<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Trichinosis and explain in detail? [/INST] Trichinosis, also known as trichinellosis, is a parasitic disease caused by roundworms of the Trichinella type. During the initial infection, invasion of the intestines can result in diarrhea, abdominal pain, and vomiting. Migration of larvae to muscle, which occurs about a week after being infected, can cause swelling of the face, inflammation of the whites of the eyes, fever, muscle pains, and a rash. Minor infection may be without symptoms. Complications may include inflammation of heart muscle, central nervous system involvement, and inflammation of the lungs.Trichinosis is mainly spread when undercooked meat containing Trichinella cysts is eaten. In North America this is most often bear, but infection can also occur from pork, boar, and dog meat. Several species of Trichinella can cause disease, with T. spiralis being the most common. After being eaten, the larvae are released from their cysts in the stomach. They then invade the wall of the small intestine, where they develop into adult worms. After one week, the females release new larvae that migrate to voluntarily controlled muscles, where they form cysts. The diagnosis is usually based on symptoms and confirmed by finding specific antibodies in the blood, or larvae on tissue biopsy.The best way to prevent trichinosis is to fully cook meat. A food thermometer can verify that the temperature inside the meat is high enough. Infection is typically treated with antiparasitic medication such as albendazole or mebendazole. Rapid treatment may kill adult worms and thereby stop further worsening of symptoms. Both medications are considered safe, but have been associated with side effects such as bone marrow suppression. Their use during pregnancy or in children under the age of 2 years is poorly studied, but appears to be safe. Treatment with steroids is sometimes also required in severe cases. Without treatment, symptoms typically resolve within three months.Worldwide, about 10,000 infections occur a year. At least 55 countries including the United States, China, Argentina, and Russia have had recently documented cases. While the disease occurs in the tropics, it is less common there. Rates of trichinosis in the United States have decreased from about 400 cases per year in the 1940s to 20 or fewer per year in the 2000s. The risk of death from infection is low.

Signs and symptoms
The great majority of trichinosis infections have either minor or no symptoms and no complications. The two main phases for the infection are enteral (affecting the intestines) and parenteral (outside the intestines). The symptoms vary depending on the phase, species of Trichinella, quantity of encysted larvae ingested, age, sex, and host immunity.

Enteral phase
A large burden of adult worms in the intestines promotes symptoms such as nausea, heartburn, dyspepsia, and diarrhea from two to seven days after infection, while small worm burdens generally are asymptomatic. Eosinophilia presents early and increases rapidly.

Parenteral phase
The severity of symptoms caused by larval migration from the intestines depends on the number of larvae produced. As the larvae migrate through tissue and vessels, the bodys inflammatory response results in edema, muscle pain, fever, and weakness. A classic sign of trichinosis is periorbital edema, swelling around the eyes, which may be caused by vasculitis. Splinter hemorrhage in the nails is also a common symptom.They may very rarely cause enough damage to produce serious neurological deficits (such as ataxia or respiratory paralysis) from worms entering the central nervous system (CNS), which is compromised by trichinosis in 10–24% of reported cases of cerebral venous sinus thrombosis, a very rare form of stroke (three or four cases per million annual incidence in adults). Trichinosis can be fatal depending on the severity of the infection; death can occur 4–6 weeks after the infection, and is usually caused by myocarditis, encephalitis, or pneumonia.

Cause
The classical agent is T. spiralis (found worldwide in many carnivorous and omnivorous animals, both domestic and sylvatic (wild), but seven primarily sylvatic species of Trichinella also are now recognized:

Species and characteristics
T. spiralis is most adapted to swine, most pathogenic in humans, and is cosmopolitan in distribution.
T. britovi is the second-most common species to infect humans; it is distributed throughout Europe, Asia, and northern and western Africa, usually in wild carnivores, crocodiles, birds, wild boar, and domesticated pigs.
T. murrelli also infects humans, especially from black bear meat; it is distributed among wild carnivores in North America.
T. nativa, which has a high resistance to freezing, is found in the Arctic and subarctic regions; reservoir hosts include polar bears, Arctic foxes, walruses, and other wild game.
T. nelsoni, found in East African predators and scavengers, has been documented to cause a few human cases.
T. papuae infects both mammals and reptiles, including crocodiles, humans, and wild and domestic pigs; this species, found in Papua New Guinea and Thailand, is also nonencapsulated.
T. pseudospiralis infects birds and mammals, and has demonstrated infection in humans; it is a nonencapsulated species.
T. zimbabwensis can infect mammals, and possibly humans; this nonencapsulated species was detected in crocodiles in Africa.

Taxonomy
Kingdom: Animalia
Phylum: Nematoda
Class: Adenophorea
Order: Trichurida
Family: Trichinellidae
Genus: Trichinella

Lifecycle
The typical lifecycle for T. spiralis involves humans, pigs, and rodents. A pig becomes infected when it eats infectious cysts in raw meat, often porcine carrion or a rat (sylvatic cycle). A human becomes infected by consuming raw or undercooked infected pork (domestic cycle). In the stomach, the cysts from infected undercooked meat are acted on by pepsin and hydrochloric acid, which help release the larvae from the cysts into the stomach. The larvae then migrate to the small intestine, and burrow into the intestinal mucosa, where they molt four times before becoming adults.Thirty to 34 hours after the cysts were originally ingested, the adults mate, and within five days produce larvae. Adult worms can only reproduce for a limited time, because the immune system eventually expels them from the small intestine. The larvae then use their piercing mouthpart, called the "stylet", to pass through the intestinal mucosa and enter the lymphatic vessels, and then enter the bloodstream.The larvae travel by capillaries to various organs, such as the retina, myocardium, or lymph nodes; however, only larvae that migrate to skeletal muscle cells survive and encyst. The larval host cell becomes a nurse cell, in which the larva will be encapsulated, potentially for the life of the host, waiting for the host to be eaten. The development of a capillary network around the nurse cell completes encystation of the larva. Trichinosis is not soil-transmitted, as the parasite does not lay eggs, nor can it survive long outside a host.

Diagnosis
Diagnosis of trichinosis is confirmed by a combination of exposure history, clinical diagnosis, and laboratory testing.

Exposure history
An epidemiological investigation can be done to determine a patients exposure to raw infected meat. Often, an infection arises from home-preparation of contaminated meat, in which case microscopy of the meat may be used to determine the infection. Exposure determination does not have to be directly from a laboratory-confirmed infected animal. Indirect exposure criteria include the consumption of products from a laboratory-confirmed infected animal, or sharing of a common exposure with a laboratory-confirmed infected human.

Clinical diagnosis
Clinical presentation of the common trichinosis symptoms may also suggest infection. These symptoms include eye puffiness, splinter hemorrhage, nonspecific gastroenteritis, and muscle pain. The case definition for trichinosis at the European Center for Disease Control states, "at least three of the following six: fever, muscle soreness and pain, gastrointestinal symptoms, facial edema, eosinophilia, and subconjunctival, subungual, and retinal hemorrhages."

Laboratory testing
Blood tests and microscopy can be used to aid in the diagnosis of trichinosis. Blood tests include a complete blood count for eosinophilia, creatine phosphokinase activity, and various immunoassays such as ELISA for larval antigens.

Prevention
Legislation
Laws and rules for food producers may improve food safety for consumers, such as the rules established by the European Commission for inspections, rodent control, and improved hygiene. A similar protocol exists in the United States, in the USDA guidelines for farms and slaughterhouse responsibilities in inspecting pork.

Education and training
Public education about the dangers of consuming raw and undercooked meat, especially pork, may reduce infection rates. Hunters are also an at-risk population due to their contact and consumption of wild game, including bear. As such, many states, such as New York, require the completion of a course in such matters before a hunting license can be obtained.

Meat testing
Testing methods are available for both individual carcasses and monitoring of the herds. Artificial digestion method is usually used for the testing of individual carcasses, while the testing for specific antibodies is usually used for herd monitoring.

Food preparation
Larvae may be killed by the heating or irradiation of raw meat. Freezing is normally only effective for T. spiralis, since other species, such as T. nativa, are freeze-resistant and can survive long-term freezing.
All meat (including pork) can be safely prepared by cooking to an internal temperature of 165 °F (74 °C) or higher for 15 seconds or more.
Wild game: Wild game meat must be cooked thoroughly (see meat preparation above) Freezing wild game does not kill all trichinosis larval worms, because the worm species that typically infests wild game can resist freezing.
Pork: Freezing cuts of pork less than 6 inches thick for 20 days at 5 °F (−15 °C) or three days at −4 °F (−20 °C) kills T. spiralis larval worms; but this will not kill other trichinosis larval worm species, such as T. nativa, if they have infested the pork food supply (which is unlikely, due to geography).Pork can be safely cooked to a slightly lower temperature, provided that the internal meat temperature is at least as hot for at least as long as listed in the USDA table below. Nonetheless, allowing a margin of error for variation in internal temperature within a particular cut of pork, which may have bones that affect temperature uniformity, is prudent. In addition, kitchen thermometers have measurement error that must be considered. Pork may be cooked for significantly longer and at a higher uniform internal temperature than listed below to be safe.
Unsafe and unreliable methods of cooking meat include the use of microwave ovens, curing, drying, and smoking, as these methods are difficult to standardize and control.

Pig farming
Incidence of infection can be reduced by:
Keeping pigs in clean pens, with floors that can be washed (such as concrete)
Not allowing hogs to eat carcasses of other animals, including rats, which may be infected with Trichinella
Cleaning meat grinders thoroughly when preparing ground meats
Control and destruction of meat containing trichinae, e.g., removal and proper disposal of porcine diaphragms prior to public sale of meatThe US Centers for Disease Control and Prevention  make the following recommendation: "Curing (salting), drying, smoking, or microwaving meat does not consistently kill infective worms."
However, under controlled commercial food processing conditions, some of these methods are considered effective by the USDA.The USDA Animal and Plant Health Inspection Service (APHIS) is responsible for the regulations concerning the importation of swine from foreign countries. The Foreign Origin Meat and Meat Products, Swine section covers swine meat (cooked, cured and dried, and fresh). APHIS developed the National Trichinae Certification Program; this is a voluntary "preharvest" program for U.S. swine producers "that will provide documentation of swine management practices" to reduce the incidence of Trichinella in swine. The CDC reports 0.013% of U.S. swine are infected with Trichinella.

Treatment
As with most diseases, early treatment is better and decreases the risk of developing disease. If larvae do encyst in skeletal muscle cells, they can remain infectious for months to years.

Primary treatment
Early administration of anthelmintics, such as mebendazole or albendazole, decreases the likelihood of larval encystation, particularly if given within three days of infection. However, most cases are diagnosed after this time.  In humans, mebendazole (200–400 mg three times a day for three days) or albendazole (400 mg twice a day for 8–14 days) is given to treat trichinosis. These drugs prevent newly hatched larvae from developing, but should not be given to pregnant women or children under two years of age.Medical references from the 1940s described no specific treatment for trichinosis at the time, but intravenous injection of calcium salts was found to be useful in managing symptoms related to severe toxemia from the infection..

Secondary treatment
After infection, steroids, such as prednisone, may be used to relieve muscle pain associated with larval migration.

Vaccine research
Researchers trying to develop a vaccine for Trichinella have tried using either "larval extracts, excretory–secretory antigen, DNA, or recombinant antigen protein." Currently, no marketable vaccine is available for trichinosis, but experimental mouse studies have suggested possibilities.

In one study, microwaved Trichinella larvae were used to immunize mice (orally or intraperitoneally), which were subsequently infected. Depending on the dosage and frequency of immunization, results ranged from a decreased larval count to complete protection from trichinosis.
Another study used extracts and excretory–secretory products from first-stage larvae to produce an oral vaccine. To prevent gastric acids from dissolving the antigens before reaching the small intestine, scientists encapsulated the antigens in microcapsules. This vaccine significantly increased CD4+ cell levels, and increased antigen-specific serum IgGq and IgA, resulting in a statistically significant reduction in the average number of adult worms in the small intestines of mice. The significance of this approach is that, if the white blood cells in the small intestine have been exposed to Trichinella antigens (through vaccination), when an individual does get infected, the immune system will respond to expel the worms from the small intestine fast enough to prevent the female worms from releasing their larvae.
A DNA vaccine tested on mice "induced a muscle larva burden reduction in BALB/c mice by 29% in response to T. spiralis infection".

Epidemiology
About 11 million humans are infected with Trichinella; T. spiralis is the species responsible for most of these infections. Infection was once very common, but this disease is now rare in the developed world, but two known outbreaks occurred in 2015. In the first outbreak, around 40 people were infected in Liguria, Italy, during a New Years Eve celebration. The second outbreak in France was associated with pork sausages from Corsica, which were eaten raw, affecting 14 people in total.
The incidence of trichinosis in the U.S. has decreased dramatically in the past century from an average of 400 cases per year mid-20th century down to an annual average of 20 cases per year (2008–10). The number of cases has decreased because of legislation prohibiting the feeding of raw meat garbage to hogs, increased commercial and home freezing of pork, and the public awareness of the danger of eating raw or undercooked pork products.China reports around 10,000 cases every year, so is the country with the highest number of cases. In China, between 1964 and 1998, over 20,000 people became infected with trichinosis, and more than 200 people died.Trichinosis is common in developing countries where meat fed to pigs is raw or undercooked, but infections also arise in developed countries in Europe where raw or undercooked pork, wild boar and horse meat may be consumed as delicacies.In the developing world, most infections are associated with undercooked pork. For example, in Thailand, between 200 and 600 cases are reported annually around the Thai New Year. This is mostly attributable to a particular delicacy, larb, which calls for undercooked pork as part of the recipe.In parts of Eastern Europe, the World Health Organization reports, some swine herds have trichinosis infection rates above 50%, with correspondingly large numbers of human infections.

United States
Historically, pork products were thought to have the most risk of infecting humans with T. spiralis. However, a trichinosis surveillance conducted between 1997 and 2001 showed a higher percentage of cases caused by consumption of wild game (the sylvatic transmission cycle). This is thought to be due to the Federal Swine Health Protection Act (Public Law 96-468) that was passed by Congress in 1980. Prior to this act, swine were fed garbage that could potentially be infected by T. spiralis. This act was put in place to prevent trichinella-contaminated food from being given to swine. Additionally, other requirements were put in place, such as rodent control, limiting commercial swine contact with wildlife, maintaining good hygiene, and removing dead pigs from pens immediately.Between 2002 and 2007, 11 trichinosis cases were reported to the CDC each year on average in the United States, and 2008–10 averaged 20 cases per year; these were mostly the result of consuming undercooked game (sylvatic transmission) or home-reared pigs (domestic transmission).

Religious groups
The kashrut and halal dietary laws of Judaism and Islam prohibit eating pork. In the 19th century, when the association between trichinosis and undercooked pork was first established, this association was suggested to be the reason for the prohibition, reminiscent of the earlier opinion of  medieval Jewish philosopher Maimonides that food forbidden by Jewish law was "unwholesome". This theory was controversial, and eventually fell out of favor.

Reemergence
The disappearance of the pathogen from domestic pigs has led to a relaxation of legislation and control efforts by veterinary public health systems. Trichinosis has lately been thought of as a re-emerging zoonosis, supplemented by the increased distribution of meat products, political changes, a changing climate, and increasing sylvatic transmission.Major sociopolitical changes can produce conditions that favor the resurgence of Trichinella infections in swine and, consequently, in humans. For instance, "the overthrow of the social and political structures in the 1990s" in Romania led to an increase in the incidence rate of trichinosis.

History
As early as 1835, trichinosis was known to have been caused by a parasite, but the mechanism of infection was unclear at the time. A decade later, American scientist Joseph Leidy pinpointed undercooked meat as the primary vector for the parasite, and two decades afterwards, this hypothesis was fully accepted by the scientific community.

Parasite
The circumstances surrounding the first observation and identification of T. spiralis are controversial, due to a lack of records. In 1835, James Paget, a first-year medical student, first observed the larval form of T. spiralis, while witnessing an autopsy at St. Bartholomew’s Hospital in London. Paget took special interest in the presentation of muscle with white flecks, described as a "sandy diaphragm".  Although Paget is most likely the first person to have noticed and recorded these findings, the parasite was named and published in a report by his professor, Richard Owen, who is now credited for the discovery of the T. spiralis larval form.

Lifecycle
A series of experiments conducted between 1850 and 1870 by the German researchers Rudolf Virchow, Rudolf Leuckart, and Friedrich Albert von Zenker, which involved feeding infected meat to a dog and performing the subsequent necropsy, led to the discovery of the lifecycle of Trichinella. Through these experiments, Virchow was able to describe the development and infectivity of T </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Trichomoniasis and explain in detail? [/INST] Trichomoniasis (trich) is an infectious disease caused by the parasite Trichomonas vaginalis. About 70% of affected people do not have symptoms when infected. When symptoms occur, they typically begin 5 to 28 days after exposure. Symptoms can include itching in the genital area, a bad smelling thin vaginal discharge, burning with urination, and pain with sex. Having trichomoniasis increases the risk of getting HIV/AIDS. It may also cause complications during pregnancy.Trichomoniasis is a sexually transmitted infection (STI) which is most often spread through vaginal, oral, or anal sex. It can also spread through genital touching. People who are infected may spread the disease even when symptoms are not present. Diagnosis is by finding the parasite in the vaginal fluid using a microscope, culturing the vaginal fluid or urine, or testing for the parasites DNA. If present, other STIs should be tested for.Methods of prevention include not having sex, using condoms, not douching, and being tested for STIs before having sex with a new partner. Although not caused by a bacteria, trichomoniasis can be cured with certain antibiotics (metronidazole, tinidazole, secnidazole). Sexual partners should also be treated. About 20% of people get infected again within three months of treatment.There were about 122 million new cases of trichomoniasis in 2015. In the United States, there are about 2 million women affected. It occurs more often in women than men. Trichomonas vaginalis was first identified in 1836 by Alfred Donné. It was first recognized as causing this disease in 1916.

Signs and symptoms
Most people infected with Trichomonas vaginalis do not have any symptoms and can be undetected for years. Symptoms experienced include pain, burning or itching in the penis, urethra (urethritis), or vagina (vaginitis). Discomfort for both sexes may increase during intercourse and urination. For women there may also be a yellow-green, itchy, frothy, foul-smelling ("fishy" smell) vaginal discharge. In rare cases, lower abdominal pain can occur. Symptoms usually appear within 5 to 28 days of exposure. Sometimes trichomoniasis can be confused with chlamydia because the symptoms are similar.

Complications
Trichomoniasis is linked to several serious complications.

Trichomoniasis is associated with increased risk of transmission and infection of HIV.
Trichomoniasis may cause a woman to deliver a low-birth-weight or premature infant.
The role of Trichomonas infection in causing cervical cancer is unclear, although trichomonas infection may be associated with co-infection with high-risk strains of HPV.
T. vaginalis infection in males has been found to cause asymptomatic urethritis and prostatitis. In the prostate, it may create chronic inflammation that may eventually lead to prostate cancer.

Causes
The human genital tract is the only reservoir for this species. Trichomonas is transmitted through sexual or genital contact.The single-celled protozoan produces mechanical stress on host cells and then ingests cell fragments after cell death.

Genetic sequence
A draft sequence of the Trichomonas genome was published on January 12, 2007, in the journal Science confirming that the genome has at least 26,000 genes, a similar number to the human genome.  An additional approximately 34,000 unconfirmed genes, including thousands that are part of potentially transposable elements, brings the gene content to well over 60,000.

Diagnosis
There are three main ways to test for trichomoniasis.

The first is known as saline microscopy. This is the most commonly used method and requires an endocervical, vaginal, or penile swab specimen for examination under a microscope. The presence of one or multiple trichomonads constitutes a positive result. This method is cheap but has a low sensitivity (60–70%) often due to an inadequate sample, resulting in false negatives.
The second diagnostic method is culture, which has historically been the "gold standard" in infectious disease diagnosis. Trichomonas vaginalis culture tests are relatively cheap; however, sensitivity is still somewhat low (70–89%).
The third method includes the nucleic acid amplification tests (NAATs) which are more sensitive. These tests are more costly than microscopy and culture, and are highly sensitive (80–90%).

Prevention
Use of male condoms or female condoms may help prevent the spread of trichomoniasis, although careful studies have never been done that focus on how to prevent this infection. Infection with trichomoniasis through water is unlikely because Trichomonas vaginalis dies in water after 45–60 minutes, in thermal water after 30 minutes to 3 hours and in diluted urine after 5–6 hours.Currently there are no routine standard screening requirements for the general U.S. population receiving family planning or STI testing. The Centers for Disease Control and Prevention (CDC) recommends trichomoniasis testing for females with vaginal discharge and can be considered for females at higher risk for infection or of HIV-positive serostatus.The advent of new, highly specific and sensitive trichomoniasis tests present opportunities for new screening protocols for both men and women. Careful planning, discussion, and research are required to determine the cost-efficiency and most beneficial use of these new tests for the diagnosis and treatment of trichomoniasis in the U.S., which can lead to better prevention efforts.A number of strategies have been found to improve follow-up for STI testing including email and text messaging as reminders of appointments.

Screening
Evidence from a randomized controlled trials for screening pregnant women who do not have symptoms for infection with trichomoniasis and treating women who test positive for the infection have not consistently shown a reduced risk of preterm birth. Further studies are needed to verify this result and determine the best method of screening. In the US, screening of pregnant women without any symptoms is only recommended in those with HIV as Trichomonas infection is associated with increased risk of transmitting HIV to the fetus.

Treatment
Treatment for both pregnant and non-pregnant women is usually with metronidazole, by mouth once. Caution should be used in pregnancy, especially in the first trimester </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tricyclic antidepressant overdose and explain in detail? [/INST] Tricyclic antidepressant overdose is poisoning caused by excessive medication of the tricyclic antidepressant (TCA) type. Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. If symptoms have not occurred within six hours of exposure they are unlikely to occur.TCA overdose may occur by accident or purposefully in an attempt to cause death. The toxic dose depends on the specific TCA. Most are non-toxic at less than 5 mg/kg except for desipramine, nortriptyline, and trimipramine, which are generally non-toxic at less than 2.5 mg/kg. In small children one or two pills can be fatal. An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose.In overdose activated charcoal is often recommended. People should not be forced to vomit. In those who have a wide QRS complex (> 100 ms) sodium bicarbonate is recommended. If seizures occur benzodiazepines should be given. In those with low blood pressure intravenous fluids and norepinephrine may be used. The use of intravenous lipid emulsion may also be tried.In the early 2000s TCAs were one of the most common cause of poisoning. In the United States in 2004 there were more than 12,000 cases. In the United Kingdom they resulted in about 270 deaths a year. An overdose from TCAs was first reported in 1959.

Signs and symptoms
The peripheral autonomic nervous system, central nervous system and the heart are the main systems that are affected following overdose. Initial or mild symptoms typically develop within 2 hours and include tachycardia, drowsiness, a dry mouth, nausea and vomiting, urinary retention, confusion, agitation, and headache. More severe complications include hypotension, cardiac rhythm disturbances, hallucinations, and seizures. Electrocardiogram (ECG) abnormalities are frequent and a wide variety of cardiac dysrhythmias can occur, the most common being sinus tachycardia and intraventricular conduction delay resulting in prolongation of the QRS complex and the PR/QT intervals. Seizures, cardiac dysrhythmias, and apnea are the most important life-threatening complications.

Cause
Tricyclics have a narrow therapeutic index, i.e., the therapeutic dose is close to the toxic dose. Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs. However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose.

Pathophysiology
Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have anticholinergic effects, cause excessive blockade of norepinephrine reuptake at the preganglionic synapse, direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having quinidine-like effects on the myocardium.

Diagnosis
A specific blood test to verify toxicity is not typically available. An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose.

Treatment
People with symptoms are usually monitored in an intensive care unit for a minimum of 12 hours, with close attention paid to maintenance of the airways, along with monitoring of blood pressure, arterial pH, and continuous ECG monitoring. Supportive therapy is given if necessary, including respiratory assistance and maintenance of body temperature. Once a person has had a normal ECG for more than 24 hours they are generally medically clear.

Decontamination
Initial treatment of an acute overdose includes gastric decontamination. This is achieved by giving activated charcoal, which adsorbs the drug in the gastrointestinal tract either by mouth or via a nasogastric tube. Activated charcoal is most useful if given within 1 to 2 hours of ingestion </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Trigeminal neuralgia and explain in detail? [/INST] Trigeminal neuralgia (TN or TGN), also called Fothergill Disease, Tic Douloureux, or Trifacial Neuralgia is a long-term pain disorder that affects the trigeminal nerve, the nerve responsible for sensation in the face and motor functions such as biting and chewing. It is a form of neuropathic pain. There are two main types: typical and atypical trigeminal neuralgia. The typical form results in episodes of severe, sudden, shock-like pain in one side of the face that lasts for seconds to a few minutes. Groups of these episodes can occur over a few hours. The atypical form results in a constant burning pain that is less severe. Episodes may be triggered by any touch to the face. Both forms may occur in the same person. It is regarded as one of the most painful disorders known to medicine, and often results in depression.The exact cause is unknown, but believed to involve loss of the myelin of the trigeminal nerve. This might occur due to compression from a blood vessel as the nerve exits the brain stem, multiple sclerosis, stroke, or trauma. Less common causes include a tumor or arteriovenous malformation. It is a type of nerve pain. Diagnosis is typically based on the symptoms, after ruling out other possible causes such as postherpetic neuralgia.Treatment includes medication or surgery. The anticonvulsant carbamazepine or oxcarbazepine is usually the initial treatment, and is effective in about 90% of people. Side effects are frequently experienced that necessitate drug withdrawal in as many as 23% of patients. Other options include lamotrigine, baclofen, gabapentin, amitriptyline and pimozide. Opioids are not usually effective in the typical form. In those who do not improve or become resistant to other measures, a number of types of surgery may be tried.It is estimated that 1 in 8,000 people per year develop trigeminal neuralgia. It usually begins in people over 50 years old, but can occur at any age. Women are more commonly affected than men. The condition was first described in detail in 1773 by John Fothergill.

Signs and symptoms
This disorder is characterized by episodes of severe facial pain along the trigeminal nerve divisions. The trigeminal nerve is a paired cranial nerve that has three major branches: the ophthalmic nerve (V1), the maxillary nerve (V2), and the mandibular nerve (V3). One, two, or all three branches of the nerve may be affected. Trigeminal neuralgia most commonly involves the middle branch (the maxillary nerve or V2) and lower branch (mandibular nerve or V3) of the trigeminal nerve.An individual attack usually lasts from a few seconds to several minutes or hours, but these can repeat for hours with very short intervals between attacks. In other instances, only 4–10 attacks are experienced daily. The episodes of intense pain may occur paroxysmally. To describe the pain sensation, people often describe a trigger area on the face so sensitive that touching or even air currents can trigger an episode; however, in many people, the pain is generated spontaneously without any apparent stimulation. It affects lifestyle as it can be triggered by common activities such as eating, talking, shaving and brushing teeth. The wind, chewing, and talking can aggravate the condition in many patients. The attacks are said, by those affected, to feel like stabbing electric shocks, burning, sharp, pressing, crushing, exploding or shooting pain that becomes intractable.The pain also tends to occur in cycles with remissions lasting months or even years. Pain attacks are known to worsen in frequency or severity over time, in some people. Pain may migrate to other branches over time but in some people remains very stable.Bilateral (occurring on both sides) trigeminal neuralgia is very rare except for trigeminal neuralgia caused by multiple sclerosis (MS). This normally indicates problems with both trigeminal nerves, since one nerve serves the left side of the face and the other serves the right side. Occasional reports of bilateral trigeminal neuralgia reflect successive episodes of unilateral (only one side) pain switching the side of the face rather than pain occurring simultaneously on both sides.Rapid spreading of the pain, bilateral involvement or simultaneous participation with other major nerve trunks (such as Painful Tic Convulsif of nerves V & VII or occurrence of symptoms in the V and IX nerves) may suggest a systemic cause. Systemic causes could include multiple sclerosis or expanding cranial tumors.The severity of the pain makes it difficult to wash the face, shave, and perform good oral hygiene. The pain has a significant impact on activities of daily living especially as those affected live in fear of when they are going to get their next attack of pain and how severe it will be. It can lead to severe depression and anxiety.However, not all people will have the symptoms described above and there are variants of TN. One of which is atypical trigeminal neuralgia ("trigeminal neuralgia, type 2" or trigeminal neuralgia with concomitant pain), based on a recent classification of facial pain. In these instances there is also a more prolonged lower severity background pain that can be present for over 50% of the time and is described more as a burning or prickling, rather than a shock.
Trigeminal pain can also occur after an attack of herpes zoster. Post-herpetic neuralgia has the same manifestations as in other parts of the body. Herpes zoster oticus typically presents with inability to move many facial muscles, pain in the ear, taste loss on the front of the tongue, dry eyes and mouth, and a vesicular rash. Less than 1% of varicella zoster infections involve the facial nerve and result in this occurring.Trigeminal deafferentation pain (TDP), also termed anesthesia dolorosa, or colloquially as phantom face pain, is from intentional damage to a trigeminal nerve following attempts to surgically fix a nerve problem. This pain is usually constant with a burning sensation and numbness. TDP is very difficult to treat as further surgeries are usually ineffective and possibly detrimental to the person.

Causes
The trigeminal nerve is a mixed cranial nerve responsible for sensory data such as tactition (pressure), thermoception (temperature), and nociception (pain) originating from the face above the jawline; it is also responsible for the motor function of the muscles of mastication, the muscles involved in chewing but not facial expression.Several theories exist to explain the possible causes of this pain syndrome. It was once believed that the nerve was compressed in the opening from the inside to the outside of the skull; but leading research indicates that it is an enlarged or lengthened blood vessel – most commonly the superior cerebellar artery – compressing or throbbing against the microvasculature of the trigeminal nerve near its connection with the pons. Such a compression can injure the nerves protective myelin sheath and cause erratic and hyperactive functioning of the nerve. This can lead to pain attacks at the slightest stimulation of any area served by the nerve as well as hinder the nerves ability to shut off the pain signals after the stimulation ends. This type of injury may rarely be caused by an aneurysm (an outpouching of a blood vessel); by an AVM (arteriovenous malformation); by a tumor; such as an arachnoid cyst or meningioma in the cerebellopontine angle; or by a traumatic event, such as a car accident.Short-term peripheral compression is often painless. Persistent compression results in local demyelination with no loss of axon potential continuity. Chronic nerve entrapment results in demyelination primarily, with progressive axonal degeneration subsequently. It is, "therefore widely accepted that trigeminal neuralgia is associated with demyelination of axons in the Gasserian ganglion, the dorsal root, or both." It has been suggested that this compression may be related to an aberrant branch of the superior cerebellar artery that lies on the trigeminal nerve. Further causes, besides an aneurysm, multiple sclerosis or cerebellopontine angle tumor, include: a posterior fossa tumor, any other expanding lesion or even brainstem diseases from strokes.Trigeminal neuralgia is found in 3–4% of people with multiple sclerosis, according to data from seven studies.  It has been theorized that this is due to damage to the spinal trigeminal complex. Trigeminal pain has a similar presentation in patients with and without MS.Postherpetic neuralgia, which occurs after shingles, may cause similar symptoms if the trigeminal nerve is damaged, called Ramsay Hunt syndrome type 2.
When there is no apparent structural cause, the syndrome is called idiopathic.

Diagnosis
Trigeminal neuralgia is diagnosed via the result of neurological and physical tests, as well as the individuals medical history.

Management
As with many conditions without clear physical or laboratory diagnosis, TN is sometimes misdiagnosed. A person with TN will sometimes seek the help of numerous clinicians before a firm diagnosis is made.There is evidence that points towards the need to quickly treat and diagnose TN. It is thought that the longer a patient has TN, the harder it may be to reverse the neural pathways associated with the pain.The differential diagnosis includes temporomandibular disorder. Since triggering may be caused by movements of the tongue or facial muscles, TN must be differentiated from masticatory pain that has the clinical characteristics of deep somatic rather than neuropathic pain. Masticatory pain will not be arrested by a conventional mandibular local anesthetic block. One quick test a dentist might perform is a conventional inferior dental local anaesthetic block, if the pain is in this branch, as it will not arrest masticatory pain but will TN.

Medical
The anticonvulsant carbamazepine is the first line treatment; second line medications include baclofen, lamotrigine, oxcarbazepine, phenytoin, topiramate, gabapentin and pregabalin. Uncontrolled trials have suggested that clonazepam and lidocaine may be effective.
Antidepressant medications, such as amitriptyline have shown good efficacy in treating trigeminal neuralgia, especially if combined with an anti-convulsant drug such as pregabalin.
There is some evidence that duloxetine can also be used in some cases of neuropathic pain, especially in patients with major depressive disorder as it is an antidepressant. However, it should, by no means, be considered a first line therapy and should only be tried by specialist advice.
There is controversy around opiate use such as morphine and oxycodone for treatment of TN, with varying evidence on its effectiveness for neuropathic pain. Generally, opioids are considered ineffective against TN and thus should not be prescribed.

Surgical
Microvascular decompression provides freedom from pain in about 75% of patients presenting with drug-resistant trigeminal neuralgia. While there may be pain relief after surgery, there is also a risk of adverse effects, such as facial numbness. Percutaneous radiofrequency thermorhizotomy may also be effective as may stereotactic radiosurgery; however the effectiveness decreases with time.Surgical procedures can be separated into non-destructive and destructive:

Non-destructive
Microvascular decompression – this involves a small incision behind the ear and some bone removal from the area. An incision through the meninges is made to expose the nerve. Any vascular compressions of the nerve are carefully moved and a sponge-like pad is placed between the compression and nerve, stopping unwanted pulsation and allowing myelin sheath healing.

Destructive
All destructive procedures will cause facial numbness, post relief, as well as pain relief.
Percutaneous techniques which all involve a needle or catheter entering the face up to the origin where the nerve splits into three divisions and then damaging this area, purposely, to produce numbness but also stop pain signals. These techniques are proven effective especially in those where other interventions have failed or in those who are medically unfit for surgery such as the elderly.
Balloon compression – inflation of a balloon at this point causing damage and stopping pain signals.
Glycerol injection – deposition of a corrosive liquid called glycerol at this point causes damage to the nerve to hinder pain signals.
Radiofrequency thermocoagulation rhizotomy – application of a heated needle to damage the nerve at this point.
Stereotactic radiosurgery is a form of radiation therapy that focuses high-power energy on a small area of the body

Support
Psychological and social support has found to play a key role in the management of chronic illnesses and chronic pain conditions, such as trigeminal neuralgia. Chronic pain can cause constant frustration to an individual as well as to those around them.

History
Trigeminal neuralgia was first described by physician John Fothergill and treated surgically by John Murray Carnochan, both of whom were graduates of the University of Edinburgh Medical School </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tropical sprue and explain in detail? [/INST] Tropical sprue is a malabsorption disease commonly found in tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine. It differs significantly from coeliac sprue. It appears to be a more severe form of environmental enteropathy.

Signs and symptoms
The illness usually starts with an attack of acute diarrhoea, fever and malaise following which, after a variable period, the patient settles into the chronic phase of diarrhoea, steatorrhoea, weight loss, anorexia, malaise, and nutritional deficiencies.
The symptoms of tropical sprue are:

Diarrhoea
Steatorrhoea or fatty stool (often foul-smelling and whitish in colour)
Indigestion
Cramps
Weight loss and malnutrition
FatigueLeft untreated, nutrient and vitamin deficiencies may develop in patients with tropical sprue.  These deficiencies may have these symptoms:

Vitamin A deficiency: hyperkeratosis or skin scales
Vitamin B12 and folic acid deficiencies: anaemia, numbness, and tingling sensation
Vitamin D and calcium deficiencies: spasm, bone pain, muscle weakness
Vitamin K deficiency: bruises

Cause
The cause of tropical sprue is not known.  It may be caused by persistent bacterial, viral, amoebal, or parasitic infections.  Folic acid deficiency, effects of malabsorbed fat on intestinal motility, and persistent small intestinal bacterial overgrowth may combine to cause the disorder. A link between small intestinal bacterial overgrowth and tropical sprue has been proposed to be involved in the aetiology of post-infectious irritable bowel syndrome (IBS). Intestinal immunologic dysfunction, including deficiencies in secretory immunoglobulin A (IgA), may predispose people to malabsorption and bacterial colonization, so tropical sprue may be triggered in susceptible individuals following an acute enteric infection.

Diagnosis
Diagnosis of tropical sprue can be complicated because many diseases have similar symptoms.  The following investigation results are suggestive:
Abnormal flattening of villi and inflammation of the lining of the small intestine, observed during an endoscopic procedure.
Presence of inflammatory cells (most often lymphocytes) in the biopsy of small intestine tissue.
Low levels of vitamins A, B12, E, D, and K, as well as serum albumin, calcium, and folate, revealed by a blood test.
Excess fat in the feces (steatorrhoea).
Thickened small bowel folds seen on imaging.Tropical sprue is largely limited to within about 30 degrees north and south of the equator.  Recent travel to this region is a key factor in diagnosing this disease in residents of countries outside of that geographical region.Other conditions which can resemble tropical sprue need to be differentiated.  Coeliac disease (also known as coeliac sprue or gluten sensitive enteropathy), has similar symptoms to tropical sprue, with the flattening of the villi and small intestine inflammation and is caused by an autoimmune disorder in genetically susceptible individuals triggered by ingested gluten.  Malabsorption can also be caused by protozoan infections, tuberculosis, HIV/AIDS, immunodeficiency, chronic pancreatitis and inflammatory bowel disease </s>