins or calcium oxalate that cause an astringent or rough sensation of the mucous membrane of the mouth or the teeth. Examples include tea, rhubarb, grapes and unripe persimmons and bananas.
Less exact terms for the astrhard", or "styptic",. The Chinese have a term for this: 澀 (sè), the Koreans have 떫다 (tteolda), the Japanese call it 渋い (shibui), while Thai have ฝาด (fard), the Malay use kelat, Filipinos use pakla, and in Russian there is вяжущий (vyazhuschimore or less in line with the Japanese approach to umami.
Most people know this taste (e.g. Cu2+, FeSO4, or blood in mouth), but it is not only taste but olfactory receptors worked in this case (Guth and Grosch, 1990). Metallic taste is commonly known, however biologists are reluctant to categorize it with the other taste sensations. One of the primary reasons is that it is not one commonly associated with consumption of food. Proponents of the theory contest that the sensation is readily detectable and distinguishable to test subjects. Therefore, metallic should be added as one of the basic types of sensations in the chemical receptor senses.
See also: Scoville scale and Pungency
Substances such as ethanol and capsaicin cause a burning sensation by inducing a trigeminal nerve reaction together with normal taste reception. The sensation of heat is caused by the food activating a nerve cell called TRP-V1, which is also activated by hot temperatures. The piquant sensation, usually referred to as being "hot" or "spicy", is a notable feature of Mexican, Hungarian, Indian, Szechuan, Korean, Indonesian, central Vietnameain capsaicin) and black pepper.
If tissue in the oral cavity has been damaged or sensitised, ethanol may be e alcohol.
In many cases, this parthe taste nerves are activated when consuming foods like chili peppers, the reaction commonly interpreted as "hot" is derived from the tongue's pain nerves firinmint, menthol, ethanol or camphor, which is caused by the food activating the TRP-M8 ion channel on nerve cells that also signal cold. Unlike theuan pepper. The cuisine of Sichuan province ese researchers refer to the kokumi in foods laden with alcohol- and thiol-groups in their amino acid extracts which has been described variously as continuity, mouthfulness, mouthfeel, and tse of sorbitol, erythritol, xylitol, mannitol, lactitol, and maltitol. When they are dry and are allowed to dissolve in saliva, heat effects can be recognized. The cooling effect upon eating may be desirable, as in a mint candy made with crystindividuals of European descent, it is estimated that about 25% of the population are supertasters. The cause of this heightened response is currently unknown, although it is thought to be, at least in part, due to an increased number of fungiform papillae. The evolutionary advantage to supertasting is unclear. In some environments, heightened taste response, particularly to bitternnergy-rich environment, supertasting may be cardioprotective, due to decreased liking and intake of fat, but may increase cancer ried out of contact with the sensory end organs for taste. Some aftertastes may be pleasant, others unpleasant.
Alcoholic beverages such as wine, beer and whiskey are noted for having particularly strong aftertastes. Foods with notable aftertastes include spicy foods, such as Mexican food (e.g. chili pepper), or Indian food (such as curry).
Medicines and tablets may also have a lingering aftertaste.
An acquired taste is an appreciation for a food or beverage that is unlikely to be enjoyed, in part or in full, by a person who has not had substantial exposure to it, usually because of some unfamiliar aspect of the food or beverage, including a strong or strange odor, taste, or appearance. The process of “acquiring” a taste involves consuming a food or beverage in the hope of learning to enjoy it. In most cases, this introductory period is considered worthwhile, as many of thecal causes
Plugged noses
Zinc deficiency
It is also important to consider that flavor is the overall, total sensation induced during mastication (e.g. taste, touch, pain and smell). Smell (olfactory stimulat |
Theory_of_cognitive_development | ge; called the co-ordination of secondary course round modest circular reactions stage, which occurs from eight to twelve months, is when Piaget (1954) thought that object permanence developed.
The fifth sub-stage; the tertiary circular reactions phase, occurs from twelve to eighteen months. New means through active experimentation and creativity in the actions of theof four stages of cognitive development. By observing sequences of play, Piaget was able to demonstrate that towards the end of the second year a qualitatively new kind of psychological functioning occurs.
(Pre)Operatory Thought in Piagetian theory is any procedure for mentally acting on objects. The hallmark of the preoperational stage is sparse and logically inadequate mental operations. During this stage the child learns to use and to represent objects by images and words, in other words they learn to use symbolic thinking. Thinking is still egocentric: The child has difficulty taking the viewpoint of others.
The child can classify objects by a single feature: e.g. groups together all the red blocks regardless of shape or all the square blocks regardless of color. According to Piaget, the Pre-Operational stage of development follows the Sensorimotor stage and occurs between 2–6 years of age. In this stage, children develop their language skills. They begin representing things with words and images. However, they still use intuitive rather than logical reasoning. At the beginning of this stage, they tend to be egocentric, that is, they are not aware that other people do not think, know and perceive the same as them. Children have highly imaginative minds at this time and actually assign emotions to inanimate objects. The theory of mind is also critical to this stage.
The Preoperational Stage can be further broken down into the Preconcvities to solve problems and obtain goals but they are unaware of how they came to their conclusions. For example a child is shown 7 dogs and 3 cats and asked if there are more dogs than cats. The child would respond positively. However when asked if there are more dogs than animals the child would once again respond positively. Such fundamental errors in logic show the transition between intuitiveness in solving problems and true logical reasoning acquired in later years when the child grows up.
Piaget considered that children primarily learn through imitation and play throughout these first two stages, as they build up symbolic images through internalized activity.
The Concrete operational stage is the third of four stages of cognitive development in Piaget's theory. This stage, which follows the Preoperational stage, occurs between the ages of 7 and 11 years and is characterized by the appropriate use of logic. Important processes during this stage are:
Seriation—the ability to sort objects in an order according to size, shape, or any other characteristic. For example, if given different-shaded objects they may make a color gradient.
Classification—the ability to name and identify sets of objects according to appearance, size or other characteristic, including the idea that one set of objects can include another.
Decentering—where the child takes into account multiple aspects of a problem to solve it. For example, the child will no longer perceive an exceptionally wide but short cup to contain less than a normally-wide, taller cup.
Reversibility—where the child understands that numbers or objects can be changed, then returned to their original state. For this reason, a child will be able to rapidly determine that if 4+4 equals 8, 8−4 will equal 4, the original quantity.
Conservation—understanding that quantity, length or number of items is unrelated to the arrangement or appearance of the object or items. For instance, when a child is presented with two equally-sized, full cups they will be able to discern that if water is transferrane comes back. A child in the concrete operations stage will say that Jane will still think it's under the box even though the child knows it is in the drawer. (See also False-belief task).
The formal operational period is the fourth and final of the periods of cognitive development in Piaget's theory. This stage, which follows the Concrete Operational stage, commences at around 12 years of age (puberty) and continues into adulthood. It is characterized by acquisition of the ability to think abstractly, reason logically and draw conclusions from the information available. During this stage the young adult is able to understand such things as love, "shades of gray", logical proofs, and values. Lucidly, biological factors may be traced to this stage as it occurs during puberty (the time at which another period of neural pruning occurs), marking the entry to adulthood in Physiology, cognition, moral judgement (Kohlberg), Psychosexual development (Freud), and psychosocial development (Erikson). Some two-thirds of people do not develop this form of reasoning fully enough that it becomes their normal mode for cognition, and so they remain, even as adults, concrete operational thinkers.
These four stages have been found to have the following characteristics:
They apply to thought rather than children
Although the timing may vary, the sequence of the stages does not.
Universal (not culturally specific)
Generalizable: the representational and logical operations available to the child should extend to all kinds of concepts and content knowledge
Stages are logically organized wholes
Hierarchical nature of stage sequences (each successive stage incorporates elements of previous stages, but is more differentiated and integrated)
Stages represent qualitative differences in modes of thinking, not merely quantitative differences
In view of its complexity, Psychology-as-an-academic-study is still in a comparatively undeveloped form the physical mechanisms. Piaget's "scheme"-concept is a good step in the right direction (just as Mendel's "gene"-concept was a useful half-solution) — but both these concepts are mere abstractions unless we can say something more concrete about them.
Piaget himself clearly toyed tentatively with the idea that his most basic schemes might be RNA, but confessed that biochemistry was beyond his competence (Piaget, 1967). This is documented in some detail by Traill (2005), who goes on to show that subsequent evidence does indeed support the RNA idea. But even if RNA is not the answer, it seems that some such physical embodiment must eventually be found if Non-clinical Psychology is to follow the lead of Genetics and Chemistry.
(2) The next needed progress is probably to find some plausible way in which these building-blocks could be harnessed. In principle this could be done
experimentally, but that hardly seems possible for the current scheme-and-Psychology problem — at any rate not until the topic is taken seriously enough to attract a large budget.
The alternative is to build up a theoretical model (based on as much existing evidence and interdisciplinary knowledge as possible) and see what can be done to "re-design" mind-mechanisms, at least in principle — meanwhile giving due credit to Piaget's stages, equilibration, decalage, etc., along with info-tech, physics, and anything else deemed relevant.
One such attempt (though without reference to Piaget), was made by the eminent Medical-Cybernetician Ross Ashby (1903-1972) in
his book Design for a Brain (1952, espec. Chapter 7). The main point of interest here is that he postulated a system of hierarchical controls in which active units at level-n, would be controlled by those at level-(n+1) — which in turn might have their parameters re-set by level-(n+2) — and so on. Note (i) that he did actually build robot "tortoises" by this formula (alarming observers by their uncanny abilities), and that (ii) this has an apparently-significant resemblance to Piaget's stages. (iii) Ashby suggested that human-intelligence may be chiefly due to a "runaway" capability, with no hard limit on how many "n" levels there might be — whereas other animals would always have a greater-or-lesser limit, for some reason. The same might well be claimed for Piaget's stages, even if they are actually different.
(3) Ashby confessed to certain shortcomings of his model, notably the fact that he had to fine-tune its details himself, whereas a proper bio-model should have been self organizing. The theoretical aspects of this venture were later carried forward (whilst incorporating Piagetian aspects) by Traill (1978, 1999, 2005), who chose to label the Sensorimotor level (or its earliest substage) "M0L", with subsequent higher levels being called M1L, M2L, etc. (e.g. 1978, section C2.3) — which could sometimes be more convenient than Piaget's names: "Pre-operational" etc.
Piagetians accounts of development have been challenged on several grounds. First, as Piaget himself noted, development does not always progress in the smooth manner his theory seems to predict. 'Decalage', or unpredicted gaps in the developmental progression, suggest that the stage model is at best a useful approximation. More broadly, Piaget's theory is 'domain general', predicting that cognitive maturation occurs concurrently across different domains of knowledge (such as mathematics, logic, understanding of physics, of language, etc). However, more recent cognitive developmentalists have been much influenced by trends in cognitive science away from domain generality and towards domain specificity or modularity of mind, under which different cognitive faculties may be largely independent of one another and thus develop according to quite different time-tables. In this vein, many current cognitive developmentalists argue that rather than being domain general learners, children come equipped with domain specific theories, sometimes referred to as 'core knowledge', which allows them to break into learning within that domain. For example, even young infants appear to understand some basic principles of physics (e.g. that one object cannot pass through another) and human intention (e.g. that a hand repeatedly reaching for an object has that object, not just a particular path of motion, as its goal). These basic assumptions may be the building block out of which more elaborate knowledge is constructed. Psychologist's such as Vygotsky thought differently to Piaget and suggested that language was more important that Piaget implied.
There are four major changes to the number of stages and their definitions. First and foremost, the half stages are now shown to be stages. Pascual-Leone (1987? Please confirm)discovered this. Almost all Post Piagetians accept this.(E.g. ... ?)
Second, postformal stages have been shown to exist. Kurt Fischer suggested two, Michael Commons presents evidence for four postformal stages has considered a stage suggested by Biggs and Biggs. It is a stage before the early preoperational. Commons and Richards call this stage the sentential because organisms can sequence representations of concepts.
Fourthly Traill (1978, Section C5.4; 1999, Section 8.4) suggests that there may be pre-sensorimotor stages ("M−1L", "M−2L", … … ) — evolved either prenatally in-the-womb and/or transmitted genetically, having been developed by the species and hence describable as "instincts". This is in the context of a search for a micro-physiological basis for human mental capacity↑. Here then, we are trying to complete the picture of the extreme-lower levels of the hierarchy, whereas the other three cases above are more concerned with application to the higher levels dealing with education and related macro effects.
↑ For various reasons it had been concluded that those most-basic micro-elements for logic-related thinking must have essentially a 1D stringlike structure (probably ncRNA). If so, then even the known sensorimotor Piagetian-schemes seem to be too complex, too evolved. Hence the need to seek lower levels which could be seen as the building-blocks. (Traill 1976, 2005).
Michael Barnes' stages of religious and scientific thinking
Michael Lamport Commons' Model of Hierarchical Complexity
Kieran Egan's stages of understanding
Suzy Gablik's stages of art history
Christopher Hallpike's stages of moral understanding
Lawrence Kohlberg's stages of moral development
Don Lepan's theory of the origins of modern thought and drama
Charles Raddings theory of the medieval intellectual development
R.J. Robinson's stages of history and theory of the origins of intelligence
Stafford Beer, a cybernetician and business-consultant, attempted to apply Ashby's principles to Companies and Government organizations. (e.g. Beer, 1972). |
Vitiligo_natural_history,_complications_and_prognosis | The natural history of vitiligo is variable. Depigmentation may be stable or progressive and can cause even a total body depigmentation or remit spontaneously, although spontaneous remission is uncommon.
The natural history of vitiligo is variable.
Approximately half of the cases present before the age of 20 years.
The onset is acute and starts with a rapid loss of pigmentation in sun-exposed and friction areas, most commonly face and extremities.
A latent period can occur, but remission is uncommon.
It is difficult to predict the progression and outcome of vitiligo
Some markers of poor prognosis have been identified: Family history, Mucosal involvement or mucosal vitiligo, Koebner phenomenon, Nonsegmental vitiligo |
Meningitis#Bacterial_meningitis | The meninges (singular meninx) is the system of membranes which envelop the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system. Meningitis is the inflammation of these protective membranes. Meningitis may have been described in the Middle Ages, but it was first accurately identified by the Swiss Vieusseux (a scientific-literary association) during an outbreak in Geneva, Switzerland in 1805. In 1661, Thomas Willis first described the inflammation of meninges and an epidemic of meningitis. In the 17th century, Robert Whytt provided a detailed explanation of tuberculous meningitis and its stages. This was further elaborated by John Cheyne in the same century. Meningococcal meningitis was than described by Gaspard Vieusseux, Andre Matthey in Geneva and Elisa North in Massachussetes. Meningitis may develop in response to a number of causes, including infectious agents (bacteria, viruses, fungi, or other organisms) or non-infectious causes, such as systemic illnesses that may involve CNS (e.g. neoplasms or connective tissue diseases, such as sarcoidosis, systemic lupus erythematosus (SLE), and wegener's) or certain drugs (e.g. nonsteroidal antiinflammatory drugs, intravenous immunoglobulin, intrathecal agents, and trimethoprim-sulfamethoxazole). While some forms of meningitis are mild and resolve spontaneously (e.g. viral meningitis), meningitis is a potentially serious condition owing to the proximity of the inflammation to the brain and spinal cord. The potential for serious neurologic damage or even death necessitates prompt medical attention and evaluation. The common presenting features of meningitis are, fever, neck stiffness and headache. Other symptoms include, photophobia (inability to tolerate bright light), phonophobia (inability to tolerate loud noises), irritability, altered mental status (in small children), and seizure. Physical examination of meningitis may vary in adults and infants. In adults, physical examination findings may include bradycardia, disorientation, papilledema, neck stiffness, positive brudzinski's and kernig's sign. However, petechial rash, bulging fontanelle, neck stiffness, jaundice, and convulsions are physical examination findings in infants. Diagnosis is based on clinical findings and CSF analysis. Treatment options are based on bacterial meningitis or chemotherapy and/or irradiation for neoplastic meningitis.
Bacterial meningitis can be community acquired or health care associated.
The major causes of community-acquired bacterial meningitis in adults in developed countries are Streptococcus pneumoniae, Neisseria meningitidis, and, primarily in patients over 50 years of age or those who have deficiencies in cell-mediated immunity, Listeria monocytogenes
The major causes of health care-associated ventriculitis and meningitis are different (usually staphylococci and aerobic gram-negative bacilli) and occur more commonly after neurosurgical procedures (eg, post-craniotomy, ventriculoperitoneal shunts, lumbar shunts, external ventricular drains or following head trauma such as basilar skull fracture with or without clinical evidence is presented elsewhere.
Meningitis could be classified to two main groups based on etiology:
Infectious
Non-infectious
Infectious meningitis may be classified as the following algorithm based on chronicity of symptoms.
Systemic illnesses, such as malignancies and connective tissue diseases (e.g. sarcoidosis, SLE, and wegener's) may involve meninges in their course and present as chronic meningitis.
Certain drugs may cause meningeal irritation and resemble as meningitis including:
Nonsteroidal antiinflammatory drugs (NSAIDs)
Intravenous immunoglobulin
Intrathecal agents
Certain antibiotics (eg, trimethoprim-sulfamethoxazole)
Diagnosis of meningitis, is based on clinical presentation in combination with CSF analysis in different types of meningitis.
Empiric therapy for meningitis must be initiated after CSF obtained.
The choice of empiric antibiotic therapy is depend on patient age and underlying comorbid disease.
Adapted from IDSA guidlines.
Recommendations for antimicrobial therapy in adult patients with presumptive pathogen identification by positive Gram stain.
Adapted from IDSA guidlines.
Surgical intervention is not recommended for the management of meningitis.
Adapted from the recommendations of the United States Centers for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices (ACIP) for the use of meningococcal vaccines.
The quadrivalent meningococcal conjugate vaccines (MenACWY) are Menactra (MenACWY-DT) and Menveo (MenACWY-CRM); these have replaced the quadrivalent meningococcal polysaccharide vaccine Menomune (MPSV4). MenHibrix (HibMenCY), a combination conjugate vaccine against meningococcus serogroups C and Y and Haemophilus influenzae type b, was discontinued in 2017. Trumenba (MenB-FHbp) and Bexsero (MenB-4C) are meningococcus serogroup B vaccines.
Secondary prevention with Antimicrobial chemoprophylaxis is necessary for individuals who have close contact with patients with invasive meningococcal disease. Close contacts include:
1.household members , 2.child-care center contacts ,3.anyone directly exposed to the patient's oral secretions (e.g., through kissing, mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management) in the 7 days before symptom onset. Health-care personnel should receive chemoprophylaxis if they were managing an airway or exposed to respiratory secretions of a patient with meningococcal disease. For travelers, antimicrobial chemoprophylaxis should be considered for any passenger who had direct contact with respiratory secretions from an index-patient or for anyone seated directly next to an index-patient on a prolonged flight (i.e., one lasting ≥8 hours)
Recommended chemoprophylaxis regimens for protection against meningococcal disease — Advisory Committee on Immunization Practices (ACIP), United States, 2012 |
Hand-foot-and-mouth_disease_ultrasound | There are no ultrasound findings associated with hand-foot-and-mouth disease.
There are no ultrasound findings associated with hand-foot-and-mouth disease.
|
Natural_orifice_translumenal_endoscopic_surgery_(NOTES)_(patient_information) | Natural orifice translumenal endoscopic surgery (NOTES) is an experimental surgical technique whereby abdominal and thoracic operations can be performed without any scars
or with very tiny ones
The procedure is performed through a hollow organ by passing surgical instruments and a tiny camera through a natural orifice (mouth
The patients recover more quickly and experience less pain and better cosmesis
The postoperative complications such as wound infections and hernias are significantly reduced
Animal models and cadavers have been used to demonstrate that NOTES procedures are safe and feasible
Some of the NOTES applications are abdominal cavity screening
colorectal resection and trans-esophageal myotomy
The evolving concept of natural orifice translumenal endoscopic surgery (NOTES) combines the techniques of minimally invasive surgery with flexible endoscopy
This permits performing certain procedures endoscopically by passing the endoscope and the surgical instruments through a natural orifice
then transluminally into areas that would not otherwise be accessible endoscopically (by the commonly used endoscope)
NOTES procedures have been expanded in the last few years to cover a wide range of complex surgical operations by using the right translumenal route and suitable instrumentation
which is a high volume and relatively simplemed successfully on many patients
Robotic surgery has been investigated to be applied in NOTES procedures
a miniature in vivo robot has been developed for NOTES
Potential advantages of NOTES over other surgical methods include the following
There are faster recovery and shorter hospital stay in NOTES than laparoscopy or laparotomy procedures
Usually the patient is discharged on postoperative days 1 or 2 if the NOTES procedure has not been complicated
There is less physiologic insult in NOTES procedures than laparoscopy or laparotomy procedures
NOTES can avoid and minimize the potential complications of wound infections
Wound infection is a common surgical complication
Eliminating all skin incisions would eliminate the adverse impact of wound infection on the health care costs and patients' recovery
NOTES Decreases the incidence of incisional hernias and postoperative adhesions
Anesthesia requirements in NOTES are relatively less than other types of surgery
NOTES causes less immunosuppression for the patient than other surgical approaches
Postoperative pulmonary and diaphragmatic function are better in NOTES procedures
Better cosmetic results with the potential for scarless abdominal surgery
NOTES may have an advantages in specific subpopulations
It can be performed in morbidly obese patients
in whom traditional access to the peritoneal cavity can be difficult because of abdominal wall thickness
thus an easy alternative in these patients
Patients usually do not need post-operative narcotic medications (analgesia)
This may be due to the minimal trauma for the muscle fibers
nerves and skin by this kind of surgery
Human cases that have been performed successfully include
Transanal rectosigmoid resection for tumors
Transgastric debridement of necrotizing pancreatitis
Puncturing one of the viscera to perform the surgical procedure
This needs to be assessed thoroughly regarding the presence of long term complications
Instrumentation is still inadequate to perform all NOTES procedures
Costly and time consuming NOTES training sessions should be provided for surgeons and gastroenterologists before they could be able to perform NOTES procedures
Cultural and geographical variations may play a roll in the decision to accept a transvaginal surgery or not
It is more difficult to handle complications in NOTES compared with other approaches because of the limited space available for the NOTES instruments
This may require conversion of the procedure to be open sometimes
Beside the complications of any surgical operation (laceration
NOTES complications may also include
Injury to abdominal organs
Bowel perforation or injury
Biliary fistulae and leaks
Urinary incontinence
Fecal incontinence
Peritonitis
Financial resources are required for the technological developments and NOTES implementation
operative time may be longer in some NOTES procedures than the standard laparoscopic approach
Adequate instrumentation and training might shorten the time required for NOTES in the future
NOTES procedures have been performed through different natural orifices
transvaginal approach is the most commonly used and has the highest success rate for certain procedures
Transvaginal route is the most common approach that has been used for NOTES procedures
This approach has been used for cholecystectomy
Transvaginal fertility procedures and oocytes procurement transvaginally have been performed for years
Transvaginal cholecystectomy and transvaginal appendectomy have been performed in humans
There s of the vagina
This is considered an advantage for the large size organs
It is relatively easier and safer to perform some procedures via this approach
Vaginal wall closure is less complex than gastric wall closure and has less complications rate
A single stitch can be easily used to close the incision
transvaginal NOTES has lower complications rate than other approaches
Transvaginal rout is considered the best rout for performing minor uterine procedures for benign uterine diseases
Sexual function is not affected by transvaginal extraction of the uterus or other organs
The long-term effects of transvaginal procedures have not been investigated yet
Some of the drawbacks of this approach include
It can be used only in females
The NOTES surgeon should have the basics of gynecological surgery before performing a transvaginal procedure
Women may present with dyspareunia and infertility after the transvaginal NOTES procedure
There is a potential risk for urinary tract infection after urinary bladder cannulation (required in transvaginal NOTES procedures)
There is a risk for injury to nearby organs
The rectum and the sigmoid colon are at higher risk than other structures
Transvaginal approach may have higher incidence rates for certain complications (bladder injury and vaginal hematoma) than other surgical approaches
there are clinical trials that aim to assess the oncological safety of this approach in treating benign and malignant colorectal tumors
This is considered a less invasive option to perform colorectal procedures
such as resection of colonic ulcers
Fecal incontinence may result from the pressure on the anal sphincter by the platform during performing the procedure
Studies have demonstrated that there is no higher risk of infection or peritonitis by entering into the peritoneal cavity via a transcolonic/transanal puncture in the presence of adequate closure for the colotomy
This NOTES approach is more sophisticated than the transvaginal route
especially in terms of gastric wall closure after extracting the organ (requires laparoscopic assistance)
the complication rate is higher in this approach compared with the transvaginal route
cholecystectomy and cancer staging have been performed by this approach
Retrieval of dislodged endoscopic gastrostomy tube via this approach has been reported as well
all cases require some degree of hybridization (laparoscopic assistance) which is required for most transgastric NOTES procedures
This approach can be used in all patients regardless their gender but the extracted specimen (through the oral cavity) needs to be relatively smaller than those extracted by other routs
Peritonitis and esophageal rupture may occur after transgastric procedures
complications are more common in transgastric procedures than in transvaginal procedures
This approach can be used for the treatment of achalasia (failure of relaxation of the lower esophageal sphincter that causes difficulty in swallowing)
Many cases of per oral endoscopic myotomy (POEM) have been performed successfully to treat achalasia
Esophageal injuries could be prevented during performing the procedure by using gastroesophageal overtubes
conventional flexible endoscopes and other instruments are used to perform the procedure
Some procedures can be performed through the urethra or the urinary bladder
Transurethral resection of the prostate (TURP)is a urological operation to treat benign prostatic hyperplasia (BPH)
it is performed by visualising the prostate through the urethra and removing tissue by electrocautery or sharp dissection
This is considered the most effective treatment for benign prostatic hyperplasia (BPH)
Outcome is considered excellent for 80-90% of BPH patients
This approach has been used to perform percutaneous needle biopsy of tumors of intraabdominal organs and retroperitoneal structures
Ovarian follicles aspiration has been performed using the transcystic approach |
Retinoblastoma_classification | There are several classification systems available for retinoblastoma. As the treatment of the tumor has evolved, a new classification system has been introduced. For intraocular disease, the available grouping systems include International Intraocular Retinoblastoma Classification (IIRC), Intraocular Classification of Retinoblastoma (ICRB), and cTNMH systems. For extraocular disease, the International Retinoblastoma Staging System (IRSS) and cTNMH schemes can be used.
Retinoblastoma has been classified according to different classification systems for variable purposes.
Each classification system has been developed depending on the change in the management of the tumor.
For treatment purposes, retinoblastoma is classified into:
This classification system incudes the following: International Intraocular Retinoblastoma Classification (IIRC), Intraocular Classification of Retinoblastoma (ICRB), The cTNMH system of American Joint Committee on Cancer (AJCC)
This classification system was first introduced in 1960 and used to predict the chance of salvaging the eye after external beam radiotherapy.
However, following the introduction of chemotherapy for retinoblastoma treatment, it lost its significance.
This classification system includes the following: International retinoblastoma staging system, cTNMH system of American Joint Committee on Cancer (AJCC)
To see the full staging system click here. |
De_Quervain%27s_thyroiditis_natural_history,_complications_and_prognosis | De Quervain's thyroiditis develops after a viral prodrome and presents as painful thyroid gland with symptoms of thyrotoxicosis. It further leads to a euthyroid phase and eventually hypothyroid phase before the complete resolution of the disease. Complications include hypothyroidism and rarely, esophageal or tracheal compression.
De Quervain's thyroiditis develops after a viral prodrome and presents as painful thyroid gland with symptoms of thyrotoxicosis. It further leads to a euthyroid phase and eventually hypothyroid phase before the complete resolution of the disease.
It includes:
Low-grade fever and viral flu-like symptoms, such as sore throat, myalgia, arthralgia, and malaise.
High-grade fever and neck pain with a tender and diffuse thyroid gland enlargement follow flu-like symptoms.
It follows the prodromal stage and includes the symptoms of thyrotoxicosis such as:
Tachycardia and tremors
Irritability and nervousness
Thyrotoxic stage is followed by a 1–3-week period of euthyroid phase.
The transient hypothyroid stage lasts for 6-12 months.
Rarely, the hypothyroid stage may persist for a longer duration.
Complications that can develop as a result of de Quervain's thyroiditis are:
Hypothyroidism
Tracheal compression
Esophageal compression
Prognosis of de Quervain's thyroiditis is usually good.
|
Peliosis_hepatis_physical_examination | Physical examination of patients with Peliosis Hepatis is usually normal.
Physical examination of patients with Peliosis Hepatis is usually normal. Other physical examination might include Hepatomegaly which should prompt further diagnosis.
|
Facial_Nerve | The neurological examination is the physical examination of the nervous system. It attempts to identify or exclude signs of nervous system disease, and - if these signs are present - to produce a likely anatomical or physiological explanation that can be tested through medical imaging, neurophysiology, blood tests, lumbar puncture or a combination.
The Neurological Examination is directed primarily towards the localization of lesions within the nervous system and is traditionally split into an examination of the cognitive state, cranial nerves, motor system, sensory system, cerebellar system, walking and gait and the extrapyramidal system.
Assessment of consciousness, often using the Glasgow Coma Scale (EMV)
Mental status examination, often including the abbreviated mental test score (AMTS) or mini mental state examination (MMSE)
Global assessment of higher functions
Intracranial pressure is roughly estimated by fundoscopy; this also enables assessment for microvascular disease
Cranial nerves (I-XII): sense of smell (I), visual fields and acuity (II), eye movements (III, IV, VI) and pupils (III, sympathetic and parasympathetic), sensory function of face (V), strength of facial (VII) and shoulder girdle muscles (XI), hearing (VII, VIII), taste (VII, IX, X), pharyngeal movement and reflex (IX), tongue movements (XII)
Reflexes: masseter, biceps and triceps tendon, knee tendon, ankle jerk and plantar (i.e. Babinski sign). Globally, brisk reflexes suggest an abnormality of the UMN or pyramidal tract, while decreased reflexes suggest abnormality in the anterior horn, LMN, peripheral nerve or motor end plate. A reflex hammer is used for this testing.
Muscle strength (typically graded on the MRC scale I-V)
Sensory system (to fine touch, pain, temperature)
Muscle tone and signs of rigidity
Finger-to-nose and ankle-over-tibia tests for ataxia
Various tests for dysdiadochokinesia
Tests for cogwheeling (abnormal tone suggestive of Parkinson's disease) or gegenhalten (more common in dementia). Gegenhalten is resistance to passive change, where the strenerate an impulse that is carried via sensory nerves to the spinal cord. At this juncture, the message is transmitted across a synapse to an appropriate lower motor neuron. An upper motor neuron, whose cell body resides in the brain, also provides input to this synapse.
The signal then travels down the lower motor neuron to the target muscle.
The sensory and motor signals that comprise a reflex arc travel over anatomically well characterized pathways. Pathologic processes affecting discrete roots or named peripheral nerves will cause the reflex to be diminished or absent. This can obviously be of great clinical significance. The Achilles reflex is dependent on the S1 and S2 nerve roots. Herniated disc material (a relatively common process) can put pressure on the S1 nerve root, causing pain along its entire distribution (i.e. the lateral aspect of the lower leg). If enough pressure if placed on the nerve, it may no longer function, causing a loss of the Achilles reflex. In extreme cases, the patient may develop weakness or even complete loss of function of the muscles innervated by the nerve root, a medical emergency mandating surgical decompression. The specific nerve roots that comprise the arcs are listed for each of the major reflexes described below.
A normal response generates an easily observed shortening of the muscle. This, in turn, causes the attached structure to move.
The vigor of contraction is graded on the following scale:
0: No evidence of contraction
1+: Decreased, but still present (hypo-reflexic)
2+: Normal
3+: Super-normal (hyper-reflexic)
4+: Clonus: Repetitive shortening of the muscle after a single stimulation
This is most easily done with the patient seated, feet dangling over the edge of the exam table. If they cannot maintain this position, have them lie supine, crossing one leg over the other. Or, failing that, arrange the legs in a frog-type position.
Identify the Achilles tendon, a taut, discrete, cord-like structure running from the heel to the muscles of the calf. If you are unsure, ask the patient to plantar flex (i.e. "step on the gas"), which will cause the calf to contract and the Achilles to become taut.
Position the foot so that it forms a right angle with the rest of the lower leg. You will probably need to support the bottom of the foot with your hand.
Strike the tendon directly with your reflex hammer. Be sure that the calf if exposed so that you can see the muscle contract. A normal reflex will cause the foot to plantar flex (i.e. move into your supporting hand).
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Achilles tendon:Tendon is outlined,
, , Achilles tendon:Tendon is grasped by forceps (gross dissection),
, , Position for checking Achilles reflex,
, , Position for checking Achilles reflex,
, , Position for checking Achilles reflex,
This is most easily done with the patient seated, feet dangling over the edge the exam table. If they cannot maintain this position, have them lie supine (i.e. on their backs).
Identify the patellth your reflex hammer. If you are having trouble identifying the exact location of the tendon (e.g. if there is a lot of subcutaneous fat), place your index finger firmly on top of it. Strike your finger, which should then transmit the impulse.
For the supine patient, support the back of their thigh with your hands such that the knee is flexed and the quadriceps muscles relaxed. Then strike the tendon as described above.
Make sure that the quadriceps are exposed so that you can see muscle contraction. In the normal reflex, the lower leg will extend at the knee.
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Patellar tendon: Outlined,
, , Patellar tendon: The tendon is grasped by forceps (gross dissection),
, , Patellar reflex testing: Seated patient,
, , Patellar reflex testing: Supine position,
This is most easily done with the patient seated.
Identify the location of the biceps tendon. To do this, have the patient flex at the elbow while you observe and palpate the antecubital fossa. The tendon will look and feel like a thick cord.
The patient's arm can be positioned in one of two ways:
Allow the arm to rest in the patient's lap, forming an angle of slightly more then 90 degrees at the elbow.
Support the arm in yours, such that your thumb is resting directly over the biceps tendon (hold their right arm with your right; and vice versa)
Make sure that the biceps muscle is completely relaxed.
It may be difficult to direct your hammer strike such that the force is transmitted directly on to the biceps tendon, and not dissipated amongst the rest of the soft tissue in the area. If you are supporting the patient's arm, place your thumb on the tendon and strike this digit. If the arm is unsupported, place your index or middle fingers firmly against the tendon and strike them with the hammer.
Make sure that the patient's sleeve is rolled up so that you can directly observe the muscle as well as watch the lower arm for movement. A normal response will cause the biceps to contract, drawing the lower arm upwards.
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Biceps tendon: The tendon is outlined,
, , Biceps tendon: The tendon is grasped by forceps (gross dissection),
, , Biceps reflex testing: The arm is not supported,
, , Biceps reflex testing: The arm is supported,
This is most easily done with the patient seated. The lower arm should be resting loosely on the patient's lap.
The tendon of the Brachioradialis muscle cannot be seen or well palpated, which makes this reflex a bit tricky to elicit. The tendon crosses the radius (thumb side of the lower arm) approximately 10 cm proximal to the wrist.
Strike this area with your reflex hammer. Usually, hitting anywhere in the right vicinity will generate the reflex.
Observe the lower arm and body of the Brachioradialis for a response. A normal reflex will cause the lower arm to flex at the elbow and the hand to supinate (turn palm upward).
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Brachioradialis tendon: The tendon is outlined,
, , Brachioradialis tendon: The tendon is grasped by forceps (gross dissection),
, , Brachioradialis reflex,
This is most easily done with the patient seated.
Identify the triceps tendon, a discrete, broad structure that can be palpated (and often seen) as it extends across the elbow to the body of the muscle, located on the back of the upper arm. If you are having trouble clearly identifying the tendon, ask the patient to extend their lower arm at the elbow while you observe and palpate in the appropriate region.
The arm can be placed in either of 2 positions:
Gently pull the arm out from the patient's body, such that it roughly forms a right angle at the shoulder. The lower arm should dangle directly downward at the elbow.
Have the patient place their hands on their hips.
Either of these techniques will allow the triceps to completely relax. If you are certain as to the precise location of the tendon, strike this area directly with your hammer. If the target is not clearly apparent or the tendon is surrounded by an excessive amount of subcutaneous fat (which might dissipate the force of your strike), place your index or middle finger firmly against the structure. Then strike your finger.
Make sure that the triceps is uncovered, so that you can observe the response. The normal reflex will cause the lower arm to extend at the elbow and swing away from the body. If the patient's hands are on their hips, the arm will not move but the muscle should shorten vigorously.
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Triceps tendon: The tendon is outlined,
, , The triceps tendon is grasped by a forceps (gross dissection),
, , Triceps reflex; the arm is supported ,
, , Triceps reflex; the arm is not supported ,
Normal reflexes require that every aspect of the system function normally. Breakdowns cause specific patterns of dysfunction. These are interpreted as follows:
Disorders in the sensory limb will prevent or delay the transmission of the impulse to the spinal cord. This causes the resulting reflex to be diminished or completely absent. Diabetes induced peripheral neuropathy (the most common sensory neuropathy seen in developed countries), for example, is a relatively common reason for loss of reflexes.
Abnormal lower motor neuron (LMN) function will result in decreased or absent reflexes. If, for example, a peripheral motor neuron is transected as a result of trauma, the reflex dependent on this nerve will be absent.
If the upper motor neuron (UMN)is completely transected, as might occur in traumatic spinal cord injury, the arc receiving input from this nerve becomes disinhibited, resulting in hyperactive reflexes. Of note, immediately following such an injury, the reflexes are actually diminished, with hyper-reflexia developing several weeks later. A similar pattern is seen with the death of the cell body of the UMN (located in the brain), as occurs with a stroke affecting the motor cortex of the brain.
Primary disease of the neuro-muscular junction or the muscle itself will result in a loss of reflexes, as disease at the target organ (i.e. the muscle) precludes movement.
A number of systemic disease states can affect reflexes. Some have their impact through direct toxicity to a specific limb of the system. Poorly controlled diabetes, as described above, can result in a peripheral sensory neuropathy. Extremes of thyroid disorder can also affect reflexes, though the precise mechanisms through which this occurs are not clear. Hyperthyroidisim is associated with hyperreflexia, and hypothyroidism with hyporeflexia.
Detection of abnormal reflexes (either increased or decreased) does not necessarily tell you which limb of the system is broken, nor what might be causing the dysfunction. Decreased reflexes could be due to impaired sensory input or abnormal motor nerve function. Only by considering all of the findings, together with their rate of progression, pattern of distribution (bilateral v unilateral, etc.) and other medical conditions can the clinician make educated diagnostic inferences about the results generated during reflex testing.
If you are unable to elicit a reflex, stop and consider the following:
Are you striking in the correct place? Confirm the location of the tendon by observing and palpating the appropriate region while asking the patient to perform an activity that causes the muscle to shorten, making the attached tendon more apparent.
Make sure that your hammer strike is falling directly on the appropriate tendon. If there is a lot of surrounding soft tissue that could dampen the force of the strike, place a finger firmly on the correct tendon and use that as your target.
Make sure that the muscle is uncovered so that you can see any contraction (occasionally the force of the reflex will not be sufficient to cause the limb to move).
Sometimes the patient is unable to relax, which can inhibit the reflex even when all is neurologically intact. If this occurs during your assessment of lower extremity reflexes, ask the patient to interlock their hands and direct them to pull, while you simultaneously strike the tendon. This sometimes provides enough distraction so that the reflex arc is no longer inhibited.
Occasionally, it will not be possible to elicit reflexes, even when no neurological disease exists. This is most commonly due to a patient's inability to relax. In these settings, the absence of reflexes are of no clinical consequence. This assumes that you were otherwise thorough in your history taking, used appropriate examination techniques, and otherwise identified no evidence of disease.
The Babinski response is a test used to assess upper motor neuron dysfunction and is performed as follows:
Use the handle end of your reflex hammer, which is solid and comes to a point.
The patient may either sit or lie supine.
Start at the lateral aspect of the foot, near the heel. Apply steady pressure with the end of the hammer as you move up towards the ball (area of the metatarsal heads) of the foot.
When you reach the ball table. Tell them what you are going to do and why. If it's unlikely to contribute important information (e.g. screening exam of the normal patient) and they are quite averse, simply skip it.
Interpretation: In the normal patient, the first movement of the great toe should be downwards (i.e. plantar flexion). If there is an upper motor neuron injury (e.g. spinal cord injury, stroke), then the great toe will dorsiflex and the remainder of the other toes will fan out.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Babinski response is present.
A few additional things to remember:
Newborns normally have a positive Babinski. It usually goes away after about 6 months.
Sometimes you will be unable to generate any response, even in the absence of disease. Responses must therefore be interpreted in the context of the rest of the exam.
If the great toe flexes and the other toes flair, the Babinski Response is said to be present. If not (i.e. normal), it is recorded as absent. For reasons of semantics, the Babinski is not recorded as '+' or '-'.
Withdrawal of the entire foot (due to unpleasant stimulation), is not interpreted as a positive response.
The cerebellum fine tunes motor activity and assists with balance. Dysfunction results in a loss of coordination and problems with gait. The left cerebellar hemisphere controls the left side of the body and vice versa.
Specifics of Testing: There are several ways of testing cerebellar function. For the screening exam, using one modality will suffice. If an abnormality is suspected or identified, multiple tests should be done to determine whether the finding is durable. That is, if the abnormality on one test is truly due to cerebellar dysfunction, other tests should identify the same problem. Gait testing, an important part of the cerebellar exam, is discussed separately (see next section).
Finger to nose testing:
With the patient seated, position your index finger at a point in space in front of the patient.
Instruct the patient to move their index finger between your finger and their nose.
Reposition your finger after each touch.
Then test the other hand.
Interpretation: The patient should be able to do this at a reasonable rate of speed, trace a straight path, and hit the end points accurately. Missing the mark, known as dysmetria, may be indicative of disease.
Rapid Alternating Finger Movements:
Ask the patient to touch the tips of each finger to the thumb of the same hand.
Test both hands.
Interpretation: The movement should be fluid and accurate. Inability to do this, known as dysdiadokinesia, may be indicative of cerebellar disease.
Rapid Alternating Hand Movements:
Direct the patient to touch first the palm and then the dorsal side of one hand repeatedly against their thigh.
Then test the other hand.
Interpretation: The movement should be performed with speed and accuracy. Inability to do this, known as dysdiadokinesia, may be indicative of cerebellar disease.
Heel to Shin Testing:
Direct the patient to move the heel of one foot up and down along the top ofple, the patient is visually impaired, they may not be able to see the target during finger to nose pointing. Alternatively, weakness due to a primary muscle disorder might limit the patient's ability to move a limb in the fashion required for somerebellar test results.
Ability to stand and walk normally is dependent on input from several systems, including: visual, vestibular, cerebellar, motor, and sensory. The precise cause(s) of the dysfunction can be determined by identifying which aspect of gait is abnormal and incorporating this information with that obtained during the rest of the exam. Difficulty getting out a chair and initiating movement, for example, would be consistent with Parkinson's Disease. On the other hand, lack of balance and a wide based gait would suggest a cerebellar disorder. In each case, finding elsewhere in the exam should help point you in the right direction.
A lot of information about neurological (and other) disorders can be gained from simply watching a patient stand and then walk. For the screening exam, simply observing while the patient walks into your office and gets up and down from the exam table will provide all of the relevant information. If there is suspicion of neurological disease (based on history, other exam findings, observation of gait) then more detailed testing should be performed. Proceed as follows:
Ask the patient to stand. If they are very weak or unsteady, make sure that you are in a position and capable of catching and supporting them if they fall. Enlist the help of a colleague if you need an extra pair of hands. If you are still unsure as to whether standing/walking can be performed safely, skip this area of testing. No test result is worth a broken hip!
Have the patient stand in one place. As mentioned above, make sure that you are capable/in position to catch and support them if they fall. This is a test of balance, incorporating input from the visual, cerebellar, proprioceptive, and vestibular systems. If they are able to do this, have them close their eyes, removing visual input. This is referred to as the Romberg test. Loss of balance suggests impaired proprioception, as it is this pathway which should provide input that allows the patient to remain stably upright.
Ask the patient to stand from a chair, walk across the room, turn, and come back towards you. Pay particular attention to:
Difficulty getting initiating movements.
Balance: Do they veer off to one side or the other as might occur with cerebellar dysfunction? Disorders affecting the left cerebellar hemisphere (as might occur with a stroke or tumor) will cause patient's to fall to the left. Right sided lesions will cause the patient to fall to the right. Diffuse disease affecting both cerebellar hemispheres will cause a generalized loss of balance.
Rate of walking: Do they start off slow and then accelerate, perhaps losing control of their balance or speed (e.g. as might occur with Parkinson's Disease)? Are they simply slow moving secondary to pain/limited range of motion in their joints, as might occur with degenerative joint disease? etc.
Attitude of Arms and Legs: How do they hold their arms and legs? Is there loss of movement and evidence of contractures (e.g. as might occur after a stroke)?
Heel to Toe Walking: Ask the patient to walk in a straight line, putting the heel of one foot directly in front of the toe of the other. This is referred to as tandem gait and is a test of balance. Realize that this may be difficult for older patients (due to the frequent coexistence of other medical conditions) even in the absence of neurological disease.
While compiling information generated from the motor and sensory examinations, the clinician tries to identify patterns of dysfunction that will allow him/her to determine the location of the lesion(s). What follows is one way of making clinical sense of neurological findings.
Is there evidence of motor dysfunction (e.g. weakness, spasticity, tremor)?
If so, does the pattern follow an upper motor neuron or lower motor neuron pattern?
If it's consistent with an upper motor neuron (UMN) process (e.g. weakness with spasticity), does this appear to occur at the level of the spinal cord or the brain? Complete cord lesions will affect both sides of the body. Brain level probleispecific distribution (e.g. following a spinal nerve root or peripheral nerve distribution)? Bilateral? Distal?
Do the findings on reflex examination support a UMN or LMN process (e.g. hyper-reflexic in UMN disorders; hyporeflexic in LMN disorders)?
Do the findings on Babinski testing (assuming the symptoms involve the lower extremities) support the presence of a UMN lesion?
Is there impaired sensation? Some disorders, for example, affect only the Upper or Lower motor pathways, sparing sensation.
Which aspects of sensation are impaired? Are all of the ascending pathways (e.g. spinothalamic and dorsal columns) affected equally, as might occur with diffuse/systemic disease?
Does the loss in sensation follow a pattern suggestive of dysfunction at a specific anatomic level? For example, is it at the level of a Spinal nerve root? Or more distally, as would occur with a peripheral nerve problem?
Does the distribution of the sensory deficit correlate with the "correct" motor deficit, assuming one is present? Radial nerve compression, for example, would lead to characteristic motor and sensory findings.
Information from the sensory, motor and reflex examinations should correlate with one another, painting the best picture of where the level of dysfunction is likely to exist.
Formal assessment of ability to smell is generally omitted, unless there is a specific complaint. If it is to be tested:
Each nostril should be checked separately. Push on the outside of the nares, occluding the side that is not to be tested.
Have the patient close their eyes. Make sure that the patient is able to inhale and exhale through the open nostril.
Present a small test tube filled with something that has a distinct, common odor (e.g. ground coffee) to the open nostril. The patient should be able to correctly identify the smell.
If you wish to test olfaction and don't have any "substance filled tubes" use an alcohol pad as a screening test. Patients should be able to identify its distinctive odor from approximately 10 cm.
This nerve carries visual impulses from the eye to the optical cortex of the brain by means of the optic tracts. Testing involves 3 phases (also covered in the section of this site dedicated to the Eye Exam):
Acuity:
Each eye is tested separately. If the patient uses glasses to view distant objects, they should be permitted to wear them (referred to as best corrected vision).
A Snellen chart is the standard, wall mounted device used for this assessment. Patients are asked to read the letters or numbers on successively lower lines (each with smaller images) until you identify the last line which can be read with 100% accuracy. Each line has a fraction written next to it. 20/20 indicates normal vision. 20/400 means that the patient's vision 20 feet from an object is equivalent to that of a normal person viewing the same object from 400 feet. In other words, the larger the denominator, the worse the vision.
There are hand held cards that look like Snellen Charts but are positioned 14 inches from the patient. These are used simply for convenience. Testing and interpretation are as described for the Snellen.
If neither chart is available and the patient has visual complaints, some attempt should be made to objectively measure visual acuity. This is a critically important reference point, particularly when trying to communicate the magnitude of a visual disturbance to a consulting physician. Can the patient read news print? The headline of a newspaper? Distinguish fingers or hand movement in front of their face? Detect light?Failure at each level correlates with a more severe problem.
Visual Field Testing: Specific areas of the retina receive input from precise areas of the visual field. This information is carried to the brain along well defined anatomic pathways. Holes in vision (referred to as visual field cuts) are caused by a disruption along any point in the path from the eyeball to the visual cortex of the brain. Visual fields can be crudely assessed as follows:
The examiner should be nose to nose with the patient, separated by approximately 8 to 12 inches.
Each eye is checked separately. The examiner closes one eye and the patient closes the one opposite. The open eyes should then be staring directly at one another.
The examiner should move their hand out towards the periphery of his/her visual field on the side where the eyes are open. The finger should be equidistant from both persons.
The examiner should then move the wiggling finger in towards them, along an imaginary line drawn between the two persons.The patient and examiner should detect the finger at more or less the same time.
The finger is then moved out to the diagonal corners of the field and moved inwards from each of these directions. Testing is then done starting at a point in front of the closed eyes. The wiggling finger is moved towards the open eyes.
The other eye is then tested.
Pupils: The pupil has afferent (sensory) nerves that travel with CN2. These nerves cr) nerves that travel with CN 3 and cause pupillary constriction. Seen under as they are using themselves for comparison.
If the examiner cannot seem to move their finger to a point that is outside the patient's field don't worry, as it simply means that their fields are normal.
Interpretation: This test is rather crude, and it is quite possible to have small visual field defects that would not be apparent on this type of testing. Prior to interpreting abnormal findings, the examiner must understand the normal pathways by which visual impulses travel from the eye to the brain.
This nerve is responsible for most of the eyeball's mobility, referred to as extra-occular movement. CN 3 function is assessed in concert with CNs 4 and 6, the other nerves responsible for controlling eyeball movement. CN 4 controls the Superior Oblique muscle, which allows each eye to look down and medially. CN 6 controls the Lateral Rectus muscle, which allows each eye to move laterally. CN 3 controls the muscles which allow motion in all other directions. The pneumonic "S O 4; L R 6; All The Rest 3" may help remind you which CN does what (Superior Oblique; CN 4, Lateral Rectus; CN 6, All The Rest of the muscles innervated by CN 3). Testing is done as follows:
Ask the patient to keep their head in one place. Then direct them to follow your finger while moving only their eyes.
Move your finger out laterally, then up and down.
Then move your finger across the patient's face to the other side of their head. When it is out laterally, move it again up and down. You will roughly trace out the letter "H", which takes both eyeballs through the complete range of movements. At the end, bring your finger directly in towards the patient's nose. This will cause the patient to look cross-eyed and the pupils should constrict, a response referred to as accommodation.
CN 3 also innervates the muscle which raises the upper eye lid. This can first be assessed by simply looking at the patient. If there is CN 3 dysfunction, the eyelid on that side will cover more of the iris and pupil compared with the other eye. This is referred to as ptosis.
It's also worth noting that disorders of the extra ocular muscles themselves (and not the CN which innervate them) can also lead to impaired eye movement. For example, pictured below is a patient who has suffered a traumatic left orbital injury. The inferior rectus muscle has become entrapped within the resulting fracture, preventing the left eye from being able to look downward.
The response of pupils to light is controlled by afferent (sensory) nerves that travel with CN 2 and efferent (motor) nerves that travel with CN 3. These innervate the ciliary muscle, which controls the size of the pupil. Testing is performed as follows:
It helps if the room is a bit dim, as this will cause the pupil to become more dilated.
Using any light source (flashlight, oto-ophthalmoscope, etc), shine the light into one eye. This will cause that pupil to constrict, referred to as the direct response.
Remove the light and then re-expose it to the same eye, though this time observe the other pupil. It should also constrict, referred to as the consensual response. This occurs because afferent impulses from one eye generate an efferent response (i.e. signal to constrict) that is sent to both pupils.
If the patient's pupils are small at baseline or you are otherwise having difficulty seeing the changes, take your free hand and place it above the eyes so as to provide some shade. This should cause the pupils to dilate additionally, making the change when they are exposed to light more dramatic. If you are still unable to appreciate a response, ask the patient to close their eye, generating maximum darkness and thus dilatation. Then ask the patient to open the eye and immediately expose it to the light. This will (hopefully) make the change from dilated to constricted very apparent.
Interpretation
Under normal conditions, both pupils will appear symmetric. Direct and consensual response should be equal for both.
Asymmetry of the pupils is referred to as aniosocoria. Some people with anisocoria have no underlying neuropathology. In this setting, the asymmetry will have been present for a long time without change and the patient will have no other neurological signs or symptoms. The direct and consensual responses should be preserved.
A number of conditions can also affect the size of the pupils. Medications/intoxications which cause generalized sympathetic activation will result in dilatation of both pupils. Other drugs(e.g. narcotics) cause symmetric constriction of the pupils. These findings can provide important clues when dealing with an agitated or comatose patient suffering from medication overdose. Eye drops known as mydriatic agents are used to paralyze the muscles, resulting marked dilatation of the pupils. They are used during a detailed eye examination, allowing a clear view of the retina. Additionally, any process which causes increased intracranial pressure can result in a dilated pupil that does not respond to light.
If the afferent nerve is not working, neither pupil will respond when light is shined in the affected eye. Light shined in the normal eye, however, will cause the affected pupil to constrict. That's because the efferent (signal to constrict) response in this case is generated by the afferent impulse received by the normally functioning eye. This is referred to as an afferent pupil defect.
If the efferent nerve is not working, the pupil will appear dilated at baseline and will have neither direct nor consensual pupillary responses.
Explained under CN 3.
This nerve has both motor and sensory components.
Assessment of CN 5 Sensory Function: The sensory limb has 3 major branches, each covering roughly 1/3 of the face. They are: the Ophthlamic, Maxillary, and Mandibular. Assessment is performed as follows:
Use a sharp implement (e.g. broken wooden handle of a cotton tipped applicator).
Ask the patient to close their eyes so that they receive no visual cues.
Touch the sharp tip of the stick to the right and left side of the forehead, assessing the Ophthalmic branch.
Touch the tip to the right and left side of the cheek area, assessing the Maxillary branch.
Touch the tip to the right and left side of the jaw area, assessing the Mandibular branch.
The patient should be able to clearly identify when the sharp end touches their face. Of course, mak assess this component:
Pull out a wisp of cotton.
While the patient is looking straight ahead, gently brush the wisp against the lateral aspect of the sclera (outer white area of the eye ball).
This should cause the patient to blink. Blinking also requires that CN 7 function normally, as it controls eye lid closure.
Assessment of CN 5 Motor Function
The motor limb of CN 5 innervates the Temporalis and [[Masseter muscle]s, both important for closing the jaw. Assessment is performed as follows:
Place your hand on both Temporalis muscles, located on the lateral aspects of the forehead.
Ask the patient to tightly close their jaw, causing the muscles beneath your fingers to become taught.
Then place your hands on both Masseter muscles, located just in from of the Temporo-Mandibular joints (point where lower jaw articulates with skull).
Ask the patient to tightly close their jaw, which should again cause the muscles beneath your fingers to become taught. Then ask them to move their jaw from side to side, another function of the Masseter.
Reviewed under CN 3.
This nerve innervates many of the muscles of facial expression. Assessment is performed as follows:
First look at the patient's face. It should appear symmetric. That is:
There should be the same amount of wrinkles apparent on either side of the forehead barring asymmetric Bo-Tox injection!
The nasolabial folds (lines coming down from either side of the nose towards the corners of the mouth) should be equal
The corners of the mouth should be at the same height
If there is any question as to whether an apparent asymmetry if new or old, ask the patient for a picture (often found on a driver's license) for comparison.
Ask the patient to wrinkle their eyebrows and then close their eyes tightly. CN 7 controls the muscles that close the eye lids (as opposed to CN 3, which controls the muscles which open the lid). You should not be able to open the patient's eyelids with the application of gentle upwards pressure.
Ask the patient to smile. The corners of the mouth should rise to the same height and equal amounts of teeth should be visible on either side.
Ask the patient to puff out their cheeks. Both sides should puff equally and air should not leak from the mouth.
Interpretation: CN 7 has a precise pattern of innervation, which has important clinical implications. The right and left upper motor neurons (UMNs) each innervate both the right and left lower motor neurons (LMNs) that allow the forehead to move up and down. However, the LMNs that control the muscles of the lower face are only innervated by the UMN from the opposite side of the face.
Thus, in the setting of CN 7 dysfunction, the pattern of weakness or paralysis observed will differ depending on whether the UMN or LMN is affected. Specifically:
UMN dysfunction: This might occur with a central nervous system event, such as a stroke. In the setting of R UMN CN 7 dysfunction, the patient would be able to wrinkle their forehead on both sides of their face, as the left CN 7 UMN cross innervates the R CN 7 LMN that controls this movement. However, the patient would be unable to effectively close their left eye or raise the left corner of their mouth.
LMN dysfunction: This occurs most commonly in the setting of Bell's Palsy, an idiopathic, acute CN 7 peripheral nerve palsy. In the setting of R CN 7 peripheral (i.e. LMN) dysfunction, the patient would not be able to wrinkle their forehead, close their eye or raise the corner of their mouth on the right side. Left sided function would be normal.
This clinical distinction is very important, as central vs peripheral dysfunction carry different prognostic and treatment implications. Bell's Palsy (peripheral CN 7 dysfunction)tends to happen in patient's over 50 and often responds to treatment with Acyclovir (an anti-viral agent) and Prednisone (a corticosteroid). Over the course of weeks or months there is usually improvement and often complete resolution of symptoms. Assessment of acute central (UMN) CN 7 dysfunction would require quite a different approach (e.g. neuroimaging to determine etiology).
CN 7 is also responsible for carrying taste sensations from the anterior 2/3 of the tongue. However as this is rarely of clinical import, further discussion is not included.
CN 8 carries sound impulses from the cochlea to the brain. Prior to reaching the cochlea, the sound must first traverse the external canal and middle ear. Auditory acuity can be assessed very crudely on physical exam as follows:
Stand behind the patient and ask them to close their eyes.
Whisper a few words from just behind one ear. The patient should be able to repeat these back accurately. Then perform the same test for the other ear.
Alternatively, place your fingers approximately 5 cm from one ear and rub them together. The patient should be able to hear the sound generated. Repeat for the other ear.
These tests are rather crude. Precise quantification, generally necessary whenever there is a subjective decline in acuity, requires special equipment and training.
The cause of subjective hearing loss can be assessed with bedside testing. Hearing is broken into 2 phases: conductive and sensorineural. The conductive phase refers to the passage of sound from the outside to the level of CN 8. This includes the transmission of sound through the external canal and middle ear. Sensorineural refers to the transmission of sound via CN 8 to the brain. Identification of conductive (a much more common problem in the general population) defects is determined as follows:
Grasp the 512 Hz tuning fork by the stem and strike it against the bony edge of your palm, generating a continuous tone. Alternatively you can get the fork to vibrate by "snapping" the ends between your thumb and index finger.
Hold the stem against the patient's skull, along an imaginary line that is equidistant from either ear.
The bones of the skull will carry the sound equally to both the right and left CN 8. Both CN 8s, in turn, will transmit the impulse to the brain.
The patient should report whether the sound was heard equally in both ears or better on one side then the other (referred to as lateralizing to a side).
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , 512 hertz tuning fork,
, , Weber test,
Grasp the 512 Hz tuning fork by the stem and strike it against the bony edge of your palm, generating a continuous tone.
Place the stem of the tuning fork on the mastoid bone, the bony prominence located immediately behind the lower part of the ear.
The vibrations travel via the bones of the skull to CN 8, allowing the patient to hear the sound.
Ask the patient to inform you when they can no longer appreciate the sound. When this occurs, move the tuning fork such that the tines are placed right next to (but not touching) the opening of the ear. At this point, the patient should be able to again hear the sound. This is because air is a better conducting medium then bone.
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Rinne test ,
, , Rinne test ,
Interpretation:
The above testing is reserved for those instances when a patient complains of a deficit in hearing. Thus, on the basis of history, there should be a complaint of hearing decline in one or both ears.
In the setting of a conductive hearing loss (e.g. wax in the external canal), the Weber test will lateralize (i.e. sound will be heard better)in the ear that has the subjective decline in hearing. This is because when there is a problem with conduction, competing sounds from the outside cannot reach CN 8 via the external canal. Thus, sound generated by the vibrating tuning fork and traveling to CN 8 by means of bony conduction is better heard as it has no outside "competition." You can transiently create a conductive hearing loss by putting the tip of your index finger in the external canal of one ear. If you do this while performing the Weber test, the sound will be heard on that side.
In the setting of a sensorineural hearing loss (e.g. a tumor of CN 8), the Weber test will lateralize to the ear which does not have the subjective decline in hearing. This is because CN 8 is the final pathway through which sound is carried to the brain. Thus, even though the bones of the skull will successfully transmit the sound to CN 8, it cannot then be carried to the brain due to the underlying nerve dysfunction.
In the setting of conductive hearing loss, bone conduction (BC) will be better then air conduction (AC) when assessed by the Rinne test. If there is a blockage in the passageway (e.g. wax) that carries sound from the outside to CN 8, then sound will be better heard when it travels via the bones of the skull. Thus, the patient will note BC to be better then or equal to AC in the ear with the subjective decline in hearing.
In the setting of a sensorineural hearing loss, air conduction will still be better then bone conduction (i.e. the normal pattern will be retained). This is because the problem is at the level of CN 8. Thus, regardless of the means (bone or air) by which the impulse gets to CN 8, there will still be a marked hearing decrement in the affected ear. As AC is normally better then BC, this will still be the case.
Summary:
Identifying conductive vs. sensorineural hearing deficits requires historical information as well as the results of Weber and Rinne testing. In summary, this data is interpreted as follows:
First, determine by history and crude acuity testing which ear has the hearing problem.
Perform the Weber test. If there is a conductive hearing deficit, the Weber will lateralize to the affected ear. If there is a sensorineural deficit, the Weber will lateralize to the normal ear.
Perform the Rinne test. If there is a conductive hearing deficit, BC will be greater then or equal to AC in the affected ear. If there is a sensorineural hearing deficit, AC will be greater then BC in the affected ear.
These nerves are responsible for raising the soft palate of the mouth and the gag reflex, a protective mechanism which prevents food or liquid from traveling into the lungs As both CNs contribute to these functions, they are tested together.
Ask the patient to open their mouth and say, "ahhhh," causing the soft palate to rise upward.
Look at the uvula, a midline structure hanging down from the palate. If the tongue obscures your view, take a tongue depressor and gently push it down and out of the way.
The Uvula should rise up straight and in the midline.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Normal Oropharynx,
Interpretation:
If CN 9 on the right is not functioning (e.g. in the setting of a stroke), the uvula will be pulled to the left. The opposite occurs in the setting of left CN 9 dysfunction.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Left CN9 Dysfunction: Patient status post stroke affecting left CN9. Uvula therefore pulled over towards right.
Be aware that other processes can cause deviation of the uvula.A peritonsillar abscess, for example, will push the uvula towards the opposite (i.e. normal) tonsil.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Left peritonsillar abscess; infection within left tonsil has pushed uvula towards the right. ,
Ask the patient to widely open their mouth. If you are unable to see the posterior pharynx (i.e. the back of their throat), gently push down with a tongue depressor.
In some patients, the tongue depressor alone will elicit a gag. In most others, additional stimulation is required. Take a cotton tipped applicator and gently brush it against the posterior pharynx or uvula. This should generate a gag in most patients.
A small but measurable percent of the normal population has either a minimal or non-existent gag reflex. Presumably, they make use of other mechanisms to prevent aspiration.
Gag testing is rather noxious. Some people are particularly sensitive to even minimal stimulation. As such, I would suggest that you only perform this test when there is reasonable suspicion that pathology exists. This would include two major clinical situations:
If you suspect that the patient has suffered acute dysfunction, most commonly in the setting of a stroke. These patients may complain of/be noted to cough when they swallow. Or, they may suffer from recurrent pneumonia. Both of these events are signs of aspiration of food contents into the passageways of the lungs. These patients may also have other cranial nerve abnormalities as lesions affecting CN 9 and 10 often affect CNs 11 and 12, which are anatomically nearby.
Patient's suffering from sudden decreased level of consciousness. In this setting, the absence of a gag might indicate that the patient is no longer able to reflexively protect their airway from aspiration. Strong consideration should be given to intubating the patient, providing them with a secure mechanical airway until their general condition improves.
CN 9 is also responsible for taste originating on the posterior 1/3 of the tongue. As this is rarely a clinically important problem, further discussion is not included.
CN 10 also provides parasympathetic innervation to the heart, though this cannot be easily tested on physical examination.
CN 11 innervates the muscles which permit shrugging of the shoulders (Trapezius) and turning the head laterally (Sternocleidomastoid).
Place your hands on top of either shoulder and ask the patient to shrug while you provide resistance. Dysfunction will cause weakness/absence of movement on the affected side.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , ,
Place your open left hand against the patient's right cheek and ask them to turn into your hand while you provide resistance. Then repeat on the other side. The right Sternocleidomasoid muscle (and thus right CN 11) causes the head to turn to the left, and vice versa.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , ,
CN 12 is responsible for tongue movement. Each CN 12 innervates one-half of the tongue.
Ask the patient to stick their tongue straight out of their mouth.
If there is any suggestion of deviation to one side/weakness, direct them to push the tip of their tongue into either cheek while you provide counter pressure from the outside.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , ,
Interpretation
If the right CN 12 is dysfunctional, the tongue will deviate to the right. This is because the normally functioning left half will dominate as it no longer has opposition from the right. Similarly, the tongue would have limited or absent ability to resist against pressure applied from outside the left cheek.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Left CN 12 Dysfunction: Stroke has resulted in L CN 12 Palsy. Tongue therefore deviates to the left.
Testing of motor and sensory function requires a basic understanding of normal anatomy and physiology. In brief:
Voluntary movement begins with an impulse generated by cell bodies located in the brain.
Signals travel from these cells down their respective axons, forming the Corticospinal (a.k.a. Pyramidal) tract. At the level of the brain stem, this motor pathway crosses over to the opposite side of the body and continue downward on that side of the spinal cord. The nerves which comprise this motor pathway are collectively referred to as Upper Motor Neurons (UMNs). It's important to note that there are other motor pathways that carry impulses from the brain to the periphery and help modulate movement.
At a specific point in the spinal cord the axon synapses with a 2nd nerve, referred to as a Lower Motor Neuron (LMN). The precise location of the synapse depends upon where the lower motor neuron is destined to travel. If, for example, the LMN terminates in the hand, the synapse occurs in the cervical spine (i.e. neck area). However, if it's headed for the foot, the synapse occurs in the lumbar spine (i.e. lower back).
The UMNs are part of the Central Nervous System (CNS), which is composed of neurons whose cell bodies are located in the brain or spinal cord. The LMNs are part of the Peripheral Nervous System (PNS), made up of motor and sensory neurons with cell bodies located outside of the brain and spinal cord. The axons of the PNS travel to and from the periphery, connecting the organs of action (e.g. muscles, sensory receptors) with the CNS.
Nerves which carry impulses away from the CNS are referred to efferents (i.e. motor) while those that bring signals back are called afferents (i.e. sensory).
Axons that exit and enter the spine at any given level generally connect to the same distal anatomic area. These bundles of axons, referred to as spinal nerve roots, contain both afferent and efferent nerves. The roots exit/enter the spinal cord through neruoforamina in the spine, paired openings that allow for their passage out of the bony protection provided by the vertebral column.
As the efferent neurons travels peripherally, components from different roots commingle and branch, following a highly programmed pattern. Ultimately, contributions from several roots may combine to form a named peripheral nerve, which then follows a precise anatomic route on its way to innervating a specific muscle. The Radial Nerve, for example, travels around the Humerus (bone of the upper arm), contains contributions from Cervical Nerve Roots 6, 7 and 8 and innervates muscles that extend the wrist and supinate the forearm.
It may help to think of a nerve root as an electrical cable composed of many different colored wires, each wire representing an axon. As the cable moves away from the spinal cord, wires split off and head to different destinations. Prior to reaching their targets, they combine with wires originating from other cables. The group of wires that ultimately ends at a target muscle group may therefore have contributions from several different roots.
Afferents carry impulses in the opposite direction of the motor nerves. That is, they bring information from the periphery to the spinal cord and brain.
Sensory nerves begin in the periphery, receiving input from specialized receptor organs. The axons then move proximally, joining in a precise fashion with other axons to form the afferent component of a named peripheral nerve. The Radial Nerve, for example, not only has a motor function (described previously) but also carries sensory information from discrete parts of the hand and forearm.
As the sensory neurons approach the spinal cord, they join specific spinal nerve roots. Each root carries sensory information from a discrete area of the body. The area of skin innervated by a particular nerve root is referred to as a dermatome. Dermatome maps describe the precise areas of the body innervated by each nerve root. These distributions are more or less the same for all people, which is clinically important. In the setting of nerve root dysfunction, the specific area supplied by that root will be affected. This can be mapped out during a careful exam, identifying which root(s) is dysfunctional.
Sensory input travels up through the spinal cord along specific paths, with the precise route defined by the type of sensation being transmitted. Nerves carrying pain impulses, for example, cross to the opposite side of the spinal cord soon after entering, and travel up to the brain on that side of the cord. Vibratory sensations, on the other hand, enter the cord and travel up the same side, crossing over only when they reach the brain stem.
Ultimately, the sensory nerves terminate in the brain, where the impulses are integrated and perception occurs.
Understanding the above neruo-anatomic relationships and patterns of innervation has important clinical implications when trying to determine the precise site of neurological dysfunction. Injury at the spinal nerve root level, for example, will produce a characteristic loss of sensory and motor function. This will differ from that caused by a problem at the level of the peripheral nerve. An approach to localizing lesions on the basis of motor and sensory findings is described in the sections which follow. Realize that there is a fair amount of inter-individual variation with regards to the specifics of innervation. Also, recognize that often only parts of nerves may become dysfunctional, leading to partial motor or sensory deficits. As such, the patterns of loss are rarely as "pure" as might be suggested by the precise descriptions of nerves and their innervations.
Sensory testing of the face is discussed in the section on Cranial Nerves. Testing of the extremities focuses on the two main afferent pathways: Spinothalamics and Dorsal Columns.
Spinothalamics: These nerves detect pain, temperature and crude touch. They travel from the periphery, enter the spinal cord and then cross to the other side of the cord within one or two vertebral levels of their entry point They then continue up that side to the brain, terminating in the cerebral hemisphere on the opposite side of the body from where they began.
Dorsal Columns: These nerves detect position (a.k.a. proprioception), vibratory sensation and light touch. They travel from the periphery, entering the spinal cord and then moving up to the base of the brain on the same side of the cord as where they started. Upon reaching the brain stem they cross to the opposite side, terminating in the cerebral hemisphere on the opposite side of the body from where they began.
A screening evaluation of these pathways can be performed as follows:
The patient's ability to perceive the touch of a sharp object is used to assess the pain pathway of the Spinothalamics. To do this, break a Q-tip or tongue depressor in half, such that you create a sharp, pointy end. Alternatively, you can use a disposable needle as the sharp-ended probe. The careful use of a disposable pointy, metal spikes that accompany some reflex hammers are discouraged.
Ask the patient to close their eyes so that they are not able to get visual clues.
Start at the top of the foot. Orient the patient by informing them that you are going to first touch them with the sharp implement. Then do the same with a non-sharp object (e.g. the soft end of a q-tip). This clarifies for the patient what you are defining as sharp and dull.
Now, touch the lateral aspect of the foot with either the sharp or dull tool, asking them to report their response. Move medially across the top of the foot, noting their response to each touch.
If they give accurate responses, do the same on the other foot. The same test can be repeated for the upper extremities (i.e. on the hand), though this would only be of utility if the patient complained of numbness/impaired sensation in that area.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , ,
This refers to the body's ability to know where it is stal aspects of the body. Thus, proprioception is checked first in the feet and then, if abnormal, more proximally (e.g. the hands).
Technique:
Ask the patient to close their eyes so that they do not receive any visual cues.
Grasp either side of the great toe. Orient the patient as to up and down. Flex the toe (pull it upwards) while telling the patient what you are doing. Then extend the toe (pull it downwards) while again informing them of which direction you are moving it.
Alternately deflect the toe up or down without telling the patient in which direction you are moving it. They should be able to correctly identify the movement and direction.
Both great toes should be checked in the same fashion. If normal, no further testing need be done in the screening exam.
If the patient is unable to correctly identify the movement/direction, move more proximally (e.g. to the ankle joint) and repeat (e.g. test whether they can determine whether the foot is moved up or down at the ankle).
Similar testing can be done on the fingers. This is usually reserved for those settings when patients have distal findings and/or symptoms in the upper extremities.
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , ,
Vibratory sensation travels to the brain via the dorsal columns. Thus, the findings generated from testing this system should corroborate those of proprioception.
Technique:
Start at the toes with the patient seated. You will need a 128 hz tuning fork.
Ask the patient to close their eyes so that they do not receive any visual cues.
Grasp the tuning fork by the stem and strike the forked ends against the heel of your hand, causing it to vibrate.
Place the stem on top of the interphalangeal joint of the great toe. Put a few fingers of your other hand on the bottom-side of this joint.
Ask the patient if they can feel the vibration. You should be able to feel the same sensation with your fingers on the bottom side of the joint.
The patient should be able to determine when the vibration stops, which will correlate with when you are no longer able to feel it transmitted through the joint. It sometimes takes a while before the fork stops vibrating. If you want to move things along, rub the index finger of the hand holding the fork along the tines, rapidly dampening the vibration.
Repeat testing on the other foot.
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , ,
, , ,
Testing Two Point Discrimination: Patients should normally be able to distinguish simultaneous touch with 2 objects which are separated by at least 5mm. These stimuli are carried via the Dorsal Columns. While not checked routinely, it is useful test if a discrete peripheral neruropathy is suspected (e.g. injury to the radial nerve).
Technique:
Testing can be done with a paperclip, opened such that the ends are 5 mm apart.
The patient should be able to correctly identify whether you are touching them with one or both ends simultaneously, along the entire distribution of the specific nerve which is being assessed.
A careful foot examination should be performed on all patients with symptoms suggestive of sensory neuropathy or at particular risk for this disorder (e.g. anyone with Diabetes). Losroblem. Disposable monofilaments (known as the Semmes-Weinstein Aethesiometer) are specially designed for a screening evaluation. These small nylon fibers are designed such that the normal patient should be able to feel the ends when they are gently pressed against the soles of their feet.
Technique:
Have the patient close their eyes so that they do not receive any visual cues.
Touch the monofilament to 5-7 areas on the bottom of the patient's foot. Pick locations so that all of the major areas of the sole are assessed. Avoid calluses, which are relatively insensate.
The patient should be able to detect the filament when the tip is lightly applied to the skin.
Interpretation:
If the examiner has to supply enough pressure such that the filament bends prior to the patient being able to detect it, they likely suffer from sensory neuropathy. Testing should be done in multiple spots to verify the results. Patient's with distal sensory neuropathy should carefully examine their feet and wear good fitting shoes to assure that skin breakdown and infections don't develop. Efforts should also be made to closely control their diabetes so that the neuropathy does not progress.
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , ,
, , ,
, , ,
Patterns of Impairment for the Spinothalamic Tracts:
Patients should be able to correctly distinguish sharp sensation, indicating normal function of the spinothalamic pathway.
Mapping out regions of impaired sensation: The examination described above is a screening evaluation for evidence of sensory loss. This is perfectly adequate in most clinical settings. Occasionally, the history or screening examination will suggest a discrete anatomic region that has sensory impairment. When this occurs, it is important to try and map out the territory involved, using careful pin testing to define the medial/lateral and proximal/distal boundaries of the affected region. You may even make pen marks on the skin to clearly identify where the changes occur. As most clinicians have not memorized the distributions of all peripheral nerves or spinal nerve roots, you can simultaneously consult a reference book to see if the mapped territory matches a specific nerve distribution. This type of mapping is somewhat tedious and should only be done in appropriate situations.
Diffuse Distal Sensory Loss: A number of chronic systemic diseases affect nerve function. The most commonly occurring of these, at least in Western countries, is Diabetes. When control has been poor over many years, the sensory nerves become dysfunctional. This first affects the most distal aspects of the nerves and then moves proximally. Thus, the feet are the first area to be affected. As it is a systemic disease, it occurs simultaneously in both limbs. Exam reveals loss of ability to detect the sharp stimulus across the entire foot. Thus, the sensory loss does not follow a dermatomal (i.e. spinal nerve root) or peripheral nerve distribution. As the examiner tests more proximally, he/she will ultimately reach a point where sensation is again normal. The more advanced the disease, the higher up the leg this will occur. Hands can be affected, though much less commonly then feet as the nerves traveling to the legs are longer and thus at much greater risk. This pattern of loss is referred to as a Stocking or Glove distribution impairment, as the area involved covers an entire distal region, much as a sock or glove would cover a foot or hand. Such deficits may be associated with neuropathic pain, a continuous burning sensation affecting the distal extremity.
Peripheral Nerve Distribution: A specific peripheral nerve can become dysfunctional. This might, for example, occur as the result of trauma or infarction (another complication of diabetes). In this setting, there will be a pattern of sensory impairment that follows the distribution of the nerve. Radial nerve palsy, for example, can occur if an intoxicated person falls asleep in a position that puts pressure on the nerve as it travels a to constant direct pressure. The resultant sensory loss would involve the back of the hand and forearm. Motor function would also be affected (see under motor exam). Pinning down the culprit nerve requires knowledge of nerve anatomy and innervation. On a practical level, most clinicians don't commit this to memory. Rather, they gather a history suggestive of a discrete nerve deficit, verify the territory of loss on exam, and then consult it with a senior specialist, or look it up in a WikiDoc differential diagnosis.
Nerve Root Impairment: A nerve root (or roots) can be damaged as it leaves the cord. This will result in a sensory deficit along its specific distribution, which can in turn be identified on examination. The S1 nerve root, for example, can be compressed by herniated disc material in the lumbar spine. This would cause sensory loss along the lateral aspect of the lower leg and the bottom of the foot. Only the leg on the affected side would have this deficit. As mentioned under peripheral nerve dysfunction, most clinicians do not memorize the dermatomes related to each nerve root. Rather, they gather a history suggestive of a discrete nerve deficit, verify a dermatomal distribution of loss on exam, or look it up in a WikiDoc differential diagnosis.
The Spinothalamics are also responsible for temperature discrimination. For practical reasons (i.e. it's often hard to find test tubes, fill them with the requisite temperature water, etc) this is omitted in the screening exam. The inf, is important if patients complain of incontinence, inability to defecate/urinate, or ther example, multiple sacral and lumbar roots become compressed bilaterally (e.g. bting it to contract. N exam. Ability to detect pin pricks in the perineal area (a.k.a. saddle distribution) is also diminished.
Patients should be able to correctly identify the motion and direction of the toe. In the setting of Dorsal Column dysfunction (a common complication of diabetes, for example), distal testing will be abnormal. This is similar to the pattern of injury which affects the Spinothalamic tracts described above.
Patients should be able to detect the initial vibration and accurately determine when it has stopped.
As described under testing of proprioception, dorsal column dysfunction tends to first affect the most distal aspects of the system. When this occurs, the patient is either unable to detect the vibration or they perceive that the sensation extinguishes too early (i.e. they stop feeling it even though you can still appreciate the sensation with your fingers on the underside of the joint).
The findings on vibrat dependent on the age, sex and the activity/fitness level of the individual. A frail elderly person, for example, will have less muscle bulk then a 25 year old body builder. With experience, you will get a sense of the normal range for given age groups, factoring in their particular activity levels and overall states of health.
Things to look for:
Using your eyes and hands, carefully examine the major muscle groups of the upper and lower extremities. Palpation of the muscles will give you a sense of underlying mass. The largest and most powerful groups are those of the quadriceps and hamstrings of the upper leg (i.e. front and back of the thighs). The patient should be in a gown so that the areas of interest are exposed.
Muscle groups should appear symmetrically developed when compared with their counterparts on the other side of the body. They should also be appropriately developed, after making allowances for the patient's age, sex, and activity level.
There should be no muscle movement when the limb is at rest. Rare disorders (e.g. Amyotrophic Lateral Sclerosis) result in death oknown as fasciculations,which can be seen on gross inspectiots in limb movement. Parkinson's Disease (PD), for example, can cause a very characteristic resting tremor of the hand (the head and other body parts can also be affected) that diminishes when the patient voluntarily moves the affected limb. Benign Essential Tremor, on the other hand, persists throughout movement and is not associated with any other neurological findings, easily distinguishing it from PD.
The major muscle groups to be palpated include: biceps, triceps, deltoids, quadriceps and hamstrings. Palpation should not elicit pain. Interestingly, myositis (a rare condition characterized by idiopathic muscle inflammation) causes the patient to experiencet some allowance must be made for handedness (i.e. right v left hand dominance).
Does the asymmetry follow a particular nerve distribution, suggesting a peripheral motor neuron injury? For example, muscles which lose their LMN innervation become very atrophic.
Is the bulk in the upper and lower extremities similar? Spinal cord transection at the Thoracic level will cause upper extremity muscle bulk to be normal or even increased due to increased dependence on arms for activity, mobility, etc. However, the muscles of the lower extremity will atrophy due to loss of innervation and subsequent disuse.
Is there another process (suggested by history or other aspects of the exam) that has resulted in limited movement of a particular limb? For example, a broken leg that has recently been liberated from a cast will appear markedly atrophic.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , ,
, , ,
When a muscle group is relaxed, the examiner should be able to easily manipulate the joint through its normal range of motion. This movement should feel fluid. A number of disease states may alter this sensation. For the screening examination, it is reasonable to limit this assessment to only the major joints, including: wrist, elbow, shoulder, hips and knees.
Technique:
Ask the patient to relax the joint that is to be tested.
Carefully move the limb through its normal range of motion, being careful not to maneuver it in any way that is uncomfortable or generates pain.
Be aware that many patients, particularly the elderly, often have other medical conditions that limit joint movement. Degenerative joint disease of the knee, for example, might cause limited range of motion, though tone should still be normal. If the patient has recently injured the area or are in pain, do not perform this aspect of the exam.
Things to look for:
Normal muscle generates some resistance to movement when a limb is moved passively by an examiner. After performing this exam on a number of patients,you'll develop an appreciation for the range of normal tone.
Increased tone (hypertonicity) results from muscle contraction. At the extreme end is spasticity, which occurs when the upper motor neuron no longer functions. In this setting, the affected limb is held in a flexed position and the examiner may be unable to move the joint. This is seen most commonly following a stroke, which results in the death of the upper motor neuron cell body in the brain.
Flaccidness is the complete absence of tone. This occurs when the lower motor neuron is cut off from the muscles that it normally innervates.
Disorders that do not directly affect the muscles, upper or lower motor neurons can still alter tone. Perhaps the most common of these is Parkinson's Disease (PD). This is a disorder of the Extra Pyramidal System (EPS). The EPS normally contributes to initiation and smoothness of movement. PD causes increased tone, generating a ratchet-like sensation (known as cog wheeling) when the affected limbs are passively moved by the examiner.
As with muscle bulk (described above), strength testing must take into account the age, sex and fitness level of the patient. For example, a frail, elderly, bed bound patient may have muscle weakness due to severe deconditioning and not to intrinsic neurological disease. Interpretation must also consider the expected strength of the muscle group being tested. The quadriceps group, for example, should be much more powerful then the Biceps.
There is a 0 to 5 rating scale for muscle strength:
0/5 No movement
1/5 Barest flicker of movement of the muscle, though not enough to move the structure to which it's attached.
2/5 Voluntary movement which is not sufficient to overcome the force of gravity. For example, the patient would be able to slide their hand across a table but not lift it from the surface.
3/5 Voluntary movement capable of overcoming gravity, but not any applied resistance. For example, the patient could raise their hand off a table, but not if any additional resistance were applied.
4/5 Voluntary movement capable of overcoming "some" resistance
5/5 Normal strength
'+' and '-' can be added to these values, providing further gradations of strength. Thus, a patient who can overcome "moderate but not full resistance" might be graded 4+ or 5- . This is quite subjective, with a fair amount of variability amongst clinicians. Ultimately, it's most important that you develop your own sense of what these gradations mean, allowing for internal consistency and interpretability of serial measurements.
In the screening examination, it is reasonable to check only the major muscles/muscle groups. More detailed testing can be performed in the setting of discrete/unexplained weakness. The names of the major muscles/muscle groups along with the spinal roots and peripheral nerves that provide their innervation are provided below.
Ask the patient to spread their fingers apart against resistance (abduction). Then squeeze them together, with your fingers placed in between each of their digits (adduction). Test each hand separately. The muscles which control adduction and abduction of the fingers are called the Interossei, innervated by the Ulnar Nerve.
, , Intrinsic muscles of the hand (abduction) (Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California),
, Intrinsic muscles of the hand (adduction) (Image courtesy of C. Michael Gibson M.S. M.D. and copylefted), Intrinsic muscles of the hand (adduction) (Image courtesy of C. Michael Gibson M.S. M.D. and copylefted),
Ask the patient to make a fist, squeezing their hand around two of your fingers. If the grip is normal, you will not be able to pull your fingers out. Test each hand separately. The Flexor Digitorum Profundus controls finger flexion and is innervated by the Median (radial) and Ulnar (medial) Nerves.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Flexors of the fingers,
Have the patient try to flex their wrist as you provide resistance. Test each hand separately. The muscle groups which control flexion are innervated by the Median and Ulnar Nerves.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Wrist flexion,
Have the patient try to extend their wrist as you provide resistance. Test each hand separately. The Extensor Radialis muscles control extension and are innervated by the Radial Nerve. Clinical Correlate: Damage to the radial nerve results in wrist drop (loss of ability to extend the hand at the wrist). This can occur via any one of a number of mechanisms. For example, the nerve can be compressed against the humerus for a prolonged period of time when an intoxicated person loses consciousness with the inside aspect of the upper arm resting against a solid object (known as a "Saturday Night Palsy").
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Wrist extension,
The main flexor (and supinator) of the forearm is the Brachialis Muscle (along with the Biceps Muscle). Have the patient bend their elbow to ninety degrees while keeping their palm directed upwards. Then direct them to flex their forearm while you provide resistance. Test each arm separately. These muscles are innervated by the Musculocutaneous Nerve.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Elbow flexion,
The main extensor of the forearm is the triceps muscle. Have the patient extend their elbow against resistance while the arm is held out (abducted at the shoulder) from the body at ninety degrees. Test each arm separately. The Triceps is innervated by the Radial nerve.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Elbow extension,
The main muscle of adduction is the Pectoralis Major, though the Latissiumus and others contribute as well. Have the patient flex at the elbow while the arm is held out from the body at forty-five degrees. Then provide resistance as they try to further adduct at the shoulder. Test each shoulder separately.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Shoulder adduction,
The deltoid muscle, innervated by the axillary nerve, is the main muscle of abduction. Have the patient flex at the elbow while the arms is held out from the body at forty-five degrees. Then provide resistance as they try to further abduct at the shoulder. Test each shoulder separately.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Shoulder abduction,
With the patient seated, place your hand on top of one thigh and instruct the patient to lift the leg up from the table. The main hip flexor is the Iliopsoas muscle, innervated by the femoral nerve.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Hip flexion,
With the patient lying prone, direct the patient to lift their leg off the table against resistance. Test each leg separately. The main hip extensor is the gluteus maximus, innervated by inferior gluteal nerve.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Hip extension,
Place your hands on the outside of either thigh and direct the patient to separate their legs against resistance. This movement is mediated by a number of muscles.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Hip abduction,
Place your hands on the inner aspects of the thighs and repeat the manted patid by the quadriceps muscle group, which is innervated by the femoral nerve.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Knee extension,
Have the patient rest prone. Then have them pull their heel up and off the table against resistance. Each leg is tested separately. Flexion is mediated by the hamstring muscle group, via branches of the sciatic nerve.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicinrovide resistance with your hand. Each foot is tested separately. The muscles which mediate dorsiflexion are innervated by the deep peroneal nerve. Clinical Correlate: The peroneal nerve is susceptible to injury at the point where it crosses the head of the fibula (laterally, below the knee). If injured, the patient develops "Foot Drop," an inability to dorsiflex the foot.
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Ankle dorsiflexion,
Have the patient "step on the gas" while providing resistance with your hand. Test each foot separately. The gastrocnemius and soleus, the muscles which mediate this movement, are innervated by a branch of the sciatic nerve. Plantar flexion and dorsiflexion can also be assessed by asking the patient to walk on their toes (plantar flexion) and heels (dorsiflexion).
(Image courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
, , Ankle plantar flexion,
Helpful Tips
It is generally quite helpful to directly compare right vs. left sided strength, as they should more or less be equivalent (taking into account the handedness of the patient). If there is weakness, try to identify a pattern, which might provide a clue as to the etiology of the observed decrease in strength. In particular, make note of differences between:
Right vs. Left
Proximal muscles vs. distal
Upper extremities vs. lower
Or is the weakness generalized, suggestive of a systemic neurological disorder or global deconditioning
Subtle weakness can be hard to detect. Pay attention to how the patient walks, uses and holds their arms and hands as they enter the room, get up and down from a seated position, move onto the examination table, etc. Pronator drift is a test for slight weakness of the upper extremities. The patient should sit with both arms extended, palms directed upward. Subtle weakness in either arm will cause slight downward drift and pronation of that limb (i.e. the arm will rotate slightly inward and down).
|
Inferior_phrenic_veins | The Inferior Phrenic Veins follow the course of the inferior phrenic arteries;
the right ends in the inferior vena cava;
the left is often represented by two branches, one of which ends in the left renal or supra |
Aphonia | e:Urinary system symptoms and signs
Template:Cognition, perception, emotional state and behaviour symptoms and signs
Template:Speech and voice symptoms and signs
Template:General symptoms and signs
vteSymptoms and signs: Symptoms concerning nutrition, metabolism and development (R62–R64, 783)Ingestion/Weightdecrease: Anorexia • Weight loss/Cachexia/Underweight
increase: Polyphagia • Polydipsia • Orexigenia • Weight gainGrowthDelayed milestone • Failure to thrive • Short stature (e.g., Idiopathic) |
Hypocalcemia_(patient_information) | Patients diagnosed with hypocalcemia should avoid using the following medications:
AlendronateIf you have been diagnosed with hypocalcemia, consult your physician before starting or stopping any of these medications.
Directions to Hospitals Treating Hypocalcemia
Template:WikiDoc Sources
|
Pneumocystis_jirovecii_pneumonia_(patient_information) | Pneumocystis jiroveci pneumonia is a fungal infection of the lungs. The disease used to be called Pneumocystis carinii.
Pneumocystis pneumonia in those with AIDS usually develops slowly over days to weeks or even months, and is less severe. People with pneumocystis pneumonia who do not have AIDS usually get sick faster and are more acutely ill. Symptoms include:
Cough -- often mild and dry
Fever
Rapid breathing
Shortness of breath -- especially with activity (exertion)
This type of pneumonia is caused by the fungus Pneumocystis jiroveci. This fungus is common in the environment and does not cause illness in healthy people. However, it can cause a lung infection in people with a weakened immune system due to:
Cancer
Chronic use of corticosteroids or other medications that weaken the immune system
HIV/AIDS
Organ or bone marrow transplant
Pneumocystis jiroveci was a relatively rare infection before the AIDS epidemic. Before the use of preventive antibiotics for the condition, most people in the United States with advanced AIDS would develop it.
This type of pneumonia is caused by the fungus Pneumocystis jiroveci. This fungus is common in the environment and does not cause illness in healthy people. However, it can cause a lung infection in people with a weakened immune system due to:
Cancer
Chronic use of corticosteroids or other medications that weaken the immune system
HIV/AIDS
Organ or bone marrow transplant
If you feel you are developing symptoms suggestive of Pneumocystis pneumonia contact your health professional.
Blood gases
Bronchoscopy (with lavage)
Lung biopsy
X-ray of the chest
Sputum exam to check for fungus that causes the infection
Antibiotics can be given by mouth (orally) or through a vein (intravenously), depending on the severity of the illness. People with low oxygen levels and moderate to severe disease are often prescribed corticosteroids as well.
Directions to Hospitals Treating Pneumocystis jirovecii pneumonia
Pneumocystis pneumonia can be life threatening, causing respiratory failure that can lead to death. People with this condition need early and effective treatment. For moderate to severe pneumocystis pneumonia in people with AIDS, the short term use of corticosteroids has decreased death.
Pleural effusion (extremely rare)
Pneumothorax (collapsed lung)
Respiratory failure (may require breathing support)
http://www.nlm.nih.gov/medlineplus/ency/article/000671.htm
Template:WSTemplate:WH
|
Pyogenic_liver_abscess_surgery | The maninstay of treatment of pyogenic liver abscess is percutaneous darinage of abscess. Other methods used are open surgical drainage and endoscopic retrograde cholangiopancreatography(ERCP).
The following methods are used for drainage of pyogenic liver abscess.
Percutaneous Drainage
The drainage method used depends on the size and number of abscesses.
A single abscess with size less than 5 cm can be drained using either percutaneous catheter drainage or needle aspiration.
If the abscess size is more than 5 cm, percutaneous catheter drainage is preferred over needle aspiration.
The catheters are placed until the drainage is minimal or upto 7 days.
For multiple or loculated abscesses which are small and easily accessible, percutaneous drainage can be used to drain the abscess.
Surgical Drainage
Indications for surgical drainage of pyogenic liver abscess include:
Ruptured abscess
Hyperbilirubinemia or renal impairement
Multiple and loculated abscesses which cannot be easily accessible by percutaneous drainage
Inadequate drainage through percutaneous methods
Blockage of catheter due to increased viscosity of abscess
Associated with an underlying disease like peritonitis
ERCP
In patients with bile duct stones or strictures, endoscopic retrograde cholangiopancreatography (ERCP) is used to drain the pyogenic liver abscess.
|
Sherman_sign | Sherman's sign refers to prominent pulsations of the dorsalis pedis artery in patients aged over 75 years and is present in patients with aortic insufficiency |
Antiphospholipid_antibody_syndrome | History and Symptoms | Physical Examination | Laboratory Findings | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention
Case #1
Template:Autoantibodies
Template:Hematology
|
Toxic_shock_syndrome_epidemiology_and_demographics | Approximately half the cases of staphylococcal TSS reported today are associated with tampon use during menstruation, usually in young women and up till now 42% of cases have occurred in females under the age of 19 years, though TSS also occurs in children, men, and non-menstruating women.
Toxic shock syndrome (TSS) became a nationally notifiable disease in 1983. After the initial epidemic, the number of reported cases decreased significantly.
Incidence rates declined from 6 to 12 per 100,000 among women 12-49 years of age in 1980 to 1 per 100,000 among women 15-44 years of age in 1986.
Apart from menstruation associated TSS, non-menstruating cases having a skin or soft tissue infection have also been identified.
In a study conducted during 2000-2006, the average annual incidence per 100,000 persons of all TSS cases was 0.52 cases (95% CI, 0.32–0.77), of menstrual cases was 0.69 (95% CI, 0.39–1.16), and of non-menstrual cases was 0.32 (95% CI, 0.12–0.67).
Women aged 13–24 years had the highest incidence with an annual rate of menstrual TSS of 1.41 cases per 100,000.
MRSA strains have increased in prevalence during the last decade and MRSA have been reported as the cause of TSS.
Approximately half the cases of staphylococcal TSS reported today are associated with tampon use during menstruation, usually in young women, though TSS also occurs in children, men, and non-menstruating women.
Menstruating females had the highest incidence with an annual rate of menstrual TSS of 1.41 cases per 100,000 based on incidence data from 2000-2003.
It has been estimated that each year 1 to 17 of every 100,000 menstruating females will get TSS. In the US in 1997, only five confirmed menstrual-related TSS cases were reported, compared with 814 cases in 1980, according to data from the Centers for Disease Control and Prevention (CDC).
About 25 percent of non-menstrual cases of Toxic shock syndrome occur in males.
Women aged 13–24 years have the highest incidence with an annual rate of menstrual TSS of 1.41 cases per 100,000.
To date, 42% of cases have occurred in females under the age of 19 years.
Epidemiology studies conducted in the late 1980s showed that women who develop mTSS tended to be predominately white.
White population are more likely to be carriers of toxigenic S. aureus than black, Hispanic, or Asian population. |
Tracheitis_history_and_symptoms | A positive history of a prior viral infection and followed by stridor and dyspnea is suggestive of tracheitis.
Patients with tracheitis may have a positive history of:
Increasing deep or barking croup cough following a previous upper respiratory infection
Common symptoms of tracheitis include:
Crowing sound when the child inhales (inspiratory stridor)
'Scratchy' feeling in the throat
Hoarseness
Shortness of breath
Mild dysphagia
Fever
Intercostal retractions (the muscles between the ribs pull in as the child attempts to breathe)
Drooling
Less common symptoms of tracheitis include:
Respiratory distress in less than 24 hours of a viral infection
Neck pain
Orthopnea
Dysphonia
Syncope
Cyanosis |
Hydroxydione | Hydroxydione (as hydroxydione sodium succinate) is a neuroactive steroid used as a general anesthetic.
vteHypnotics/sedatives (N05C)GABAAAlcohols
2M2B
Chloralodol
Ethanol (alcohol)
Ethchlorvynol
Methylpentynol
Trichloroethanol
Barbiturates
Allobarbital
Amobarbital
Aprobarbital
Barbital
Butabarbital
Butobarbital
Cyclobarbital
Ethallobarbital
Heptabarb
Hexobarbital
Mephobarbital
Methohexital
Narcobarbital
Pentobarbital
Phenallymal
Phenobarbital
Propylbarbital
Proxibarbal
Reposal
Secobarbital
Talbutal
Thiamylal
Thiopental
Thiotetrabarbital
Vinbarbital
Vinylbital
Benzodiazepines
Brotizolam
Cinolazepam
Climazolam
Doxefazepam
Estazolam
Flunitrazepam
Flurazepam
Flutoprazepam
Lorazepam
Loprazolam
Lormetazepam
Midazolam
Nimetazepam
Nitrazepam
Phenazepam
Quazepam
Temazepam
Triazolam
Carbamates
Carisoprodol
Emylcamate
Ethinamate
Hexapropymate
Meprobamate
Methocarbamol
Phenprobamate
Procymate
Tybamate
Imidazoles
Etomidate
Metomidate
Propoxate
Monoureides
Acecarbromal
Apronal (apronalide)
Bromisoval
Capuride
Carbromal
Ectylurea
Neuroactive steroids
Acebrochol
Allopregnanolone
Alphadolone
Alphaxolone
Eltanolone
Hydroxydione
Minaxolone
Progesterone
Nonbenzodiazepines
Eszopiclone
Indiplon
Lirequinil
Necopidem
Pazinaclone
Saripidem
Suproclone
Suriclone
Zaleplon
Zolpidem
Zopiclone
Phenols
Propofol
Piperidinediones
Glutethimide
Methyprylon
Pyrithyldione
Piperidione
Quinazolinones
Afloqualone
Cloroqualone
Diproqualone
Etaqualone
Mebroqualone
Mecloqualone
Methaqualone
Methylmethaqualone
Nitromethaqualone
Others
Acetophenone
Acetylglycinamide chloral hydrate
Bromide compounds
Lithium bromide
Potassium bromide
Sodium bromide
Centalun
Chloral betaine
Chloral hydrate
Chloralose
Clomethiazole
Dichloralphenazone
Gaboxadol
Kavalactones
Loreclezole
Paraldehyde
Petrichloral
Sulfonylalkanes
Sulfonmethane (sulfonal)
Tetronal
Trional
Triclofos
Sesquiterpene
Isovaleramide
Isovaleric acid
Valerenic acid
GABAB
1,4-Butanediol
4-Fluorophenibut
Aceburic acid
Baclofen
GABOB
GHB (sodium oxybate)
GBL
GVL
Phenibut
Tolibut
H1Antihistamines
Captodiame
Cyproheptadine
Diphenhydramine
Doxylamine
Hydroxyzine
Methapyrilene
Perlapine
Pheniramine
Promethazine
Propiomazine
Antidepressants
Serotonin antagonists and reuptake inhibitors
Etoperidone
Nefazodone
Trazodone
Tricyclic antidepressants
Amitriptyline
Doxepin
Trimipramine, etc.
Tetracyclic antidepressants
Mianserin
Mirtazapine, etc.
Antipsychotics
Typical antipsychotics
Chlorpromazine
Thioridazine, etc.
Atypical antipsychotics
Olanzapine
Quetiapine
Risperidone, etc.
α2-Adrenergic
Clonidine
Detomidine
Dexmedetomidine
Lofexidine
Medetomidine
Romifidine
Tizanidine
Xylazine
5-HT2AAntidepressants
Trazodone
Tricyclic antidepressants
Amitriptyline
Doxepin
Trimipramine, etc.
Tetracyclic antidepressants
Mianserin
Mirtazapine, etc.
Antipsychotics
Typical antipsychotics
Chlorpromazine
Thioridazine, etc.
Atypical antipsychotics
Olanzapine
Quetiapine
Risperidone, etc.
Others
Niaprazine
Melatonin
Agomelatine
Melatonin
Ramelteon
Tasimelteon
Orexin
Almorexant
Filorexant
Suvorexant
α2δ VDCC
Gabapentin
Gabapentin enacarbil
Mirogabalin
Phenibut
Pregabalin
Others
Cannabidiol
Cannabis
Chlorophenylalkyldiols
Fenpentadiol
Metaglycodol
Phenaglycodol
Diethylpropanediol
Evoxine
Fenadiazole
Guaifenesin-related muscle relaxants
Chlorphenesin
Mephenesin
Mephenoxalone
Metaxalone
Methocarbamol
Opioids (e.g., morphine)
Passion flower
Scopolamine
Trazodone
UMB68
Valnoctamide
Template:WH
Template:WS
|
Pancreatic_cancer_CT | Findings on CT scan that may be suggestive of pancreatic cancer include morphological changes of the gland, destruction of the peripancreatic fat and loss of the sharp margins with surrounding structures, involvement of the regional lymph nodes and adjacent vasculature, pancreatic ductal dilatation, pancreatic atrophy and obstruction of the common bile duct . MDCT (Multi-detector row computed tomography) the imaging modality widely used in suspected pancreatic cancer patients as the pre-operative examination. MDCT is used as the primary imaging modality, and is used in conjunction with PET/CT. MDCT helps in local and distant disease assessment in a single scan. MDCT is useful in the evaluation of vascular involvement, which helps in predicting the tumor resectability.
MDCT (Multi-detector row computed tomography) the imaging modality widely used in suspected pancreatic cancer patients as the pre-operative examination.
MDCT is used as the primary imaging modality, and is used in conjunction with PET/CT. MDCT helps in local and distant disease assessment in a single scan.
MDCT is useful in the evaluation of vascular involvement, which helps in predicting the tumor resectability.
Findings on CT scan that may be suggestive of pancreatic cancer include: , Morphological changes of the gland, Destruction of the peripancreatic fat and loss of the sharp margins with surrounding structures, Involvement of the regional lymph nodes and adjacent vasculature, Pancreatic ductal dilatation, Pancreatic atrophy, Obstruction of the common bile duct (CBD)
By Hellerhoff (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons |
Venereal_Disease_Research_Laboratory_test | The Venereal Disease Research Laboratory test (VDRL) is a nontreponemal serological screening for syphilis, the monitoring of the response to therapy, the detection of CNS involvement, and as an aid in the diagnosis of congenital syphilis. The basis of the test is that an antibody produced by a patient with syphilis reacts with an extract of ox heart (diphosphatidyl glycerol). It therefore detects anti-cardiolipin antibodies (IgG, IgM or IgA).
Many other conditions can produce false positive results, including some viruses (mononucleosis, hepatitis), drugs, rheumatic fever, rheumatoid arthritis, lupus, and leprosy.
The syphilis anti-cardiolipin antibodies are beta-2 glycoprotein independent, where as those that occur in the antiphospholipid antibody syndrome (associated to lupus for example) are beta-2 glycoprotein dependent, and this can be used to tell them apart in an ELISA assay. This test is very useful as the trend of titres are correlated to disease activity (i.e. falling titres indicate successful treatment). It has a very good sensitivity for syphilis, except in late tertiary form.
FTA-ABS is a far more specific test for syphilis and, in the presence of a positive VDRL test, indicates active infection.
Syphilis |
Fonsecaea_pedrosoi | Fonsecaea pedrosoi is a fungal species in the family Herpotrichiellaceae, and the major causative agent of chromoblastomycosis. This species is commonly found in tropical and sub-tropical regions where it grows as a soil saprotroph. Farming activities in the endemic zone are a risk factor for the development of chromoblastomycosis.
Fonsecaea is a genus of ascomycetous fungi affiliated with the family Herpotrichiellaceae. The genus comprises three sibling species, all with pathogenic potential: F. pedrosoi, F. monophora and F. nubica.
Fonsecaea pedrosoi occurs in soil and on plants and trees where it grows as a saprotroph. It is found predominantly in tropical regions especially South- and Central America. All three recognized species of Fonsecaea exhibit geographically patterned genetic variation. The closely related species F. monophora and F. nubica are distributed worldwide and show the greater population-level genetic diversity than the geographically restricted F. pedrosoi. Environmental surveys have documented the recovery of F. pedrosoi on rotting wood of the Cambara tree, (Gochnatia polymorpha) from the Brazilian Corporation of Agricultural Research forest in Colombo, Paraná, Brazil. It has been also isolated from living trees, stumps, woodpiles and fence posts in central Nigeria.
Clinical isolates of grow consistently at temperatures up to 35 °C (95 °F). In contrast, environmental isolates of F. pedrosoi exhibit growth consistently up to 35°C, and irregularly up to 37 °C (98.6 °F) Physiological studies have shown the degradation of urea and tyrosine, and the lack of growth on the proteins gelatin, casein and the purines xanthine and hypoxanthine. Likewise, lipase activity was demonstrated, but phospholipase, collagenase and amylase were not expressed.
Fonsecaea pedrosoi is one of several main causative agents of human chromoblastomycosis, a chronic fungal infection localized to skin and subcutaneous tissue. The disease was first described by Alexandrino Pedroso in 1911. The fungus infects the host through the traumatic implantation of sexual spores known as conidia or hyphal fragments. Once introduced in the subcutaneous tissues, the propagules germinate to establish an invasive mycelium associated with sclerotic cells. This proliferation manifests as a well-defined, chronically progressive, crusted ulceration of the skin known as chromoblastomycosis. Clinically it is often misdiagnosed as squamous cell carcinoma.
The disease is characterized by the appearance of spherical, brownish yellow cells with thick, darkly pigmented walls. The presence of the agent is associated with host cell proliferation and enlargement known as hyperplasia localized to the stratified squamous epithelium and the formation of mycotic granulomas. Sclerotic bodies are present both extracellularly and intracellularly throughout the affected tissue and are a defining feature of chromoblastomycosis. The melanin content of sclerotic bodies may be important in the establishment of host immune responses.
Farmers in Central and South America are most susceptible to chromoblastomycosis due to F. pedrosoi. Infection often occurs in the upper body and legs of agricultural laborers since these areas are more prone to exposure to infected soil, plant debris or other fomites. The sex ratio of disease is globally variable. In Brazil, the agent has shown a 4:1 proclivity for men, likely as a function of exposure differences relating to work and lifestyle, while Japanese infections have shown evenly distributed infection rates between the sexes.
Infections by F. pedrosoi are more difficult to treat than those of F. monophora. In severe cases, treatment is quite complex and involves a combination of antifungal drug therapy and surgical excision. Antifungal agents like itraconazole and terbinafine are commonly used. Surgery is often used to treat small, localized infections, although cryotherapy has been suggested an alternative approach. Topical application of amphotericin B followed by long-term administration of oral antifungal therapy has been shown to be effective in the treatment of corneal chromoblastomycosis from F. pedrosoi. The diagnosis and treatment of chromoblastomycosis by F. pedrosoi remains clinically challenging due to the relative rarity of the disease, its slow, chronic nature, the absence of clinical features readily differentiating it from other more common diseases such as squamous cell carcinoma, the restricted nature of therapies, and the lack of literature.
|
Cicatricial_alopecia | Cicatricial alopecia presents clinically with the effacement/scarring of follicular orifices, always in a patchy or focal distribution.
Causes of noncicatricial alopecia include:
Acne necrotica
Alopecia mucinosa
Atrichia with papular lesions
Central centrifugal cicatricial alopecia
Erosive pustular dermatitis of the scalp (Erosive pustular dermatosis of the scalp)
Folliculitis decalvans
Hot comb alopecia
Keratosis pilaris atropicans
Lichen planopilaris
Lupus erythematosus
Perifolliculitis capitis abscedens et suffodiens (Dissecting cellulitis of the scalp, Dissecting folliculitis, Perifolliculitis capitis abscedens et suffodiens of Hoffman)
Pressure alopecia
Pseudopelade of Brocq (Alopecia cicatrisata)
Sarcoidosis
Traction alopecia
Tufted folliculitis
Tumor alopecia
Noncicatricial alopecia |
Jugular_Venous_Distention | The jugular venous pressure (JVP, sometimes referred to as jugular venous pulse) is the indirectly observed pressure over the venous system. It can be useful in the differentiation of various forms of heart and lung disease.
Classically three upward deflections (waves) and two downward deflections (toughs) have been described. The upward deflections are the "a" (atrial filling), "c" (ventricular contraction and resulting bulging of tricuspid into the right atrium during isovolumic syst |
Heparin-induced_thrombocytopenia_future_or_investigational_therapies | Future therapies involve use of factor X inhibitors or direct thrombin inhibitors. The data is currently not mature enough to make any clinical recommendations.
Future therapies for HIT focus on use of new oral anticoagulants. Director factor X inhibitors and newer direct thrombin inhibitors are being studied, but the data is currently in its infancy. Cost-effectiveness analyses will need to be done to determine whether it is appropriate to use these new agents.
|
Extramammary_Paget%27s_disease_secondary_prevention | Secondary prevention strategies following extramammary Paget's disease include an annual complete physical examination, proctosigmoid |
Didrex | Benzphetamine is a Sympathomimetic amine that is FDA approved for the treatment of exogenous obesity. Common adverse reactions include Increased blood pressure, Palpitations, Tachyarrhythmia, Urticaria, Diarrhea, Nausea, Unpleasant taste in mouth, Xerostomia, Central nervous system stimulation, Overstimulation, Dizziness, Headache, Insomnia, Tremor, Depression following drug withdrawal, Restlessness, Changes in libido.
Benzphetamine Hydrochloride Tablets are indicated in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction. The limited usefulness of agents of this class should be weighed against possible risks inherent in their use such as those described below.
Benzphetamine Hydrochloride Tablets are supplied as follows:
50 mg (peach, round, imprinted with BP 650, scored)
12634-118-56 Bottle of 56
12634-118-44 Bottle of 84
There is limited information regarding Off-Label Guideline-Supported Use of Benzphetamine in adult patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Benzphetamine in adult patients.
There is limited information regarding FDA-Labeled Use of Benzphetamine in pediatrenhance the effects of tricyclic antidepressants.
Urinary alkalinizing agents increase blood levels and decrease excretion of amphetamines. Urinary acidifying
agents decrease blood levels and increase excretion of amphetamines.
Pregnancy Category (FDA): X
Benzphetamine Hydrochloride Tablets may cause fetal harm when administered to a pregnant woman. Amphetamines have been shown to be teratogenic and embryotoxic in mammals at high multiples of the human dose. Benzphetamine Hydrochloride Tablets are contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Pregnancy Category (AUS):
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Benzphetamine in women who are pregnant.
There is no FDA guidance on use of Benzphetamine during labor and delivery.
Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.
Use of benzphetamine hydrochloride is not recommended in individuals under 12 years of age.
There is no FDA guidance on the use of Benzphetamine with respect to geriatric patients.
There is no FDA guidance on the use of Benzphetamine with respect to specific gender populations.
There is no FDA guidance on the use of Benzphetamine with respect to specific racial populations.
There is no FDA guidance on the use of Benzphetamine in patients with renal impairment.
There is no FDA guidance on the use of Benzphetamine in patients with hepatic impairment.
There is no FDA guidance on the use of Benzphetamine in women of reproductive potentials and males.
There is no FDA guidance one the use of Benzphetamine in patients who are immunocompromised.
Oral
There is limited information regarding Monitoring of Benzphetamine in the drug label.
There is limited information regarding IV Compatibility of Benzphetamine in the drug label.
Acute overdosage with amphetamines may result in restlessness, tremor, tachypnea, confusion, assaultiveness and panic states.
Fatigue and depression usually follow the central stimulation. Cardiovasculas effects include arrhythmias,
hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting,
diarrhea, and abdominal cramps. Hyperpyrexia and rhabdomyolysis have been reported and can lead to a number
of associated complications. Fatal poisoning is usually preceded by convulsion and coma.
Information concerning the effects of overdosage with benzphetamine hydrochloride tablets is extremely limited. The following
is based on experience with other anorexiants.
Management of acute amphetamine intoxication is largely symptomatic and includes sedation with a barbiturate. If hypertension
is marked, the use of a nitrite or rapidly acting alpha receptor blocking agent should be considered.
Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendations in this regard.
Acidification of the urine increases amphetamine excretion. The oral LD50 is 174 mg/kg in mice and 104 mg/kg in rats. The intraperitioneal LD50 in mice is 153 mg/kg.
Benzphetamine is a controlled substance under the Controlled Substance Act by the Drug Enforcement Administration and has been assigned to Schedule III
Benzphetamine hydrochloride is related chemically and pharmacologically to the amphetamines. Amphetamines and
related stimulant drugs have been extensively abused, and the possibility of abuse of benzphetamine Hydrochloride Tablets
should be kept in mind when evaluating the desirabilityof including a drug as part of a weight reduction program.
Abuse of amphetamines and related drugs may be associated with intense psychological dependence and severe social
dysfunction. There are reports of patients who have increased dosage to many times that recommended.
Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression;
changes are also noted on the sleep EEG. Manifestations of chronic intoxication with anorectic drugs include
severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes. The most severe manifestation
of chronic intoxication is psychosis, often clinically indistinguishable from schizophirenia.
Benzphetamine hydrochloride is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.
Drugs of this class used in obesity are commonly known as "anorectics" or "anorexigenics". It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions, or metabolic effects, may be involved.
Benzphetamine hyrochloride tablets 50 mg contain the anorectic agent benzphetamine hydrochloride.Benzephet-
amine hydrochloride is a white crystalline powder readily soluble in water and 95% ethanol. The chemical name
for benaphetamine hydrochloride is d-N,a-Dimethyl-N-(phenylmethyl)-benzeneethanamine hydrochloride and its
moleculas weight is 275.82.
The structural formula (dextro form) is represented as follows below:
This image is provided by the National Library of Medicine.
Each Benzphetamine hydrochloride tablets 50 mg, for oral administration, contains 50 mg of benzphetamine hydrochloride.
Inactive ingredients: Calcium Stearate, Polyethylene Glycol, FD and C Yellow No. 6, Lactose Anhydrous, Sorbitol.
There is limited information regarding Pharmacodynamics of Benzphetamine in the drug label.
Adult obese subjects instructed in dietary management and treated with "anorectic" drugs, lose more weight on the average than those treated with placebo and diet, as determined in relatively short-term clinical trials.
The magnitude of increased weight loss of drug-treated patients over placebo-treated patients is only a fraction of a pound a week. The rate of weight loss is the greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. The possible origins of the increased weight loss due to the various drug effects are not established. The amount of weight loss associated with the use of an "anorectic" drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician-investigator, the population treated, and the diet prescribed. Studies do not permit conclusions as to the relative importance of the drug and non-drug factors on weight loss.
The natural history of obesity is measured in years, whereas the studies cited are restricted to a few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered to be clinically limited.
Animal studies to evaluate the potential for carcinogenesis, mutagenesis or impairment of fertility have not been performed.
There is limited information regarding Clinical Studies of Benzphetamine in the drug label.
Benzphetamine Hydrochloride Tablets are supplied as follows:
50 mg (peach, round, imprinted with BP 650, scored)
12634-118-56 Bottle of 56
12634-118-44 Bottle of 84
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F).
Dispense in a tight, light-resistant container as defined in the USP.
A Schedule CS-III controlled drug substance.
{{#ask: Page Name::Benzphetamine
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosage
|?Pill Color
|?Pill Shape
|?Pill Size (mm)
|?Pill Scoring
|?NDC
|?Drug Author
|format=template
|template=DrugPageImages
|mainlabel=-
|sort=Pill Name
}}
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
{{#ask: Label Page::Benzphetamine
|?Label Name
|format=template
|template=DrugLabelImages
|mainlabel=-
|sort=Label Page
}}
Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or
driving a vehicle; the patient should therefore be cautioned accordingly.
Alcohol-Benzphetamine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Didrex®
There is limited information regarding Benzphetamine Look-Alike Drug Names in the drug label.
|
Krabbe%E2%80%99s_disease | Krabbe disease (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare, often fatal degenerative disorder that affects the nervous system. This condition is inherited in an autosomal recessive pattern. It is caused by the shortage (deficiency) of an enzyme called galactosylceramidase. This enzyme deficiency impairs the growth and maintenance of myelin, the protective covering around certain nerve cells that ensures the rapid transmission of nerve impulses. Krabbe disease is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination). This disorder is also characterized by the abnormal presence of globoid cells, which are globe-shaped cells that usually have more than one nucleus.
The symptoms of Krabbe disease usually begin before the age of 1 year (the infantile form). Initial signs and symptoms typically include irritability, muscle weakness, feeding difficulties, episodes of fever without any sign of infection, stiff posture, and slowed mental and physical development. As the disease progresses, muscles continue to weaken, affecting the infant's ability to move, chew, swallow, and breathe. Affected infants also experience vision loss and seizures.
Less commonly, onset of Krabbe disease can occur in childhood, adolescence, or adulthood (late-onset forms). Visual problems and walking difficulties are the most common initial symptoms in this form of the disorder, however, signs and symptoms vary considerably among affected individuals.
Former Buffalo Bills quarterback Jim Kelly has been a leader in gaining recognition and research funding for the disease, following the diagnosis of his son, Hunter, with Krabbe disease in 1997. Hunter Kelly died of the disease August 5, 2005 at the age of 8. He was the longest known living survivor of infantile Krabbe disease.
Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability, inexplicable crying, fevers, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development. In the first stages of the disease, doctors often mistake the symptoms with those of cerebral palsy. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy and blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur. There are also juvenile- and adult-onset cases of Krabbe disease, which have similar symptoms but slower progression.
Worldwide, Krabbe disease occurs in about 1 in 100,000–200,000 births. A higher incidence (6 cases per 1,000 live births) has been reported in a few isolated arab communities in Israel.
Krabbe disease is caused by mutations in the GALC gene, which causes a deficiency of an enzyme called galactosylceramidase. The buildup of undigested fats affects the growth of the nerve’s protective myelin sheath (the covering that insulates many nerves) and causes severe degeneration of mental and motor skills. As part of a group of disorders known as leukodystrophies, Krabbe disease results from the imperfect growth and development of myelin.
In infants, the disease is generally fatal before age 2. Patients with a later onset form of the disease have a milder course of the disease and live significantly longer.
The disease may be diagnosed by its characteristic grouping of certain cells (multinucleated globoid cells), nerve demyelination and degeneration, and destruction of brain cells. Special stains for myelin (e.g; luxol fast blue) may be used to aid diagnosis.
Although there is no cure for Krabbe disease, bone marrow transplantation has been shown to benefit mild cases early in the course of the disease. Generally, treatment for the disorder is symptomatic and supportive. Physical therapy may help maintain or increase muscle tone and circulation. A recent study in the New England Journal of Medicine reports that cord blood transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.
This article incorporates public domain text from The U.S. National Library of Medicine and the National Institute of Neurological Disorders and Stroke.
[2]
The Stennis Foundation
The Stennis Foundation's MySpace site
Hunter's Hope Foundation
[3]
[4]
Template:Chorus
Template:WhoNamedIt
The Myelin Project
The Stennis Foundation |
Acute_liver_failure_causes | The causes of acute liver failure can be categorized into viral, drugs and toxins, vascular, and metabolic. Common causes of acute liver failure include acetaminophen toxicity, viral hepatitis (most commonly hepatitis A, hepatitis B and hepatitis E), alcoholic hepatitis, autoimmune, sepsis, right heart failure, and idiopathic. Acetaminophen toxicity is the most common cause of acute liver failure in the developed world and viral hepatitis (most commonly hepatitis A, hepatitis B and hepatitis E) is most common in the developing world.
The common causes of acute liver failure are:
Acetaminophen overdose, the reason is usually suicidal intent. Additionally, the toxic threshold dose of acetaminophen decreases in some cases, such as in chronic alcoholics, diabetics, and while fasting. Drug-induced acute liver failure is the most common cause in the developed world. It is responsible for more than 50% of the cases of acute liver failure in the United States.
Idiosyncratic reactions to medications such as tetracycline, troglitazone, antituberculosis drugs, and anti-epileptic drugs
Viral hepatitis (hepatitis A, B and hepatitis E) are the most common. The incidence of acute liver failure in post-viral hepatitis has decreased due to the vaccination and improved sanitation in the developed world. However, it is still the most common cause in the developing world.
Alcohol
Autoimmune hepatitis
Acute fatty liver of pregnancy
Reye syndrome
Wilson's disease
Idiopathic (without an obvious cause)
Diseases of fatty acid oxidation pathways
Parvovirus B19 infection
Budd–Chiari syndrome
Malignancy such as lymphomas
Shock
Sepsis
Hyperthermia
Hypothermia
HELP syndrome
8-Hyydroxyquinoline
Abacavir
Acetaminophen
Acute fatty liver of pregnancy
Adenovirus
Adult onset Still's disease
Alcohol
Allopurinol
Alpha1-antitrypsin deficiency
Amanita phalloides
Amatoxins
Amiodarone
Amitriptyline
Amoxicillin-clavulanate
Ampicillin
Anticonvulsants
Antituberculosis drugs
Asphyxia
Aspirin
Atorvastatin
Autoimmune hepatitis
Bacillus cereus
Bromfenac
Budd-Chiari syndrome
Carbamazepine
Carbon tetrachloride
Cardiomyopathy
Carnitine palmitoyltransferase 1 deficiency
Chaparral
Chelidonium
Ciprofloxacin
Cirrhosis
Cocaine
Comfrey
Congestive heart failure
Cryptogenic
Cyanobacteria
Cyclophosphamide
Cytomegalovirus
Dantrolene
Dapsone
Didanosine
Dideoxyinosine
Disulfiram
Doxycycline
Echovirus
Ecstacy
Efavirenz
Ephedra
Epstein-Barr virus
Erlotinib
Erythromycin
Ethanol
Etodolac
Extracorporeal membrane oxygenation
Fasciola hepatica
Fatty acid oxidation pathway diseases
Fluoroquinolones
Flutamide
Fructose intolerance
Galactosemia
Gemtuzumab
Gemtuzumab
Germander tea
Ginseng
Gold
Graft versus host disease
Gyromitrin
Halothane
He Shou Wu
Heart surgery
Heat stroke
HELLP syndrome
Hemochromatosis
Hemosiderosis
Hepatectomy
Hepatic arterial thrombosis
Hepatic veno-occlusive disease
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Herpes simplex
Hyperthermia
Hypoplastic left heart syndrome
Hypotension
Hypothermia
Imipramine
Interferon beta
Iron compounds
Ischemic hepatitis
Isoflurane
Isoniazid
Ixabepilone
Kava kava
Ketoconazole
Labetalol
LCAT deficiency
Leflunomide
Leptospirosis
Leukemia
Liver tumor
Loratadine
Lovastatin
Ma Huang
MAO inhibitors
Meloxicam
Methotrexate
Methyldopa
Moxifloxacin
Mushroom poisoning
Myocarditis
Nevirapine
Niacin
Nicotinic acid
Nitisinone
Nitrofurantoin
Non A non B hepatitis
Nortriptyline
NSAIDs
Oral contraceptive pills
Parainfluenza viruses
Parvovirus
Pazopanib
Pemoline
Pennyroyal
Phenytoin
Portal vein thrombosis
Propylthiouracil
Pyrazinamide
Regorafenib
Reye's syndrome
Rifampin
Senecio
Sepsis
Shock
Sickle cell disease
Simvastatin
Skull cap
Statins
Sulfasalazine
Suloctidil
Terbinafine
Tetracycline
Teucrium polium
Tolcapone
Toluene
Tricyclic antidepressants
Troglitazone
Tyrosinemia
Valproic acid
Viral hemorrhagic fever
Viral hepatitis
Visceral leishmaniasis
Wilson's disease
Yellow phosphorous |
Burn_physical_examination | Patients with burn injury usually appear as burned(injury) skin . When a doctor or physician has been admitted burned patient, the diagnosis is usually known by physical examination of the patient. Physical examination of burn injury consists of a thorough of thickness and total body surface area of the patient body. Patient may be have burn on his head, neck, arm, leg, Anterior trunk,Posterior trunk, and genatilia.
Key factors |
Cortical_dysplasia_--_focal_epilepsy_syndrome | Cortical dysplasia is a congenital abnormality where the neurons in an area of the brain failed to migrate in the proper formation in utero. Occasionally neurons will develop that are larger than normal in certain areas. This causes the signals sent through the neurons in these areas to misfire, which sends an incorrect signal. It is commonly found near the cerebral cortex and is associated with seizures and may be associated with some level of developmental delay(s). Instead of using medication to suppress the seizures, surgery is increasingly becoming a popular solution for the problem.
Focal cortical dysplasia is the most common cause of intractable epilepsy in children and is a frequent cause of epilepsy in adults. All forms of focal cortical dysplasia lead to disorganization of the normal structure of the cerebral cortex. Focal cortical dysplasia associated with enlarged cells is known as FCDIIB. The enlarged |
Stent_thrombosis_risk_factors | A number of clinical, angiographic, and procedural factors increase the risk of stent thrombosis. Predictors of stent thrombosis can be classified into anatomic variables, procedure related variables and clinical variables. ASA and clopidogrel resistances associated with an increased risk of stent thrombosis include .:
Stent underexpansion
Dissections at the stent margin
Incomplete wall apposition
Residual inflow and outflow disease
Overlapping stents
Polymer materials
Self expanding or coil stents
Lesion-specific factors that increase the likelihood of stent thrombosis include.:
A residual dissection at the margin of the stent
Impaired flow into or out of the stent
Small stent diameters (<3 mm)
Long stent lengths
A thrombus containing lesions such as that observed in the treatment of an acute myocardial infarction
Clinical variables include. :
Acute myocardial infarction
Noncompliance and discontinuation of clopidogrel,
Hyporesponsiveness to antiplatelet agents
Higher baseline platelet count
Diabetes mellitus
Renal failure
Congestive heart failure
Prior radiation orbrachytherapy
Off-label indication of BMS and DES:
In addition to these, stent implantation for off-label indication of both DES and BMS(such as restenotic lesions, bypass graft lesions, left main coronary artery disease, as well as ostial, bifurcated, and totally occluded lesions) has been associated with higher rates of ischemic complications, including stent thrombosis, as compared with standard indications.
In a case control study of 145 patients with stent thrombosis by Rinaldi et al, presence of angiographic thrombus prior to stenting, greater total stent length, higher baseline platelet count, acute MI indication, the use of a self expanding or coil stent, and GpIIb-IIIa exposure were identified as the strongest predictors of stent thrombosis.
In another study by Marroquin et al to compare the outcomes in bare-metal versus drug-elting stents for off-label indications showed that one year after intervention, there were no significant differences in the adjusted risk of death or myocardial infarction in patients with drug eluting stents as compared with those with bare metal stents. These findings implicate that the poorer outcome observed after stenting for off-label indications are related to patient and lesion characteristics but not to the stent itself. Therefore, large randomized clinical trial are needed to further study the use of DES for off label versus standard indications.
Premature discontinuation of antiplatelet/clopidogrel
Clopidogrel resistance: Absence/dysfunction of CYP2C19 allele which is required for the conversion of clopidogrel to its active metabolite.
Improper opposition of the stent or undersized stent
Length of the stent- greater the length, higher the risk
Malignancy
Cocaine use
Small caliber of the vessels
Slow intra coronary flow post PCI
Bifurcation lesion
Inadequate periprocedural anticoagulation
Low ejection fraction (<30%)
Nonionic contrast media
Prior brachytherapy
Small stent area on intracoronary ultrasound
Residual plaque/thrombus/dissection after stent placement
CAD ≥50% proximal of culprit lesion
Chronic kidney disease
Diabetes mellitus
Black race
Elevated C-reactive protein levels
Hypersensitivity to stents
Young age
Paclitaxel-eluting stent implantation
Multivessel disease
Acute coronary syndrome at presentation
Ongoing vessel inflammation
Delayed neointimal coverage which is usually seen with DES when compared to BMS |
Phenylalanine | Phenylalanine (abbreviated as Phe or F) is an α-amino acid with the formula HO2CCH(NH2)CH2C6H5. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. The codons for L-phenylalanine are UUU and UUC. It is a white, powdery solid. L-Phenylalanine (LPA) is an electrically-neutral amino acid, one of the twenty common amino acids used to biochemically form proteins, coded for by DNA.
Phenylalanine cannot be made by animals, which have to obtain it from their diet. It is produced by plants and most microorganisms from prephenate, an intermediate on the shikimate pathway.
Prephenate is decarboxylated with loss of the hydroxyl group to give phenylpyruvate. This species is transaminated using glutamate as the nitrogen source to give phenylalanine and α-ketoglutarate.
L-phenylalanine can also be converted into L-tyrosine, another one of the DNA-encoded amino acids. L-tyrosine in turn is converted into L-DOPA, which is further converted into dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) (the latter three are known as the catecholamines).
Phenylalanine uses the same active transport channel as tryptophan to cross the blood-brain barrier, and, in large quantities, interferes with the production of serotonin.
Lignin is derived from phenylalanine and from tyrosine. Phenylalanine is converted to cinnamic acid by the enzyme phenylalanine ammonia lyase.
Main article: Phenylketonuria
The genetic disorder phenylketonuria (PKU) is the inability to metabolize phenylalanine. Individuals with this disorder are known as "phenylketonurics" and must abstain from consumption of phenylalanine. This dietary restriction also applies to pregnant women with hyperphenylalanine (high levels of phenylalanine in blood) because they do not properly metabolize the amino acid phenylalanine. Persons suffering from PKU must monitor their intake of protein to control the buildup of phenylalanine as their bodies convert protein into its component amino acids.
A related issue is the compound present in many sugarless gums and mints, snack foods, sugarless soft drinks (such as diet sodas including CocaCola Zero, Pepsi Max, some forms of Lipton Tea, diet Nestea, Clear Splash flavored water), and a number of other low calorie food products. The artificial sweetener aspartame, sold under the names "Equal" and "NutraSweet", is an ester that is hydrolyzed in the body to give phenylalanine, aspartic acid, and methanol (wood alcohol). The breakdown problems phenylketonurics have with protein and the attendant build up of phenylalanine in the body also occurs with the ingestion of aspartame, although to a lesser degree. Accordingly, all products in the U.S. and Canada that contain aspartame must be labeled: "Phenylketonurics: Contains phenylalanine." In the UK, foods containing aspartame must carry ingredients panels that refer to the presence of 'aspartame or E951', [2]and they must be labeled with a warning "Contains a source of phenylalanine". These warnings are specifically placed to aid individuals who suffer from PKU so that they can avoid such foods.
Interestingly, the macaque genome was recently sequenced and it was found that macaques naturally have a mutation that is found in humans who have PKU.[3]
D-phenylalanine (DPA) either as a single enantiomer or as a component of the racemic mixture is available through conventional organic synthesis. It does not participate in protein biosynthesis although it is found in proteins, in small amounts, particularly aged proteins and food proteins that have been processed. The biological functions of D-amino acids remain unclear. Some D-amino acids, such as D-phenylalanine, may have pharmacological activity.
DL-Phenylalanine is marketed as a nutritional supplement for its putative analgesic and antidepressant activities. The putative analgesic activity of DL-phenylalanine may be explained by the possible blockage by D-phenylalanine of enkephalin degradation by the enzyme carboxypeptidase A. The mechanism of DL-phenylalanine's putative antidepressant activity may be accounted for by the precursor role of L-phenylalanine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
D-phenylalanine is absorbed from the small intestine, following ingestion, and transported to the liver via the portal circulation. A fraction of D-phenylalanine appears to be converted to L-phenylalanine. D-phenylalanine is distributed to the various tissues of the body via the systemic circulation. D-phenylalanine appears to cross the blood-brain barrier with less efficiency than L-phenylalanine. A fraction of an ingested dose of D-phenylalanine is excreted in the urine.
The genetic codon for phenylalanine was the first to be discovered. Marshall W. Nirenberg discovered that insertion of m-RNA made up of multiple uracil repeats into E. coli, the bacterium produced a new protein, made up solely of repeated phenylalanine amino acids.
|
Ovarian_cancer_physical_examination | Ovarian cancer physical exam findings varies from patient to another but usually the symptoms and signs are nonspecific and the cancer is discovered in its late stages. The findings in the physical exam can be palpable adnexal mass, ascites, pleural effusion, bowel obstruction.
Signs of ovarian cancer can vary based on the advancement of the disease. Women with advanced disease presents with acute symptoms such as: Pleural effusion, Bowel obstruction, Palpable abdominal or adnexal mass, Venous thromboembolism signs as lower limb swelling and tenderness, Women with early, late or advanced disease presents with subacute symptoms and signs, Fatigue, Weight loss, |
Hypolipoproteinemia#Classification | Hypolipoproteinemia (also known as hypolipidemia or low lipoproteins) is defined as presence of low levels of one or more type of lipoproteins. Hypolipoproteinemia may present as primary genetic disorders oteinemia, the clinician must begin the work-up for primary causes.
Patients with hypoproteinemia may present with low LDL, or low HDL. Patients with low LDL commonly present with diarrhea, vomiting, or failure to thrive (in infanthood). Patients with primary low HDL are usually asymptomatic however, patients diagnosed with low HDL due to Tangier's disease, ApoA1 deficiency, or LCAT deficiency have specific clinical findings such as corneal othe lipid panel and may involve screening of family members. Confirmatory gene sequencing is the gold standard diagnostic test for all hypolipoproteinemias.
The following are the list of conditions which can cause low LDL C and low HDL C levels:
Primary lipoprotein abnormalities
Hypoalphalipoproteinemia (Apolipoprotein A-1 deficiency). Low HDL
Hypobetalipoproteinemia and Abetalipoproteinemia. Low LDL and VLDL, but not low HDL
Chylomicron retention disease
Cholesteryl ester transfer protein (CETP) elevation
F mutations, Familial HDL deficiency. This is the most common cause of low HDL and coronary artery disease. Tangier disease
Secondary causes
Anemia
Chronic inflammation
Chronic liver disease
Critical illness
Hyperthyroidism
Infection
Malndary hypolipoproteinemias. The following algorithm is a list of various etiologies under primary and secondary hypolipoproteinemias:
The table below provides a brief synopsis of the lipid profile findings in several of the most common primary hypolipidemic disorders affecting the LDL C levels:
Abetalipoprotienemia
Familial Homozygous
Hypobetalipoproteinemia
Familial Heterozygous
Hypobetalipoproteinemia
PCSK9 deficiency
Chylomicron Retention
Disease
Familial Combined
Hypolipidemia
LDL C
↓↓↓ (0)
↓↓↓
↓
↓
↓↓
↓↓
Apo B
↓↓↓( 0)
↓↓↓
↓
N
↓↓
N
TG
↓↓↓
↓↓↓
↓
↓
N
↓
TC
↓↓↓
↓↓↓
↓
↓
↓↓
↓
HDL
↓↓
↓↓
N
N
↓↓
↓↓
VLDL
↓↓
↓↓
↓
N
↓↓
↓
Apo A1
↓↓
↓↓
↓
N
↓↓
N
The table below is a differential diagnosis for low HDL C disorders:
Familial LCAT
Deficiency
Fish Eye
Disease
Homozygous Tangier
Disease
Heterozygcessive
Autosomal Recessive
Autosomal Recessive
Autosomal Recessi formation.
Loss of alpha function only
Pre beta-1 HDL fails to picks up free cholesterol from cells due to mutation in ABCA1 transporter.
Similar to homozygous
Defective synthesis of Apo A1 resulting in failure of maturation of HDL and defective reverse cholesterol transport.
Clinical Features
Annular corneal opacity
Anaemia
Progressive renal disease with proteinuria
Corneal opacities only
Normal renal function
Large yellow-orange tonsils
Dense central corneal opacity
Relapsing and remitting course of neuropathy
Asymptomatic
Corneal Opacities
Tuboeruptive, Planar and palmar Xanthomas
Premature Heart Disease
Lipid Panel
Elevated Free cholesterol
HDL-C < 10 mg/dL
Low Apo A1 and Apo AII
Elevated Apo E and Triglycerides
Low LDL C
Elevated free cholesterol
HDL C < 27 mg/dL
Apo A1＜30mg/dl and low Apo A2
Elevated Apo E and Triglycerides
Normal LDL and VLDL
HDL < 5% of normal
Apo A1 < 1% of normal
LDL < 40% of normal
HDL C, Apo A1 and LDL 50% less than normal.
Undetectable Apo A1
HDL C less than 10mg/dl
Normal or low Apo AII
LDL C normal
Triglyceride normal or elevated
2D Gel Electrophoresis
Pre β-1 and α-4 HDL, LDL with β mobility due to Lipoprotien-X
Pre β-1and α-4 HDL with normal pre-β LDL.
Only preβ-1 HDL present
Lack of large α-1 and α-2 HDL particles
Normal preβ-1 HDL
Lack of Apo A1 containing HDL particles.
Approch algorithm to a patient with low HDL C:
HDL <20mg/dl in the absence of severe hypertriglyceridemia
Rule out secondary causes of low HDL CParaproteinemia from multiple myelomaAnabolic steriod useFibrate useThiazolidinedione use
Consider Monogenic primary disordersOrder ApoA1
>5mg/dl Undetectable or <5mg/dl
Familial LCAT deficiency High plasma FC:CE ratio2D electrophoresis: Prebeta and Alpha-4, Beta mobility of LDL Do 2D Gel Electrophoresis with Apo A1 Immunoassay
Complete absence of Apo A1 containing HDL C Only Pre-Beta HDL C
Apo A1 Deficiency(Confirm with gene sequencing) Homozygous Tangier Disease(Confirm with gene sequencing)
Approach algorithm to a patient with low low LDL C:
Low LDL C <5th percentile
Rule out secondary causes of low LDL
Lipid panel
Normal Triglycerides Low Triglycerides
Chlyomicron retention disease(Confirm with gene sequencing) Screen the lipid panel of the patient's parents
Normal Parental Lipid Panel If Parental Lipid Panel <50% of Normal on:*LDL*Total Cholesterol*Triglycerides
Abetalipoproteinemia(Confirm with gene sequencing) Familial homozygous hypobetalipoproteinemia(Confirm with gene sequencing)
|
Oral_cancer_(patient_information) | Oral cancer refers to cancers that develop on the tongue, oral mucosa (tissue lining the mouth and gums), and on the floor of the mouth. There are several types of oral lesions that have the potential to become cancerous. These include white lesions (leukoplakia), the most commonly diagnosed precancerous lesions in the mouth, or red, velvet-like lesions (erythroplakia). Of those lesions that become cancerous, about 90% are a type of tumor called squamous cell carcinoma.
Mucous membrane lesion, lump, or ulcer:
May be a deep, hard-edged crack in the tissue
Most often pale colored, may be dark or discolored
On the tongue, lip, or other mouth area
Usually painless at first (may develop a burning sensation or pain when the tumor is advanced)
Usually small
Additional symptoms that may be associated with this disease:
Abnormal taste in the mouth
Mouth sores
Swallowing difficulty
Tongue problems
Oral cancer most commonly involves the tissue of the lips or the tongue. It may also occur on the floor of the mouth, cheek lining, gums (gingiva), or roof of the mouth (palate).
Most oral cancers look very similar under the microscope and are called squamous cell carcinomas. These are malignant and tend to spread rapidly.
Smoking and other tobacco use are associated with 70 - 80% of oral cancer cases. Smoke and heat from cigarettes, cigars, and pipes irritate the mucous membranes of the mouth. Use of chewing tobacco or snuff causes irritation from direct contact with the mucous membranes. Heavy alcohol use is another activity associated with increased risk for oral cancer.
Other factors that increase the risk of oral cancer include poor dental and oral hygiene and chronic irritation (such as from rough teeth, dentures, or fillings). Some oral cancers begin as a white plaque (leukoplakia) or as a mouth ulcer. Recently, an infection with HPV (human papilloma virus) has been shown to be a risk factor.
Oral cancer accounts for about 8% of all malignant growths. Men get oral cancer twice as often as women do, particularly men older than 40.
Smokers
People infected with HPV
People who practice poor dental and oral hygiene
An examination of the mouth by the health care provider or dentist shows a visible or palpable (can be felt) lesion of the lip, tongue, or other mouth area. As the tumor enlarges, it may become an ulcer and bleed. Speech difficulties, chewing problems, or swallowing difficulties may develop, particularly if the cancer is on the tongue.
A tongue biopsy, gum biopsy, or a microscopic examination of the lesion confirm the diagnosis of oral cancer.
Oral cancer may be discovered when the dentist performs a routine cleaning and examination.
Call for an appointment with your health care provider if you have a lesion of the mouth or lip or a lump in the neck that does not go away within 1 month. Early diagnosis and treatment of oral cancer greatly increases the chances of survival.
Surgical removal of the tumor is usually recommended if the tumor is small enough. Radiation therapy and chemotherapy would likely be used when the tumor is larger or has spread to lymph nodes in the neck. Surgery may be necessary for large tumors.
Rehabilitation may include speech therapy or other therapy to improve movement, chewing, swallowing, and speech.
Head and neck cancer
Laryngead once a year. Many oral cancers are discovered by routine dental examination.
Other tips:
Have dental problems corrected
Minimize or avoid alcohol use
Minimize or avoid smoking or other tobacco use
Practice good oral hygiene
Approximately half of people with oral cancer will live more than 5 years after diagnosis and treatment. If the cancer is detected early, before it has spread to other tissues, the cure rate is nearly 75%. Unfortunately, more than half of oral cancers are advanced at the time the cancer is detected. By the time of diagnosis, most have spread to the throat or neck.
Approximately 25% of people with oral cancer die because of delayed diagnosis and treatment.
National Library of Medicine
Template:WH
Template:WS
|
Danon_disease | Danon disease (or glycogen storage disease Type IIb) is a lysosomal storage disease that was first characterized in 1981 by Dr. M.J. Danon. Danon Disease is an X-linked dominant disorder that predominantly affects cardiac muscle. It affects both males and females, although males tend to see the majority of mental retardation and muscle weakness.
A mutated gene that codes a protein called LAMP2 causes Danon Disease. LAMP2 protein is a glycoprotein molecule comprised of a carbohydrate and a protein. It is typically found on the membrane of the lysosome. LAMP2 is deficome.
Muscle weakness, heart disease, and mental retardation are three main symptoms associated with this disorder. Signs of muscle weakness and heart disease begin to manifest in early childhood or adolescence. Some affected individuals are unable to walk as muscular complications progress. Heart disease associated with Danon Disease involves heart arrhythmias and cardiomyopathy, or severe heart muscle disease. Visual problems may also occur.
In females, the symptoms of Danon Disease are less severe and manifest later than they do in affected males. Muscle weakness is present, but commonly less debilitating than it is in males. Heart disease, which may occur, will manifest in adulthood. Symptoms may include visual problems.
Danon Disease is an X-linked dominant disorder. It selectively and more often affects boys, since males have only one X chromosome. Females have two X chromosomes and therefore have an extra X to protect them from disorders of this inheritance nature, but cases of Danon Disease afflicting females have been reported. Danon Disease also commonly affects males more severely than it does females. Boys often develop symptoms in childhood or in adolescence. Symptoms may not appear in females until adolescence or adulthood.
Life expectancy for Danon Disease is 30 years of age or younger and result from cardiac failure.
Several mutations have been found on the LAMP2 gene, and gene screening is available. A muscle tissue biopsy, which reveals large vacuoles containing elevated levels of glycogen, a kind of a sugar, used in conjunction with genetic screening may confirm a diagnosis. Cardiac MRI is also used to diagnose heart disease.
Medications to treat the heart disease are often prescribed and in severe cases, a heart transplant is often needed. Supportive treatment, such as physical therapy, may improve muscle strength and balance.
Hide and Seek Foundation For Lysosomal Disease Research |
Glycogen_storage_disease_type_III_history_and_symptoms | The hallmark of glycogen storage disease type 3 is hepatomegaly. The most common symptoms of glycogen storage disease include abdominal protuberance and muscle weakness.
The hallmark of glycogen storage disease type 3 is hepatomegaly. The most common symptoms of glycogen storage disease include abdominal protuberanifestations of severe fasting hypoglycemia
Hepatomegaly with abdominal protuberance
Muscle weakness
Common symptoms of glycogen storage disease type 3 include:
Protruded abdomen due to hepatomegaly
Muscle weakness
Hypotonia
Wasting of skeletal muscle
Symptoms due to cardiac involvement
Less common symptoms of glycogen storage disease type 3 include:
Associated peripheral neuropathy
Symptoms due to polycystic ovary disease
Ketoacidosis
Hyperlipidemia
Growth retardation |
Aluminum_chloride | Aluminium chloride is a chemical that is FDA approved for the treatment of indicated for the control of minor hemorrhage during dental restorative procedures. Common adverse reactions include hypersensitivity.
Indicated for the control of minor hemorrhage during dental restorative procedures.
Dispense a small amount of Hemoban into a clean dappen dish or disposable cup.
For hemorrhage control prior to making a restorative impression, soak a suitable length of retraction cord in aluminium chloride, then using a cord-packing instrument, place the retraction cord into the gingival sulcus. Aluminium chloride is compatible with all impression techniques – though it is recommended that critical areas be gently rinsed with water prior to application of addition-type (VPS) impression materials to preclude inhibition of the setting reaction of the impression material.
For minor hemorrhage control in situations other than making restorative impressions, soak a cotton pellet in aluminium chloride and apply for several seconds to the area, then rinsult patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Aluminium chloride in adult patients.
There is limited information regarding FDA-Labeled Use of Aluminium chloride in pediatric patients.
There is limited information regarding Off-Label Guideline-Supported Use of Aluminium chloride in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Aluminium chloride in pediatric patients.
This product should not be used with individuals with known sensitivities to aluminum chloride.
Do not swallow. Keep out of reach of children. For professional dental use only.
There is limited information regarding Clinical Trial Experience of Aluminium chloride in the drug label.
There is limited information regarding Postmarketing Experience of Aluminium chloride in the drug label.
There is limited information regarding Aluminium chloride Drug Interactions in the drug label.
Pregnancy Category (FDA):
Pregnancy Category
Pregnancy Category (AUS):
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Aluminium chloride in women who are pregnant.
There is no FDA guidance on use of Aluminium chloride during labor and delivery.
There is no FDA guidance on the use of Aluminium chloride with respect to nursing mothers.
There is no FDA guidance on the use of Aluminium chloride with respect to pediatric patients.
There is no FDA guidance on the use of Aluminium chloride with respect to geriatric patients.
There is no FDA guidance on the use of Aluminium chloride with respect to specific gender populations.
There is no FDA guidance on the use of Aluminium chloride with respect to specific racial populations.
There is no FDA guidance on the use of Aluminium chloride in patients with renal impairment.
There is no FDA guidance on the use of Aluminium chloride in patients with hepatic impairment.
There is no FDA guidance on the use of Aluminium chloride in women of reproductive potentials and males.
There is no FDA guidance one the use of Aluminium chloride in patients who are immunocompromised.
Topical
There is limited information regarding Monitoring of Aluminium chloride in the drug label.
There is limited information regarding IV Compatibility of Aluminium chloride in the drug label.
There is limited information regarding Chronic Overdose of Aluminium chloride in the drug label.
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox entry
Template:Chembox E number
Template:Chembox RTECS
Template:Chembox Appearance
Template:Chembox Density
Template:Chembox MeltingPt
Template:Chembox BoilingPt
Template:Chembox SolubilityInWater
Template:Chembox Solubility
Template:Chembox VaporPressure
Template:Chembox Viscosity
Template:Chembox Structure
Template:Chembox Thermochemistry
Template:Chembox GHSPictograms
Template:Chembox GHSSignalWord
Template:Chembox HPhrases
Template:Chembox PPhrases
Template:Chembox NFPA
Template:Chembox Lethal amounts (set)
Template:Chembox OtherAnions
Template:Chembox OtherCations
Template:Chembox Supplement
aluminium chloride is formulated to control minor hemorrhage during dental restorative procedures. aluminium chloride may be used on a cotton pellet or more commonly with retraction cord. aluminium chloride contains 25% aluminum chloride.
There is limited information regarding Aluminium chloride Structure in the drug label.
There is limited information regarding Pharmacodynamics of Aluminium chloride in the drug label.
There is limited information regarding Pharmacokinetics of Aluminium chloride in the drug label.
There is limited information regarding Nonclinical Toxicology of Aluminium chloride in the drug label.
There is limited information regarding Clinical Studies of Aluminium chloride in the drug label.
There is limited information regarding Aluminium chloride How Supplied in the drug label.
Store between 59°-86°F (15°-30°C). Protect from freezing.
{{#ask: Page Name::Aluminium chloride
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosage
|?Pill Color
|?Pill Shape
|?Pill Size (mm)
|?Pill Scoring
|?NDC
|?Drug Author
|format=template
|template=DrugPageImages
|mainlabel=-
|sort=Pill Name
}}
{{#ask: Label Page::Aluminium chloride
|?Label Name
|format=template
|template=DrugLabelImages
|mainlabel=-
|sort=Label Page
}}
There is limited information regarding Patient Counseling Information of Aluminium chloride in the drug label.
Alcohol-Aluminium chloride interaction has not been established. Talk to your doctor abo |
Reactive_lymphocyte | tes that become large as a result of antigen stimulation. Typically they can be more than 30 µm in diameter with varying size and shape.
The nucleus of a reactive lymphocyte can be round, elliptic, indented, cleft or folded. The cytoplasm is often abundant and can be basophilic. Vacuoles and/or azurophilic granules are also sometimes present. Most often the cytoplasm is gray, pale blue or deep blue in colour.
The distinctive cell associated with EBV or CMV is known as a "Downey cell", after Hal Downey, who contributed to the characterization of it in 1923. It is sometimes erroneously called a "Downy cell".
Reactive lymphocytes are usually associated with viral illnesses, however, they can also be present as a result of drug reactions (such as phenytoin), immunisations, radiation, hormonal causes (such as stress and Addison's disease) as well as some auto-immune disorders (such as rheumatoid arthritis).
Some pathogen-related causes include:
Epstein-Barr virus
Cytomegalovirus
Treponema pallidum (Syphilis)
Streptococcus agalactiae (Group B Streptococci),
Hepatitis C
Hantavirus |
Diaphyseal_aclasis | Hereditary multiple exostoses (HME) is a rare medical condition in which multiple bony spurs or lumps (also known as exostoses, or osteochondromas) develop on the bones of a child. HME is synonymous with Multiple hereditary exostoses and Multiple osteochondromatosis, which is the preferred term used by the World Health Organization.
HME is estimated to occur in 1 in 50,000 people. It is characterized by the growth of cartilage-capped benign bone tumours around areas of active bone growth, particularly the metaphysis of the long bones. HME can lead to the shortening and bowing of bones, as such affected individuals often have a short stature. Depending on their location the exostoses can cause the following problems: pain or numbness from nerve compression, vascular compromise, inequality of limb length, irritation of tendon and muscle, as well as a limited range of motion at the joints upon which they encroach. Generally, when a person with HME reaches maturity, and their bones stop growing, the exostoses also stop growing. A person with HME is also more likely to develop a rare form of bone cancer called chondrosarcoma as an adult.
HME begins to manifest itself in childhood and currently has no cure.
Surgery, physical therapy and pain management are currently the only options available to HME patients, but success varies from patient to patient and many struggle with pain, fatigue and mobility problems throughout their lives.
It is not uncommon for HME patients to undergo numerous surgical procedures throughout their lives to remove painful or deforming exostoses, correct limb length discrepancies or improve range of motion.
HME is an autosomal dominant hereditary disorder. This means that a patient with HME has a 50% chance of transmitting this disorder to his or her children. Most individuals with HME have a parent who also has the condition, however, approximately 10% -20% of individuals with HME have the condition as a result of a spontaneous mutation and are thus the first person in their family to be affected.
HME has thus far been linked with mutations in three genes. EXT1 which maps to chromosome 8q24.1 , EXT2 which maps to 11p13, and EXT3 which maps to the short arm of Chromosome 19 (though its exact location has yet to be precisely determined). Mutations in these genes typically lead to the synthesis of a truncated EXT protein which does not function normally. It is known that EXT proteins are important enzymes in the synthesis of heparan sulfate, however the exact mechanism by which altered synthesis of heparan sulfate could lead to the abnormal bone growth associated with HME is unclear. It is thought that normal chondrocyte proliferation and differentiation may be affected, leading to abnormal bone growth.
For individuals with HME who are considering starting a family, preimplantation genetic testing and prenatal diagnosis are available to determine if their unborn child has inherited the disease. HME has a 96% penetrance, which means that if the disease is indeed transmitted to a child, he/she will have a 96% of actually manifesting the disease, and 4% chance of having the disease but never manifesting it.
Patient #1
, , ,
, , ,
Patient #2
, , ,
, , , |
Familial_amyloidosis_medical_therapy | The optimal therapy for familial amyloidosis is preventing further organ damage and correcting the effects of organ failure. The mainstay of treatment for TTR amyloidosis is liver transplant. We may also use tafamidis, patisiran, Inoteresen, diflunisal, and epigallocathechin-3-gallate.
The mainstay of treatment for familial amyloidosis is removal of the source of abnormal TTR production. Since the liver is the dominant source of transthyretin, liver transplant is considered in patients with less advanced disease. Patients with severe cardiac complications may benefit from a heart transplant.
Newer therapies have been studied and assessed in clinical trials. These therapies may slow or halt progression of familial ATTR amyloidosis. Tafamidis, 2-(3,5–dichloro–phenyl)-benzox-azole-6-carboxylic acid is an orally administered drug that acts to stabilize the TTR tetramer through its affinity for the T4-binding site, and it does not carry the risks associated with nonsteroidal anti-inflammatory drug use. Recently approved for familial amyloid polyneuropathy (FAP) in Europe. This agent is being tested in ongoing trials for other forms of ATTR. Patisiran and Inoteresen, TTR gene silencers. FDA recently approved their use for ATTRm amyloidosis with peripheral neuropathy. Diflunisal, Nonsteroidal anti-inflammatory drug that stabilizes tetrameric TTR in vitro by binding via the thyroid hormone receptor sites. Epigallocathechin-3-gallate, The most abundant catechin in green tea. Recent in vitro experiments show that 50μmol/l epigallocatechin-3-gallate efficiently inhibits fibril formation from amyloid β-protein, α-synucleine, and TTR. Converts existing fibrils into nonfibril conformers.
Genetic counseling is recommended for individuals with hereditary amyloidosis and their family members.
|
Equilibrium_unfolding#Thermal_denaturation | equilibrium unfolding is the process of unfolding a protein or RNA molecule by gradually changing its solution conditions
Since equilibrium is maintained at all steps
the process is reversible (equilibrium folding)
Equilibrium unfolding is used to determine the conformational stability of the molecule
equilibrium unfolding assumes that the molecule may belong to only two thermodynamic states
the folded state (typically denoted N for "native" state) and the unfolded state (typically denoted U)
This "all-or-none" model of protein folding was first proposed by Tim Anson (1945)
but is believed to hold only for small
single structural domains of proteins (Jackson
larger domains and multi-domain proteins often exhibit intermediate states
As usual in statistical mechanics
these states correspond to ensembles of molecular conformations
The molecule may transition between the native and unfolded states according to a simple kinetic model
with rate constants <math>k_{f}</math> and <math>k_{u}</math> for the folding (<math>U \rightarrow N</math>) and unfolding (<math>N \rightarrow U</math>) reactions
The dimensionless equilibrium constant <math>K_{eq} \ \stackrel{\mathrm{def}}{=}\ \frac{k_{u}}{k_{f}} = \frac{\left[ U \right]_{eq}}{\left[ N \right]_{eq}}</math> can be used to determine the conformational stability <math>\Delta G</math> by the equation
\Delta G = -RT \ln K_{eq}
</math>
where <math>R</math> is the gas constant and <math>T</math> is the absolute temperature in kelvins
<math>\Delta G</math> is positive if the unfolded state is less stable (i
disfavored) relative to the native state
The most direct way to measure the conformational stability <math>\Delta G</math> of a molecule with two-state folding is to measure its kinetic rate constants <math>k_{f}</math> and <math>k_{u}</math> under the solution conditions of interest
since protein folding is typically completed in milliseconds
such measurements can be difficult to perform
usually requiring expensive stopped-flow or (more recently) continuous-flow mixers to provoke folding with a high time resolution
In the less expensive technique of equilibrium unfolding
the fractions of folded and unfolded molecules (denoted as <math>p_{N}</math> and <math>p_{U}</math>
respectively) are measured as the solution conditions are gradually changed from those favoring the native state to those favoring the unfolded state
by adding a denaturant such as guanidinium hydrochloride or urea
the reverse process is carried out
) Given that the fractions must sum to one and their ratio must be given by the Boltzmann factor
p_{N} = \frac{1}{1 + e^{-\Delta G/RT}}
</math>
p_{U} = \frac{e^{-\Delta G/RT}}{1 + e^{-\Delta G/RT}}
</math>
Protein stabilities are typically found to vary linearly with the denaturant concentration
A number of models have been proposed to explain this observation prominent among them being the denaturant binding model
solvent-exchange model (both by Schellman
JA) and the Linear Energy Model (LEM
All of the models assume that only two thermodynamic states are populated/de-populated upon denaturation
They could be extended to interpret more complicated reaction schemes
The denaturant binding model assumes that there are specific but independent sites on the protein molecule (folded or unfolded) to which the denaturant binds with an effective (average) binding constant k
The equilibrium shifts towards the unfolded state at high denaturant concentrations as it has more binding sites for the denaturant relative to the folded state (<math>\Delta n</math>)
the increased number of potential sites exposed in the unfolded state is seen as the reason for denaturation transitions
An elementary treatment results in the following functional form
\Delta G = \Delta G_{w} - RT \Delta n \ln \left(1 + k [D] \right)
</math>
where <math>\Delta G_{w}</math> is the stability of the protein in water and [D] is the denaturant concentration
Thus the analysis of denaturation data with this model requires 7 parameters
and the slopes and intercepts of the folded and unfolded state baselines
The solvent exchange model (also called the ‘weak binding model’ or ‘selective solvation’) of Schellman invokes the idea of an equilibrium between the water molecules bound to independent sites on protein and the denaturant molecules in solution
\Delta G = \Delta G_{w} - RT \Delta n \ln \left(1 + (K-1) X_{D} \right)
</math>
where <math>K</math> is the equilibrium constant for the exchange reaction and <math>X_{d}</math> is the mole-fraction of the denaturant in solution
This model tries to answer the question of whether the denaturant molecules actually bind to the protein or they seem to be bound just because denaturants occupy about 20-30 % of the total solution volume at high concentrations used in experiments
non-specific effects – and hence the term ‘weak binding’
As in the denaturant-binding model
fitting to this model also requires 7 parameters
One common theme obtained from both these models is that the binding constants (in the molar scale) for urea and guanidinium hydrochloride are small
2 <math>M^{-1}</math> for urea and 0
the difference in the number of binding sites between the folded and unfolded states is directly proportional to the differences in the accessible surface area
This forms the basis for the LEM which assumes a simple linear dependence of stability on the denaturant concentration
The resulting slope of the plot of stability versus the denaturant concentration is called the m-value
m-value is the derivative of the change in stabilization free energy upon the addition of denaturant
a strong correlation between the accessible surface area (ASA) exposed upon unfolding
difference in the ASA between the unfolded and folded state of the studied protein (dASA)
and the m-value has been documented by Pace and co-workers
In view of this observation
the m-values are typically interpreted as being proportional to the dASA
There is no physical basis for the LEM and is purely empirical
though it is widely used in interpreting solvent-denaturation data
It has the general form
\Delta G = m \left( [D]_{1/2} - [D] \right)
</math>
where the slope <math>m</math> is called the "m-value"(> 0 for the above definition) and <math>\left[ D \right]_{1/2}</math> (also called Cm) represents the denaturant concentration at which 50% of the molecules are folded (the denaturation midpoint of the transition
where <math>p_{N} = p_{U} = 1/2</math>)
the observed experimental data at different denaturant concentrations are fit to a two-state model with this functional form for <math>\Delta G</math>
together with linear baselines for the folded and unfolded states
The <math>m</math> and <math>\left[ D \right]_{1/2}</math> are two fitting parameters
along with four others for the linear baselines (slope and intercept for each line)
the slopes are assumed to be zero
giving four fitting parameters in total
The conformational stability <math>\Delta G</math> can be calculated for any denaturant concentration (including the stability at zero denaturant) from the fitted parameters <math>m</math> and <math>\left[ D \right]_{1/2}</math>
When combined with kinetic data on folding
the m-value can be used to roughly estimate the amount of buried hydrophobic surface in the folding transition state
the probabilities <math>p_{N}</math> and <math>p_{U}</math> cannot be measured directly
we assay the relative population of folded molecules using various structural probes
absorbance at 287 nm (which reports on the solvent exposure of tryptophan and tyrosine)
far-ultraviolet circular dichroism (180-250 nm
which reports on the secondary structure of the protein backbone) and near-ultraviolet fluorescence (which reports on changes in the environment of tryptophan and tyrosine)
nearly any probe of folded structure will work
since the measurement is taken at equilibrium
there is no need for high time resolution
measurements can be made of NMR chemical shifts
solvent exposure (chemical reactivity) of side chains such as cysteine
To convert these observations into the probabilities <math>p_{N}</math> and <math>p_{U}</math>
one generally assumes that the observable <math>A</math> adopts one of two values
corresponding to the native or unfolded state
the observed value equals the linear sum
A = A_{N} p_{N} + A_{U} p_{U}
</math>
By fitting the observations of <math>A</math> under various solution conditions to this functional form
one can estimate <math>A_{N}</math> and <math>A_{U}</math>
as well as the parameters of <math>\Delta G</math>
The fitting variables <math>A_{N}</math> and <math>A_{U}</math> are sometimes allowed to vary linearly with the solution conditions
when the asymptotes of <math>A</math> are observed to vary linearly under strongly folding or strongly unfolding conditions
Assuming a two state denaturation as stated above
one can derive the fundamental thermodynamic parameters namely
<math>\Delta S</math> and <math>\Delta G</math> provided one has knowledge on the <math>\Delta C_p</math> of the system under investigation
The thermodynamic observables of denaturation can be described by the following equations
<math>\ \Delta H(T)=\Delta H(T_d)+ \int_{T_d}^T \Delta C_p dT</math>
→ <math>\ \Delta H(T)=\Delta H(T_d)+ \Delta C_p[T-T_d] </math>
<math>\ \Delta S(T)=\frac{\Delta H(T_d)}{T_d}+ \int_{T_d}^T \Delta C_p dlnT</math>
→ <math>\ \Delta S(T)=\frac{\Delta H(T_d)}{T_d}+ \Delta C_pln \frac{T}{T_d} </math>
<math>\ \Delta G(T)=\Delta H -T \Delta S</math>
→ <math>\ \Delta G(T)=\Delta H(T_d) \frac{T_d-T}{T_d}+ \int_{T_d}^T \Delta C_p dT - T\int_{T_d}^T \Delta C_p dlnT </math>
→ <math>\ \Delta G(T)=\Delta H(T_d)(1-\frac{T}{T_d}) - \Delta C_p[T_d -T +Tln(\frac{T}{T_d})]</math>
<math>\ \Delta S</math> and <math>\ \Delta G</math> indicate the enthalpy
entropy and Gibbs free energy of unfolding under a constant pH and pressure
<math>\ T</math> is varied to probe the thermal stability of the system and <math>\ T_d</math> is the temperature at which half of the molecules in the system are unfolded
The last equation is known as the Gibbs-Helmholtz equation
In principle one can calculate all the above thermodynamic observables above from a single differential scanning calorimetry thermogram of the system assuming that the <math>\ \Delta C_p</math> is independent of the temperature
it is difficult to obtain accurate values for <math>\ \Delta C_p</math> this way
the <math>\ \Delta C_p</math> can be derived from a the variations in <math>\ \Delta H(T_d)</math> vs
<math>\ T_d</math> which can be achieved from measurements with slight variations in <math>\ pH</math> or protein concentration
The slope of the linear fit is equal to the <math>\ \Delta C_p</math>
Note that any non-linearity of the datapoints indicates that <math>\ \Delta C_p</math> is probably not independent of the temperature
the <math>\ \Delta C_p</math> can be estimated very accurately from the calculation of the accessible solvent area (ASA) of a protein prior and after thermal denaturation as follows
For proteins that have a known 3d structure
the <math>\ ASA_{native}</math> can be calculated through computer programs such as Deepview (also known as swiss PDB viewer
The ASA_{unfolded}</math> can be calculated from tabulated values of each amino acid through the semi-empirical equation
<math>\ ASA_{unfolded}=a_{polar}*ASA_{polar} + a_{aromatic}*ASA_{aromatic}+ a_{non-polar}*ASA_{non-polar}</math>
non-polar and aromatic indicate the parts of the 20 naturally occurring amino acids
Finally for proteins there is a linear correlation between <math>\ \Delta ASA</math> and <math>\ \Delta C_p</math> through the following equation
one can assess whether the folding proceeds according to a two-state unfolding as described above
The can be done with differential scanning calorimetry by comparing the calorimetric enthalpy of denaturation i
the area under the peak
<math>\ A_{peak}</math> to the van 't Hoff enthalpy described as follows
at <math>\ T=T_d</math> the <math>\ \Delta H_{vH}(T_d)</math> can be described as
<math>\ \Delta H_{vH}(T_d)= \frac{RT_d^2 \Delta C_p}{A_{peak}}</math>
When a two-state unfolding is observed the <math>\ A_{peak}=\Delta H_{vH}(T_d)</math>
Analogous functional forms are possible for denaturation by pressure |
Myelodysplastic_syndrome_CT | CT scan may be helpful in the diagnosis of myelodysplastic syndrome. Findings on CT scan of the spine suggestive of myelodysplastic syndrome include osteosclerosis and myelosclerosis.
CT scan may be helpful in the diagnosis of myelodysplastic syndrome. Findings on CT scan of the spine suggestive of myelodysplastic syndrome include: Osteosclerosis, Myelosclerosis
, , CT in the bone window demonstrates marked heterogenous sclerosis of the complete thoracic skeleton, especially pronounced in the spine. |
Breast_cancer_classification | Breast cancer may be classified according to anatomy into 4 subtypes: ductal, lobular, sarcoma, and lymphoma. There are also other methods of classification such as classification based on gene expression, and classification based on hormone receptors present. In practice, a combination of all above mentioned classification is combined with the surgical characteristics of tumors and radiologic findings is being applied for patient management, treatment planning, and prognosis determination.
Phyllodes tumor
Mammary fibromatosis: 0.2% of all breast tumors 5
Benign papillary lesions of the breast
Papilloma
Intraductal papilloma
Solitary papilloma of breast
Central solitary papilloma of breast
Peripheral solitary papilloma of breast
Multiple papillomata of breast
Juvenile papillomatosis of breast
Granular cell tumor of the breast
Hormone receptor positive: either estrogen or progesterone receptors are present
Hormone receptor negative: breast cancer cells do not have either estrogen or progesterone receptors
HER2 positive: If excess copies of HER2 gene
HER2 negative: If excess copies of HER2 gene are not present
Triple positive: cancers that are ER-positive, PR-positive, and have too much HER2
Triple negative: If the breast cancer cells don not have estrogen or progesterone receptors and don’t have too much HER2
Luminal type: are estrogen receptor (ER)–positive
Luminal A:
Expression of luminal (low molecular weight) cytokeratins, high expression of hormone receptors and related genes
50% of invasive bresat cancer, ER/PR positive, HER2/neu negative
Tubular carcinoma, Cribriform carcinoma, Low grade invasive ductal carcinoma, NOS, Classic lobularcarcinoma
Response to endocrine therapy
Variable response to chemotherapy
Low grade,
Grows slowly,
Good prognosis (the best prognosis)
Luminal B :
Expression of luminal (low molecular weight) cytokeratins, moderate-low expression of hormone receptors and related genes
20% of invasive breast cancer, ER/PR positive, HER2/neu expression variable, higher proliferation than Luminal A, higher histologic grade than Luminal A
Invasive ductal carcinoma, NOS Micropapillary carcinoma
Response to endocrine therapy (tamoxifene and aromatase inhibitors) not as good as Luminal A
Variable response to chemotherapy (better than Luminal A)
Prognosis not as good as Luminal A
Grows faster
HER2/neu
High expression of HER2/neu, low expression of ER and related genes
15% of invasive breast cancer, ER/PR negative, HER2/neu positive, high proliferation, diffuse TP53 mutation, high histologic grade and nodal positivity
High grade invasive ductal carcinoma, NOS
Response to trastuzumab (Herceptin)
Response to chemotherapy with antracyclins
Usually unfavorable prognosis
Basal like
High expression of basal epithelial genes and basal cytokeratins, low expression of ER and related genes, low expression of HER2/neu
~15% of invasive breast cancer, most ER/PR, HER2/neu negative (triple negative), high proliferation, diffuse TP53 mutation, BRCA1 dysfunction (germline, sporadi
High grade invasive ductal carcinoma, NOS Metaplastic carcinoma, Medullary carcinoma
No response to endocrine therapy or trastuzumab
Sensitive to platinum group chemotherapy and PARP inhibitors
Not all, but usually worse prognosis |
Affective_disorders | The affective spectrum is a grouping of related psychiatric and medical disorders which may accompany bipolar, unipolar, and schizoaffective disorders at statistically higher rates than would normally be expected. These disorders are identified by a common positive response to the same types of pharmacologic treatments. They also aggregate strongly in families and may therefore share common heritable underlying physiologic anomalies.
Affective spectrum disorders include:
Attention-deficit hyperactivity disorder
Bipolar disorder
Body dysmorphic disorder
Bulimia nervosa and other eating disorders
Cataplexy
Dysthymia
General anxiety disorder
Hypersexuality
Impulse-control disorders
Kleptomania
Migraine[citation needed]
Major Depressive Disorder
Narcolepsy[citation needed]
Obsessive-compulsive disorder
Panic disorder
Posttraumatic stress disorder
Premenstrual dysphoric disorder[citation needed]
Social phobia
The following may also be part of the spectrum accompanying affective disorders[citation needed].
Chronic pain
Intermittent explosive disorder
Pathological gambling
Personality disorder
Pyromania
Substance abuse and addiction (includes alcoholism)
Trichotillomania
Also, there are now studies linking heart disease[citation needed].
Please note that many of the terms above overlap. The generally accepted definition of these terms can be found in the Diagnostic and Statistical Manual of Mental Disorders (DSM).
International Society for Bipolar Disorders
|
Physiological_dependence | Physical dependence (or drug dependence) refers to a state resulting from habitual use of a drug, where negative physical withdrawal symptoms result from abrupt discontinuation. From the point of view of the dependent person, "dependence is duress," argues addiction researcher Griffith Edwards.
Increased heart rate and/or blood pressure, sweating, and tremors are common signs of withdrawal. More serious symptoms such as confusion, seizures, and visual hallucinations indicate a serious emergency and the need for immediate medical care. Alcohol, benzodiazepines, and barbiturates are the only commonly abused substances that can be fatal in withdrawal. Abrupt withdrawal from other drugs, such as opioids or psychostimulants, can exaggerate mild to moderate neurotoxic side effects due to hyperthermia and generation of free radicals, but life-threatening complications are very rare.
Treatment for physical dependence depends upon the drug being withdrawn and often includes administration of another drug, especially for substances that can be dangerous when abruptly discontinued. Treatment usually requires the initiation and then tapering of a medication that has a similar action in the brain but a longer half-life.
Physical dependence is different from drug addiction. The latter is often characterized by a psychological need for a drug, whileoholic beverage)
GHB
methaqualone (Quaalude®)
nicotine
opioids
amphetamines |
Acute_febrile_neutrophilic_dermatosis | Sweet's syndrome, or acute febrile neutrophilic dermatosis, is a condition characterized by the sudden onset of fever, leukocytosis, and tender, erythematous, well-demarcated papules and plaques which show dense neutrophilic infiltrates on histologic examination.
Sweet, in 1964, described a disease with four features: fever; leukocytosis; acute, tender, red plaques; and a papillary dermal infiltrate of neutrophils. This ot consistently present. The diagnosis is based on the two constant features, a typical eruption and the characteristic histologic features; thus the eponym Sweet's syndrome (SS) is used.
Sweet's syndrome can be classified based upon the clinical setting in which it occurs: classical or idiopathic Sweet's syndrome, malignancy-associated Sweet's syndrome, and drug-induced Sweet's syndrome.
SS is a reactive phenomenon and should be considered a cutaneous marker of systemic disease.[139] Careful systemic evaluation is indicated, especially when cutaneous lesions are severe or hematologic values are abnormal. Approximately 20% of cases are associated with malignancy, predominantly hematological, especially acuemia and other hematologic malignancies, solid tumors, pregnancy) is found in up to 50% of cases. Attacks of SS may precede the hematologic diagnosis by 3 months to 6 years, so that close evaluation of patients in the “idiopathic” group is required.
There is now good evidence that treatment with hematopoietic growth factors, including granulocyte colony-stimulating factor, which is used to treat acute myelogenous leukemia, and granulocyte-macrophage colony-stimulating factor, can cause Sweet's syndrome. Lesions typically occur when the patient has leukocytosis and neutrophilia but not when the patient is neutropenic. However, G-CSF may cause SS in neutropenic patients because of the induction of stem cell proliferation, the differentiation of neutrophils, and the prolongation of neutrophil survival.
Although it may occur in the absence of other known disease, Sweet's syndrome is often associated with hematologic disease (including leukemia), and immunologic disease (rheumatoid arthritis, inflammatory bowel disease).
Acute, tender, erythematous plaques, nodes, pseudovesicles and, occasionally, blisters with an annular or arciform pattern occur on the head, neck, legs, and arms, particularly the back of the hands and fingers. The trunk is rarely involved. Fever (50%); arthralgia or arthritis (62%); eye involvement, most frequently conjunctivitis or iridocyclitis (38%); and oral aphthae (13%) are associated features. Differential diagnosis includes erythema multiforme, erythema nodosum, adverse drug reaction, and urticaria. Recurrences are common and affect up to one third of patients.
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>,
, , url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=439>ase in alkaline phosphatase (83%). Skin biopsy shows a papillary and mid-dermal mixed infiltrate of polymorphonuclear leukocytes with nuclear fragmentation and histiocytic cells. The infiltrate is predominantlent, or immunoglobulins within the vessel walls; red blood cell extravasation;inflammatory infiltration of vascular walls) are absent in early lesions.
Vasculitis occurs secondary to noxious products released from neutrophils. Blood vessels in lesions of longer durat Therefore, vasculitis does not exclude a diagnosis of Sweet's syndrome
Systemic corticosteroids (prednisone 0.5 to 1.5 mg/kg of body weight per day) produce rapid improvement and are the “gold standard” for treatment. The temperature, WBC count, and eruption improve within 72 hours. The skin lesions clear within 3 to 9 days. Abnormal laboratory values rapidly return to normal. There are, however, frequent recurrences. Corticosteroids are tapered within 2 to 6 weeks to zero. Resolution of the eruption is occasionally followed by milia and scarring. The disease clears spontaneously in some patients. Topical and/or intralesional corticosteroids may be effective as either monotherapy or adjuvant therapy.
Oral potassium iodide or colchicine may induce rapid resolution. Patients who have a potential systemic infection or in whom corticosteroids are contraindicated can use these agents as a first-line therapy.
In one study, indomethacin, 150 mg per day, was given for the first week, and 100 mg per day was given for 2 additional weeks. Seventeen of 18 patients had a good initial response; fever and arthralgias were markedly attenuated within 48 hours, and eruptions cleared between 7 and 14 days. Patients whose cutaneous lesions continued to develop were successfully treated with prednisone (1 mg/kg per day). No patient had a relapse after discontinuation of indomethacin.
Other alternatives to corticosteroid treatment include dapsone, doxycycline, clofazimine, and cyclosporine. All of these drugs influence migration and other functions of neutrophils.
|
Pegvisomant | Pegvisomant is a growth hormone receptor antagonist that is FDA approved for the treatment of acromegaly in patients who have had an inadequate response to surgery or radiation therapy, or for whom these therapies are not appropriate. Common adverse reactions include infection, pain, nausea, diarrhea, abnormal liver tests, flu syndrome, injection site reaction.
Dosing Information
The recommended loading dose of SOMAVERT is 40 mg given subcutaneously, under healthcare provider supervision. Provide proper training in subcutaneous injection technique to patients or their caregivers so they can receive once daily subcutaneous injections. On the next day following the loading dose, instruct patients or their caregivers to begin daily subcutaneous injections of 10 mg of SOMAVERT.
Ti). The dosage should not be based on growth hormone (GH) concentrations or signs and symptoms of acromegaly. It is unknown whether patients who remain symptomatic while achieving normalized IGF-I concentrations would benefit from increased SOMAVERT dosage.
Increase the dosag every 4–6 weeks if IGF-I concentrations are below the normal range.
IGF-I levels should also be monitored when a Somavert dose given in multiple injections is converted to a single daily injection.
The recommended dosage range is between 10 to 30 mg given subcutaneously once daily and the maximum daily dosage is 30 mg given suatients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pegvisomant in adult patients.
There is limited information regarding FDA-Labeled Use of Pegvisomant in pediatric patients.
There is limited information regarding Off-Label Guideline-Supported Use of Pegvisomant in pediatric patie.
None.
Hypoglycemia associated with GH lowering in patients with Diabetes Mellitus
GH opposes the effects of insulin on carbohydrate metabolism by decreasing insulin sensitivity; thus, glucose tolerance may improve in some patients treated with SOMAVERT. Patients should be carefully monitored and doses of anti-diabetic drugs reduced as necessary to avoid hypoglycemia in patients with diabetes mellitus.
Liver Test Elevations
Baseline serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total bilirubin (TBIL), and alkaline phosphatase (ALP) levels should be obtained prior to initiating therapy with SOMAVERT. Table 1 lists recommendations regarding initiation of treatment with SOMAVERT, based on the results of these liver tests (LTs).
Asymptomatic, transient elevations in transaminases up to 15 times ULN have been observed in < 2% of subjects among two open-label trials (with a total of 147 patients). These reports were not associated with an increase in bilirubin. Transaminase elevations normalized with time, most often after suspending treatment (SOMAVERT should be used in accordance with the information presented in Table 2 with respect to liver test abnormalities while on Somavert treatment).
This image is provided by the National Library of Medicine.
If a patient develops LT elevations, or any other signs or symptoms of liver dysfunction while receiving SOMAVERT, the following patient management is recommended (Table 2).
This image is provided by the National Library of Medicine.
Cross-Reactivity with GH Assays
SOMAVERT has significant structural similarity to growth hormone (GH) which causes it to cross-react in commercially available GH assays. Since serum concentrations of therapeutically effective doses of SOMAVERT are generally 100 to 1000 times higher than the actual serum GH concentrations seen in patients with acromegaly, measurements of serum GH concentrations will appear falsely elevated.
Lipohypertrophy
There have been cases of lipohypertrophy in patients treated with SOMAVERT. In a double-blind, 12-week, placebo-controlled study, there was one case (1.3%) of injection site lipohypertrophy reported in a subject receiving 10 mg/day. The subject recovered while on treatment. Among two open-label trials (with a total of 147 patients), there were two subjects, both receiving 10 mg/day, who developed lipohypertrophy. One case recovered while on treatment, and one case resulted in a discontinuation of treatment. Injection sites should be rotated daily to help prevent lipohypertrophy (different area than the last injection).
Systemic Hypersensitivity
In subjects with systemic hypersensitivity reactions, caution and close monitoring should be exercised when re-initiating Somavert therapy.
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
In a 12-week randomized, placebo-controlled, double-blind, fixed-dose study of SOMAVERT in subjects with acromegaly, 32 subjects received placebo and 80 subjects received SOMAVERT once daily. A total of 108 subjects (30 placebo, 78 Somavert) completed 12 weeks of study treatment. .
Overall, eight patients with acromegaly (5.3%) withdrew from pre-marketing clinical studies because of adverse events, including two patients with marked transaminase elevations, one patient with lipohypertrophy at the injection sites, and one patient with substantial weight gain. Most adverse events did not appear to be dose-dependent. Table 3 shows the incidence of adverse events that were reported in at least two patients treated with SOMAVERT and at frequencies greater than placebo during the 12-week, placebo-controlled study.
This image is provided by the National Library of Medicine.
The following adverse reactions have been identified during post-approval use of SOMAVERT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Systemic hypersensitivity reactions including anaphylactic reactions, laryngospasm, angioedema, generalized skin reactions (rash, erythema, pruritus, urticaria) have been reported in post-marketing use. Some patients required hospitalization. Symptoms did not re-occur in all patients after re-challenge.
Registry of Patients with Acromegaly Treated with SOMAVERT
ACROSTUDY is an international observational registry that captures long term safety data in patients with acromegaly treated with SOMAVERT, as used in clinical practice. Treatment dose and schedule were at the discretion of each treating physician. Although safety monitoring as per the recommended schedule was mandatory, not all assessments were performed at all time points for every patient. Because of this, comparison of rates of adverse events to those in the original clinical trial is not appropriate. In an interim report, there were 1288 patients enrolled (mean duration of treatment 3.7 years).
At the start of SOMAVERT treatment 648 patients were on SOMAVERT monotherapy for acromegaly. Of the 454 patients who had a normal AST and ALT at baseline, 4 patients had elevated tests >3 times ULN, two of whom had elevated tests >5 times ULN.
Lipohypertrophy was reported in 6 (0.5%) patients.
MRIs were compared to any previous ones, and a change in tumor volume was reported as significant locally only if the diameter increased by more than 3 mm for microadenomas or volume increased by more than 20% for macroadenomas. All MRI changes considered significant at the local reading were reanalyzed centrally. Of the 747 patients who had a MRI reported at baseline and at least once during follow up in the study, 51 (7%) were reported to have an increase by local MRI. Of these, 16 patients (2%) had confirmation of this increase, 6 patients had a decrease, 12 had "no change"; there was 1 with insufficient data and 16 patients did not have a central MRI reading.
Insulin and/or Oral hypoglycemic Agents
After initiation of SOMAVERT, patients with acromegaly and diabetes mellitus treated with insulin and/or oral hypoglycemic agents may require dose reductions of insulin and/or oral hypoglycemic agents.
Opioids
In clinical studies, patients taking opioids often needed higher SOMAVERT doses to normalize IGF-I concentrations compared with patients not receiving opioids. The mechanism of this interaction is not known.
Pregnancy Category (FDA):
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Early embryonic development and teratology studies were conducted in pregnant rabbits with pegvisomant at subcutaneous doses of 1, 3, and 10 mg/kg/day. There was no evidence of teratogenic effects associated with pegvisomant treatment during organogenesis. At the 10-mg/kg/day dose (10 times the maximum human therapeutic dose based on body surface area), a reproducible, slight increase in post-implantation loss was observed in both studies. Because animal reproduction studies are not always predictive of human responses, SOMAVERT should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pegvisomant in women who are pregnant.
There is no FDA guidance on use of Pegvisomant during labor and delivery.
It is not known whether pegvisomant is excreted in human milk. Because many drugs are excreted in milk, caution should be exercised when SOMAVERT is administered to a nursing woman.
The safety and effectiveness of SOMAVERT in pediatric patients have not been established.
Clinical studies of SOMAVERT did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In geing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
There is no FDA guidance on the use of Pegvisomant with respect to specific gender populations.
There is no FDA guidance on the use of Pegvisomant with respect to specific racial populations.
There is no FDA guidance on the use of Pegvisomant in patients with renal impairment.
There is no FDA guidance on the use of Pegvisomant in patients with hepatic impairment.
There is no FDA guidance on the use of Pegvisomant in women of reproductive potentials and males.
There is no FDA guidance one the use of Pegvisomant in patients who are immunocompromised.
Subcutaneous
There is limited information regarding Monitoring of Pegvisomant in the drug label.
There is limited information regarding IV Compatibility of Pegvisomant in the drug label.
In one reported incident of acute overdose with SOMAVERT during pre-marketing clinical studies, a patient self-administered 80 mg/day (2.7 times the maximum recommended maintenance dosage) for seven days. The patient experienced a slight increase in fatigue, had no other complaints, and demonstrated no significant clinical laboratory abnormalities.
In cases of overdose, administration of SOMAVERT should be discontinued and not resumed until IGF-I levels return to within or above the normbinds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH, and thus interferes with GH signal transduction.
Inhibition of GH action results in decreased serum concentrations of IGF-I, as well as other GH-responsive serum proteins such as free IGF-I, the acid-labile subunit of IGF-I (ALS), and insulin-like growth factor binding protein-3 (IGFBP-3).
SOMAVERT contains pegvisomant, an analog of human growth hormone (GH) that has been structurally altered to act as a GH receptor antagonist.
Pegvisomant is a protein of recombinant DNA origin containing 191 amino acid residues to which several polyethylene glycol (PEG) polymers are covalently bound (predominantly 4 to 6 PEG/protein molecule). The molecular weight of the protein of pegvisomant is 21,998 Daltons. The molecular weight of the PEG portion of pegvisomant is approximately 5000 Daltons. The predominant molecular weights of pegvisomant are thus approximately 42,000, 47,000, and 52,000 Daltons. The schematic shows the amino acid sequence of the pegvisomant protein (PEG polymers are shown attached to the 5 most pronetically modified by the addition of a plasmid that carries a gene for GH receptor antagonist. Biological potency is determined using a cell proliferation bioassay. Binding of Somavert to the GH receptor results in disruption of the proper binding of the second GH receptor with inhibition of functional receptor dimerization and subsequent intracellular signaling.
This image is provided by the National Library of Medicine.
SOMAVERT for injection is supplied as a sterile, white lyophilized powder intended for subcutaneous injection after reconstitution with 1 mL of Sterile Water for Injection. SOMAVERT is available in single-dose sterile vials containing 10, 15, 20, 25 or 30 mg of pegvisomant protein (approximately 10, 15, 20, 25 and 30 U activity, respectively). Each vial 10, 15 and 20 also contains 1.36 mg of glycine, 36.0 mg of mannitol, 1.04 mg of sodium phosphate dibasic anhydrous, and 0.36 mg of sodium phosphate monobasic monohydrate. Each 25 mg vial also contains 1.7 mg of glycine, 46.1 mg of mannitol, 1.3 mg of sodium phosphate dibasic anhydrous, and 0.5 mg of sodium phosphate monobasic monohydrate. Each 30 mg vial also contains 2.1 mg of glycine, 56.5 mg of mannitol, 1.6 mg of sodium phosphate dibasic anhydrous, and 0.6 mg of sodium phosphate monobasic monohydrate.
SOMAVERT is supplied in packages that include a vial containing diluent. Sterile Water for Injection, USP, is a sterile, nonpyrogenic preparation of water for injection that contains no bacteriostat, antimicrobial agent, or added buffer, and is supplied in single-dose containers to be used as a diluent.
Pegvisomant binds selectively to the GH receptor, and does not cross-react with 19 other cytokine receptors tested, including prolactin. Pegvisomant leads to decreased serum concentrations of IGF-I, free IGF-I, ALS, and IGFBP-3.
Absorption: Following subcutaneous administration, peak serum pegvisomant concentrations are not generally attained until 33 to 77 hours after administration. The mean extent of absorption of a 20-mg subcutaneous dose was 57%, relative to a 10-mg intravenous dose.
Distribution: The mean apparent volume of distribution of pegvisomant is 7 L (12% coefficient of variation), suggesting that pegvisomant does not distribute extensively into tissues. reasing dose. Mean ± SEM serum pegvisomant concentrations after 12 weeks of therapy with daily doses of 10, 15, and 20 mg were 6600 ± 1330; 16,000 ± 2200; and 27,000 ± 3100 ng/mL, respectively.
The relative bioavailability of 1 × 30 mg pegvisomant was compared to 2 × 15 mg pegvisomant in a single dose study. The AUCinf and Cmax of pegvisomant when administered as one injection of 30 mg strength was approximately 6% and 4% greater, respectively, as compared to when administered as two injections of 15 mg strengths.
Metabolism and Elimination: The pegvisomant molecule contains covalently bound polyethylene glycol polymers in order to reduce the clearance rate. Clearance of pegvisomant following multiple doses is lower than seen following a single dose. The mean total body systemic clearance of pegvisomant following multiple doses is estimated to range between 36 to 28 mL/h for subcutaneous doses ranging from 10 to 20 mg/day, respectively. Clearance of pegvisomant was found to increase with body weight. Pegvisomant is eliminated from serum with a mean half-life estimates ranging from 60 to 138 hours following either single or multiple doses. Less than 1% of administered drug is recovered in the urine over 96 hours. The elimination route of pegvisomant has not been studied in humans.
Drug Interaction Studies
In clinical studies, patients on opioids often needed higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opioids. The mechanism of this interaction is not known.
Specific Populations
No pharmacokinetic studies have been conducted in patients with renal impairment, patients with hepatic impairment, geriatric patients, or pediatric patients and the effects of race on the pharmacokinetics of pegvisomant has not been studied. No gender effect on the pharmacokinetics of pegvisomant was found in a population pharmacokinetic analysis.
Carcinogenesis
Pegvisomant was administered subcutaneously to rats daily for 2 years at doses of 2, 8 and 20 mg/kg (about 2, 10 and 25-fold a single 20 mg dose in humans on an AUC basis). Long term treatment with pegvisomant at 8 and 20 mg/kg caused an increase in malignant fibrous histiocytoma at injection sites in males. Injection site tumors were not seen in female rats at the same doses. The increased incidence of injection site tumors was most probably caused by irritation and the high sensitivity of the rat to repeated subcutaneous injections.
Mutagenesis
Pegvisomant did not cause genetic damage in standard in vitro assays (bacterial mutation, human lymphocyte chromosome aberration).
Impairment of Fertility
Pegvisomant was found to have no effect on fertility or reproductive performance of female rabbits at subcutaneous doses up to 10 mg/kg/day (10-fold the recommended human dose on a body surface area basis).
A total of one hundred twelve patients (63 men and 49 women) with acromegaly participated in a 12-week, randomized, double-blind, multi-center study comparing placebo and SOMAVERT. The mean ±SD age was 48±14 years, and the mean duration of acromegaly was 8±8 years. Ninety three had undergone previous pituitary surgery, of which 57 had also been treated with conventional radiation therapy. Six patients had undergone irradiation without surgery, nine had received only drug therapy, and four had received no previous therapy. At study start, the mean ± SD time since the subjects' last surgery and/or irradiation therapy, respectively, was 6.8 ± 0.93 years (n=63) and 5.6 ± 0.57 years (n=93).
Subjects were qualified for enrollment if their serum IGF-I, drawn after the required drug washout period, was ≥1.3 times the upper limit of the age-adjusted normal range. They were randomly assigned at the baseline visit to one of four treatment groups: placebo (n=32), 10 mg/day (n=26), 15 mg/day (n= 26), or 20 mg/day (n=28) of SOMAVERT subcutaneouslyIGF-I. The primary efficacy endpoint was IGF-Ipercent change in IGF-I concentrations from baseline to week 12. The three groups that received SOMAVERT showed statistically.
This image is provided by the National Library of Medicine.
There were also reductions in serum levels of free IGF-I, IGFBP-3, and ALS compared with placebo at all post-baseline visits (Figure 1).
This image is provided by the National Library of Medicine.
After 12 weeks of treatment, the following percentages of patients had normalized IGF-1 (Figure 2):
This image is provided by the National Library of Medicine.
Table 5 shows the effect of treatment with SOMAVERT on ring size (standard jeweler's sizes converted to a numeric score ranging from 1 to 63), and on signs and symptoms of acromegaly. Each individual score for a sign or symptom of acromegaly (for soft-tissue swelling, arthralgia, headache, perspiration and fatigue) was based on a nine-point ordinal rating scale (0 = absent and 8 = severe and incapacitating), and the total score for signs or symptoms of acromegaly was derived from the sum of the individual scores. Mean baseline scores were as follows: ring size = 47.1; total signs and symptoms = 15.2; soft tissue swelling = 2.5; arthralgia = 3.2; headache = 2.4; perspiration = 3.3; and fatigue = 3.7.
This image is provided by the National Library of Medicine.
Serum growth hormone (GH) concentrations, as measured by research assays using antibodies that do not cross-react with pegvisomant, rose within two weeks of beginning treatment with SOMAVERT. The largest increase in GH concentration was seen in patients treated with doses of SOMAVERT 20 mg/day. This effect is presumably the result of diminished inhibition of GH secretion as IGF-I levels fall. As shown in Figure 3, when patients with acromegaly were given a loading dose of SOMAVERT followed by a fixed daily dose, the rise in GH was inversely proportional to the fall in IGF-I and generally stabilized by week 2. Serum GH concentrations remained stable in patients treated with SOMAVERT for the average of 43 weeks (range, 0–82 weeks).
This image is provided by the National Library of Medicine.
In the open-label extension to the clinical study, 109 subjects (including 6 new patients) with mean treatment exposure of 42.6 weeks (range 1 day – 82 weeks), 93 (85.3%) subjects had an adverse event, 16 (14.7%) had an SAE, and 4 (3.7%) discontinued due to an AE (headaches, elevated liver function tests, pancreatic cancer, and weight gain). A total of 100 (92.6%) of the 108 subjects with available IGF-I data had a normal IGF-I concentration at any visit during the study.
SOMAVERT (pegvisomant) is supplied in the following strengths and package configurations:
This image is provided by the National Library of Medicine.
Each package of SOMAVERT also includes a single-dose vial containing Sterile Water for Injection, USP.
Storage
Prior to reconstitution, SOMAVERT should be stored in a refrigerator at 2 to 8°C (36 to 46°F). Do not freeze.
There is limited information regarding Pegvisomant Storage in the drug label.
{{#ask: Page Name::Pegvisomant
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosage
|?Pill Color
|?Pill Shape
|?Pill Size (mm)
|?Pill Scoring
|?NDC
|?Drug Author
|format=template
|template=DrugPageImages
|mainlabel=-
|sort=Pill Name
}}
{{#ask: Label Page::Pegvisomant
|?Label Name
|format=template
|template=DrugLabelImages
|mainlabel=-
|sort=Label Page
}}
Inform patients (and/or their caregivers) of the following information to aid in the safe and effective use of SOMAVERT:
Not to use SOMAVERT if they are allergic to SOMAVERT or anything in it.
They will need blood testing to check IGF-I levels and liver tests before and during treatment with SOMAVERT and that the dose of SOMAVERT may be changed based on the results of these tests
SOMAVERT has not been studied in pregnant women and instruct them to notify their healthcare provider as soon as they are aware that they are pregnant.
It is not known whether SOMAVERT is excreted in human milk and instruct them to notify their healthcare provider if they plan to do so.
Advise patients (and/or their caregivers) of the following adverse reactions:
The most common reported adverse reactions are injection site reaction, elevations of liver tests, pain, nausea, and diarrhea.
If they have liver test elevations they may need to have more frequent liver tests and/or discontinue SOMAVERT. Instruct patients to immediately discontinue therapy and contact their physician if they become jaundiced.
GH-secreting tumors may enlarge in people with acromegaly and that these tumors need to be watched carefully and monitored by MRI imaging.
Thickening under the skin may occur at the injection site that could lead to lumps and that switching sites may prevent or lessen this.
If they have diabetes mellitus, they may require careful monitoring and dose reductions of insulin and/or oral hypoglycemic agents while on SOMAVERT.
If they take opioids, they may need higher SOMAVERT doses to achieve appropriate IGF-I suppression.
Advise patients that SOMAVERT is supplied as lyophilized powder in different strengths of 10 mg, 15 mg, 20 mg, 25 mg, and 30 mg in a sterile glass vial within a package also containing a single-dose flip top vial of sterile water (diluent) for injection. Advise patients that the stoppers on both vials are not made with natural rubber latex. Advise patients to follow the directions for reconstitution provided with each package including shaking may cause denaturation (destruction) of the active ingredient (therefore do not shake).
Advise patients that the package of SOMAVERT should be stored in a refrigerator 2 to 8°C (36 to 46°F) prior to use. It should NOT BE FROZEN.
This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.
Alcohol-Pegvisomant interaction has nomation regarding Pegvisomant Look-Alike Drug Names in the drug label.
|
Microscopic_polyangiitis_pathophysiology | The pathogenesis of microscopic polyangiitis is currently not fully understood. However, certain hypothesizes have been made to determine possible factors that may trigger the disease such as environmental factors and anti-neutrophil cytoplasmic antibodies. Capillaries and venules are involved in the pathogenesis of microscopic polyangiitis.The paucity of immunoglobulin deposition is shown in immunohistochemical staining.
The exact etiology of Microscopic polyangiitis is not fully understood.
Certain hypothesizes have been made to determine possible factors that may trigger the disease.
Triggers such as environmental factors and anti-neutrophil cytoplasmic antibodies.
Environmental triggers such as exposure to silica have been found to influence the progression of the disease.But, its role in disease progression is not fully understood.
Key-points regarding ANCA in microscopic polyangiitis include:
The majority of patients who are affected with microscopic polyangiitis are positive for anti-neutrophil cytoplasmic antibodies (ANCA) with myeloperoxidase antigen activity.
The presence of anti-neutrophil cytoplasmic antibodies (ANCA) activates neutrophil production do to proinflammatory cytokines such as interleukin-1 and tumor necrosis factor-α (TNF-α).
Stimulation of interleukin-1 and tumor necrosis factor-α (TNF-α) results in producing reactive oxygen species and causing the release of lytic enzymes.
These two processes, induce detachment and lyses of the endothelium.
The destruction of the endothelial cells results in necrotizing crescentic glomerulonephritis and necrotizing vasculitis of the pulmonary capillaries.
Microscopic polyangiitis is correlated with HLA-DRB1*09:01-DQB1*03:03 haplotype in the Japanese population. This haplotype however, in the Caucasian population is not typically seen.
On gross pathology, the characteristic findings of microscopic polyangiitis incude: Hemorrhagic necrotizing alveolar capillaritis, Fibrinoid necrosis of the lung, Intra-alveolar hemosiderosis
On microscopic histopathological analysis of the kidney in patients with microscopic polyangiitis, characteristic findings include: Focal segmental necrotizing glomerulonephritis, Crescents of glomeruli, Minimal deposition of immunoglobulins, Compliment in glomeruli and renal vasculature can be seen
The majority of patients who are affected with Microscopic polyangiitis are positive for anti-neutrophil cytoplasmic antibodies (ANCA) with myeloperoxidase antigen activity.
The presence of anti-neutrophil cytoplasmic antibodies (ANCA) activates neutrophil production do to proinflammatory cytokines such as interleukin-1 and tumor necrosis factor-α (TNF-α).
Stimulation of interleukin-1 and tumor necrosis factor-α (TNF-α) results in producing reactive oxygen species and causing the release of lytic enzymes.
These two processes, induce detachment and lyses of the endothelium.
The destruction of the endothelial cells results in necrotizing crescentic glomerulonephritis and necrotizing vasculitis of the pulmonary capillaries. |
Hyperkalemia_medical_therapy | Treatment of hyperkalemia includes lowering of serum potassium levels,cardiac membrane stabilization and removal of excess potassium from the body.When arrhythmias occur, or when potassium levels exceed 6.5 mmol/l, emergency lowering of potassium levels is mandated. Several agents are used to lower potassium levels. Choice depends on the degree and cause of the hyperkalemia, and other aspects of the patient's condition.Treatment also depends on the cause of hyperkalemia.
The treatment of hyperkalemia is CKD has been reviewed.
Pharmacological therapy in hyperkalemia is dependent on serum potassium levels and the development of symptoms.
Therapy 1 is used in hyperkalemic emergency(emergency lowering of serum K+ required) which is : Serum potassium level >6.5 mEq/L, ECG changes present. Serum K+ >5.5 mEq/L and patient has severe renal impairment.
Therapy 2 is used when emergency lowering of potassium levels not required:
1.1. Pharmacotherapy
1.1.1. Cardiac membrane stabilization
Preferred regime:Calcium gluconate 10% 0.5ml/kg IV loading dose.(contraindicated in digoxin toxicity and hypercalcemia)
Alternate regime:Magnesium sulfate 2gm IV over 5 minutes(in digoxin toxicity and hypercalcemia)
1.1 ml/kg/h 20% dextrose (0.5-1 g/kg/h) with insulin 0.2 units for every gram of glucose administered..
Preferred regime(2):Salbutamol nebulization: 2.5 mg if <25 kg and 5 mg if >25 kg.
Alternate regime:Sodium bicarbonate 8.4%- 1-2 mmol/kg IV over 30-60 min only in cases of acidosis.
1.1.3. Loop diuretics
Preferred regime:Furosemide 40mg IV laoding dose and then 1-2mg/kg/day tillpotassium levels <5.1 mEq/L.
1.2 Renal replacement therapy.
Haemodialysis ( when renal function is impaired)
2.1. Pharmacotherapy
2.1.1.O till serum k+ <5.1 mEq/L.
2.1.2. Loop diuretics
Preferred regime:Furosemide 40mg/kg PO till serum K+ <5.1 mEq/L.
2.2 Renal replacement therapy
Haemodialysis(when renal function is impaired)
Hype
Hyperkalemia (Serum potassium >5.5 mEq/L) is considered an absolute contraindication to the use of the following medications:
Eplerenone
Spironolactone
Hydrochlorothiazide |
Pulmonary_laceration_overview | A pulmonary laceration is a chest injury in which lung tissue is torn or cut. An injury that is potentially more serious than pulmonary contusion, pulmonary laceration involves disruption of the architecture of the lung.
Pulmonary laceration is a common result of penetrating trauma but may also be caused by blunt trauma; broken ribs may perforate the lung, or the tissue may be torn due to shearing forces that result from differenenetrating forces that occur in the same injury and may be associated with pulmonary contusion. As with contusions, pulmonary lacerations usually occur near solid structures in the chest such as ribs. Pulmonary laceration is suspected when rib fractures are present.
CT scanning is more sensitive and better at detecting pulmonary laceration than X-rays are, and monary laceration was considered unusual because it was not common to find with X-ray alone. On a CT scan, pulmonary lacerations show up in a contused area of the lung, typically appearing as cavities filled with air or fluid that usually have an elliptical or ovoid shape. The (coughing up blood or of blood-stained sputum).Tracheobronchial injury can be ruled out using bronchoscopy. Thoracoscopy may be used in both diagnosis and treatment of pulmonary laceration.
|
Repotrectinib | Repotrectinib is a kinase inhibitor that is FDA approved for the treatment oformation regarding Repotrectinib FDA-Labeled Indications and Dosage (Adult) in the drug label.
There is limited information regarding Repotrectinib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
None
5.1 Central Nervous System Adverse Reactions
AUGTYRO can cause central nervl nervous system (CNS) adverse reactions including dizziness, ataxia, and cognitive disorders occurred in 75% with Grade 3 or 4 events occurring in 4% of patients.
Dizziness, including vertigo, occurred in 64%interruption was required in 9% of patients, and 12% required dose reduction of AUGTYRO due to dizziness.
Ataxia, including gait disturbance and balance disorder, occurred in 29% of the 351 patients; Grade 3 at patients, 8% required dose reduction, and one patient (0.3%) permanently discontinued AUGTYRO due to ataxia.
Cognitive disorder, including memory impairment and disturbanattention (11%), and confusional state (2%); Grade 3 cognitive disorders occurred in 0.9% of patients. The median time to onset of cognitive disorders was 37 days (1 day to 1.4 yeaYRO due to cognitive adverse reactions.
Mood disorders occurred in 6% of the 351 patients. Mood disorders occurring in > 1% of patients included anxiety (2.8%), irritability (1.1%), and depressia dose reduction due to mood disorders.
Sleep disorders including insomnia and hypersomnia occurred in 15% of the 351 patients. Sleep disorders observed in > 1% of patients were somnolence (8%), insomnia (6%) and hypersomnia (he incidences of CNS adverse reactions observed were similar in patients with and without CNS metastases.
Advise patients and caregivers of the risk of CNS adverse reactions with AUGTYRO. Advise patients not to drive or use machines if they are experiencing CNS adverse reactions. Withhold and then resume at same or reduced dose upon improvement, or permanently discontinue AUGTYRO based on severity [see DOSAGE AND ADMINISTRATION (2.5)].
5atients treated with AUGTYRO, ILD/pneumonitis (pneumonitis [2.6%] and interstitial lung disease [0.3%]) occurred in 2.9% of patients; Grade 3 ILD/pneumonitis occurred in 1.1% of patients. The median time to onset was 45 days (19 days to 0.9 years). Dose interruption was required in 1.4% of patients, 0.6% of patients required dose reduction, and 1.1% of patients permanently discontinmediately withhold AUGTYRO in patients with suspected ILD/pneumonitis and permanently discontinue AUGTYRO if ILD/pneumonitis is confirmed [see DOSAGE AND ADMINISTRATION (2.5)].
5.3 Hepatotoxicity
AUGTYRO can cause hepatotoxicity.
Among the 351 patients treated with AUGTYRO, increased alanine transaminase (ALT) occurred in 35%, increased aspartate aminotransferase (AST) occurred in 40%, including Grade 3 or 4 increased ALT in 2% and increased AST in 2.6%. The median time to onset of increased ALT or AST was 15 days (range: 1 day to 1.9 years). Increased ALT or AST leading to dose interruptions or reductions occurred in 2.8% and 1.4% of patients, respectively. Hyperbilirubinemia leading to dose interruptions occurred in 0.6%.
Monitor liver function tests, including ALT, AST and bilirubin, every 2 weeks during the first month of treatment, then monthly thereafter and as clinically indicated. Withhold and then resume at the same or reduced dose upon improvement, or permanently discontinue AUGTYRO based on the severity [see DOSAGE AND ADMINISTRATION (2.5)].
s. AUGTYRO was interrupted in one patient with myalgia and concurrent CPK elevation.
Advise patients to report any unexplained muscle pain, tenderness, or weakness.
Monitor serum CPK levels during AUGTYRO treatment and monitor CPK levels every 2 weeks during the first month of treatment and as needed in patients reporting unexplained muscle pain, tenderness, or weakness. Initiate supportive care as clinically indicated. Based on severity, withhold and then resume AUGTYRO at the same or reduced dose upon improvement [see DOSAGE AND ADMINISTRATION (2.5)].
5.5 Hyperuricemia
AUGTYRO can cause hyperuricemia.
Among the 351 patients treated with AUGTYRO, 18 patients (5%) experienced hyperuricemia reported as an adverse reaction and 0.9% of patients experienced Grade 3 or 4 hyperuricemia. One patient without pre-existing gout required urate-lowering medication.
Monitor serum uric acid levels prior to initiating AUGTYRO and periodically during treatment. Initiate treatment with urate-lowering medications as clinically indicated. Withhold and then resume at the same or reduced dose upon improvement, or permanently discontinue AUGTYRO based on severity [see DOSAGE AND ADMINISTRATION (2.5)].
5.6 Skeletal Fractures
AUGTYRO can cause skeletal fractures.
Among 351 adult patients who received AUGTYRO, fractures occurred in 2.3%. Fractures involved the ribs (0.6%), feet (0.6%), spine (0.3%), acetabulum (0.3%), sternum (0.3%), and ankles (0.3%). Some fractures occurred at sites of disease and prior radiation therapy. The median time to fracture was 71 days (range: 31 days to 1.4 years). AUGTYRO was interrupted in 0.3% of patients.
Promptly evaluate patients with signs or symptoms (e.g., pain, changes in mobility, deformity) of fractures. There are no data on the effects of AUGTYRO on healing of known fractures and risk of future fractures.
5.7 Embryo-Fetal Toxicity
Based on literature reports in humans with congenital mutations leading to changes in tropomyosin receptor tyrosine kinase (TRK) signaling, findings from animal studies, and its mechanism of action, AUGTYRO can cause fetal harm when administered to a pregnant woman.
Oral administration of repotrectinib to pregnant rats during the period of organogenesis resulted in fetal malformations at doses approximately 0.3 times the recommended 160 mg twice daily dose based on body surface area (BSA).
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with AUGTYRO and for 2 months following the last dose, since AUGTYRO can render some hormonal contraceptives ineffective [see DRUG INTERACTIONS (7.2)]. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with AUGTYRO and for 4 months after the last dose
The following clinically significant adverse reactions are described elsewhere in the labeling:
(14.1)]. Eligible patients had an ECOG status of ≤1. Patients with a history of ILD, drug-related pneumonitis, significant, uncontrolleGTYRO at a dose of 160 mg orally once daily for the first 14 days, then increased to 160 mg orally twice daily until disease progression or unacceptable toxicity. Among patients who received AUGTYRO, 52% were exposed for at least 6 months, and 27% were exposed for greater than 1 year.
The median age of patients who received AUGTYRO was 56 years (range: 27 to 93); 62% female; 43% White, 49% Asian, 2.7% Black, 0.8% Native Hawaiian or Other Pacific Islander, 0.4% American Indian or Alaska Native, 3.4% race not repsudden cardiac death, cardiac failure, sudden death, hypoxia, dyspnea, respiratory failure, tremor, and disseminated intravascular coagulation.
Permanent discontinuation of AUGTYRO was required in 8% of patients due to adverse reactions. The adverse reactions resulting in permanent discontinuation of AUGTYRO in ≥1% of patients were dyspnea, pneumonitis, and muscular weakness.
Dosage interruptions of AUGTYRO due to an adverse reaction occurred in 48% of patients. Adverse reactions that required dosage interruption in ≥5% of patients included CNS toxicity, dyspnea, and muscular weakness.
Dose reductions of AUGTYRO due to an adverse reaction occurred in 35% of patients. Adverse reactions that required dosage reductions in ≥5% of patients included dizziness.
The most common adverse reactions (≥20%) were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased hemoglobin, decreased lymphocytes, decreased leukocytes, increased alanine aminotransferase, a moderate CYP3A inhibitor may increase repotrectinib exposure, which may increase the incidence and severity of adverse reactions of AUGTYRO. Discontinue CYP3A inhibitors for 3 to 5 elimination half-lives of the CYP3A inhibitor prior to initiating AUGTYRO [see CLINICAL PHARMACOLOGY (12.3)].
P-gp Inhibitors
Avoid concomitant use with P-gp inhibitors. Concomitant use of AUGTYRO with a P-gp inhibitor may increase repotrectinib exposure, which may increase the incidence and severity of adverse reactions of AUGTYRO [see CLINICAL PHARMACOLOGY (12.3)].
Strong and Moderate CYP3A Inducers
Avoid concomitant use with strong or moderate CYP3A inducers. Concomitant use of AUGTYRO with a strong or moderate CYP3A inducer may decrease repotrectinib plasma concentrations, which may decrease efficacy of AUGTYRO [see CLINICAL PHARMACOLOGY (12.3)].
7.2 Effects of AUGTYRO on Other Drugs
Certain CYP3A4 Substrates
Avoid concomitant use unless otherwise recommended in the Prescribing Information for CYP3A substrates, where minimal concentration changes can cause reduced efficacy. If concomitant use is unavoidable, increase the CYP3A4 substrate dosage in accordance with approved product labeling.
Repotrectinib is a CYP3A4 inducer. Concomitant use of repotrectinib decreases the concentration of CYP3A4 substrates [see CLINICAL PHARMACOLOGY (12.3)], which can reduce the efficacy of these substrates.
Contraceptives
Repotrectinib is ant ug, findings from animal studies, and its mechanism of action [see CLINICAL PHARMACOLOGY (12.1)], AUGTYRO can cause fetal harm when administered to a pregnant woman. There are no available data on AUGTYRO use in pregnant women. Oral administration of repotrectinib to pregnant rats during the period of organogenesis resulted in fetal malformations at doses approximately 0.3 times the recommended dose of 160 mg twice daily based on BSA (see Data). Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Human Data
Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.
Animal Data
In an embryo-fetal development study, once daily oral administration of repotrectinib to pregnant rats during the period of organogenesis from gestation day 6 to 17 resulted in maternal effects of increased body weight and skin abrasions/ulcerations at recommended dose of 160 mg twice daily based on BSA]. No embryolethality was observed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Repotrectinib in women who are pregnant.
There is no FDA guidance on use of Repotrectinib during labor and delivery.
Risk Summary
There are no data on the presence of AUGTYRO in human milk or its effects on either the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children from AUGTYRO, advise a lactating woman to discontinue breastfeeding during treatment with AUGTYRO and for 10 days after the last dose.
The safety and effectiveness of AUGTYRO in pediatric patients with ROS1-positive NSCLC has not been established.
Juvenile Animal Data
Daily oral administration of repotrectinib to juvenile rats for 8 weeks starting on postnatal day 12 (approximately equal to a human pediatric age of a newborn) resulted in toxicities similar to those observed in adult rats, though juvenile animals showed decreased body weight gain at doses ≥1 mg/kg (approximately ≥0.04 times the human exposure based on AUC at the recommended clinical dose of 160 mg BID) and decreased femur lengths at 3 mg/kg (approximately 0.1 times the human exposure based on AUC at the recommended clinical dose of 160 mg BID). Decreased body weight gain and decreased femur lengths persisted following 4 weeks of recovery.
Of the 351 patients who received AUGTYRO, 21% were 65 to 75 years old, and 7% were 75 years of age or older. There were no clinically meaningful differences in safety and efficacy between patients younger than 65 years of age and patients 65 years of age or older.
There is no gions and mutations inCardiac Electrophysiology
AUGTYRO does not cause a mean increase in the QTc interval > 20 milliseconds (ms) at 160 mg QD followed by 160 mg BID, the approved recommended dosage.
The geometric mean (CV%) of repotrectinib steady state peak concentration (Cmax,ss) is 713 (32.5%) ng/mL and the area under the time concentration curve (AUC0-24h,ss) is 7210 (40.1%) ng•h/mL following the approved recommended twice daily ut less than linear with estimated slopes of 0.78 and 0.70, respectively) over the single dose range of 40 mg to 240 mg (0.25 to 1.5 times the approved recommended dosage). Steady state PK was time-dependent with an autoinduction of CYP3A4. Steady state is achieved within 14 days of daily administration of 160 mg.
Absorption
The geometric mean (CV%) absolute bioavurs post a single oral dose of 40 mg to 240 mg (0.25 to 1.5 times the approved recommended dosage) under fasted conditions.
Effect of Food
No clinically significant differences in repotrectinib pharmacokinetics were observed in patients with cancer following administration of a high-fat meal (approximately 800-1000 calories, 50% fat).
Distribution
The geometric mean (CV%) apparent volume of distribution (Vz/F) was 432 L (55.9 %) in patients with cancer following a single 160 mg oral dose of AUGTYRO.
AUGTYRO binding to plasma protein was 95.4% in vitro. The blood-to-plasma ratio was 0.56 in vitro.
Elimination
Repotrectinib elimination is time-dependent due to autoinduction of CYP3A4.
The repotrectinib mean terminal half-life is approximately 50.6 h for patients with cancer following a single dose. The steady state repotrectinib terminal half-life is approximately 35.4 h for patients with cancer.
The geometric mean (CV%) apparent oral clearance (CL/F) was 15.9 L/h (45.5%) in patients with cancer following a single 160 mg oral dose of AUGTYRO.
Metabolism
Repotrectinib is primarily metabolized by CYP3A4 followed by secondary glucuronidation.
Excretion
Following a single oral 160 mg dose of radiolabeled repotrectinib, 4.84erapy and/or immunotherapy for locally advanced or metastatic disease.
Among the 56 patients who had received 1 prior ROS1 TKI (including crizotinib [82%] and entrectinib [16%]) with no prior platinum-based chemotherapy or immunotherapy, the median age was 57 years (range: 33 – 78); female (67.9%); Asian (48.2%), White (44.6%), Black or African American and Hispanic or Latino (1.8% each); never smoked (64.3%); and ECOG performance status of 1 at baseline (67.9%). At baseline, 98.2% patients had metastatic disease, 42.9% with CNS metastases by BICR, and 94.6% had adenocarcinoma.
Among TKI-naïve patients, 8 had measurable CNS metastases at baseline as assessed by BICR; responses in intracranial lesions were observed in 7 of these 8 patients. Among the TKI pretreated patients with no prior platinu |
Hemodynamic_instability | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
Obstructive shock
Cardiogenic shock
Acute respiratory distress sy |
Cardiomegaly_surgery | In patients who are awaiting a transplant for end-stage symptomatic heart failure, implantable ventricular assist devices may serve as a temporary aid for compensation. Transplantation may be considered in a few cases.
In patients who are awaiting a transplant for end-stage symptomatic heart failure, implantable ventricular assist devices may serve as a temporary aid for compensation.
In patients who are in end-stage symptomatic heart failure, a heart transplant my be necessary. |
Plenaxis | Abarelix is an injectable gonadotropin-releasing hormone antagonist (GnRH antagonist). It is primarily used in oncology to reduce the amount of testosterone made in patients with advanced symptomatic prostate cancer for which no other treatment options are available. It belongs to the family of drugs called Gonadotropin-releasing hormone antagonists.
It is marketed by Speciality European Pharma as Plenaxis. Plenaxis has received marketing authorisation in Germany.
|
Tetralogy_of_fallot_chest_xray | An x-ray may be helpful in the diagnosis of tetralogy of fallot. Findings on an x-ray diagnostic of tetralogy of fallot include normal or decreased pulmonary vascularity, concave pulmonary artery segment, "boot-like" heart, and right sided aortic arch.
An x-ray may be helpful in the diagnosis of tetralogy of fallot. Findings on an x-ray diagnostic of tetralogy of fallot include: , Normal or decreased pulmonary vascularity, Concave pulmonary artery segment, In tetralogy of Fallot, the heart may present with a "boot-like" or "coeur en sabot" appearance (an upturned right ventricular apex and a concave main pulmonary arterial segment), rather than the symmetric appearance of a normal heart. A right sided aortic arch may also be present. There is pruning or reduction in the prominence of the pulmonary vasculature over time. |
Bentoquatam | Bentoquatam is a Protectant, Dermatological that is FDA approved for the prevention of poison ivy, oak and sumac rash when applied before exposure. Common adverse reactions include erythema.
Helps prevent poison ivy, oak and sumac rash when applied before exposure.
Shake well before use
apply 15 minutes before risk exposure
avoid intentional contact with poison ivy, oak and sumac
adults and children 6 and older: apply every 4 hours for continued protection or sooner if needed
children under 6 years: ask a doctor
remove with soap and water after risk of exposure |
Intermittent_angle-closure_glaucoma | clusion
Retinopathy
diabetic
hypertensive
Purtscher's
of prematurity
Bietti's crystalline dystrophy
Coats' disease
Macular degeneration
Retinitis pigmentosa
Retinal haemorrhage
Central serous retinopathy
Macular edema
Epiretinal membrane (Macular pucker)
Vitelliform macular dystrophy
Leber's congenital amaurosis
Birdshot chorioretinopathy
Other
Glaucoma / Ocular hypertension / Primary juvenile glaucoma
Floater
Leber's hereditary optic neuropathy
Red eye
Globe rupture
Keratomycosis
Phthisis bulbi
Persistent fetal vasculature / Persistent hyperplastic primary vitreous
Persistent tunica vasculosa lentis
Familial exudative vitreoretinopathy
PathwaysOptic nerveOptic disc
Optic neuritis
optic papillitis
Papilledema
Foster Kennedy syndrome
Optic atrophy
Optic disc drusen
Optic neuropathy
Ischemic
anterior (AION)
posterior (PION)
Kjer's
Leber's hereditary
Toxic and nutritional
StrabismusExtraocular musclesBinocular visionAccommodationParalytic strabismus
Ophthalmoparesis
Chronic progressive external ophthalmoplegia
Kearns–Sayre syndrome
palsies
Oculomotor (III)
Fourth-nerve (IV)
Sixth-nerve (VI)
Other strabismus
Esotropia / Exotropia
Hypertropia
Heterophoria
Esophoria
Exophoria
Cyclotropia
Brown's syndrome
Duane syndrome
Other binocular
Conjugate gaze palsy
Convergence insufficiency
Internuclear ophthalmoplegia
One and a half syndrome
Refraction
Refractive error
Hyperopia
Myopia
Astigmatism
Anisometropia / Aniseikonia
Presbyopia
Vision disordersBlindness
Amblyopia
Leber's congenital amaurosis
Diplopia
Scotoma
Color blindness
Achromatopsia
Dichromacy
Monochromacy
Nyctalopia
Oguchi disease
Blindness / Vision loss / Visual impairment
Anopsia
Hemia pupil
Adie syndrome
Miosis
Mydriasis
Cycloplegia
Parinaud's syndrome
Other
Nystagmus
Childhood blindness
Infections
Trachoma
Onchocerciasis
Template:WH
Template:WS
|
Adrenoleukodystrophy_secondary_prevention | The objective of secondary prevention in adrenoleukodystrophy is to diagnose it early, preferably before neurological symptoms appear so as to prevent nerve cell damage from occurring, initiating timely adrenal steroid replacement therapy following detection of adrenal insufficiency, and for providing allogeneic hematopoietic stem cell transplantation (HSCT) as a means of treating cerebral ALD. In February 2016, adrenoleukodystrophy was added to the Recommended Uniform Screening Panel (RUSP) in the USA, which is the federal list of all genetic diseases recommended for state newborn screening programs.
The objective of secondary p |
Thyroid_gland_failure | History and Symptoms | Physical Examination | Electrocardiogram | Laboratory Findings | X-Ray Findings | Echocardiography and Ultrasound | CT-Scan Findings | MRI Findings | Other Diagnostic Studi |
Carbinol | Methanol, also known as methyl alcohol, carbinol, wood alcohol, wood naphtha or wood spirits, is a chemical compound with chemical formula CH3OH (often abbreviated MeOH). It is the simplest alcohol, and is a light, volatile, colourless, flammable, poisonous liquid with a distinctive odor that is somewhat milder and sweeter than ethanol (ethyl alcohol). At room temperature it is a polar liquid and is used as an antifreeze, solvent, fuel, and as a denaturant for ethyl alcohol. It is also used for producing biodiesel via transesterification reaction.
Methanol is produced naturally in the anaerobic metabolism of many varieties of bacteria. As a result, there is a small fraction of methanol vapor in the atmosO2 + 4 H2O
A methanol flame is almost colorless, causing an additional safety hazar— this addition of a poison economically exemptges. Methanol is often called wood alcohol because it was once produced chiefly as a byproduct of and stssure in the presence of a catalyst.
An entire methanol economy, based on methanol as a primans used a mixture of substances, including methanol, which they obtained from the pyrof box, because he produced it via the distillation of boxwood. It later became known as pyroxylic spirit. In 1834, the French chemists Jean-Baptiste Dumas and Eugene Peligot determined its elemental composition. They also introduced the word methylees of radicals, was extracted from the word "methyl."
In 1923, the German chemists Matthias and Pier, working for BASF developed a means to convert synthesis gas (a mixture of carbon oxides and hydrogen) into methanol. A patent was filed Jan 12 1926 (reference no. 1,569,775). This process used a chromium and manganese oxid catalyst, and required extremely vigorous conditions—pressures ranging from 50 to 220 atm), and temperatures up to 450 °C. Modern methanol production has been made more efficient through use of catalysts (commonly copper) capable of operating at lower pressures.
The use of methanol as a motor fuel received attention during the oil crises of the 1970s due to its availability and low cost. Problems occurred early in the develd handling techniques.
In 2006 astronomers using the MERLIN array of radio telescopes at Jodrell Bank Observatory discovered a large cloud of methanol in space, 300 billion miles across.
Today, synthesis gas is most commonly produced from the methane component in natural gas rather than from coal. Three processes are commercially practiced. At moderate pressures of 1 to 2 MPa (10–20 atm) and high temperatures (around 850 °C), methane reacts with steam on a nickel catalyst to produce syngas according to the chemical equation:
CH4 + H2O → CO + 3 H2
This reaction, commonly called steam-methane reforming or SMR, is endothermic and the heat transfer limitations place limits on the size of and pressure in the catalytic reactors used. Methane can also undergo partial oxidation with molecular oxygen to produce syngas, as the following equation shows:
2 CH4 + O2 → 2 CO + 4 H2
this reaction is exothermic and the heat given off can be used in-situ to drive the steam-methane reforming reaction. When the two processes are combined, it is referred to as autothermal reforming. The ratio of CO and H2 can be adjusted to some extent by the water-gas shift reaction,
CO + H2O → CO2 + H2,
to p+ 2 H2 → CH3OH
It is worth noting that the production of synthesis gas from methaneof carbon monoxide. One way of dealing with the excess hydrogen is to inject carbon dioxide into the methanol synthesis reactor, where it, too, reacts to form methanol according to the chemical equation
CO2 + 3 H2 → CH3OH + H2O
Although natural gas is the most economical and widely used feedstock for methanol production, other feedstocks can be used. Where natural gas is unavailable, light petroleum products can be used in its place.
Main article: Alcohol § Toxicity
Methanol is poisonous to the central nervous system and may cause blindness, coma, and death. However, in small amounts, methanol is a natural endogenous compound found in normal, healthy human individuals. A study found a mean of 4d may be metabolized from pectin found in fruit; one kilogram of apple produces up to 1.4 g methanol.
Methanol has a high toxicity in humans. If as little as 10 mL of pure methanol is ingested, for example, it can break down into formic acid, which can cause permanent blindness by destruction of the optic nerve, and 30 mL is potentially fatal, although the median lethal dose is typically 100 mL (3.4 fl oz) (i.e. 1–2 mL/kg body weight of pure methanol). Reference dose for methanol is 2 mg/kg/day. Toxic effects take hours to start, and effective antidotes can often prevent permanent damage. Because of its similarities in both appearance and odor to ethanol (the alcohol in beverages), it is difficult to differentiate between the two (such is also the case with denatured alcohol). However, there are cases of methanol resistance, such as that of Mike Malloy, who was the victim of a failed murder attempt by methanol in the early 1930s.
Methanol is toxic by two mechanisms. First, methanol (whether it enters the body by ingestion, inhalation, orol poisoning. Second, in a process of toxication, it is metabolized to formic acid (which is present as the formate ion) via formaldehyde in a process initiated by the enzyme alcohol dehydrogenase in the liver. Methanol is converted to formaldehyde via alcohol dehydrogenase (ADH) and formaldehyde is converted to formic acid (formate) via aldehyde dehydrogenase (ALDH). The conversion to formate via ALDH proceeds completely, with no detectable formaldehyde remaining. Formate is toxic because it inhibits mitochondrial cytochrome c oxidase, causing the symptoms of hypoxia at the cellular level, and also causing metabolic acidosis, among a variety of other metabolic disturbances.
Methanol poisoning can be treated with fomepizole, or if unavailable, ethanol. Both drugs act to reduce the action of alcohol dehydrogenase on methanol by means of competitive inhibition, so it iing sodium bicarbonate for metabolic acidosis, and hemodialysis or hemodiafiltration can be used to remove methanol and formate from the blood. Folinic acid or folic acid is also administered to enhance the metabolism of formate.
The initial symptoms of methanol intoxication include central nervous system depression, headache, dizziness, nausea, lac methanol exposure are usually less severe than the symptoms resulting from the ingestion of a similar tl examination may show tachypnea, and ophthalmologic examination may show dilated pupils with hyperemia of the optic disc and retinal edema.
Ethanol is sometimes denatured (adulterated), and made poisonous, by the addition of methanol. The result is known as methylated spirit, "meths" (British use) or "metho" (Australian slang). These are not to be confused with "meth", a common abbreviation for methamphetamine, and an abbreviation for methadone in Britain.
Small amounts of methanol are produced by the metabolism of food and are generally harmless, being metabolized quickly and completely.
Methanol is a common laboratory solvent. It is especially useful for HPLC and UV/VIS spectroscopy due to its low UV cutoff.
The largest use of methanol by far, is in making other chemicals. About 40% of methanol wd in radio controlled model airplanes (required in the "glow-plug" engines that primarily power them), cars and trucks. Drag racers and mud racers also use methanol as their primary fuel source. Methanol is required with a supercharged engine in a Top Alcohol Dragster and, until the end of the 2006 season, all vehicles in the Indianapolis 500 had to run methanol. Mud racers have mixed methanol with gasoline and nitrous oxide to produce more power than gasoline and nitrous oxide alone.
One of the drawbacks of methanol as a fuel is its corrosivity to some metals, including aluminium. Methanol, although a weak acid, atectively fuels corrosion until either the metal is eaten away or the concentration of CH3OH is negligible.
When produced from wood or other organic materials, the resulting organic methanol (bioalcohol) has been suggested as renewable alternative to petroleum-based hydrocarbons. However, one cannot use pure methaitional denaturant for ethanol, thus giving the term methylated spirit.
Methanol is also used as a solvent, |
Gastrointestinal_stromal_tumor_primary_prevention | There are no established measures for the primary prevention of gastrointestinal stromal tumor (GIST).
There are no established measures for the primary prevention of gastrointestinal stromal tumor (GIST).
|
Urticaria_(patient_information) | Hives are raised, often itchy, red welts on the surface of the skin. They are usually an allergic reaction to food or medicine.
Itching
Swelling of the surface of the skin into red- or skin-colored welts (called wheals) with clearly defined edges.
The hives may get bigger, spread, and join together to form larger areas of flat, raised skin.
They can also change shape, disappear, and reappear within minutes or hours. A true hive comes and goes. When you press the center of one, it turns white. This is called blanching.
When you have an allergic reaction to a substance, your body releases histamine and other chemicals into your bloodstream. This causes itching, swelling, and other symptoms. Hives are a common reaction, especially in people with other allergies such as hay fever.
When swelling or welts occur around the face, especially the lips and eyes, it is called angioedema. Swelling from angioedema can also occur around your hands, feet, and throat.
Many substances can trigger hives, including:
Animal dander (especially cats)
Insect bites
Medications
Pollen
Shellfish, fish, nuts, eggs, milk, and other foods
Hives may also develop as a result of:
Emotional stress
Extreme cold or sun exposure
Excessive perspiration
Illness (including lupus, other autoimmune diseases, and leukemia
Infections such as mononucleosis
Your doctor can tell if you have hives by looking at your skin.
If you have a history of an allergy, then the diagnosis is even more obvious.
Occasionally, skin or blood tests are done to confirm that you had an allergic reaction and to test for the substance that caused the allergic response. A skin biopsy can confirm the diagnosis.
Call 911 or your local emergency number if you have:
Fainting
Shortness of breath
Tightness in your throat
Tongue or face swelling
Wheezing
Call your health care provider if the hives are severe, uncomfortable, and do not respond to self-care measures.
Treatment may not be needed if the hives are mild. They may disappear on their own. To reduce itching and swelling:
Avoid hot baths or showers.
Avoid irritating the area with tight-fitting clothing.
Take antihistamines. Diphenhydramine is considered most effective, but make some people tired. Other options include loratodine or ceterizine.
If your reaction is severe, especially if the swelling involves your throat, you may require an emergency shot of epinephrine (adrenaline) or steroids. Hives in the throat can block your airway, making it difficult to breathe.
Patients diagnosed with urticaria should avoid using the following medications:
Erythromycin/Benzoyl Peroxide
NabumetoneIf you have been diagnosed with urticaria, consult your physician before starting or stopping any of these medications.
Directions to Hospitals Treating Urticaria
Avoid exposure to substances that give you allergic reactions.
Don't wear tight-fitting clothing and avoid hot baths or showers just after an episode of hives. These can both cause the hives to return.
Hives may be uncomfortable, but they generally are harmless and disappear on their own. In most cases, the exact cause of hives cannot be identified.
Anaphylaxis (a life-threatening, whole-body allergic reaction that causes breathing difficulty).
Swelling in the throat can lead to life-threatening airway blockage.
http://www.nlm.nih.gov/medlineplus/ency/article/000845.htm
Template:WH
Template:WS
|
Zinc_chloride | Zinc chloride is an nutritional agent that is FDA approved for the {{{indicationType}}} of zinc deficiency. Common adverse reactions include none known.
Zinc 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutioistration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of zinc blood levels is suggested for patients receiving more than the usual maintenance dosage level of zinc.
For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
There is limited information regarding Off-Label Guideline-Supported Use of Zinc chloride in adult patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Zinc chloride in adult patients.
There is limited information regarding FDA-Labeled Use of Zinc chloride in pediatric patients.
There is limited information regarding Off-Label Guideline-Supported Use of Zinc chloride in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Zinc chloride in pediatric patients.
None
Direct intramuscular or intravenous injection of Zinc 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.
Severe kidney disease may make it necessary to reduce or omit chromium and zinc doses because these elements are primarily eliminated in the urine.
WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Do not use unless the solution is clear and the seal is intact.
Zinc 1 mg/mL (Zinc Chloride Injection, USP) should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.
Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of zinc from a bolus injection. Administration of zinc in the absence of copper may cause a decrease in serum copper levels.
There is limited information regarding Clinical Trial Experience of Zinc chloride in the drug label.
There is limited information regarding Postmarketing Experience of Zinc chloride in the drug label.
There is limited information regarding Zinc chloride Drug Interactions in the drug label.
Pregnancy Category (FDA):
Pregnancy Category C
Animal reproduction studies have not been conducted with zinc chloride. It is also not known whether zinc chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Zinc chloride should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Zinc chloride in women who are pregnant.
There is no FDA guidance on use of Zinc chloride during labor and delivery.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Zinc 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.
There is no FDA guidance on the use of Zinc chloride with respect to pediatric patients.
An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
There is no FDA guidance on the use of Zinc chloride with respect to specific gender populations.
There is no FDA guidance on the use of Zinc chloride with respect to specific racial populations.
There is no FDA guidance on thre immunocompromised.
Intravenous
There is limited information regarding Monitoring of Zinc chloride in the drug label.
There is limited information regarding IV Compatibility of Zinc chloride in the drug label.
Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg zinc was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fofer. The pH is 2.0 (1.5 to 2.5); product may contain hydrochloric acid and sodium hydroxide for pH adjustment. The osmolarity is 0.354um Chloride, USP is chemically designated NaCl, a white crystalline compound freely soluble in water.
The semi-rigid vial is fabricated from a specially formulated polyolefin. It is a copolymer of ethylene and propylene. The safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers. The small amount of water vapor that can pass through the plastic container wall will not significantly alter the drug concentration.
Providing zinc helps prevent development of deficiency symptoms such as: Para.
The initial manifestations of hypozincemia in TPN are diarrhea, apathy and depression. At plasma levels below 20 mcg zinc/100 mL dermatitis followed by alopecia has been reported for TPN patients. Normal zinc plasma levels are 100 ± 12 mcg/100 mL.
Zinc resides in muscle, bone, skin, kidney, liver, pancreas, retina, prostate and particularly in the red and white blood cells. Zinc binds to plasma albumin, α2-macroglobulin, and some plasma amino acids including histidine, cysteine, threonine, glycine, and asparagine. Ingested zinc is excreted mainly in the stool (approximately 90%), and to a lesser extent in the urine and in perspiration.
Long-term animal studies to evaluate the carcinogenic potential of Zinc 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.
There is limited information regarding Clinical Studies of Zinc chloride in the drug label.
Zinc 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).
Store at 20 to 25°C (68 to 77°F).
There is limited information regarding Zinc chloride Storage in the drug label.
{{#ask: Page Name::Zinc chloride
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosabemaon.
ZINC®
Th |
Sarcomatoid_carcinoma_of_the_lung_physical_examination | nation findings of sarcomatoid carcinoma of the lung will depend on the location of voice hoarseness, and tachypnea. Peripheral location can present with physical findings suggestive of pleurisy. Common physical examination of patients with sarcomatoid carcinoma of the lung include crackling or bubbling noises and decreased or absent breath sounds.
The following physical examination findings may be present among the early stage of malignancy.
Patient may present with following findings in later stage of malignancy:
Well-appearing
Older age in relation to chronological age
Lethargic
Confused
Low-grade fever
Decreased oxygen saturation at room air
Tachypnea
Tachycardia
Lymphadenopathy
Pallor
Acanthosis nigricans
Slurred speech
Confusion
A |
Pontine_reticular_formation | section passing through the middle of the olive. ,
Template:Reticular formation
Template:Rhombencephalon
de:Formatio reticularis
nl:Formatio reticularis
fi:Aivoverkosto
Template:WikiDoc Sources
Template:Jb1
|
Herpes_simplex_anogenital_infection | HSV-2 is widespread, affecting an estimated 1 in 4 females and 1 in 5 males in the United States. Most young, sexually active patients who have genital, anal, or perianal ulcers have either genital herpes or syphilis. The frequency of each condition differs by geographic area and population; however, genital herpes is the most prevalent of these diseases.
Genital herpes in a male
Clusters of inflammed papules and vesicles on the outer surface of the gen |
Neurofibromatosis_type_1_physical_examination | Neurofibromatosis type 1 physical examination may vary widely among patients. The most common features are the presence of neurofibromas, plexiform neurofibromas, Lisch nodules, cafe au lait macules (CALM), delayed puberty features, and cognitive impairment. Neurofibromatosis type 1 may be diagnosed clinically with great specificity and sensitivity by the presence of 2 characteristic features on physical examination, although many children with the NF1 gene mutation may not meet the criteria at age 1, but will do so at 8 years olde nt in 1 to 4% of the individuals)
Cryptorchidism (present in 30 to 79% of the individuals)
Abnormality of the upper urinary tract (present in 5 to 29% of the individuals)
Urinary tract neoplasm (present in 5 to 29% of the individuals)
Renal artery stenosis (present in 1 to 4% of the individuals)
Paresthesias (present in 30 to 79% of the individuals)
Genu valgum (present in 30 to 79% of the individuals)
Slender long bones (present in 30 to 79% of the individuals)
Skeletal dysplasia (present in 30 to 79% of the individuals)
Joint stiffness (present in 5 to 29% of the individuals)
Tibial pseudarthrosis (present in 1 to 4% of the individuals)
|
Diaphragmatic_paralysis_other_imaging_findings | Fluoroscopic sniff test may be helpful in the diagnosis of diaphragmatic paralysis. Findings on sniff test suggestive of diaphragmatic paralysis include paradoxical elevation of the paralyzed hemidiaphragm during inspiration.
Fluoroscopic sniff test may be helpful in the diagnosis of diaphragmatic paralysis. Findings on sniff test suggestive of diaphragmatic paralysis include: Paradoxical elevation of the paralyzed hemidiaphragm during inspiration. |
Low_VLDL_causes | Inherited disorders of lipoprotein metabolism such as abetalipoproteinemia, lipid lowering medications and diet are some of the causes of low VLDL levels.
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.
Pyrethroid insecticides
Abetalipoproteinemia
Chronic liver disease
Hypobetalipoproteinemia
Abetalipoproteinemia
Amyloidosis
Apolipoprotein B deficiency
Autoimtrition
Ménétrier's disease
Mutations of the MTTP gene
Nicotinic acid
Omega-3 polyunsaturated fatty acids
Parkinson's disease
Portosystemic shunts
Prazosin
Probucol
Protein losing enteropathy
Pyrethroid insecticides
Resveratrol
Short bowel syndrome
Shwachman-Diamond syndrome
Sjögren's syndrome
Statins
|
Amyloid_plaques | Amyloids are insoluble fibrous protein aggregations sharing specific structural traits.
The name amyloid comes from the early mistaken identification of the substance "starch" (amylum in Latin), based on crude iodine-staining techniques. For a period, the scientific community debated whether or not amyloid deposits were fatty deposits or carbohydrate deposits until it was finally resolved that it was neither, but rather a deposition of proteinaceous mass.
The classical, histopathological definition of amyloid is an extracellular, proteinaceous deposit exhibiting cross-beta structure. This is due to misfolding of unstable proteins. Common to most cross-beta type structures, they are generally identified by apple-green birefringence when stained with Congo Red and seen under polarized light. These deposits often recruit various sugars and other components such as Serum Amyloid P component, resulting in complex, and sometimes heterogeneous structures.
Recently, this definition has come into question as some classic amyloid species have been observed in distinctly intracellular locations.
A more recent, biophysical definition is broader, including any polypeptbirefringence test. Microbiologists and biophysicists have largely adopted this definition, leading to some conflict in the biological community over the issue of language.
Amyloidosis
Medulary Carcinoma of the Thyroid
Alzheimer's disease
Transmissible spongiform encephalopathy
Yeast Prions [Sup35] Rnq1
Sporadic Inclusion Body Myositis (S-IBM)
(Mostly using the biophysical definition)
Native amyloids in organisms: Curli E. coli Protein (curlin), Podospora Anserina Prion Het-s, Malarial coat protein, Spider silk (not all spiders), Mammalian melanosomes (pMel), Tissue-type plasminogen activator (tPA)
Proteins and peptides known to make amyloid without any known disease, Calcitonin
Proteins and peptides engineered to make amyloid
Amyloid is characterized by a cross-beta sheet quaternary structure; that is, the strands come from different monomers and align perpendicular to the axis of the fibril. While amyloid is usually identified using fluorescent dyes, stain polarimetry, circular dichroism, or FTIR (all indirect measurements), the gold standard test to see if a structure contains cross-beta fibers is by placing a sample in an x-ray diffraction beam; there are two characteristic scattering diffraction signals produced at 4.7 and 10 Ångstroms (0.47 nm and 1.0 nm), corresponding to the interstrand and stacking distances in beta sheets. It should be noted that the "stacks" of beta sheet are short and traverse the breadth of the amyloid fibril; the length of the amyloid fibril is built by aligned strands.
Amyloid polymerization is generally sequence-sensitive, that is, causing mutations in the sequence can prevent self-assembly, especially if the mutation is a beta-sheet breaker, such as proline. For example, humans produce an amyloidogenic peptide associated with type II diabetes, but, in Rodentia, a proline is substituted in a critical location and amyloidogenesis does not occur.
There are two broad classes of amyloid-forming polypeptide sequences. Glutamine-rich polypeptides are important in the amyloidogenesis of yeast and mammalian prions, as well as Huntington's disease. When peptides are in a beta-sheet conformation, particularly when the residues are parallel and in-register (causing alignment), glutamines can brace the structure by forming intrastrand hydrogen bonding between its amide carbonyls and nitrogens. In general, for this class of diseases, toxicity correlates with glutamine content. This has been observed in studies of onset age for Huntington's disease (the longer the polyglutamine sequence, the sooner the symptoms appear), and has been confirmed in a C. elegans model system with engineered polyglutamine peptides.
Other polypeptides and proteins, such as amylin and the Alzheimer's beta protein do not have a simpn vitro. This phenomenon is important since it would explain interspecies preen Alzheimer's and diabetes. In general, cross-polymerization is more efficient the more similar the peptide sequence, though entirely dissimilar sequences can cross-polymerize and highly similar sequences can even be "blockers" which prevent polymerization. Polypeptides will not cross-polymerize their mirror-image counterparts, indicating that the phenomenon involves specific binding and r |
Diatomic | Diatomic molecules are molecules made only of two atoms, of either the same or different chemical elements. The prefix di- means two in Greek.
Huber and Herzberg's book, Molecular Spectra and Molecular Structure IV. Constants of Diatomic Molecules, lists hundreds of diatomic molecules, some which have been detected spectroscopically in interstellar space. However, few diatomics are found to occur naturally on Earth outside of laboratories. About 99% of the Earth's atmosphere is composed of diatomic molecules, specifically oxygen O2 (21%) and nitrogen N2 (78%), with the remaining 1% being mostly argon (0.9340%). The natural abundance of hydrogen (H2) in the Earth's atmosphere is only on the order of parts per million, but H2 is, in fact, the most abundant molecule seen in nature, dominating the composition of stars.
Elements that consist of diatomic molecules, under typical laboratory conditions of 1 bar and 25 oC, include hydrogen (H2), nitrogen (N2), oxygen (O2), and the halogens: fluorine (F2), chlorine (Cl2), bromine (Br2), iodine (I2), and, perhaps, astatine (At2). Again note that many other diatomics are possible, such as metals heated to their gaseous states. Also, many diatomic molecules are unstable and highly reactive, such as diphosphorus. A few compounds are made of diatomic molecules, including CO and HBr.
If a diatomic molecule consists of two atoms of the same element, such as H2 and O2, then it is said to be homonuclear, but otherwise it is said to heteronuclear, such as with CO or NO. The bond in a homonuclear diatomic molecule is non-polar and fully covalent.
The diatomic molecule molecular geometry is the simplest spatial arrangement of atoms.. This configuration is more commonly referred to in the VSEPR theory as the AX1E*. Unlike other systems in VSEPR, there is no central atom.
Diatomic elements played an important role in the elucidation of the concepts of element, atom, and molecule in the 19th century, because some of the most common elements, such as hydrogen, oxygen, and nitrogen, occur as diatomic molecules. John Dalton's original atomic hypothesis assumed that all elements were monatomic and that the atoms in compounds would normally have the simplest atomic ratios with respect to one another. For example, Dalton assumed that water's formula was HO, giving the atomic weight of oxygen as 8 times that of hydrogen, instead of the modern value of about 16. As a consequence, confusion existed regarding atomic weights and molecular formulas for about half a century.
As early as 1805, Gay-Lussac and von Humboldt showed that water is formed of two volumes of hydrogen and one volume of oxygen, and by 1811 Amedeo Avogadro had arrived at the correct interpretation of water's composition, based on what is now called Avogadro's law and the assumption of diatomic elemental molecules. However, these results were mostly ignored until 1860. Part of this rejection was due to the belief that atoms of one element would have no chemical affinity towards atoms of the same element, and part was due to apparent exceptions to Avogadro's law that were not explained until later in terms of dissociating molecules.
At the 1860 Karlsruhe Congress on atomic weights, Cannizzaro resurrected Avogadro's ideas and used them to produce a consistent table of atomic weights, which mostly agree with modern values. These weights were an important pre-requisite for the discovery of the periodic law by Dmitri Mendeleev and Lothar Meyer.
It is convenient, and common, to represent a diatomic molecule as two point masses (tfrac{L^2}{2 I} \,</math>
where
<math>L \,</math> is the angular momentum
<math>I \,</math> is the moment of inertia of the molecule
For microscopic, atomic-level systems like a molecule, angular momentum can only have specific discrete values given by
<math>L^2 = l(l+1) \hbar^2 \,</math>
where l is a positive integer and <math>\hbar</math> is Planck's reduced constant.
Also, for a diatomic molecule the moment of inertia is
<math>I = \mu r_{0}^2 \,</math>
where
<math>\mu \,</math> is the reduced mass of the molecule and
<math>r_{0} \,</math> is the average distance between the two atoms in the molecule.
So, substituting the angular momentum and moment of inertia into Erot, the rotational energy levels of a diatomic molecule are given by:
<math style="border:2px solid #ccccff">E_{rot} = \frac{l(l+1) \hbar^2}{2 \mu r_{0}^2} \ \ \ \ \ l=0,1,2,... \,</math>
Another way a diatomic molecule can move is to have each atom oscillate - or vibrate - along a line (the bond) connecting the two atoms. The vibrational energy is approximately that of a quantum harmonic oscillator:
<math style="border:2px solid #ccccff">E_{vib} = \left |
Pott%27s_disease_overview | Pott's disease or Pott disease is a presentation of extrapulmonary tuberculosis that affects the spine. The lower thoracic and upper lumbar vertebrae are most commonly affected. Scientifically, it is called tuberculous spondylitis and it is most commonly localized in the thoracic portion of the spine. Pott’s disease results from haematogenous spread of tuberculosis from other sites, often pulmonary. The infeum kongterm corticosteriod use.
If left untreated, Pott's disease can cause severe vertebral deformity and collapse resulting in kyphosis, cord compression and paraplegia. With treatment the prognosis is good with improvement in the spine deformity and neurological deficit.
The history and symptoms of Pott's disease depends upon the stage of disease, affected site, and presence of complications. Back pain most common symptom of Pott's disease. Other constitutional symptoms include fever, night sweating, anorexia, and weight loss.
Physical examination findings suggestive of spinal tuberculosis include local tenderness on the spine, stiffness and spasm of the muscles, cold abscess demonstrates absence of signs of inflammatioep tendon reflexes, numbness and paraesthesias.
Plain radiographs of the spine demonstrate changes suggestive of spinal tuberculosis in majority of the patients. The radiographic changes on plain X-Rays are not evident in the early stages of infection, therefore the changes are present in the late stages of the disease. Findings on the plain radiograph include rarefaction of the vertebral end plates, lytic destruction of anterior portion of vertebral body, collapse of the vertebral body, loss of disc height.
CT scan of sotic vertebral end plates. It is helpful to detect early lesions and is more effective for defining the shape and calcification of soft-tissue abscesses.
MRI provides provides the extent of soft tissue involvement and the accurate dimensions of the abscess and its extent.
Radionuclide bone scanning may be done, but findings are not specific for Pott's disease.
Pott's disease is treated with standard antitubercular therapy for a duration of 6 to 12 months. Compliance to the treatment should be monitored. Response to the treatment is assessed by the improvement of neurological function and reduction of the spinal deformity.
Surgery is not the primary treatment option, but it is preferred in patients unresponsive to medical therapy and worsening neurological function. Surgical debridement is performed in such cases.
Pott's disease can be prevented by controlling the spread of tuberculosis infection. Patients who have a positive PPD test (but not active tuberculosis) may decrease their risk by properly taking medicines to prevent tuberculosis.
|
Hyperaldosteronism_(patient_information) | Primary and secondary hyperaldosteronism are conditions in which the adrenal gland releases too much of the hormses it to release too much aldosterone.
In secondary hyperaldosteronism, the excess aldosterone is caused by something outside the adrenal gland that mimics the primary condition. Primary hyperaldosteronism used to be considered a rare condition, but some experts believe that it may be the cause of hypertension in some patients. Most cases of primary hyperaldosteronism are caused by a noncancerous (benign) tumor of the adrenal gland. Secondary hyperaldosteronism is generally related to hypertension. It is also related to disorders such as:
Cirrhosis of the liver
Heart failure
Nephrotic syndrome
The condition is common in people ages 30 - 50.
Abdominal CT scan
ECG
Plasma aldosterone level
Plasma renin activity
Serum potassium level
Urinary aldosterone
Occasionally, it is necessary to insert a catheter into the veins of the adrenal glands to determine which of the adrenals contains the growth.
This disease may also affect the results of the following tests:
CO2
Serum magnesium
Serum sodium
Urine potassium
Urine sodium
Call for an appointment with your health care provider if you develop symptoms of hyperaldosteronism.
Primary hyperaldosteronism caused by a tumor is usually treated with surgery. Removing adrenal tumors may control the symptoms. Even after surgery, some people have hypertension and need to take medication.
Watching your salt intake and taking medication may control the symptoms without surgery. Medications used to treat hyperaldosteronism include:
Spironolactone (Aldactone; Aldactazide), a diuretic
Eplerenone (Inspra), which blocks the action of aldosterone
Surgery is not used for secondary hyperaldosteronism, but medications and diet are part of treatment.
Directions to Hospitals Treating Hyperaldosteronism
The prognosis for primary hyperaldosteronism is good with early diagnosis and treatment. The prognosis for secondary hyperaldosteronism will vary depending on the cause of the condition.
Impotence and gynecomastia (enlarged breasts in men) may occur with long-term spironolactone treatment in men, but this is uncommon.
http://www.nlm.nih.gov/medlineplus/ency/article/000330.htm
Template:WH
Template:WS
|
AASLD_guidelines_classification_scheme#Class_of_recommendation | AASLD (American Association of Study of Liver Disease) provides recommendations for various liver diseases. It develops clinical practice guidelines which are supported by a high level of scientific evidence. They assist in appropriate health care to patients. The clinical practice guidelines should not be looked at as "standards of care". They are provided to aid in the diagnosis and management of liver diseases.
AASLD recommendations are classified into five grades based on quality of evidence.
AASLD has adapted the recommendations classification from American Heart Association recommendations classification. The adapated classification is as follows:
The AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment,Development, and Evaluation (GRADE) workgroup with minor modifications. The classification is as follows
|
Omega_3_fatty_acids | ω−3 fatty acids (commonly spelled omega-3 fatty acids) are a family of polyunsaturated fatty acids which have in common a carbon-carbon double bond in the ω−3 position.
Important nutritionally essential ω−3 fatty acids are: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). For a more complete list, see list of ω−3 fatty acids. The human body cannot synthesize ω−3 fatty acids de novo, but it can form 20- and 22-carbon unsaturated ω−3 fatty acids from the eighteen-carbon ω−3 fatty acid, α-linolenic acid. These conversions occur competitively with ω−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. Both the ω−3 α-linolenic acid and ω−6 linoleic acid are essential nutrients which must be obtained from food. Synthesis of the longer ω−3 fatty acids from linolenic acid within the body is competitively slowed by the ω−6 analogues. Thus accumulation of long-chain ω−3 fatty acids in tissues is more effective when they are obtained directly from food or when competing amounts of ω−6 analogs do not greatly exceed the amounts of ω−3.
Chemical structure of alpha-linolenic acid (ALA), an essential ω−3 fatty acid, (18:3Δ9c,12c,15c). Although chemists count from the carbonyl carbon (blue numbering), physiologists count from the ω (omega) carbon (red numbering). Note that from the ω end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "ω−3"
For detail on ω (omega) nomenclature and numbering, see EFA Nomenclature.
The term ω−3 (aka "n−3", "omega-3") signifies that the first double bond exists as the third carbon-carbon bond from the terminal methyl end (ω) of the carbon chain.
ω−3 fatty acids which are important in human nutrition are: α-linolenic acid (18:3, ALA), eicosapentaenoic acid (20:5, EPA), and docosahexaenoic acid (22:6, DHA). These three polyunsaturates have either 3, 5 or 6 double bonds in a carbon chain of 18, 20 or 22 carbon atoms, respectively. All double bonds are in the cis-configuration, i.e. the two hydrogen atoms are on the same side of the double bond.
The biological effects of the ω-3 are largely mediated by their interactions with the ω-6 fatty acids; see Essential fatty acid interactions for detail.
A 1992 article by biochemist William E.M. Lands provides an overview of the research into ω−3 fatty acids, and is the basis of this section.
The 'essential' fatty acids were given their name when researchers found that they were essential to normal growth in young children and animals. (Note that the modern definition of 'essential' is more strict.) A small amount of ω−3 in the diet (~1% of total calories) enabled normal growth, and increasing the amount had little to no additional benefit.
Likewise, researchers found that ω−6 fatty acids (such as γ-linolenic acid and arachidonic acid) play a similar role in normal growth. However, they also found that ω−6 was "better" at supporting dermal integrity, renal function, and parturition. These preliminary findings led researchers to concentrate their studies on ω−6, and it was only in recent decades that ω−3 has become of interest.
In 1963 it was discovered that the ω−6 arachidonic acid was converted by the body into pro-inflammatory agents called prostaglandins. By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins and the leukotrienes. The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. However, if the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may have deleterious effects. Researchers found that ω−3 is also converted into eicosanoids, but at a much slower rate. Eicosanoids made from ω−3 fats often have opposing functions to those made from ω−6 fats (ie, anti-inflammatory rather than inflammatory). If both ω−3 and ω−6 are present, they will "compete" to be transformed, so the ratio of ω−3:ω−6 directly affects the type of eicosanoids that are produced.
This competition was recognized as important when it was found that thromboxane is a factor in the clumping of platelets, which leads to thrombosis. The leukotrienes were similarly found to be important in immune/inflammatory-system response, and therefore relevant to arthritis, lupus, and asthma. These discoveries led to greater interest in finding ways to control the synthesis of ω−6 eicosanoids. The simplest way would be by consuming more ω−3 and fewer ω−6 fatty acids.
September 8, 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ω−3 fatty acids, stating that "supportive but not conclusive research shows that consumption of EPA and DHA ω−3 fatty acids may reduce the risk of coronary heart disease." This updated and modified their hen clot and scar formation, and it lowers the blood pressure. There is strong scientific evidence, that ω−3 fatty acids significantly reduce blood triglyceride levels and regular intake reduces the risk of secondary and primary heart attack.
Some benefits have been reported in such conditions as rheumatoid arthritis and cardiac arrhythmias.
There is a promising preliminary evidence, that ω−3 fatty acids supplementation might be helpful in cases of depression and anxiety. Studies report highly significant improvement from ω−3 fatty acids supplementation alone and in conjunction with medication.
Some research suggests that fish oil intake reduces the risk of ischemic and thrombotic stroke. However, very large amounts may actually increase the risk of hemorrhagic stroke (see below). Lower amounts are not related to this risk. 3 grams of total EPA/DHA daily are considered safe with no increased risk of bleeding involved and many studies used substantially higher doses without major side effects (for example: 4.4 grams EPA/2.2 grams DHA in 2003 study).
Several studies report possible cancer prevention effects of ω−3 fatty acids (particularly breast, colon and prostate cancer). No clear conclusion can be drawn at this time, though.
A 2006 report in the Journal of the American Medical Association concluded that their review of literature covering cohorts from many countries with a wide variety of demographic characteristics demonstrating a link between ω−3 fatty acids and cancer prevention gave mixed results. This is similar to the findings of a review by tain ω−3 fats on total mortality, combined cardiovascular events and cancer.
In 1999, the GISSI-Prevenzione Investigators reported in the Lancet the results of major clinical study in 11 324 patients with a recent myocardial infarction. Treatment with omega-3 fatty acids 1 g/d reduced the occurrence of death, cardiovascular death and sudden cardiac death by 20%, 30% and 45% respectively. These beneficial effects were seen already from three months onwards.
In April 2006, a team led by Lee Hooper at the University of East Anglia in Norwich, UK, published a review of almost 100 separate studies into ω−3 fatty acids, found in abundance in oily fish. It concluded that they do not have a significant protective effect against cardiovascular disease. This meta-analysis was controversial and stands in stark contrast with two different re disorders such as aggression and ADHD (Attention Deficit Hyperactive Disorder).
Several studies published in 2007 have been more positive. In the March 2007 edition of the journg daily of eicosapentaenoic acid (EPA - an ω−3 essential fatty acid from fish oil) with the other half being a control group. The thickness of the carotid arteries and certain measures of hose given the EPA had a statistically significant decrease in the thickness of the carotid arteries along with improvement in blood flow. The authors indicated that this was the first demonstration that administration of purified EPA improves the thickness of carotid arteries along with improving blood flow in patients with unhealthy blood sugar levels.
In another study published in the American Journal of Health System Pharmacy March 2007, patients with high triglycerides and poor coronary artery health were given 4 grams a day of a combination of EPA and DHA along with some monounsaturated fatty acids. Those patients with very unhealthy triglyceride levels (above 500 mg/dl) reduced their triglycerides on average 45% and their VLDL cholesterol by more than 50%. VLDL is a bad type of cholesterol and elevated triglycerides can also be deleterious for cardiovascular health.
There was another study published on the benefits of EPA in the journal The Lancet in March 2007. This study involved over 18,000 patients with unhealthy cholesterol levels. The patients were randomly assigned to receive either 1,800 mg a day of EPA with a statin drug or a statin drug alone. The trial went on for a total of five years. It was found at the end of the study those patients in the EPA group had superior cardiovascular function. Non-fatal coronary events were also significantly reduced in the EPA group. The authors concluded that EPA is a promising treatment for prevention of major coronary events,especially non-fatal coronary events.
Another study regarding fish oil was published in the journal Nutrition in April 2007. Sixty four healthy Danish infants received either cow's milk or infant formula alone or with fish oil from nine to twelve months of age. It was found that those infants supplemented with fish oil had improvement in immune function maturation with no apparent reduction in immune activation.
There was yet another study on ω−3 fatty acids published in the April 2007 Journal of NeuroScience. A group of mice were genetically modified to develop accumulation of amyloid and tau proteins in the brain similar to that seen in people with poor memory. The mice were divided into four groups with one group receiving a typical American diet (with high ratio of ω−6 to ω−3 fatty acids being 10 to 1). The other three groups were given food with a balanced 1 to 1 ω−6 to ω−3 ratio and two additional groups supplemented with DHA plus long chain ω−6 fatty acids. After three months of feeding, all the DHA supplemented groups were noted to have a lower accumulation of beta amyloid and tau protein. It is felt that these abnormal proteins may contribute to the development of memory loss in later years.
Finally, there was a study published regarding ω−3 supplementation in children with learning and behavioral problems. This study was published in the April 2007 edition of the Journal of the Developmental and Behavioral Pediatrics (5), where 132 children, between the ages of seven to twelve years old, with poor learning, participated in a randomized, placebo-controlled, double-blinded interventional trial. A total of 104 children completed the trial. For the first fifteen weeks of this study, the children were given polyunsaturated fatty acids (ω−3 and ω−6, 3000 mg a day), polyunsaturated fatty acids plus multi-vitamins and minerals or placebo. After fifteen weeks, all groups crossed over to the polyunsaturated fatty acids (PUFA) plus vitamins and mineral supplement. Parents were asked to rate their children's condition after fifteen and thirty weeks. After thirty weeks, parental ratings of behavior improved significantly in nine out of fourteen scales. The lead author of the study, Dr. Sinn, indicated the present study is the largest PUFA trial to date with children falling in the poor learning and focus range. The results support those of other studies that have found improvement in poor developmental health with essential fatty acid supplementation.
Research in 2005 and 2006 has suggested that the in-vitro anti-inflammatory activity of ω−3 acids translates into clinical benefits. Cohorts of neck pain patients and of rheumatoid arthritis sufferers have demonstrated benefn d some degree of protection against coronary heart disease. Because the physiological potency of EPA and DHA is much greater than that for α-linolenic acid, it is not possible to estimate one AMDR for all n-3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA." There was insufficient evidence as of 2005 to set a UL (upper tolerable limit) for n-3 fatty acids.
Researchers believe the ideal ω−6 intake should be no more than 4-5 times that of our ω−3 intake. The National Institutes of Health recently published recommended daily intakes of fatty acids, specific recommendations include 650 mg of EPA and DHA, 2.22 g/day of alpha-linolenic acid and 4.44 g/day of linoleic acid.
A perceived risk of fish oil ω−3 supplementation has been heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic and cadmium as well as other contaminants (PCBs, furans, dioxins), which potentially might be found especially in less-refined fish oil supplements. An independent test in 2006 of 44 fish oils on the US market found that all of the products passed safety standards for potential contaminants. The FDA recommends that total dietary intake of ω−3 fatty acids from fish not exceed 3 grams per day, of which no more than 2 grams per day are from nutritional supplements.
Historically, the Council for Responsible Nutrition (CRN) and the World Health Organization (WHO) have published acceptable standards regarding contaminants in fish oil. The most stringent current standard is the International Fish Oils Standard (IFOS).
Fish oils that typically make this highest grade are those that are molecularly distilled under vacuum, and have virtuallytion in food has been a significant recent trend in food fortification, with global food compan, conhen, inter-tidal herbivorous shellfish such as mussels and clams can help people reach a healthy balance of ω−3 and ω−6 fats in their diets.
The most widely available source of EPA and DHA is cold water oily fish such as salmon, herring, mackerel, anchovies and sardines. Oils from these fish have a profile of around seven times as much ω−3 as ω−6. Other oily fish such as tuna also contain ω−3 in somewhat lesser amounts. Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins which may accumulate up the food chain. Some supplement manufacturers remove heavy metals and other contaminants from the oil through various means, such as molecular distillation (see above), which increases purity, potency and safety.
Even some forms of fish oil may not be optimally digestible. Of four studies that compare bioavailability of the triglyceride form of fish oil vs. the ester form, two have concluded that the natural triglyceride form is better, and the other two studies did not find a significant difference. No studies have shown the ester form to be superior although it is cheaper to manufacture.
Although fish is a dietary source of ω−3 fatty acids, fish do not synthesize them; they obtain them from the algae in their diet.
Six times richer than most fish oils in ω−3, Flax (aka linseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical source of ω−3. Flaxseed oil consists of ca. 55% ALA (alpha-linolenic acid). Flax, like chia, contains approximately three times as much ω−3 as ω−6.
15 grams of flaxseed oil provides ca. 8 grams of ALA, which is converted in the body to EPA and then DHA at an efficiency of (2%-15%), and (2%-5%) respectively.
Table 1. ω−3 content as the percentage of ALA in the seed oil.
Table 2. ω−3 content as the percentage of ALA in the whole food.
Eggs produced by chickens fed a diet of greens and insects produce higher levels of ω−3 fatty acids (mostly ALA) than chickens fed corn or soybeans.In addition to feeding chickens insects and greens, fish oils are added to their diet to increase the amount of fatty acid concentrations in eggs.Invalid parameter in <ref> tag
Krill, which are small, shrimp-like zooplankton, also contain the ω−3 fatty acids EPA and DHA. One advantage of extracting ω−3 fatty acids from krill, as opposed to sources higher in the food chain, is that krill contain fewer heavy metals and PCBs harmful to humans. However, in comparison to higher animals, they also contain fewer ω−3 fatty acids per gram.
The ω−6 to ω−3 ratio of grass-fed beef is about 2:1, making it a more useful source of ω−3 than grain-fed beef, which usually has a ratio of 4:1. Commercially available lamb is almost always grass-fed, and subsequently higher in ω−3 recommended daily intake (RDI) of ALA, while a piece of organic cheese the size of a matchbox may provide up to 88%".
The microalgae Crypthecodinium cohnii and Schizochytrium are rich sources of DHA (22:6 ω-3) and can be produced commercially in bioreactors. Oil from brown algae (kelp) is a source of EPA. Walnuts are one of few nuts that contain appreciable ω−3 fat, with approximately a 1:4 ratio of ω−3 to ω−6. Acai palm fruit also contains ω−3 fatty acids.
Main article: Essential fatty acid interactions
Clinical studies indicate that the ingested ratio of ω−6 to ω−3 (especially Linoleic vs Alpha Linolenic) fatty acids is important to maintaining cardiovascular health.
Both ω−3 and ω−6 fatty acids are essential, i.e. humans must consume them in the diet. ω−3 and ω−6 compet.g. pro−6. Metabolites of ω−6 are significantly more inflammatory (esp. arachidonic acid) than those of ω−3. This necessitates that ω−3 and ω−6 be consumed in a balanced proportion; healthy ratios of ω−6:ω−3 range from 1:1 to 4:1. Studies suggest that the evolutionary human diet, rich in seafood and other sources of ω−3, may have provided such a ratio. recommend daily intakes of three ω−3 forms: 650 mg of EPA and DHA, and 2.22 grams of ALA, and one ω−6 form: 4.44 grams of LA. This translates to a 3:2 ω−6 to ω−3 ratio. (i.e. 1.5:1)
Typical Western diets provide ratios of between 10:1 and 30:1 - i.e., dramatically skewed toward ω−6. Here are the ratios of ω−6 to ω−3 fatty acids in some common oils: canola 2:1, soybean 7:1, olive 3-13:1, sunflower (no ω−3), flax 1:3 cottonseed (almost no ω−3), peanut (no ω−3), grapeseed oil (almost no ω−3) and corn oil 46 to 1 ratio of ω−6 to ω−3. It should be noted that olive, peanut and canola oils consist of approximately 80% monounsaturated fatty acids, (i.e. neither ω−6 nor ω−3) meaning that they contain relatively small amounts of ω−3 and ω−6 fatty acids. Consequently, the ω−6 to ω−3 ratios for these oils (i.e. olive, canola and peanut oils) are not as significant as they are for corn, soybean and sunflower oils.
It has been reported that conversion of ALA to EPA and further to DHA in humans is limited, but varies with individuals . Women have higher ALA conversion efficiency than men, probably due to the lower rate of utilization of dietary ALA for beta-oxidation. This suggests that biological engineering of ALA conversion efficiency is possible. In the online book of The Benefits of Omega 3 Fatty Acids found in Seal Oil, as Opposed to Fish and Flaxseed Oils, Dr. Ho listed the several factors that inhibit the ALA conversion , which again indicate that the efficiency of ALA conversion could be adjusted by altering one's dietary habits, such as rebalancing the ratio of ω−3 and ω−6 fatty acid intake , , restraining direct alcohol consumptions, and supplementing vitamins and minerals. However, Goyens et al. argues that it is the absolute amount of ALA, rather than the ratio of ω−3 and ω−6 fatty acids, which affects the conversion .
List of ω−3 fatty acids
ω−6 fatty acid
ω−9 fatty acid
Essential fatty acid
Essential fatty |
Dispensaries | A hospital is an institution for health care providing treatment by specialised staff and equipment, and often but not always providing for longer-term patient stays.
Today, hospitals are usually funded by the state, health organizations (for profit or non-profit), health insurances or charities, including direct charitable donations. In history, however, they were often founded and funded by religious orders or charitable individuals and leaders. Similarly, modern-day hospitals are largely staffed by professional physici for pilgrims, or hospital school. The name comes from Latin hospes (host), which is also the root for the English words hotel, hostel, and hospitality. The modern word hotel derives from the French word hostel, which featured a silent s, which was eventually removed from the word. (The circumflex on modern French hôtel hints at the vanished s)
Grammar of the word differs slightly depending on the dialect. ral weeks or months ('inpatients'). Hospitals are usually distinguished from other types of medical facilities by their ability to admit and care for inpatients.
The best-known type of hospital is the general hospital, which is set up to deal with many kinds of disease and injury, and typically has an emergency ward to deal with immediate threats to health and the capacity to dispatch emergency medical services. A general hospital is typically the major health care facilityor surgery, plastic surgery, childbirth, bioassay laboratories, and so forth. Larger cities may have many different hospitals of varying sizes and facilities.
Types of specialized hospitals include trauma centers, rehabilitation hospitals, children's hospitals, seniors' (geriatric) hospitals, and hospitals for dealing with specific medical needs such as psychiatric problems (see psychiatric hospital), certain disease categories, and so forth.
A hospital may be a single building or a campus. (Many hospitals with pre-20th-century origins began as one building and evolved into campuses.) Some hospitals are affiliated with universities for medical research and the training of medical personnel. Worldwide, most hospitals are run on a non-profit basis by governments or charities. Within the United States, most hospitals are not-for-profit.
A teaching hospital (or university hospital) is that who combines assistance to patients with teaching to medical students.
A medical facility smaller than a hospital is called a clinic, and is often run by a government agency for health services or a private partnership of physicians (in nations where private practice is allowed). Clinics generally provide only outpatient services.
Intensive care bed after a trauma intervention, showing the highly technical equipment of modern hospitals.
Empty Chamber and the iron bed in a hospital the city of Kharkov, Ukraine.
Template:Seealso
Hospitals may have any of the following departments or units:
Behavioral Health Services
Burn unit
Cancer Center
Coronary care unit
Dispensary
Emergency department
Intensive Care Unit, Neonatal intensive care unit, Trauma center
Labor and Delivery
Laboratory Services
Nursing unit
Orthopedic Services
Outpatient Department
Pharmacy
Psychiatric ward
Rehabilitation Services
Physical Therapy
Post anesthesia care unit
Radiology
Respiratory Therapy
Surgery
Urgent care
Non-medical departments include:
Medical records department
Release of Information department
A physician visiting the sick in a hospital. German engraving from 1682.
In ancient cultures, religion and medicine were linked. The earliest known institutions aiming to provide cure were Egyptian temples. Greek temples dedicated to the healer-god Asclepius might admit the sick, who would wait for guidance from the god in a dream. The Romans adopted his worship. Under his Roman name Æsculapius, he was provided with a temple (291 BC) on an island in the Tiber in Rome, where similar rites were performed.
The Sinhalese (Sri Lankans) are perhaps responsible for introducing the concept of dedicated hospitals to the world. According to the Mahavamsa, the ancient chronicle of Sinhalese royalty written in the 6th century A.D., King Pandukabhaya (4th century BC) had lying-in-homes and hospitals (Sivikasotthi-Sala) built in various parts of the country. This is the earliest documentary evidence we have of institutions specifically dedicated to the care of the sick anywhere in the world. Mihintale Hospital is perhaps the oldest in the world.
Institutions created specifically to care for the ill also appeared early in India. King Ashoka is said to have founded at least 18 hospitals ca. 230 BC, with physicians and nursing staff, the expense being borne by the royal treasury. However, there are historians who strictly dispute the claim that Ashoka built any hospitals at all, and argue that it is based on a mistranslation, with references to 'rest houses' being mistaken for hospitals. The error is thought to have occurred because similar edicts and records talk of Ashoka importing medicinal supplies.
State-supported hospitals later appeared in China during the first millennium A.D. The first teaching hospital where students were authorized to methodically practice on patients under the supervision of physicians as part of their education, was the Academy of Gundishapur in the Persian Empire. One expert has argued that "to a very large extent, the credit for the whole hospital system must be given to Persia".
The Romans created valetudinaria for the care of sick slaves, gladiators and soldiers around 100 BC, and many were identified by later archeology. While their existence is considered proven, there is some doubt as to whether they were as widespread as was once thought, as many were identified only according to the layout of building remains, and not by means of surviving records or finds of medical tools.
The adoption of Christianity as the state religion of the empire drove an expansion of the provision of care. The First Council of Nicaea in 325 A.D. urged the Church to provide for the poor, sick, widows and strangers. It ordered the construction of a hospital in every cathedral town. Among the earliest were those built by the physician Saint Sampson in Constantinople and by Basil, bishop of Caesarea. The latter was attached to a monastery and provided lodgings for poor and travelers, as well as treating the sick and infirm. There was a separate section for lepers.
Main article: Bimaristan
Further information: Islamic medicine
The earliest recorded hospitals in the medieval Islamic world refer to the hopital of al-Walid ibn 'Abdul Malik (ruled 705-715 CE) which he built in 86 AH (706-707 CE). It somewhat resembled the Byzantine nosocomia, but was more general as it extended its services to the lepers and the invalid and destitute people. All treatment and care was free of charge and there was more than one physician employed in this hospital.
In the medieval Islamic world, the word "Bimaristan" was used to indicate a hospital in the modern sense, an establishment where the ill were welcomed and cared for by qualified staff. In this way, Muslim physicians were the first to make a distinction between a hospital and other different forms of healing temples, sleep temples, hospices, assylums, lazarets and leper-houses, all of which in ancient times were more concerned with isolating the sick and the mad from society "rather than to offer them any way to a true cure." Some thus consider the medieval Bimaristan hospitals as "the first hospitals" in the modern sense of the word. The first public hospitals, psychiatric hospitals and medical universities were also introduced by medieval Muslim physicians.
Between the eighth and twelfth centuries CE Muslim hospitals developed a high standard of care. Hospitals built in Baghdad in the ninth and tenth centuries employed up to twenty-five staff physicians and had separate wards for different conditions. Al-Qairawan hospital and mosque, in Tunisia, were built under the Aghlabid rule in 830 CE and was simple but adequately equipped with halls organized into waiting rooms, a attended the sick, thereded bloodletting, bone setting, and cauterisation. During Ottoman rule, when hospitals reached a particular distinction, Sultan Bayazid II built a mental hospital and medical madrasa in Edirne, and a number of other early hospitals were also built in Turkey. Unlike in Greek temples to healing gods, the clerics working in these facilities employed scientific methodology far beyond that of their contemporaries in their treatment of patients.
According to Sir John Bagot Glubb:
.mw-parser-output .templatequote{overflow:hidden;margin:1em 0;padding:0 40px}.mw-parser-output .templatequote .templatequotecite{line-height:1.5em;text-align:left;padding-left:1.6em;margin-top:0}
"By Mamun's time medical schools were extremely active in Baghdad. The first free public hospital was opened in Baghdad during the Caliphate of Haroon-ar-Rashid. As the system developed, physicians and surgeons were appointed who gave lectures to medical students and issued diplomas to those who were considered qualified to practice. The first hospital in Egypt was opened in 872 AD and thereafter public hospitals sprang up all over the empire from Spain and the Maghrib to Persia."
Hospicio Cabañas was the largest hospital in colonial America.
The church at Les Invalides in France showing the often close connection between historical hospitals and churches.
Medieval hospitals in Europe followed a similar pattern. They were religious communities, with care provided by monks and nuns. (An old French term for hospital is hôtel-Dieu, "hostel of God.") Some were attached to monasteries; others were independent and had their own endowments, usually of property, which provided income for their support. Some hospitals were multi-function while others were founded for specific purposes such as leper hospitals, or as refuges for the poor or for pilgrims: not all cared for the sick. Not until later where most hospitals multi-functional, though the first Spanish hospital, founded by the Catholic Visigoth bishop Masona in 580 at Mérida, was a xenodochium designed as an inn for travellers (mostly pilgrims to the shrine of Eulalia of Mérida) as well as a hospital for citizens and local farmers. The hospital's endowment consisted of farms to feed its patients and guests.
It is believed that the first Spanish style hospital founded in the Americas following Columbus arrival to the island now known as Hispaniola was the Hospital San Nicolás de Bari Calle Hostos in Santo Domingo, Distrito Nacional Dominican Republic.
Fray Nicolas de Ovando, Spanish governor and colonial administrator from 1502-1509, authorized its construction in or after 1504. It is believed that this hospital also served as a church during its lifetime. The first phase of its construction was completed in 1519. Erwin Walter Palm, [former author and professor of Spanish American art, culture, and history] wrote that "the Brotherhood of Our Lady of the Conception continued the construction of the hospital in 1533, adding modern elements, including additional buildings." Abandoned in the mid-18th century the hospital now lies in ruins near the Cathedral in the colonial zone in Santo Domingo, DR, amid additional historical New World sights.
The Hospital de Jesús Nazareno in Mexico City is the oldest hospital in North America. It was founded in 1524 with the economic support of conquistador Hernán Cortés to care for poor Spanish soldiers and the native inhabitants.
The first hospital in North America north of Mexico is the Hôtel-Dieu de Québec. It was established in New France in 1639 by three Augustinians from l'Hôtel-Dieu de Dieppe in France. The project of the niece of Cardinal de Richelieu was granted a royal charter by King Louis XIII and staffed by colonial physician Robert Giffard de Moncel.
In Europe the medieval concept of Christian care evolved during the sixteenth and seventeenth centuries into a secular one, but it was in the eighteenth century that the modern hospital began to appear, serving only medical needs and staffed with physicians and surgeons. The Charité (founded in Berlin in 1710) is an early example.
Guy's Hospital was founded in London in 1724 from a bequest by wealthy merchant Thomas Guy. Other hospitals sprang up in London and other British cities over the century, many paid for by private subscriptions. In the British American colonies the Pennsylvania General Hospita, physicians acquired a new facility that gradually developed into the most important research center. During the 19th century, the Second Viennese Medical School emerged with the contributions of physicians such as Carl Freiherr von Rokitansky, Josef Škoda, Ferdinand Ritter von Hebra and Ignaz Philipp Semmelweis. Basic medical science expanded and specialization advanced. Furthermore, the first dermatology, eye, as well as ear, nose and throat clinics in the world were founded in Vienna, being considered was the birth of specialized medicine.[citation needed]
By the mid-nineteenth century most of Europe and the United States had established a variety of public and private hospital systems. In Continental Europe the new hospitals were generally built and run from public funds. The National Health Service, the principle provider of healthcare in the United Kingdom, was founded in 1948.
In the United States the traditional hospital is a non-profit hospital, usually sponsored by a religious denomination. One of the earliest of these "almshouses" in what would become the United States was started by William Penn in Philadelphia in 1713. These hospitals are tax-exempt due to their charitable purpose, but provide only a minimum of charitable medical care. They are supplemented by large public hospitals in major cities and research hospitals often affiliated with a medical school. In the late twentieth century, chains of for-profit hospitals arose in the USA.
While hospitals, by concentrating equipment, skilled staff and other resources in one place, clearly provide important help to patients with serious or rare health problems, hospitals are also criticised for a number of faults, some of which are endemic to the system, others which develop from what some consider wrong approaches to health care.
One cricitism often voiced is the 'industrialised' nature of care, with constantly shifting treatment staff, which dehumanises the patient and prevents more effective care as doctors and nurses are rarely intimately familiar with the patient. The high working pressures often put on the staff exacerbates such rushed and impersonal treatment. The architecture and setup of modern hospitals is often voiced as a contributing factor to the feelings of faceless treatment many people complain about.
Another criticism is that hospitals are in themselves a dangerous plargery oll patients in the United States contract a nosocomical (hospital-caused) infection. Due to the environment in which antibiotics are used in large quantities, the infections are also often multi-resistant to various treatment methods, such as the relatively common MRSA infection.
In the modern era, hospitals are, broadly, either funded by the government of the country in which they are situated, or survive financially by competing in the private sector (a number of hospitals are also still supported by the historical type of charitable or religious associations).
In the United Kingdom for example, a relatively comprehensive, "free at the point of delivery" healthcare system exists, funded by the state. Hospital care is thus relatively easily available to all legal residents (although as hospitals prioritize their limited resources, there is a tendency for 'waiting lists' to be generated for non-emergency treatment, and those who can afford it may take out private healthcare to get treatment faster). On the other hand, many countries, including for example the USA, have in the 20th Century followed a largely private-based, for-profit-approach to providing hospital care, with few state-money supported "charity" hospitals remaining today. Where for-profit hospitals in such countries admit uninsured patients in emergency situations (such as during and after the Hurricane Katrina in the USA), they incur direct financial losses, ensuring that there is a clear disincentive to admit such patients.
While for-profit-based systems have produced some of the best hospitals in the world, a proportion of the populace may have little or no access to healthcare services of adequate quality.[citation needed]
As quality of healthcare has increasingly become an issue around the world, hospitals have increasingly had to pay serious attention to this. Independent external assessment of quality is one of the most powerful ways of assessing the quality of healthcare, and hospital accreditation is one means by which this is achieved. In many parts of the world such accreditation is sourced from other countries, a phenomenon known as international healthcare accreditation, by groups such as the Joint Commission from the USA and the Trent Accreditation Scheme from Great Britain.
The National Health Service Norfolk and Norwich University Hospital in the UK, showing the utilitarian architecture of many modern hospitals.
Modern hospital buildings are designed to mis dictate. As a result, Dutch architectural historian Cor Wagenaar has called many hospitals:
"... built catastrophes, anonymous institutional complexes run by vast bureaucracies, and totally unfit for the purpose they have been d better views and more pleasant color schemes. These ideas harken back to the late 18th century, when the concept of providing fresh air and access to the 'healing powers of nature' were first employed by hospital architects in improving their buildings.
Another major change which is still ongoing in many parts of the world is the change from a ward-based system (where patients are treated and accommodated in communal rooms, separated at best by movable partititions) to a room-based environment, where patients are accommodated in private rooms. The ward-based system has been described as very efficient, especially for the medical staff, but is considered to be more stressful for patients and detrimental to their privacy. A major constraint on providing all patients with their own rooms is however found in the higher cost of building and operating such a hospital, which causes some hospitals to charge for the privilege of private rooms.
The surgical, special procedures, radiological, intensive care unit, and patient rooms typically have medical gases, emergency and normal electrical power; and heating, air conditioning and ventilation systems.
The reliability of the electrical power systems that serve a hospital is important. In order to provide higher electrical reliability, the National Institutes of Health, NIH, requires that all secondary substations > 500 kVA at their Bethesda, MD campus be the spot network type. The spot network substations cost more than other arrangements.
Pneumatic tube conveying systems are often used to move the actual paper prescriptions for medicines to the Pharmacies, and to move medicines, especially intra-venous, IV, bags to the patient care rooms. Tissue samples can be sent to the Laboratory. Medical notes can be transcribed, printed, and then transported via a Pneumatic Tube Conveying System.
As measured by the weight of the item be transferred, the 15 cm (6”) diameter tube systems have about 225% of the lifting and moving capacity of a 10 cm (4”) system. When the seals are new, the 10 cm tube carriers will move a 1 kg (2+ pound) IV bag. But when the seals on the tube carriers are worn, the tubes can stop moving in the piping, and require a trained technician to recover the tube carrier.
Modern hospitals have information infrastructure such as secured patient information system and PACS.
|
Nephrogenic_diabetes_insipidus_future_or_investigational_therapies | In an individual with a milder V2R mutation resulting in a partial response to AVP and DDAVP, high doses of DDAVP in combination with a thiazide diuretic significantly decreased urinary volume [Mizuno et al 2003]. Effectiveness of this treatment in partial NDI needs to be explored further.
Because of the known gastrointestinal safety of selective cyclooxygenase (COX)-2 inhibitors compared to nonselective COX-inhibitors (such as indomethacin), use of these drugs has been proposed for the trQP2 mutations in autosomal recessive NDI result in normal protein that is retained within the endoplasmic reticulum (ER), agents that restore plasma routing are under investigation as potential treatments. Promising agents for X-linked NDI are cell-permeable V2R antagonists or agonists that in vitro rescue the intracellular retention of several V2R mutants [Morello et al 2000, Tan et al 2003, Bernier et al 2004, Robben et al 20ested in with a non-f peptide V1a receptor antagonist had beneficial effects on urine volume and osmolality starting a few hours after administration. However, the long-term effect of this drug could not be tested because the clinical development of this V1a receptor antagonist was interrupted during the course of this study as a result of possible interference with the cytochrome P450 metabolic pathway. Confirmation of the putative beneficial effect of pharmacologic chaperones in NDI awaits further in vivo testing.
Aminoglycosides, such as gentamicin, allow read-through of stop codon V2R mutants in vitro, resulting in the production of full-length proteins [Schulz et al 2002]. However, in view of the toxiceffect of these antibiotics on the kidney, the application of such a therapy to NDI in the future is unlikely.
|
Pediatric_Advanced_Life_Support | Pediatric Advanced Life Support (PALS) is a system of Advanced Life Support applied to infants and children. Professional healthcare providers use PALS during the stabilization and transportation phases of a pediatric emergency, in or out of hospital.
The skills and knowledge required to complete PALS training include the prerequisite Basic Life Support (BLS), team cardiopulmonary resuscitation, ECG rhythm identification, and basic pharmacology for infants and children.
|
Syncope_echocardiography | Transthoracic echocardiography can be useful in the diagnostic workup of patients presenting with syncope. This evaluation is especially warranted in patients who are suspected to have underlying cardiovascular disorders.
Transthoracic echocardiography can be useful in the diagnostic workup of patients presenting with syncope. This evaluation is especially warranted in patients who are suspected to have underlying cardiovascular disorders. |
Bromine | Bromine (Template:PronEng, Template:Lang-el, meaning "stench (of he-goats)" ), is a chemical element with the symbol Br and atomic number 35. A halogen element, bromine is a red volatile liquid at standard room temperature that is intermediate in reactivity between chlorine and iodine. Bromine vapours are corrosive toxic. Approximately 730,000,000 kg were produced in 1993. The main applications for bromine are in fire retardants and fine chemicals.
Bromine was discovered by Antoine Balard at the salt marshes of Montpellier in 1826, but was not produced in quantity until 1860. The French chemist and physicist Joseph-Louis Gay-Lussac suggested the name bromine due to the characteristic smell of the vapors. Some also suggest that it may have been discovered by Bernard Courtois, the man who discovered iodine.
Bromine has 2 stable isotopes: Br-79 (50.69%) and Br-81 (49.31%). At least another
23
isotopes are known to exist. Many of the bromine isotopes are fission products. Several of the heavier bromine isotopes from fission are delayed neutron emitters. All of the radioactive bromine isotopes are relatively short lived. The longest half life is the neutron deficient Br-77 at 2.376 days. The longest half life on the neutron rich side is Br-82 at 1.471 days. A number of the bromine isotopes exhibit metastable isomers. Stable Br-79 exhibits a radioactive isomer, with a half life of 4.86 seconds. It decays by isomeric transition to the stable ground state.
Bromine is the only liquid nonmetallic element at room temperature and one of only six elements on the periodic table that are liquid at or close to room temperature. The pure chemical element has the physical form of a diatomic molecule, Br2. It is a dense, mobile, reddish-brown liquid, that evaporates easily at standard temperature and pressures to give a red vapor (its color resembles nitrogen dioxide) that has a strong disagreeable odor resembling that of chlorine. Bromine is a halogen, and is less reactive than chlorine and more reactive than iodine. Bromine is slightly soluble in water, and highly soluble in carbon disulfide, aliphatic alcohols (such as methanol), and acetic acid. It bonds easily with many elements and has a strong bleaching action.
Certain bromine-related compounds have been evaluated to have an ozone depletion potential or bioaccumulate in living organisms. As a result many industrial bromine compounds are no longer manufactured, are being restrictter, as well as most organic compounds, especially upon illumination.
Bromine has no known role in human health. Organobromine compounds do occur naturally, a famous example being Tyrian purple. Most organobromine compounds in nature arise via the action of vanadium bromoperoxidase.
See also Halide minerals.
The diatomic compound Br2 does not occur naturally. Instead, bromine exists exclusively as bromide salts in diffuse amounts in crustal rock. Due to leaching, bromide salts have accumulated in sea water (85 ppm), but at a lower concentration than chloride. Bromine may be economically recovered from bromide-rich brine wells and from the Dead Sea waters (up to 50000 ppm).
Approximately 500,000 metric tons (worth around US$350 million) of bromine are produced per year (2001) worldwide with the United States and Israel being the primary producers. Bromine production has increased sixfold since the 1960s. The largest bromine reserve in the United States is located in Columbia and Union County, Arkansas, U.S. Israel's bromine reserves are contained in the waters of the Dead Sea. The bromide-rich brines are treated with chlorine gas, flushing through with air. In this treatment, bromide anion is oxidized to bromine by the chlorine gas.
2 Br− + Cl2 → 2 Cl− + Br2
Because of its commercial availability and long shelf-life, bromine is not typically prepared. Small amounts of bromine can however be generated through the reaction of solid sodium bromide with concentrated sulfuriBr is oxidized by further the sulfuric acid to form bromine (Br2) and sulfur dioxide (SO2).
NaBr (s) + H2SO4 (aq) → HBr (aq) + NaHSO4 (aq)
2 HBr (aq) + H2SO4 (aq) → Br2 (g) + SO2 (g) + 2 H2O (l)
Similar alternatives, such as the use of dilute hydrochloric acid with sodium hypochlorite, are also available. The most important thing is that the anion of the acid (in the above examples, sulfate and chloride, respectively) be more electronegative than bromine, allowing the substitution reaction to occur.
Organic compounds are brominated by either addition or substitution reactions). Bromine undergoes electrophilic addition to the double-bonds of alkenes, via a cyclic bromonium intermediate. In non-aqueous solvents such as carbon disulfide, this affords the di-bromo product. For example, reaction with ethylene will produce 1,2-dibromoethane. Bromine also undergoes electrophilic addition to phenols and anilines. When used as bromine water, the corresponding bromohydrin is formed instead. So reliable is the reactivity or bromine that bromine water is employed as a reagent to test for the presence alkenes, phenols, and anilines. Like the other halogens, bromphorus, esromine, beintive chlorides and more expensive iodide-containing reagent]]s. Thus, Grignard and organolithium compound are most often generated from the corresponding bromides.
Bromine is an oxidizer, and it will oxidize iodide ions to iodine, being itself reduced to bromide:
Br2 + 2 I− → 2 Br− + I2
Bromine will also oxidizly with aluminium, titanium, mercury as well as alkaline earths and alkali metals.
A wide variety of organobromine compounds are used in industry. Some are prepared from bromine and others are prepared from hydrogen bromide, which is obtained by burning hydrogen in bromine.
Illustrative of the addition reaction is the preparation of 1,2-Dibromoethane, the organobromine compound produced in the largest amounts:
C2H4 + Br2 → CH2BrCH2Br
Ethylene bromide is a additive in gasolines containing lead anti-engine knocking agents. It scavenges lead by forming volatile lead bromide, which is exhausted from the engine. This application has declined since the 1970's due to environmental regulations. Ethylene bromide is also used as a fumigant, but again this application is declining.
Brominated flame retardants represent a commodity of growing importance. Specific compound used produced for this purpose include tetrabromobisphenol A, decabromodiphenyl ether, and vinyl bromide.
The bromides of calcium, sodium, and zinc account for a sizable part of the bromine market. These salts form dense solutions in water that are used as drilling fluids.
Miscellaneous uses:
Several dyes, agrichemicals, and pharmaceuticals are organobromine compounds. 1-Bromo-3-chloropropane, 1-bromoethylbenzene, and 1-bromoalkanes are prepared by the antimarkovnikov addition of HBr to alkenes. Ethidium bromide, EtBr, is used as a DNA stain in gel electrophoresis.
Bromine is also used in for the production of brominated vegetable oil, which is used as an emulsifier in many citrus-flavored soft drinks.
High refractive index compounds
Water purification compounds, Disinfectants
Elemental bromine is toxic and causes burns. As an oxidizing agent, it is incompatible with most organic and inorganic compounds.
|
Fasting_plasma_glucose | Blood sugar is a term used to refer to the amount of glucose in the blood. Glucose, transported via the bloodstream, is the primary source of energy for the body's cells.
Blood sugar concentration, or glucose level, is tightly regulated in the human body. Normally, the blood glucose level is maintained between about 4 and 8 mmol/L (70 to 150 mg/dL). The total amount of glucose in the circulating blood is therefore about 3.3 to 7g (assuming an ordinary adult blood volume of 5 liters). Glucose levels rise after meals and are usually lowest in the morning, before the first meal of the day.
Failure to maintain blood glucose in the normal range leads to conditions of persistently high (hyperglycemia) or low (hypoglycemia) blood sugar. Diabetes mellitus, characterized by persistent hyperglycemia of several causes, is the most prominent disease related to failure of blood sugar regulation.
Though it is called "blood sugar" and sugars besides glucose are found in the blood, like fructose and galactose, only glucose levels are regulated via insulin and glucagon.
Glucose can be measured in whole blood, serum, or plasma. Historically, blood glucose values were given in terms of whole blood, but most laboratories now measure and report the serum glucose levels. Because RBC (erythrocytes) have a higher concentration of protein (i.e. hemoglobin) than serum, serum has a higher water content and consequently more dissolved glucose than does whole blood. To convert from whole-blood glucose, multiply the value by 1.15 to give the serum/plasma level.
Collection of blood in clot (red-top) tubes for serum chemistry analysis permits the metabolism of glucose in the sample by blood cells until separated by centrifugation. Higher than normal amounts of white or red blood cell counts can lead to excessive glycolysis in the sample with substantial reduction of glucose level if the sample is not processed quickly. Ambient temperature at which the blood sample is kept prior to centrifugation and separation of Plasma/Serum also affects glucose levels. At refrigerator temperatures, glucose remains relatively stable for several hours in the blood sample. At room temperature (25°Crevented by using Fluoride top (gray-top) as the anticoagulant of choice upon blood collection, as Fluoride inhibits glycolysis. However, this should only be used when blood will be transported from one hospital laboratory to another for glucose measurement. Red-top serum separator tubes also preserve glucose in samples once they have been centrifugated to isolate the serum from cells, this tube would be the most efficient. Particular care should be given to drawing blood samples from the arm opposite the one in which an intravenous line is inserted, to prevent contamination of the sample with intravenous fluids (IV). Alternatively, blood can be drawn from the same arm with an IV line after the IV was turned off for at least 5 minutes and the arm is elevated to drain the infused fluids away from the vein. As little as 10% contamination with 5% dextrose (D5W) will elevate glucose in a sample by 500mg/dl or more. Arterial, capillary and venous blood have comparable glucose levels in a fasting individual, whereas after meals venous levels are lower than capillary or arterial blood.
There are two different major methods that have been used to measure glucose. The older one is a chemical method that exploits the nonspecific reducing property of glucose in a reaction with an indicator substance that acquires or changes color on its reduction. Since other blood compounds also have reducing properties (e.g., urea, which can build up in uremic patients), this method can have erroneous measurements up to 5 to 15 mg/dl. This is solved by the Enzymatic methods that are highly specific for glucose. The two most common employed enzymes are glucose oxidase and hexokinase.
Fasting Blood Sugar or Glucose test (FBS)
Urine Glucose test
Two-hr Postprandial Blood Sugar Test (2-h PPBS)
Oral Glucose Tolerance test (OGTT)
Intravenous Glucose Tolerance test (IVGTT)
Glycosylated Hemoglobin (HbA1C)
Self-monitoring of Glucose level via Home Kits
The fasting blood glucoselities in the multiple control mechanism of glucosments after a standardized amount of oral glucose intake, is used to aid in the diagnosis of Diabetes.
If blood sugar levels drop too low, a potentially fatal condition called hypoglycemia develops. Symptoms may include lethargy, impaired mental functioning, irritability, and loss of consciousness.
If levels remain too high, appetite is suppressed over the short term. Long-term hyperglycemia causes many of the long-term health problems associated with diabetes, including eye, kidney, and nerve damage.
Some people report drowsiness or impaired cognitive function several hours after meals, which they believe is related to a drop in blood sugar, or "low blood sugar". For more information, see:
idiopathic postprandial s
Divide the mg/dL by 18 to get mmol/L (or multiply by 0.055).
Multiply the mmol/L by 18 to get mg/dL (or divide with 0.055).
John Bernard Henry, M.D.: Clinical diagnosis and Management by Laboratory Methods 20th edition, Saunders, Philadelphia, PA, 2001.
Ronald A. Sacher and Richard A. McPherson: Widmann's Clinical Interpretation of Laboratory Tests 11th edition, F.A. Davis Company, 2001.
Other medical conversions (Albumin, Protein, Creatinine, Creatinine clearance, Cholesterol, Lipid profile, Insulin, Etc..)
Lab Tests Online: Glucose
Alcohol and Blood Sugar |
Neuromeres | Neuromeres are transient segments during the early development of the human brain. Around the fifth week of biological development, there are 15 visible neuromeres.
Template:Development of nervous system
Template:WH
Template:WikiDoc Sources
|
Hashimoto%27s_disease | Diagnostic Criteria | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Medical Therapy | Surgery | Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
Template:WikiDoc Sources
|
Bite | A bite is a wound received from the mouth (and in particular, the teeth) of an animal or person. Most animal bites are from dogs or cats, and the pathogens in the wound are composed by the normal oral flora of the biting animal and human skin flora.
Animals may bite in self-defense, in an attempt to predate food, as well as part of normal interactions. Other bite attacks may be apparently unprovoked, especially in the case of bites committed by psychologically or emotionally disturbed humans. Some disorders such as Lesch-Nyhan syndrome may cause people to bite themselves.
Bite wounds can be very complex and it is important to address the following aspects:
Generalized tissue damage due to tearing and scratching.
Serious hemorrhage if major blood vessels are pierced.
Infection by bacteria or other pathogens, including rabies.
Introduction of venom into the wound by venomous animals such as some snakes.
Introduction of other irritants into the wound, causing inflammation and itching.
Almost every bite will have a polimicrobial contamination and some bites have characteristic pathogens associated to the oral flora of the animal that bit.
All bite wounds should be cleaned profusely with iodide soap and water.
Bites are contaminated by a polimicrobial flora and antibiotic prophylaxis treatment is recommended to avoid subsequent infection.
The route of administration depends on the depth and severity of the wound, as well as the time that has passed since the bite.
▸ Cunization, depends on the condition of the wound and the patient’s immunization history.
The following table summarizes the indications for tetanus prophylaxis.
Animal bites inflicted by carnivores (except rodents) are considered possible cases of rabies. The animal is caught alive or dead with its head preserved, so the head can later be analyzed to detect the disease.
If the animal lives for ten days and does not develop rabies, then it is probable that no rabies infection has occurred.
If the animal is gone, prophylactic rabies treatment is recommended.
Signs of animal rabies include:
Foaming at the mouth
Self-mutilation
Growling
Jerky behavior
Red eyes.
▸ Click on the following categories to expand prophylactic regimens.
Wash the wound thoroughly with soap and water.
Apply an antibiotic cream.
Cover the wound with a clean bandage.
See a healthcare provider if the woutrangely.
Apply pressure with a clean, dry cloth to stop the bleeding.
If you cannot stop the bleeding or you feel faint or weak, call 911 or your local emergency medical services immediately.
See a healthcare provider as soon as pos |
Cervical_Cancer_During_Pregnancy | cervix, including carcinoma in situ, during pregnancy, but colposcopy can be done to rule out invasive cancer. Patients with early stage (IA) disease may safely undergo fertility-sparing treatments. For patients with advanced disease, waiting for viability is generally not acceptable.The standard of care is curative intent chemotherapy and radiation therapy.
During pregnancy, no therapy is warranted for preinvasive lesions of the cervix, including carcinoma in situ, although expert colposcopy is recommended to exclude invasive cancer.
Treatment of cervical cancer in pregnancy is predicated on the extent of disease and the gestational age at diagnosis. Patients should undergo biopsy as needed and imaging to establish the extent of disease to make the most informed choices. The most appropriate imaging modality in pregnancy is magnetic resonance imaging, when indicated.
Pregnancy does not alter the course of cervical cancer. As a result, in certain cases, patients may elect to postpone treatment until its effects on the pregnancy are minimized. This may be considered for patients with the more common, and less aggressive histologic subtypes: squamous, adenocarcinoma, and adenosquamous. Patients with high-risk subtypes, such as small cell or neuroendocrine tumors, should be counseled toward immediate treatment despite the effects on the fetus, given their risk of progression.
Patients with early stage (IA) disease may safely undergo fertility-sparing treatments including cervical conization or radical trachelectomy, as indicated. The optimal timing for this procedure is in the second trimester, before viability. Some authors have suggested waiting until the completion of a pregnancy to initiate treatment.For patients with IA2 and IB disease such a delay may also be safe, but because of a risk of lymphatic spread, assessment of lymph-node status should first be ascertained. The status is best determined surgically via a laparoscopic or open lymph-node dissection, which can be safely performed up to approximately 20 weeks of pregnancy.In patients without lymphatic spread, waiting for fetal viability to initiate treatment is an option. Patients with positive lymph nodes should be counseled toward immediate treatment.
For patients with stage II or greater disease, waiting for viability is generally not acceptable.The standard of care is curative intent chemotherapy and radiation therapy. This treatment is toxic to the fetus and without ovarian transposition will render the ovaries nonfunctional after treatment. Evacuation of the fetus should be performed before the initiation of radiation. When this is not possible, the radiation will generally cause a spontaneous abortion 3 to 5 weeks after initiating treatment.
Neoadjuvant chemotherapy has been offered to patients with locally advanced disease as a way to initiate treatment while maintaining the pregnancy. Most chemotherapy agents can be initiated safely in the second trimester of pregnancy and beyond; mild growth restriction of the fetus is the most common side effect. Restriction of growth has been reported in a relatively small number of patients, and data is lacking on long-term outcomes for these women; as a result, this strategy should be considered with caution. Most of the patients in the reports underwent standard treatment (either surgery or radiation) after completion of the pregnancy.
|
Non_small_cell_lung_cancer_future_or_investigational_therapies | The KEYNOTE-024 trial used pembrolizumab (a monoclonal antibody against programmed death 1) in patients with advanced non-small cell lung cancer and PD-L1 expression. Pembrolizumab was associated with significantly longer progression-free and overall survival. The reported adverse events were lower than those of platinum-based chemotherapy.
Phase III, open-label, randomized clinical trial
Patients with untreated, advanced non-small cell lung cancer and PD-L1 expression
Pembrolizumab was associated with:
Significantly longer progression-free (10.3 months) and overall survival at 6 months (80.2%)
Low adverse events compared to platinum-based chemotherapy |
Neuroreceptor | The shapes and actions of receptors are commonly determined by X-ray crystallography and computer modelling. These methods have increased the current understanding of drug action at binding sites on the receptors.
Transmembrane receptor:E=extracellular space; I=intracellular space; P=plasma membrane
Receptors exist in different types, dependent on their ligand and function:
Some receptor proteins are peripheral membrane proteins;
Many hormone receptors and neurotransmitter receptors are transmembrane proteins: transmembrane receptors are embedded in the phospholipid bilayer of cell membranes, that allow the activation of signal transduction pathways in response to the activation by the binding molecule, or ligand. Metabotropic receptors are coupled to G proteins and affect the cell indirectly through enzymes which control ion channels. Ionotropic receptors contain a central pore which functions as a ligand-gated ion channel.
Another major class of receptors are intracellular proteins such as those for steroid and intracrine peptide hormone receptors. These receptors often can enter the cell nucleus and modulate gene expression in response to the activation by the ligand.
Ligand binding to a receptor is an equilibrium process: Ligands bind to an empty receptor and they dissociate from it (according to the law of mass action):
:<math>\left[\mathrm{Ligand}\right] \cdot \left[\mathrm{Receptor}\right]\;\;\overset{ K_d}{\rightleftharpoons}\;\;\left[\mbox{Ligand-receptor complex}\right]</math>
(the brackets stand for concentrations)
A measure of how well a certain molecule fits into a given receptor is the binding affinity which is measured as the dissociation constant Kd (good fit means high affinity and a low Kd). The activation of the second messenger cascade and the final biological response is achieved only when at a certain time point a significant number of receptors are activated by bound ligands.
If the receptor exists in two states (see this picture), then the ligand binding must account for these two receptor states. For a more detailed discussion of two-state binding, which is thought to occur as an activation mechanism in many receptors see this link.
Constitutive activity
Receptors which are active in the absence of a ligand. The constitutive activity of these receptors may be reversed by inverse agonist binding. Mutations in receptors that result in increased constitutive receptor signaling underlie some heritable diseases, such as precocious puberty (luteinizinverse agonists at dopamine receptors.
For the use of statistical mechanics in a quantitative study of the
ligand-receptor binding affinity, see the comprehensive article.
Not every ligand that binds to a receptor also activates the receptor. The following classes of ligands exist:
(Full) agonists are able to activate the receptor and result in a maximal biological response. Most natural ligands are full agonists
Partial agonists are not able to activate the receptor maximally, resulting in a partial biological response compared to a full agonist.
Antagonists bind to the receptor but do not activate it. This results in a receptor blockade that inhibits the binding of agonists.
Inverse agonists are antagonists that are able to further reduce the receptor activation by decreasing its basal activity
Template:Seealso
Main article: Transmembrane receptor
Main article: Metabotropic receptor
Main article: G protein-coupled receptor
These receptors are also known as seven transmembrane receptors or 7TM receptors.
Muscarinic acetylcholine receptor (Acetylcholine and Muscarine)
Adenosine receptors (Adenosine)
Adrenoceptors (also known as Adrenergic receptors, for adrenaline, and other structurally related hormones and drugs)
GABA receptors, Type-B (γ-Aminobutyric acid or GABA)
Angiotensin receptors (Angiotensin)
Cannabinoid receptors (Cannabinoids)
Cholecystokinin receptors (Cholecystokinin)
Dopamine receptors (Dopamine)
Glucagon receptors (Glucagon)
Metabotropic glutamate receptors (Glutamate)
Histamine receptors (Histamine)
Olfactory receptors (for the sense of smell)
Opioid receptors (Opioids)
Rhodopsin (a photoreceptor)
Secretin receptors (Secretin)
Serotonin receptors, except Type-3 (Serotonin, also known as 5-Hydroxytryptamine or 5-HT)
Somatostatin receptors (Somatostatin)
Calcium-sensing receptor (Calcium)
Chemokine receptors (Chemokines)
many more ...
Main article: Receptor tyrosine kinase
These receptors detect ligands and propagate signals via the tyrosine kinase of their intracellular domains.
This family of receptors includes;
Erythropoietin receptor (Erythropoietin)
Insulin receptor (Insulin)
Eph receptors
Insulin-like growth faic peptide (ANP) and other natriuretic peptides
GC-C: Guanylin receptor
Ionotropic receptors are heteromeric or homomeric oligomers . They are receptors that respond to extracellular ligands and receptors that respond to intracellular ligands.
The entire repertoire of human plasma membrane receptors is listed at the Human Plasma Membrane Receptome (http://receptome.stanford.edu).
Main article: Intracellular receptor
nuclear receptor: Steroid hormone receptor
Ionotropic receptors (IP3 receptor above)
sigma1 (neurosteroids)
G protein-coupled receptors
Many genetic disorders involve hereditary defects in receptor genes. Often, it is hard to determine whether the receptor is nonfunctional or the hormone is produced at decreased level; this gives rise to the "pseudo-hypo-" group of endocrine disorders, where there appears to be a decreased hormonal level while in fact it is the receptor that is not responding sufficiently to the hormone.
Cells can increasecepto that receptor for a stimulus. Receptor desensitization results in altered affinity for the ligand. Receptor desensitization can modeled by a two-state model that also predicts that antagonists combined with agonists can prevent receptor desensitization See this link [2] for detailed molecular description
Desensitation may be accomplished by
Receptor phosphorylation.
Uncoupling of receptor effector molecules.
Receptor sequestration (internalization).
Main article: Immune receptor
The main receptors in the immune system are pattern recognition receptors (PRRs), Toll-like receptors (TLRs), killer activated and killer inhibitor receptors (KARs and KIRs), complement receptors, Fc receptors, B cell receptors and T cell receptors.
vteTransmembrane receptors: immunoglobulin superfamily immune receptorsAntibody receptor:Fc receptorEpsilon (ε)
FcεRI
(FcεRII is C-type lectin)
Gamma (γ)
FcγRI
FcγRII
FcγRIII
Neonatal
Alpha (α)/mu (μ)
FcαRI
Fcα/μR
Secretory
Polymeric immunoglobulin receptor
Antigen receptorB cellsAntigen receptor
BCR
Co-receptorstimulate:
CD21/CD19/CD81
inhibit:
CD22
Accessory molecules
Ig-α/Ig-β (CD79)
T cellsLigands
MHC
MHC class I
MHC class II
Antigen receptor
TCR: TRA@
TRB@
TRD@
TRG@
Co-receptors
CD8 (with two glycoprotein chains CD8α anr
see cytokine receptors
Killer-cell IG-like receptors
KIR2DL1
KIR2DL2
KIR2DL3
KIR2DL4
KIR2DL5A
KIR2DL5B
KIR2DS1
KIR2DS2
KIR2DS3
KIR2DS4
KIR2DS5
KIR3DL1
KIR3DL2
KIR3DL3
KIR3DS1
Leukocyte IG-like receptors
LILRA1
LILRA2
LILRA3
LILRA4
LILRA5
LILRA6
LILRB1
LILRB2
LILRB3
LILRB4
LILRB5
LILRA6
LILRA5
Signal transduction
Neuropsychopharmacology
Schild regression for ligand receptor inhibition
Ki Database |
Zika_virus_infection_other_diagnostic_studies | There are no other diagnostic studies associated with Zika virus infection.
There are no other diagnostic studies associated with Zika virus infectio |
Brain_abscess_MRI | Magnetic resonance imaging (MRI) is the diagnostic procedure of choice to diagnose a brain abscess.
MRI scans appear more sensitive than CT for detecting cerebral edema and early changes correlated to a brain abscess. It can stage the abscess and gauge the respe with a MRI scan.
T1-weighted images are similar to CT, with a central hypodense signal and surrounding ring-enhancement.
T2-weighted images reveal a central hyperintense area surrounded by a well-defined hypointense capsule with surrounding edema.
(Images courtesy of RadsWiki)
, , Brain abscess,
, , Brain abscess,
, , Brain abscess,
, , Brain abscess,
, , Brain abscess,
, , Brain abscess,
, , Brain abscess,
, , Brain abscess,
, , Brain abscess,
, , Brain abscess, |
Concussion_history_and_symptoms | Common symptoms in MTBI include headache and difficulty concentrating.
Concussion can be associated with a variety of symptoms, which typically occur rapidly after the injury. Early symptoms usually subside within days or weeks. The number and type of symptoms a person suffers varies widely.
Concussion may be under-diagnosed. The lack of the highly noticeable signs and symptoms that are frequently present in ot to remain in the competition. A retrospective survey in 2005 found that more than 88% of concussions go unreon botsleeping patterns and difficulty with reasoning, concentrating, and performing everyday activities.
Affective results of concussion include crankiness, loss of interest in favorite activities or items, tearfulness, and displays of emotion that are inappropriate to the situation. Common symptoms in concussed children include restlessness, lethargy, and irritability.
|
Pulmonary_valve_stenosis_overview | Pulmonary valve stenosis is a valvular heart disease in which outflow of blood from the right ventricle of the heart is obstructed at the level of the pulmonic valve
This results in the reduction of flow of blood to the lungs |
Extranodal_NK-T-cell_lymphoma_Xray | X-rays graphy of patients with extranodal NK/T cell lymphoma is not very usefull in order of diagnosis. Radiography show non-specific tumor changes.
Relapse of extranodal NK/T cell lymphoma causes lymphadenopathy which can be detected by X-rays.
In some rare cases, mediastinal metastasis is reported.
To view findings on biopsy characteristics of each morphological variant of extranodal NK-T-cell lymphoma, click here.
Blunting of costophrenic angle, not specific sign fore existing tumor. |
Croup | History and Symptoms | Physical Examination | Laboratory Findings | X Ray | Other Diagnostic Studies
Medical Therapy | Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case #1
Template:Respiratory pathology
Template:WH
Template:WS
|
Vascular_injury | Hard signs of vascular injury: expanding hematoma, bruit, thrill, active bleeding, severely ischemic extremity.
Soft signs of vascular injury: proximity of wound to major vessels, hx of hemorrhage/shock, non-expanding hematoma, diminished pulse and anatomically related nerve injury.
Prep contralateral saphenous vein in field, direct pressure (DP) to control bleeding (tourniquet only if DP fails).
Duplex scan when available.
Observe for evidence of compartment syndrome, change in vascular status. Ensure at least one follow-up vascular examination is performed.
Injured extremity to non-injured extremity systolic Doppler pressure ratio:
With the patient supine the patient’s leg just above the maleoli, and the Doppler probe at 45 degrees to the dorsal pedis or posterior tibial artery.
Inflate the cuff until the Doppler signal stops. Slowly deflate the cuff until the signal returns and record the numbers as the ankle systolic pressure.
To get the ABI ratio, divide the highest ankle pressure by the highest brachial pressure. For example, with systolic brachial pressures of 120 and 129 and an ankle systolic of 65, the ABI is 0.5. Perform on both right and left extremities. Farther from the heart, leg pressure is supposed to be higher than or at least equal to arm pressure. Interpret your ABI results based on these guidelines:
0.9: Normal
0.5 to 0.9: Claudication mild to moderate
< 0.5: Resting ischemic pain, claudication
< 0.2: Gangrenous extremity; suggests near total occlusion
It is important to know the patients total trauma burden and physiology when deciding how to manage their vascular injury
Surgeons should become familiar with the key anatomical landmarks for several vascular exposures but different than dealing with vascular disease in the elderly
Get proximal control outside of the hematoma / one level above the injury
Once controlled, define the full extent of the vascular injury
Gradually develop and optimize your work space so your hands are free to work
Decide between complex vascular repair and damage control
The safest place when dissecting out arteries is in the periadvential plane immediately next to the artery.
When performing vascular trauma systemic anticoagulation is not always possible if the patient has multisystem injuries, in these cases consider local heparinized saline infusion (10 units heparin in 1000 cc of normal saline), proximally and distally
Clear the inflow and outflow tracts before performing vascular repair or shunt insertion, using an appropriately sized Fogarty balloon embolectomy catheter, generally #5 for large arteries and #3 for small ones
Do not pass embolectomy catheters too much, you will be rewarded with intense vasospasm and worse outcomes
Healthy traumatized arteries often exhibit intense vasospasm when manipulated, this may effect post reoverall condition allows.
Completion arteriography is not always possible but some form of assessm not anfor problematic distal control
Bleeding and ischemia are different priorities
Balloon tamponade controls external bleeding in transition zones
Intra-arterial shunts are good damage control options in unstable patients, this can be accomplished using Rummel tourniquets and either internal shunts (Argyle) or external shunts (Javid)
External shunts that are placed entirely m / leg still dies
General Principles
If possible try to get a baseline neurologic exam in your patient, this is one of the best predictors in the outcome of carotid trauma
Zone IIIascular injury
Zone II (betwsternocleidomastoid muscle
Identify the facial vein, and divide it this marks the bifurcation of the carotid artery, retract the internal jugular posteriorly using a self retaining retractor
After fixing vascular injuries in this zone, have high index of suspicion and assess for esophageal and tracheal injuries
Internal Jugular Vein
Injuries to the internal jugular vein can be repaired with lateral venorraphy or ligated.
Common Carotid artery
Obtain proximal control outside of the hematoma at the base of the neck using a Rummel tourniquet on the CCA being careful not to ensnare the vagus nerve
If possible obtain distal CCA control proximal to the CCA bifurcation, with this technique no shunt is needed
Repair injury using lateral arterrioraphy, patch angioplasty, end to end anastomosis or bypass
If patient is in extremis the CCA may be ligated with a low incidence of stroke due to the perfusion of the ICA from the intact ECA
External Carotid artery
Injuries to the ECA may be repaired using standard techniques or ligated since this is usually well tolerated
Internal carotid artery
Injuries to the ICA should be repaired if at all possible, while ligation is possible the incidence of stroke is considerable
If there is poor inflow from the injured carotid, carefully pass a #3 Fogarty balloon embolectomy catheter no more than 2-3cm past the bifurcation to retrieve any thrombus
If there is still no inflow from the ICA, ligation may be your best answer (this is a controversial point)
ICA injuries with segmental loss may be repaired using RGSV interposition graft or ECA transposition
If the injury is to the high internal carotid artery exposure is facilitated by nasotracheal intubation, division of the omohyoid muscle, the descendans hypoglossal nerve or mandibular subluxation.
In the case of a distal carotid injury that is too high for reconstruction then ligation is appropriate
In the case of a distal ICA lesion that you cannrteryepair intrathoracic CCA injury
General Principlthe Innominate artery and continue north
Be careful not to injure the right vagus nerve as it runs in front of the right subclavian artery
When ing do not explore
Expose through Kocher or Catell-Braasch maneuver
Insert Deaver over inferior surface of liver and tow in to give exposure and compress suprarenal IVC
Mobilize the right kidney and divide the left renal vein to improve exposure to this portion of the cava
Do your best to perform lateral repair of suprarenal IVC
Bail outs include packing or ligation
Infrarenal IVC
Is associated with central hematoma that is inframesocolic
Expose through Catell-Braasch maneuver
When unroofing this hematoma prepare for big trouble by getting anesthesia ready for blood loss
Unroof the hematoma and compress theitation if patient too unstably and return later for femoral – femoral bypass
Don’t chase a bleeder into the psoas muscle, these may result from ascending lumbar artery or vein which will be difficult to control if dhe |
Focal_segmental_glomerulosclerosis_history_and_symptoms | The hallmark of focal segmental glomerulosclerosis is nephrotic-range proteinuria.
Patients with focal segmental glomerulosclerosis may have a positive history of:
Positive family history of FSGN
Heroin abuse
Chronic viral infections such as hepatitis B
Medications such as bisphosphonates, sunitinib, and interferon
Common symptoms of focal segmental glomerulosclerosis include:
Proteinuria
Hematuria
Anasarca
Headache and blurry vision which is suggestive of high blood pressure
Less common symptoms of focal segmental glomerulosclerosis include
Fatigue
Malaise
Symptoms of chronic renal failure such as anuria, edema |
Subsets and Splits