Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Drugs in systemic circulation have a certain concentration in the blood, which serves as a surrogate marker for how much drug will be delivered throughout the body (how much drug the rest of the body will "see"). There exists a minimum concentration of drug within the blood that will give rise to the intended therapeutic effect (minimum effective concentration, MEC), as well as a minimum concentration of drug that will give rise to an unintended adverse drug event (minimum toxic concentration, MTC). The difference between these two values is generally referred to as the therapeutic window. Different drugs have different therapeutic windows, and different people will have different MECs and MTCs for a given drug. If someone has a very low MTC for a drug, they are likely to experience adverse effects at drug concentrations lower than what it would take to produce the same adverse effects in the general populace; thus, the individual will experience significant toxicity at a dose that is otherwise considered "normal" for the average person. This individual will be considered "intolerant" to that drug.
There are a variety of factors that can affect the MTC, which is often the subject of clinical pharmacokinetics. Variations in MTC can occur at any point in the ADME (absorption, distribution, metabolism, and excretion) process. For example, a patient could possess a genetic defect in a drug metabolizing enzyme in the cytochrome P450 superfamily. While most individuals will possess the effective metabolizing machinery, a person with a defect will have a difficult time trying to clear the drug from their system. Thus, the drug will accumulate within the blood to higher-than-expected concentrations, reaching a MTC at a dose that would otherwise be considered normal for the average person. In other words, in a person that is intolerant to a medication, it is possible for a dose of 10 mg to "feel" like a dose of 100 mg, resulting in an overdose—a "normal" dose can be a "toxic" dose in these individuals, leading to clinically significant effects.
There is also an aspect of drug intolerance that is subjective. Just as different people have different pain tolerances, so too do people have different tolerances for dealing with the adverse effects from their medications. For example, while opioid-induced constipation may be tolerable to some individuals, other people may stop taking an opioid due to the unpleasantness of the constipation even if it brings them significant pain relief.
Intolerance to analgesics, particularly NSAIDs, is relatively common. It is thought that a variation in the metabolism of arachidonic acid is responsible for the intolerance. Symptoms include chronic rhinosinusitis with nasal polyps, asthma, gastrointestinal ulcers, angioedema, and urticaria.
The prognosis of children diagnosed with intolerance to milk is good: patients respond to diet which excludes cow's milk protein and the majority of patients succeed in forming tolerance. Children with non-IgE-mediated cows milk intolerance have a good prognosis, whereas children with IgE-mediated cows milk allergy in early childhood have a significantly increased risk for persistent allergy, development of other food allergies, asthma and rhinoconjunctivitis.
A study has demonstrated that identifying and appropriately addressing food sensitivity in IBS patients not previously responding to standard therapy results in a sustained clinical improvement and increased overall well being and quality of life.
Depending on whether the salicylate is a component of food or medicine, salicylate intolerance is a form of food intolerance or of drug intolerance.
Salicylate sensitivity is a pharmacological reaction, not a true IgE-mediated allergy. However, it is possible for aspirin to trigger non-allergic hypersensitivity reactions. About 5–10% of asthmatics have aspirin hypersensitivity, but dietary salicylates have been shown not to contribute to this. The reactions in AERD (Samter's triad) are due to inhibition of the COX-1 enzyme by aspirin, as well as other NSAIDs that are not salicylates. Dietary salicylates have not been shown to significantly affect COX-1.
Samter's triad refers to aspirin sensitivity in conjunction with nasal polyps and asthma.
An important salicylate drug is aspirin, which has a long history. Aspirin intolerance was widely known by 1975, when the understanding began to emerge that it is a pharmacological reaction, not an allergy.
A Low FODMAP diet now has an evidence base sufficiently strong to recommend its widespread application in conditions such as IBS and IBD. Restriction of Fermentable Oligo-, Di- and Mono-
saccharides and Polyols globally, rather than individually, controls the symptoms of functional gut disorders (e.g. IBS), and the majority of IBD patients respond just as well. It is more successful than restricting only Fructose and Fructans, which are also FODMAPs, as is recommended for those with Fructose malabsorption. Longer term compliance with the diet was high.
A randomised controlled trial on IBS patients found relaxing an IgG-mediated food intolerance diet led to a 24% greater deterioration in symptoms compared to those on the elimination diet and concluded food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.
Intestinal or bowel hyperpermeability, so called leaky gut, has been linked to food allergies and some food intolerances. Research is currently focussing on specific conditions and effects of certain food constituents. At present there are a number of ways to limit the increased permeability, but additional studies are required to assess if this approach reduces the prevalence and severity of specific conditions.
Risk factors for drug allergies can be attributed to the drug itself or the characteristics of the patient. Drug-specific risk factors include the dose, route of administration, duration of treatment, repetitive exposure to the drug, and concurrent illnesses. Host risk factors include age, sex, atopy, specific genetic polymorphisms, and inherent predisposition to react to multiple unrelated drugs (multiple drug allergy syndrome).
A drug allergy is more likely to develop with large doses and extended exposure.
Milk allergy typically presents in the first year of life. The majority of children outgrow milk allergy by the age of ten years. One large clinical trial reported resolutions of 19% by age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by 16 years. Children are be able to tolerate milk as an ingredient in baked goods relative to liquid milk. Resolution was more likely if baseline serum IgE was lower, or if IgE-mediated allergy was absent so that all that was present was cell-mediated, non-IgE allergy.
People with confirmed cow's milk allergy may also demonstrate an allergic response to beef, moreso to rare beef versus well-cooked beef. The offending protein appears to be bovine serum albumin. This is not the same beef allergy that is seen primarily in the southeastern United States, triggered by being bitten by a Lone Star tick.
Milk allergy has consequences. In a U.S. government diet and health surveys conducted in 2007-2010, 6,189 children ages 2-17 years were assessed. For those classified as cow's milk allergic at the time of the survey, mean weight, height and body-mass index were significantly lower than their non-allergic peers. This was not true for children with other food allergies. Diet assessment showed a significant 23% reduction of calcium intake and near-significant trends for lower vitamin D and total calorie intake.
When a medication causes an allergic reaction, it is called an allergen. The following is a short list of the most common drug allergens:
- Antibiotics
- Penicillin
- Sulfa drugs
- Tetracycline
- Analgesics
- Codeine
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Antiseizure
- Phenytoin
- Carbamazepine
Symptoms of OI are triggered by the following:
- An upright posture for long periods of time (e.g. standing in line, standing in a shower, or even sitting at a desk).
- A warm environment (such as in hot summer weather, a hot crowded room, a hot shower or bath, after exercise).
- Emotionally stressful events (seeing blood or gory scenes, being scared or anxious).
- Astronauts returning from space not yet re-adapted to gravity.
- Extended bedrest
- Inadequate fluid and salt intake.
Incidence and prevalence are terms commonly used in describing disease epidemiology. Incidence is newly diagnosed cases, which can be expressed as new cases per year per million people. Prevalence is the number of cases alive, expressible as existing cases per million people during a period of time. Milk allergies are usually observed in infants and young children, and often disappear with age (see Prognosis), so prevalence of egg allergy may be expressed as a percentage of children under a set age. Milk allergy affects between 2% and 3% of infants in developed countries. This estimate is for antibody-based allergy; prevalence of allergy based on cellular immunity is unknown.
For all age groups, a review of fifty studies conducted in Europe estimated 6.0% for self-reported milk allergy and 0.6% for confirmed. National survey data in the United States collected 2005-2006 showed that from age six and older, the prevalence of serum IgE confirmed milk allergy was under 0.4%.
Overall, about 65% of people experience some form of lactose intolerance as they age past infancy, but there are significant differences between populations and regions, with rates as low as 5% among Northern Europeans and as high as more than 90% of adults in some communities of Asia.
Some populations, from an evolutionary perspective, have a better genetic makeup for tolerating lactose than others. In Northern European countries, lack of Vitamin D from the sun is balanced by intaking more milk and calcium. These countries have built up tolerance to lactose. Oppositely, regions of the south, Africa for example, rarely experienced Vitamin D deficiency and therefore tolerance from milk consumption did not develop the same way as in Northern European countries. Different populations will present certain gene constructs depending on the evolutionary and cultural pre-settings of the geographical region.
The principal symptom of lactose intolerance is an adverse reaction to products containing lactose (primarily milk), including abdominal bloating and cramps, flatulence, diarrhea, nausea, borborygmi, and vomiting (particularly in adolescents). These appear one-half to two hours after consumption. The severity of symptoms typically increases with the amount of lactose consumed; most lactose-intolerant people can tolerate a certain level of lactose in their diets without ill effects.
A pseudoallergy is a condition named for its similar presentation to a true allergy, though due to different causes.
It may be due to alterations in the metabolism of histamine.
It can be the cause of some forms of food intolerance.
Orthostatic intolerance is divided, roughly based on patient history, in two variants: acute and chronic.
For those allergic to fruits, cooking may help reduce or eliminate the reaction to some fruits.
People with this allergy might not necessarily be allergic to citrus fruits.
FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) that are present in gluten-containing grains have recently been identified as a possible cause of gastrointestinal symptoms in people with NCGS, in place of, or in addition to, gluten. FODMAPs cause mild wheat intolerance mainly limited to gastrointestinal symptoms.
Chronic diarrhea of infancy, also called toddler's diarrhea, is a common condition typically affecting children between ages 6–30 months, usually resolving by age 4. Symptoms include multiple loose bowel movements per day, sometimes with undigested food visible; normal growth with no evidence of malnutrition; and no evidence blood in the stool or infection. The condition may be related to irritable bowel syndrome.
Proper nutrition is important for health and functioning, including the prevention of infectious diarrhea. It is especially important to young children who do not have a fully developed immune system. Zinc deficiency, a condition often found in children in developing countries can, even in mild cases, have a significant impact on the development and proper functioning of the human immune system. Indeed, this relationship between zinc deficiency and reduced immune functioning corresponds with an increased severity of infectious diarrhea. Children who have lowered levels of zinc have a greater number of instances of diarrhea, severe diarrhea, and diarrhea associated with fever. Similarly, vitamin A deficiency can cause an increase in the severity of diarrheal episodes. However, there is some discrepancy when it comes to the impact of vitamin A deficiency on the rate of disease. While some argue that a relationship does not exist between the rate of disease and vitamin A status, others suggest an increase in the rate associated with deficiency. Given that estimates suggest 127 million preschool children worldwide are vitamin A deficient, this population has the potential for increased risk of disease contraction.
The pathogenesis of NCGS is not yet well understood. It was hypothesized that gluten, as occurs in celiac disease, is the cause of NCGS. Besides gluten, other components in wheat, rye, barley, and their derivatives, including amylasetrypsin inhibitors (ATIs) and FODMAPs, may cause symptoms.
Alcohol intolerance is due to a genetic deficiency of the enzyme alcohol dehydrogenase, the enzyme that metabolises ingested alcohol. It can also be an effect or side effect associated with certain drugs such as disulfiram, metronidazole, or nilutamide. It is characterized as intolerance of and unpleasant symptoms upon the ingestion of alcohol, causing hangover symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or chronic fatigue syndrome.
If people are intolerant, some nearly non-alcoholic beverages may be a problem, similar to alcohol-containing medications, vinegar, inhalation of alcohol or the vapour of alcohol-containing cleaning agents.
Drinking alcohol first or afterwards together with Calcium cyanamide, an inorganic compound used as a fertilizer, can cause permanent or long lasting intolerance (nitrolime disease), contributing together with other substances to the accumulation of harmful Acetaldehyde by inhibiting the enzyme acetaldehyde dehydrogenase.
One of the most common causes of infectious diarrhea, is a lack of clean water. Often, improper fecal disposal leads to contamination of groundwater. This can lead to widespread infection among a population, especially in the absence of water filtration or purification. Human feces contains a variety of potentially harmful human pathogens.
Histamine intolerance, sometimes called histaminosis, is an over-accumulation of histamine in the human body. Histamine intolerance is sometimes informally called an allergy; however, the intolerance is technically caused by the gradual accumulation of extracellular histamine due to an imbalance.
Roughly 1% of the population suffers from histamine intolerance; of those, 80% are middle-aged.
Treatment is primarily through diet. Dietary fiber and fat can be increased and fluid intake, especially fruit juice intake, decreased. With these considerations, the patient should consume a normal balanced diet to avoid malnutrition or growth restriction. Medications such as loperamide should not be used. Studies have shown that certain probiotic preparations such as "Lactobacillus rhamnosus" (a bacterium) and "Saccharomyces boulardii" (a yeast) may be effective at reducing symptoms.
There are many different types of fruits that people have been shown to react allergically such as mangoes and bananas. Some foods are clearly more allergenic than others. In adults, peanuts, tree nuts, finned fish, crustaceans, fruit, and vegetables account for 85% of the food-allergic reactions(O'Neil, Zanovec and Nickla).
People suffering from allergies may suffer from a hypersensitivity to the allergic food, which is what causes the allergic reaction. Most fruit allergies are oral syndrome allergies because they are consumed but may also be an external allergy if the fruit touches the skin.