<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Inflammatory bowel disease and can you explain it in depth? [/INST] Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohns disease and ulcerative colitis being the principal types. Crohns disease affects the small intestine and large intestine, as well as the mouth, esophagus, stomach and the anus, whereas ulcerative colitis primarily affects the colon and the rectum.IBD also occurs in dogs and is thought to arise from a combination of host genetics, intestinal microenvironment, environmental components and the immune system. There is an ongoing discussion, however, that the term "chronic enteropathy" might be better to use than "inflammatory bowel disease" in dogs because it differs from IBD in humans in how the dogs respond to treatment. For example, many dogs respond to only dietary changes compared to humans with IBD, who often need immunosuppressive treatment. Some dogs may also need immunosuppressant or antibiotic treatment when dietary changes are not enough. After having excluded other diseases that can lead to vomiting, diarrhea, and abdominal pain in dogs, intestinal biopsies are often performed to investigate what kind of inflammation is occurring (lymphoplasmacytic, eosinophilic, or granulomatous). In dogs, low levels of cobalamin in the blood have been shown to be a risk factor for negative outcome.

Signs and symptoms
In spite of Crohns and UC being very different diseases, both may present with any of the following symptoms: abdominal pain, diarrhea, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis and weight loss. Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease. Associated complaints or diseases include arthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and non-thyroidal illness syndrome (NTIS). Associations with deep vein thrombosis (DVT) and bronchiolitis obliterans organizing pneumonia (BOOP) have also been reported. Diagnosis is generally by assessment of inflammatory markers in stool followed by colonoscopy with biopsy of pathological lesions.

Causes
IBD is a complex disease which arises as a result of the interaction of environmental and genetic factors leading to immunological responses and inflammation in the intestine.

Diet
People living with IBD are very interested in diet, but little is known about the impact of diet on these patients. Recent reviews underlined the important role of nutritional counselling in IBD patients. Patients should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation.A 2022 study found that diets with increased intake of fruits and vegetables, reduction of processed meats and refined carbohydrates, and preference of water for hydration were associated with lower risk of active symptoms with IBD, although increased intake of fruits and vegetables alone did not reduce risk of symptoms with Crohns disease.Dietary patterns are associated with a risk for ulcerative colitis. In particular, subjects who were in the highest tertile of the healthy dietary pattern had a 79% lower risk of ulcerative colitis.Gluten sensitivity is common in IBD and associated with having flareups. Gluten sensitivity was reported in 23.6 and 27.3% of Crohns disease and ulcerative colitis patients, respectively.A diet high in protein, particularly animal protein, and/or high in sugar may be associated with increased risk of inflammatory bowel disease and relapses.

Microbiota
As a result of microbial symbiosis and immunity, alterations in the gut microbiome may contribute to inflammatory gut diseases. IBD-affected individuals have been found to have 30–50 percent reduced biodiversity of commensal bacteria, such as decreases in Bacillota (namely Lachnospiraceae) and Bacteroidota. Further evidence of the role of gut flora in the cause of inflammatory bowel disease is that IBD-affected individuals are more likely to have been prescribed antibiotics in the 2–5 year period before their diagnosis than unaffected individuals. The enteral bacteria can be altered by environmental factors, such as concentrated milk fats (a common ingredient of processed foods and confectionery) or oral medications such as antibiotics and oral iron preparations. The mucosal microbiota in the large intestine of IBD patients with active inflammation was found to be associated with pro-inflammatory changes to the host epigenome. However, large international studies have failed to identify a single microbial biomarker of IBD indicating its not driven by any single micro-organism.

Breach of intestinal barrier
Loss of integrity of the intestinal epithelium plays a key pathogenic role in IBD. Dysfunction of the innate immune system as a result of abnormal signaling through immune receptors called toll-like receptors (TLRs)—which activates an immune response to molecules that are broadly shared by multiple pathogens—contributes to acute and chronic inflammatory processes in IBD colitis and associated cancer. Changes in the composition of the intestinal microbiota are an important environmental factor in the development of IBD. Detrimental changes in the intestinal microbiota induce an inappropriate (uncontrolled) immune response that results in damage to the intestinal epithelium. Breaches in this critical barrier (the intestinal epithelium) allow further infiltration of microbiota that, in turn, elicit further immune responses. IBD is a multifactorial disease that is nonetheless driven in part by an exaggerated immune response to gut microbiota that causes defects in epithelial barrier function.

Oxidative stress and DNA damage
Pereira et al. reviewed evidence from numerous studies indicating that oxidative stress and DNA damage likely have a role in the pathophysiology of IBD.  Oxidative DNA damage as measured by 8-OHdG levels was found to be significantly increased in patients with IBD compared to control patients, and in inflamed mucosa compared with non-inflamed mucosa.

Genetics
A genetic component to IBD has been recognized for over a century. Research that has contributed to understanding of the genetics include studies of ethnic groups (e.g., Ashkenazi Jews, Irish), familial clustering, epidemiological studies, and twin studies. With the advent of molecular genetics, understanding of the genetic basis has expanded considerably, particularly in the past decade. The first gene linked to IBD was NOD2 in 2001. Genome-wide association studies have since added to understanding of the genomics and pathogenesis of the disease. More than 200 single nucleotide polymorphisms (SNPs or "snips") are now known to be associated with susceptibility to IBD. One of the largest genetic studies of IBD was published in 2012 . The analysis explained more of the variance in Crohns disease and ulcerative colitis than previously reported. The results suggested that commensal microbiota are altered in such a way that they act as pathogens in inflammatory bowel diseases. Other studies show that mutations in IBD-associated genes might interfere with the cellular activity and interactions with the microbiome that promote normal immune responses. Many studies identified that microRNAs dysregulation involved in IBD and to promote colorectal cancer. By 2020, single-cell RNA sequencing analysis was launched by a small consortium using IBD patient biopsy material in a search for therapeutic targets.

Diagnosis
The diagnosis is usually confirmed by biopsies on colonoscopy. Fecal calprotectin is useful as an initial investigation, which may suggest the possibility of IBD, as this test is sensitive but not specific for IBD.

Differential diagnosis
Other diseases may cause an increased excretion of fecal calprotectin, such as infectious diarrhea, untreated coeliac disease, necrotizing enterocolitis, intestinal cystic fibrosis and neoplastic pediatric tumor cells.Conditions with similar symptoms as Crohns disease includes intestinal tuberculosis, Behçets disease, ulcerative colitis, nonsteroidal anti-inflammatory drug enteropathy, irritable bowel syndrome and coeliac disease.Conditions with similar symptoms as ulcerative colitis includes acute self-limiting colitis, amebic colitis, schistosomiasis, Crohns disease, colon cancer, irritable bowel syndrome, intestinal tuberculosis and nonsteroidal anti-inflammatory drug enteropathy.Liver function tests are often elevated in inflammatory bowel disease, and are often mild and generally return spontaneously to normal levels. The most relevant mechanisms of elevated liver functions tests in IBD are drug-induced hepatotoxicity and fatty liver.

Classification
The chief types of inflammatory bowel disease are Crohns disease and ulcerative colitis (UC). Inflammatory bowel diseases fall into the class of autoimmune diseases, in which the bodys own immune system attacks elements of the digestive system.Accounting for fewer cases are other forms of IBD, which are not always classified as typical IBD:
Microscopic colitis subdivided into collagenous colitis and lymphocytic colitis
Diversion colitis
Behçets disease
Early Onset IBD
Indeterminate colitisNo disease specific markers are currently known in the blood, enabling the reliable separation of Crohns disease and ulcerative colitis patients. The way doctors can tell the difference between Crohns disease and UC is the location and nature of the inflammatory changes. Crohns can affect any part of the gastrointestinal tract, from mouth to anus (skip lesions), although a majority of the cases start in the terminal ileum. Ulcerative colitis, in contrast, is restricted to the colon and the rectum. Microscopically, ulcerative colitis is restricted to the mucosa (epithelial lining of the gut), while Crohns disease affects the full thickness of the bowel wall ("transmural lesions"). Lastly, Crohns disease and ulcerative colitis present with extra-intestinal manifestations (such as liver problems, arthritis, skin manifestations and eye problems) in different proportions.In 10–15% of cases, a definitive diagnosis neither of Crohns disease nor of ulcerative colitis can be made because of idiosyncrasies in the presentation. In this case, a diagnosis of indeterminate colitis may be made. Although a recognised definition, not all centres refer to this.

Treatment
Surgery
CD and UC are chronic inflammatory diseases, and are not medically curable. However, ulcerative colitis can in most cases be cured by proctocolectomy, although this may not eliminate extra-intestinal symptoms. An ileostomy will collect feces in a bag. Alternatively, a pouch can be created from the small intestine; this serves as the rectum and prevents the need for a permanent ileostomy. Between one-quarter and one-half of patients with ileo-anal pouches do have to manage occasional or chronic pouchitis.Surgery cannot cure Crohns disease but may be needed to treat complications such as abscesses, strictures or fistulae. Severe cases may require surgery, such as bowel resection, strictureplasty or a temporary or permanent colostomy or ileostomy. In Crohns disease, surgery involves removing the worst inflamed segments of the intestine and connecting the healthy regions, but unfortunately, it does not cure Crohns or eliminate the disease. At some point after the first surgery, Crohns disease can recur in the healthy parts of the intestine, usually at the resection site. (For example, if a patient with Crohns disease has an ileocecal anastomosis, in which the caecum and terminal ileum are removed and the ileum is joined to the ascending colon, their Crohns will nearly always flare-up near the anastomosis or in the rest of the ascending colon).

Medical therapies
Medical treatment of IBD is individualised to each patient. The choice of which drugs to use and by which route to administer them (oral, rectal, injection, infusion) depends on factors including the type, distribution, and severity of the patients disease, as well as other historical and biochemical prognostic factors, and patient preferences. For example, mesalazine is more useful in ulcerative colitis than in Crohns disease. Generally, depending on the level of severity, IBD may require immunosuppression to control the symptoms, with drugs such as prednisone, tumor necrosis factor inhibitors (TNF inhibitors), azathioprine, methotrexate, or 6-mercaptopurine.Steroids, such as the glucocorticoid prednisone, are frequently used to control disease flares and were once acceptable as a maintenance drug. Biological therapy for inflammatory bowel disease, especially the TNF inhibitors, are used in people with more severe or resistant Crohns disease and sometimes in ulcerative colitis.Treatment is usually started by administering drugs with high anti-inflammatory effects, such as prednisone. Once the inflammation is successfully controlled, another drug to keep the disease in remission, such as mesalazine in UC, is the main treatment. If further treatment is required, a combination of an immunosuppressive drug (such as azathioprine) with mesalazine (which may also have an anti-inflammatory effect) may be needed, depending on the patient. Controlled release budesonide is used for mild ileal Crohns disease.

Nutritional and dietetic therapies
Exclusive enteral nutrition is a first-line therapy in pediatric Crohns disease with weaker data in adults.: 331  Evidence supporting exclusive enteral nutrition in ulcerative colitis is lacking.: 333 Nutritional deficiencies play a prominent role in IBD. Malabsorption, diarrhea, and GI blood loss are common features of IBD. Deficiencies of B vitamins, fat-soluble vitamins, essential fatty acids, and key minerals such as magnesium, zinc, and selenium are extremely common and benefit from replacement therapy. Dietary interventions, including certain exclusion diets like the specific carbohydrate diet (SCD) can be beneficial for symptom management. Dietary fiber interventions, such as psyillium supplementation (a mixture of soluble and insoluble fibers), may relieve symptoms as well as induce/maintain remission by altering the microbiome composition of the GI tract, thereby improving regulation of immune function, reducing inflammation, and helping to restore the intestinal mucosal lining.Anaemia is commonly present in both ulcerative colitis and Crohns disease. Due to raised levels of inflammatory cytokines which lead to the increased expression of hepcidin, parenteral iron is the preferred treatment option as it bypasses the gastrointestinal system, has lower incidence of adverse events and enables quicker treatment. Hepcidin itself is also an anti-inflammatory agent. In the murine model very low levels of iron restrict hepcidin synthesis, worsening the inflammation that is present. Enteral nutrition has been found to be efficient to improve hemoglobin level in patients with inflammatory bowel disease, especially combined with erythropoietin.

Microbiome
There is preliminary evidence of an infectious contribution to inflammatory bowel disease in some patients that may benefit from antibiotic therapy, such as with rifaximin. The evidence for a benefit of rifaximin is mostly limited to Crohns disease with less convincing evidence supporting use in ulcerative colitis.Fecal microbiota transplant is a relatively new treatment option for IBD which has attracted attention since 2010. Some preliminary studies have suggested benefits similar to those in Clostridium difficile infection but a review of use in IBD shows that FMT is safe, but of variable efficacy. A 2014 review stated that more randomized controlled trials were needed.

Alternative medicine
Complementary and alternative medicine approaches have been used in inflammatory bowel disorders. Evidence from controlled studies of these therapies has been reviewed; risk of bias was quite heterogeneous. The best supportive evidence was found for herbal therapy, with Plantago ovata and curcumin in UC maintenance therapy, wormwood in CD, mind/body therapy and self-intervention in UC, and acupuncture in UC and CD.

Novel approaches
Stem cell therapy is undergoing research as a possible treatment for IBD. A review of studies suggests a promising role, although there are substantial challenges, including cost and characterization of effects, which limit the current use in clinical practice.

Psychological interventions
Currently, there is no evidence to recommend psychological treatment, such as psychotherapy, stress management and patients education, to all adults with IBD in general. These treatments had no effect on quality of life, emotional well-being and disease activity. The need for these approaches should be individually assessed and further researched to identify subgroups and determine type of therapy that may benefit individuals with IBD. In adolescents population such treatments may be beneficial on quality of life and depression, although only short-term effects have been found, which also imposes the need for further research.

Treatment standards
Crohns and Colitis Australia, the peak body for IBD in Australia, where prevalence is one of the highest in the world, reviewed the quality of care for patients admitted to Australian hospitals. They found that only one hospital met accepted standards for multidisciplinary care, but that care was improved with the availability of even minimal specialised services.

Prognosis
While IBD can limit quality of life because of pain, vomiting, and diarrhea, it is rarely fatal on its own. Fatalities due to complications such as toxic megacolon, bowel perforation and surgical complications are also rare.. Fatigue is a common symptom of IBD and can be a burden.Around one-third of individuals with IBD experience persistent gastrointestinal symptoms similar to irritable bowel syndrome (IBS) in the absence of objective evidence of disease activity. Despite enduring the side-effects of long-term therapies, this cohort has a quality of life that is not significantly different to that of individuals with uncontrolled, objectively active disease, and escalation of therapy to biological agents is typically ineffective in resolving their symptoms. The cause of these IBS-like symptoms is unclear, but it has been suggested that changes in the gut-brain axis, epithelial barrier dysfunction, and the gut flora may be partially responsible.While patients of IBD do have an increased risk of colorectal cancer, this is usually caught much earlier than the general population in routine surveillance of the colon by colonoscopy, and therefore patients are much more likely to survive.New evidence suggests that patients with IBD may have an elevated risk of endothelial dysfunction and coronary artery disease.The goal of treatment is toward achieving remission, after which the patient is usually switched to a lighter drug with fewer potential side effects. Every so often, an acute resurgence of the original symptoms may appear; this is known as a "flare-up". Depending on the circumstances, it may go away on its own or require medication. The time between flare-ups may be anywhere from weeks to years, and varies wildly between patients – a few have never experienced a flare-up.Life with IBD can be challenging; however, many with the conditionlead relatively normal lives. IBD carries a psychological burden due to stigmatization of being diagnosed, leading to high levels of anxiety, depression, and a general reduction in the quality of life. Although living with IBD can be difficult, there are numerous resources available to help families navigate the ins and out of IBD, such as the Crohns and Colitis Foundation of America (CCFA).

Epidemiology
IBD resulted in a global total of 51,000 deaths in 2013 and 55,000 deaths in 1990. The increased incidence of IBD since World War 2 has been correlated to the increase in meat consumption worldwide, supporting the claim that animal protein intake is associated with IBD. However, there are many environmental risk factors that have been linked to the increased and decreased risk of IBD, such as smoking, air pollution and greenspace, urbanization and Westernization. Inflammatory bowel diseases are increasing in Europe. Incidence and prevalence of IBD has risen steadily for the last decades in Asia, which could be related changes in diet and other environmental factors.Around 0.8% of people in the UK have IBD. Similarly, around 270,000 (0.7%) of people in Canada have IBD, with that number expected to rise to 400,000 (1%) by 2030.

Research
The following treatment strategies are not used routinely, but appear promising in some forms of inflammatory bowel disease.
Initial reports suggest that "helminthic therapy" may not only prevent but even control IBD: a drink with roughly 2,500 ova of the Trichuris suis helminth taken twice monthly decreased symptoms markedly in many patients. It is even speculated that an effective "immunization" procedure could be developed—by ingesting the cocktail at an early age.Prebiotics and probiotics are focusing increasing interest as treatments for IBD. Currently, there is evidence to support the use of certain probiotics in addition to standard treatments in people with ulcerative colitis but there is no sufficient data to recommend probiotics in people with Crohns disease. Both single strain and multi-strain probiotics have been researched for mild to moderate cases of ulcerative colitis.  The most clinically researched multi-strain probiotic with over 70 human trials is the De Simone Formulation.  Further research is required to identify specific probiotic strains or their combinations and prebiotic substances for therapies of intestinal inflammation.Currently, the probiotic strain, frequency, dose and duration of the probiotic therapy are not established. In severely ill people with IBD there is a risk of the passage of viable bacteria from the gastrointestinal tract to the internal organs (bacterial translocation) and subsequent bacteremia, which can cause serious adverse health consequences. Live bacteria might not be essential because of beneficial effects of probiotics seems to be mediated by their DNA and by secreted soluble factors, and their therapeutic effects may be obtained by systemic administration rather than oral administration.In 2005 New Scientist published a joint study by Bristol University and the University of Bath on the apparent healing power of cannabis on IBD. Reports that cannabis eased IBD symptoms indicated the possible existence of cannabinoid receptors in the intestinal lining, which respond to molecules in the plant-derived chemicals. CB1 cannabinoid receptors – which are known to be present in the brain – exist in the endothelial cells which line the gut, it is thought that they are involved in repairing the lining of the gut when damaged.The team deliberately damaged the cells to cause inflammation of the gut lining and then added synthetically produced cannabinoids; the result was that gut started to heal: the broken cells were repaired and brought back closer together to mend the tears </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Winchester syndrome and can you explain it in depth? [/INST] Winchester syndrome is a rare hereditary connective tissue disease described in 1969, of which the main characteristics are short stature, marked contractures of joints, opacities in the cornea, coarse facial features, dissolution of the carpal and tarsal bones (in the hands and feet, respectively), and osteoporosis. Winchester syndrome was once considered to be related to a similar condition, multicentric osteolysis, nodulosis, and arthropathy (MONA). However, it was discovered that the two are caused by mutations found in different genes; however they mostly produce the same phenotype or clinical picture. Appearances resemble rheumatoid arthritis. Increased uronic acid is demonstrated in cultured fibroblasts from the skin and to a lesser degree in both parents. Despite initial tests not showing increased mucopolysaccharide excretion, the disease was regarded as a mucopolysaccharidosis. Winchester syndrome is thought to be inherited as an autosomal recessive trait.

Symptoms
Symptoms of Winchester or MONA syndrome begin with the deterioration of bone within the hands and feet. This loss of bone causes pain, pathological fractures and limited mobility. The abnormalities of the bone spread to other areas of the body, mostly the joints. This causes arthropathy: stiffening of the joints (contractures) and swollen joints. Many people develop osteopenia and osteoporosis throughout their entire body. The bone and joint manifestations characteristically start in the hands and feet then spread to the larger joints eventually like elbows and shoulders in the upper extremities and knees and hips in the lower extremities.  Due to the damage to the bones, many affected individuals suffer from bone fractures, arthritis and occasionally short stature. Many individuals experience leathery skin where the skin appears dark and thick. Excessive hair growth is known to be found in these darker areas of the skin   (hypertrichosis). The eyes may develop a white or clear covering the cornea (corneal opacities) which can cause problems with vision.

Mechanism
Winchester syndrome is believed to be inherited through autosomal recessive inheritance. It believed that this disease is caused by a nonlysosomal connective-tissue disturbance. The protein inactivation mutation is found on the matrix metalloproteinase 2 gene (MMP2).  MM2 is responsible for bone remodeling. Bone remodeling is the process in which old bone is destroyed so that new bone can be created to replace it. This mutation causes a multicentric osteolysis and arthritis syndrome. It is hypothesized that the loss of an upstream MMP-2 protein activator MT1-MMP, results in decreased MMP-2 activity without affecting MMP2. The inactivating homoallelic mutation of MT1-MMP can be seen at the surface of fibroblasts. It was determined that fibroblasts lacking MT1-MMP lack the ability to degrade type I collagen which leads to anomalous function.

Diagnosis
In 1989, a set of diagnostic criteria were created for the diagnosing of Winchester syndrome. The typical diagnosis criteria begin with skeletal radiological test results and two of the defining symptoms, such as short stature, coarse facial features, hyperpigmentation, or excessive hair growth. The typical tests that are performed are x-ray and magnetic resonance imaging. A complete skeletal radiographic survey is mandatory for diagnosis of Winchester or MONA syndrome together with a detailed musculoskeletal examination and craniofacial morphology assessment. It appears that Winchester syndrome is more common in women than men. Winchester syndrome is very rare. There have only been a few individuals worldwide who were reported to have this disorder.

Treatment
There is no known cure for Winchester syndrome; however, there are many therapies that can aid in the treatment of symptoms. Such treatments can include medications: anti-inflammatories, muscle relaxants, and antibiotics. Many individuals will require physical therapy to promote movement and use of the limbs affected by the syndrome. Bisphosphonates have been used to improve bone quality and density or at least halt the progression of bone damages or osteolysis. Genetic counseling is typically prescribed for families to help aid in the understanding of the disease. There are a few clinical trials available to participate in </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hemothorax and can you explain it in depth? [/INST] A hemothorax (derived from hemo- [blood] + thorax [chest], plural hemothoraces) is an accumulation of blood within the pleural cavity. The symptoms of a hemothorax may include chest pain and difficulty breathing, while the clinical signs may include reduced breath sounds on the affected side and a rapid heart rate. Hemothoraces are usually caused by an injury, but they may occur spontaneously due to cancer invading the pleural cavity, as a result of a blood clotting disorder, as an unusual manifestation of endometriosis, in response to a collapsed lung, or rarely in association with other conditions.
Hemothoraces are usually diagnosed using a chest X-ray, but they can be identified using other forms of imaging including ultrasound, a CT scan, or an MRI. They can be differentiated from other forms of fluid within the pleural cavity by analysing a sample of the fluid, and are defined as having a hematocrit of greater than 50% that of the persons blood. Hemothoraces may be treated by draining the blood using a chest tube. Surgery may be required if the bleeding continues. If treated, the prognosis is usually good. Complications of a hemothorax include infection within the pleural cavity and the formation of scar tissue.

Background
The lungs are surrounded by two layers of tissue called the pulmonary pleurae. In most healthy people, these two layers are tightly apposed, separated only by a small amount of pleural fluid. In certain disease states, the space between these two layers, called the pleural cavity, swells with fluid. This accumulation of fluid in the pleural cavity is called pleural effusion. Pleural effusions are given specific names depending on the nature of the fluid: hydrothorax for serous fluid, pyothorax for pus, hemothorax for blood, and urinothorax for urine.

Signs and symptoms
Signs and symptoms include anxiety, rapid breathing, restlessness, shock, and pale, cool, clammy skin. When the affected area is percussed, a dull feeling may be observed. Neck veins may be flat and breathing sounds reduced. It can also cause a collapsed lung (atelectasis). Massive hemothorax, often defined as over 1.5 liters of blood initially when an intercostal drain is placed, or a bleeding rate greater than .2 liters/hr, can result in shock with two causes: massive bleeding resulting from hypovolemic shock, and venous pressure from the retained blood, impairing blood flow.

Causes
Hemothoraces are classified in three broad categories according to the cause and in order of frequency: traumatic, iatrogenic, or nontraumatic. All three categories have the potential to affect major arteries and result in death by blood loss.

Traumatic
Hemothorax is most often caused by blunt or penetrating trauma to the chest. In blunt traumatic cases, hemothorax typically occurs when rib fracture damages the intercostal vessels or the intraparenchymal pulmonary vessel, while in penetrating trauma, hemothorax occurs due to injuries directly affecting blood vessels in the thoracic wall, lung parenchyma, or the heart. If large blood vessels such as the aorta are damaged, the blood loss can be massive. Minor chest trauma can cause hemothorax when the bloods ability to clot is diminished as result either of anticoagulant medications or when there are bleeding disorders such as hemophilia.

Iatrogenic
Iatrogenic hemothorax can occur as a complication of heart and lung surgery, for example the rupture of lung arteries caused by the placement of catheters, thoracotomy, thoracostomy, or thoracentesis. The most common iatrogenic causes include subclavian venous catheterizations and chest tube placements, with an occurrence rate of around 1% Sometimes, a Swan-Ganz catheter causes rupture of the pulmonary artery, causing a massive hemothorax. It can also be caused by other procedures like pleural, lung, or transbronchial biopsies, CPR, Nuss procedure, or endoscopic treatment of esophageal varices. Iatrogenic hemothorax is more common in people who have chronic kidney disease in the intensive care unit.

Nontraumatic
Less frequently, hemothoraces may occur spontaneously. Nontraumatic hemothoraces most frequently occur as a complication of some forms of cancer if the tumour invades the pleural space. Cancers responsible for hemothoraces include angiosarcomas, schwannomas, mesothelioma, thymomas, germ cell tumours, and lung cancer. Significant hemothoraces can occur with spontaneous rupture of small vessels when the bloods ability to clot is diminished as result of anticoagulant medications. In cases caused by anticoagulant therapy, the hemothorax becomes noticeable 4–7 days after anticoagulant therapy is started. In cases of hemothorax complicating pulmonary embolism treatment, the hemothorax is usually on the side of the original embolism. Those with an abnormal accumulation of air within the pleural space (a pneumothorax) can bleed into the cavity, which occurs in about 5% of cases of spontaneous pneumothorax, especially when lung bullae rupture. The resulting combination of air and blood within the pleural space is known as a hemopneumothorax. Bone growth in exostosis can create sharp edges, which can result in hemothorax by damaging adjacent arteries. It can occur postpartum due to the change in thoracic pressure during labor.

Vascular
Vascular causes of hemothorax include rupture of the descending aorta, in which case it initially involves the left pleural and mediastinal area due to the close vicinity of the pleural cavity. Rarely, a rupture of the thoracic aorta can result in a hemothorax, but the bleeding usually occurs in the pericardial space. Spontaneous tearing of blood vessels is more likely to occur in those with disorders that weaken blood vessels such as some forms of Ehlers-Danlos syndrome, disorders that lead to malformed blood vessels as seen in Rendu-Osler-Weber syndrome, or in bleeding disorders such as hemophilia and Glanzmann thromboastenia. Other rare causes of hemothorax include neurofibromatosis type 1 and extramedullary hematopoiesis.

Catamenial
Rarely, hemothoraces can arise due to extrapelvic endometriosis, a condition in which tissue similar to the lining that normally covers the inside of the uterus forms in unusual locations outside the pelvis. Endometriotic tissue that implants on the pleural surface can bleed in response to the hormonal changes of the menstrual cycle, causing what is known as a catamenial hemothorax as part of thoracic endometriosis along with catamenial pneumothorax, catamenial hemoptysis, and lung nodules of endometriosis. Catamenial hemothorax represents 14% of cases of thoracic endometriosis syndrome while catamenial pneumothorax is seen in 73%, catamenial hemoptysis in 7%, and pulmonary nodules in 6%.

Mechanism
When a hemothorax occurs, blood enters the pleural cavity. The blood loss from the circulation has several effects. Firstly, as blood builds up within the pleural cavity, it begins to interfere with the normal movement of the lungs, preventing one or both lungs from fully expanding and thereby interfering with the normal transfer of oxygen and carbon dioxide to and from the blood. Secondly, blood that has been lost into the pleural cavity can no longer be circulated. Hemothoraces can lead to significant blood loss – each half of the thorax can hold more than 1500 milliliters of blood, representing more than 25% of an average adults total blood volume. The body may struggle to cope with this blood loss, and tries to compensate by maintaining blood pressure by forcing the heart to pump harder and faster, and by squeezing or constricting small blood vessels in the arms and legs. These compensatory mechanisms can be recognised by a rapid resting heart rate and cool fingers and toes.If the blood within the pleural cavity is not removed, it will eventually clot. This clot tends to stick the parietal and visceral pleura together and has the potential to lead to scarring within the pleura, which if extensive leads to the condition known as a fibrothorax. Following the initial loss of blood, a small hemothorax may irritate the pleura, causing additional fluid to seep out, leading to a bloodstained pleural effusion. Furthermore, as enzymes in the pleural fluid begin to break down the clot, the protein concentration of the pleural fluid increases. As a result, the osmotic pressure of the pleural cavity increases, causing fluid to leak into the pleural cavity from the surrounding tissues.

Diagnosis
Hemothoraces are most commonly detected using a chest X-ray, although ultrasound is sometimes used in an emergency setting. It can be suspected in any person with any form of chest trauma. However, plain X-rays may miss smaller hemothoraces while other imaging modalities such as computed tomography (CT), or magnetic resonance imaging may be more sensitive. In cases where the nature of an effusion is in doubt, a sample of fluid can be aspirated and analysed in a procedure called thoracentesis. Physical examination is used initially. Auscultation has been reported to have an accuracy of nearly 100% in diagnosing hemopneumothorax.

Chest X-ray
A chest X-ray is the most common technique used to diagnosis a hemothorax. X-rays should ideally be taken in an upright position (an erect chest X-ray), but may be performed with the person lying on their back (supine) if an erect chest X-ray is not feasible. On an erect chest X-ray, a hemothorax is suggested by blunting of the costophrenic angle or partial or complete opacification of the affected half of the thorax. On a supine film the blood tends to layer in the pleural space, but can be appreciated as a haziness of one half of the thorax relative to the other. A small hemothorax may be missed on a chest X-ray as several hundred milliliters of blood can be hidden by the diaphragm and abdominal viscera on an erect film. Supine X-rays are even less sensitive and as much as one liter of blood can be missed on a supine film.

Other methods
Ultrasonography may be used to detect hemothorax and other pleural effusions. This technique is of particular use in the critical care and trauma settings as it provides rapid, reliable results at the bedside. Ultrasound is more sensitive than chest x-ray in detecting hemothorax. Ultrasound can cause issues in people who are morbidly obese or have subcutaneous emphysema. When CT is unavailable in the current setting or the person cannot be moved to the scan, ultrasound is used.Computed tomography (CT or CAT) scans may be useful for diagnosing retained hemothorax as this form of imaging can detect much smaller amounts of fluid than a plain chest X-ray. However, CT is less used as a primary means of diagnosis within the trauma setting, as these scans require a critically ill person to be transported to a scanner, are slower, and require the subject to remain supine.Magnetic resonance imaging (MRI) can be used to differentiate between a hemothorax and other forms of pleural effusion, and can suggest how long the hemothorax has been present for. Fresh blood can be seen as a fluid with low T1 but high T2 signals, while blood that has been present for more than a few hours displays both low T1 and T2 signals. MRI is used infrequently in the trauma setting due to the prolonged time required to perform an MRI, and the deterioration in image quality that occurs with motion.

Thoracentesis
Although imaging techniques can demonstrate that fluid is present within the pleural space, it may be unclear what this fluid represents. To establish the nature of the fluid, a sample can be removed by inserting a needle into the pleural cavity in a procedure known as a thoracentesis or pleural tap. In this context, the most important assessment of the pleural fluid is the percentage by volume that is taken up by red blood cells (the hematocrit) A hemothorax is defined as having a hematocrit of at least 50% of that found in the affected persons blood, although the hematocrit of a chronic hemothorax may be between 25 and 50% if additional fluid has been secreted by the pleura. Pleural fluid can dilute hemothoraces in as low as 3–4 days. The red blood cells in the effusion spontaneously break down. Distinguishing the pleural fluid from blood by colour is impossible when the hematocrit value is over 5%. For these reasons, even if there is a hematocrit value under 50%, further investigations can be done in order to figure out if there is a source of bleeding. Hematocrit can be roughly calculated by dividing the red blood cell count of the pleural fluid by 100,000. Thoracentesis is the test most commonly used to diagnose a hemothorax in animals. Hemothorax can itself be a rare complication of thoracentesis if the intercostal artery is punctured.

Treatment
The treatment of a hemothorax depends largely on the extent of bleeding. While small hemothoraces may require little in the way of treatment, larger hemothoraces may require fluid resuscitation to replace the blood that has been lost, drainage of the blood within the pleural space using a procedure known as a tube thoracostomy, and potentially surgery in the form of a thoracotomy or video-assisted thoracoscopic surgery (VATS) to prevent further bleeding. Occasionally, transcatheter arterial embolization may be used to stop ongoing arterial bleeding. Additional treatment options include antibiotics to reduce the risk of infection and fibrinolytic therapy to break down clotted blood within the pleural space.

Thoracostomy
Blood in the cavity can be removed by inserting a drain (chest tube) in a procedure called a tube thoracostomy. This procedure is indicated for most causes of hemothorax, but should be avoided in aortic rupture which should be managed with immediate surgery. The thoracostomy tube is usually placed between the ribs in the sixth or seventh intercostal space at the mid-axillary line. It is important to avoid a chest tube becoming obstructed by clotted blood as obstruction prevents adequate drainage of the pleural space. Clotting occurs as the clotting cascade is activated when the blood leaves the blood vessels and comes into contact with the pleural surface, injured lung or chest wall, or the thoracostomy tube. Inadequate drainage may lead to a retained hemothorax, increasing the risk of infection within the pleural space (empyema) or the formation of scar tissue (fibrothorax). Thoracostomy tubes with a diameter of 24–36 F (large-bore tubes) should be used, as these reduce the risk of blood clots obstructing the tube. Manual manipulation of chest tubes (referred to as milking, stripping, or tapping) is commonly performed to maintain an open tube, but no conclusive evidence has demonstrated that this improves drainage. If a chest tube does become obstructed, the tube can be cleared using open or closed techniques. Tubes should be removed as soon as drainage has stopped, as prolonged tube placement increases the risk of empyema.

Surgery
About 10–20% of traumatic hemothoraces require surgical management. Larger hemothoraces, or those that continue to bleed following drainage, may require surgery. This surgery may take the form of a traditional open-chest procedure (a thoracotomy), but may be performed using video-associated thoracoscopic surgery (VATS). While there is no universally accepted cutoff for the volume of blood loss required before surgery is indicated, generally accepted indications include more than 1500 mL of blood drained from a thoracostomy, bleeding rate of over 500mL/hr in the first hour followed by over 200 mL, hemodynamic instability, or the need for repeat blood transfusions. VATS is less invasive and cheaper than an open thoracotomy, and can reduce the length of hospital stay, but a thoracotomy may be preferred when hypovolemic shock is present, in order to watch bleeding. The procedure should ideally be performed within 72 hours of the injury as delay may increase the risk of complications. In clotted hemothorax, VATS is the generally preferred procedure to remove the clot, and is indicated if the hemothorax fills 1/3 or more of a hemithorax. The ideal time to remove a clot using VATS is at 48–96 hours, but can be attempted up to nine days after the injury.

Other
Thoracentesis is no longer used in the treatment of hemothorax, although it may still be used to treat small hemothoraces. In catamenial hemothorax, the bleeding is typically self-limiting and mild. Most people with the condition are stable and can be treated with hormonal therapies. They are only partially effective. Surgical removal of the endometrial tissue may be necessary in recurrent cases. However, the disease frequently recurs. Resuscitation with intravenous fluids or with blood products may be required. In fulminant cases, transfusions may be administered before admission to the hospital. Clotting abnormalities, such as those caused by anticoagulant medications, should be reversed. Prophylactic antibiotics are given for 24 hours in the case of trauma. Blood clots may be retained within the pleural cavity despite chest tube drainage. They are a risk factor for complications like fibrothorax and empyema. Such retained clots should be removed, preferably with video-assisted thoracoscopic surgery (VATS). If VATS is unavailable, an alternative is fibrinolytic therapy such as streptokinase or urokinase given directly into the pleural space seven to ten days after the injury. The issues with fibrinolytic therapy include having a high cost and lengthened hospital stay. Residual clot that does not dissipate in response to fibrinolytics may require surgical removal in the form of decortication.

Prognosis
The prognosis following a hemothorax depends on its size, the treatment given, and the underlying cause. While small hemothoraces may cause little in the way of problems, in severe cases an untreated hemothorax may be rapidly fatal due to uncontrolled blood loss. If left untreated, the accumulation of blood may put pressure on the mediastinum and the trachea, limiting the hearts ability to fill. However, if treated, the prognosis following a traumatic hemothorax is usually favourable and dependent on other non-thoracic injuries that have been sustained at the same time, the age of the person, and the need for mechanical ventilation. Hemothoraces caused by benign conditions such as endometriosis have a good prognosis, while those caused by neurofibromatosis type 1 has a 36% rate of death, and those caused by aortic rupture are often fatal. Penetrating trauma is significantly less common, and has a much higher death rate, with up to 90% dying before arriving at the hospital. Gunshot wounds are associated with a higher death rates compared to stab wounds. In cases of penetrating trauma involving the heart, less than 1% survive.

Complications
Complications can occur following a hemothorax, and are more likely to occur if the blood has not been adequately drained from the pleural cavity. Blood that remains within the pleural space can become infected, and is known as an empyema. It occurs in 3–4% of traumatic cases, and 27-33% of retained hemothoraces. It is more likely in people who develop shock, had a contaminated pleural space during the injury, persistent bronchopleural fistulae, and lung contusions. The likelihood of it can be reduced by keeping thoracostomy tubes sterile and by keeping the pleural surfaces close together to prevent fluid or blood from accumulating between the surfaces. The retained blood can irritate the pleura, causing scar tissue (adhesions) to form. If extensive, this scar tissue can encase the lung, restricting movement of the chest wall, and is then referred to as a fibrothorax. Less than 1 percent of cases go on to develop a fibrothorax. Cases with hemopneumothorax or infection more often develop fibrothorax. After the chest tube is removed, over 10% of cases develop pleural effusions that are mostly self-limited and leave no lasting complications. In such cases, thoracentesis is performed to eliminate the possibility of an infection being present. Other potential complications include atelectasis, lung infection, pneumothorax, sepsis, respiratory distress, hypotension, tachycardia, pneumonia, adhesions, and impaired lung function.

Epidemiology
Trauma to the thorax results in approximately 16,000 to 30,000 deaths every year. There are about 300,000 cases of hemothorax in the U.S every year. Polytrauma (injury to multiple body systems) involves chest injuries in 60% of cases and commonly leads to hemothorax. In a case study, 37% of people hospitalized for blunt chest trauma had traumatic hemothorax. Hemothorax commonly occurs with a displaced rib fracture.

Other animals
Horses
In horses, hemothorax is uncommon and usually traumatic. It may occur along with pneumothorax. It is mainly diagnosed by ultrasound. Treatment involves supportive care, correction of the underlying cause, and occasionally drainage. The prognosis is variable.
Hemothorax is usually caused by trauma to the thorax. It can result from any injury that involves the pleural, intercostal, intervertebral, cardiac, or thoracic wall muscle. It can rarely be caused by diaphragmatic rupture that results in abdominal herniation. Hemothorax can be caused be cancers involving the thoracic, pulmonary, and mediastinal wall. The most common cancer resulting in hemothorax is a hemangiosarcoma.Clinical signs and symptoms may be variable and cause-dependant. They may include rapid breathing, pain, and shallow breathing in cases with a rib fracture. In the case of extensive bleeding, signs of hypovolemia may occur, and rapid death may result within hours. In less acute cases with slower bleeding, anemia and hypoproteinemia may gradually develop.Ultrasound can detect blood in the pleural cavity. Blood in the thorax is shown by a uniform area without flocculation. Pleural effusions without blood are usually hypoechoic. Echogenicity is indicated by cellular debris and/or fibrin. Bloody pleural effusions are shows by a swirling, hyperechoic pattern. When a stethoscope is used (auscultation), the heartbeat sounds are faint. When percussion is performed, it produces a dull area. However, especially in traumatic cases, percussion may be painful </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Reflex syncope and can you explain it in depth? [/INST] Reflex syncope is a brief loss of consciousness due to a neurologically induced drop in blood pressure and/or a  decrease  in  heart  rate. Before an affected person passes out, there may be sweating, a decreased ability to see, or ringing in the ears. Occasionally, the person may twitch while unconscious. Complications of reflex syncope include injury due to a fall.Reflex syncope is divided into three types: vasovagal, situational, and carotid sinus. Vasovagal syncope is typically triggered by seeing blood, pain, emotional stress, or prolonged standing. Situational syncope is often triggered by urination, swallowing, or coughing. Carotid sinus syncope is due to pressure on the carotid sinus in the neck. The underlying mechanism involves the nervous system slowing the heart rate and dilating blood vessels, resulting in low blood pressure and thus not enough blood flow to the brain. Diagnosis is based on the symptoms after ruling out other possible causes.Recovery from a reflex syncope episode happens without specific treatment. Prevention of episodes involves avoiding a persons triggers. Drinking sufficient fluids, salt, and exercise may also be useful. If this is insufficient for treating vasovagal syncope, medications such as midodrine or fludrocortisone may be tried. Occasionally, a cardiac pacemaker may be used as treatment. Reflex syncope affects at least 1 in 1,000 people per year. It is the most common type of syncope, making up more than 50% of all cases.

Signs and symptoms
Episodes of vasovagal syncope are typically recurrent and usually occur when the predisposed person is exposed to a specific trigger. Before losing consciousness, the individual frequently experiences early signs or symptoms such as lightheadedness, nausea, the feeling of being extremely hot or cold (accompanied by sweating), ringing in the ears, an uncomfortable feeling in the heart, fuzzy thoughts, confusion, a slight inability to speak or form words (sometimes combined with mild stuttering), weakness and visual disturbances such as lights seeming too bright, fuzzy or tunnel vision, black cloud-like spots in vision, and a feeling of nervousness can occur as well. The symptoms may become more intense over several seconds to several minutes before the loss of consciousness (if it is lost). Onset usually occurs when a person is sitting up or standing.When people lose consciousness, they fall down (unless prevented from doing so) and, when in this position, effective blood flow to the brain is immediately restored, allowing the person to regain consciousness. If the person does not fall into a fully flat, supine position, and the head remains elevated above the trunk, a state similar to a seizure may result from the bloods inability to return quickly to the brain, and the neurons in the body will fire off and generally cause muscles to twitch very slightly but mostly remain very tense.The autonomic nervous systems physiological state (see below) leading to loss of consciousness may persist for several minutes, so

If patients try to sit or stand when they wake up, they may pass out again
The person may be nauseated, pale, and sweaty for several minutes or hours

Causes
Reflex syncope occurs in response to a trigger due to dysfunction of the heart rate and blood pressure regulating mechanism. When heart rate slows or blood pressure drops, the resulting lack of blood to the brain causes fainting.

Vasovagal
Typical triggers include:

Prolonged standing
Emotional stress
Pain
The sight of blood
Fear of needles
Time varying magnetic field (i.e. transcranial magnetic stimulation)

Situational
After or during urination (micturition syncope)
Straining, such as to have a bowel movement
Coughing
Swallowing
Lifting a heavy weight

Carotid sinus
Pressing upon a certain spot in the neck. This may happen when wearing a tight collar, shaving, or turning the head.

Pathophysiology
Regardless of the trigger, the mechanism of syncope is similar in the various vasovagal syncope syndromes. The nucleus tractus solitarii of the brainstem is activated directly or indirectly by the triggering stimulus, resulting in simultaneous enhancement of parasympathetic nervous system (vagal) tone and withdrawal of sympathetic nervous system tone.This results in a spectrum of hemodynamic responses:

On one end of the spectrum is the cardioinhibitory response, characterized by a drop in heart rate (negative chronotropic effect) and in contractility (negative inotropic effect) leading to a decrease in cardiac output that is significant enough to result in a loss of consciousness. It is thought that this response results primarily from enhancement in parasympathetic tone.
On the other end of the spectrum is the vasodepressor response, caused by a drop in blood pressure (to as low as 80/20) without much change in heart rate. This phenomenon occurs due to dilation of the blood vessels, probably as a result of withdrawal of sympathetic nervous system tone.
The majority of people with vasovagal syncope have a mixed response somewhere between these two ends of the spectrum.One account for these physiological responses is the Bezold-Jarisch reflex.
Vasovagal syncope may be part of an evolved response, specifically, the fight-or-flight response.

Diagnosis
In addition to the mechanism described above, a number of other medical conditions may cause syncope. Making the correct diagnosis for loss of consciousness is difficult. The core of the diagnosis of vasovagal syncope rests upon a clear description of a typical pattern of triggers, symptoms, and time course.It is pertinent to differentiate lightheadedness, seizures, vertigo, and low blood sugar as other causes.
In people with recurrent vasovagal syncope, diagnostic accuracy can often be improved with one of the following diagnostic tests:

A tilt table test (results should be interpreted in the context of patients clinical presentations and with an understanding of the sensitivity and specificity of the test)
Implantation of an insertable loop recorder
A Holter monitor or event monitor
An echocardiogram
An electrophysiology study

Treatment
Treatment for reflex syncope focuses on avoidance of triggers, restoring blood flow to the brain during an impending episode, and measures that interrupt or prevent the pathophysiologic mechanism described above.

Lifestyle changes
The cornerstone of treatment is avoidance of triggers known to cause syncope in that person. However, research has shown that people show great reductions in vasovagal syncope through exposure-based exercises with therapists if the trigger is mental or emotional, e.g., sight of blood. However, if the trigger is a specific drug, then avoidance is the only treatment.
A technique known as "applied tension" may be additionally useful in those who have syncope with exposure to blood. The technique is done by tightening the skeletal muscles for about 15 seconds when the exposure occurs and then slowing releasing them. This is then repeated every 30 seconds for a few minutes.
Because vasovagal syncope causes a decrease in blood pressure, relaxing the entire body as a mode of avoidance is not favorable. A person can move or cross their legs and tighten leg muscles to keep blood pressure from dropping so significantly before an injection.
Before known triggering events, the affected person may increase consumption of salt and fluids to increase blood volume. Sports drinks or drinks with electrolytes may be helpful.
People should be educated on how to respond to further episodes of syncope, especially if they experience prodromal warning signs: they should lie down and raise their legs, or at least lower their head to increase blood flow to the brain </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Juvenile polyposis syndrome and can you explain it in depth? [/INST] Juvenile polyposis syndrome is an autosomal dominant genetic condition characterized by the appearance of multiple juvenile polyps in the gastrointestinal tract. Polyps are abnormal growths arising from a mucous membrane. These usually begin appearing before age 20, but the term juvenile refers to the type of polyp (i.e benign hamartoma, as opposed to adenoma for example), not to the age of the affected person. While the majority of the polyps found in juvenile polyposis syndrome are non-neoplastic, hamartomatous, self-limiting and benign, there is an increased risk of adenocarcinoma.
Solitary juvenile polyps most commonly occur in the rectum and present with rectal bleeding. The World Health Organization criteria for diagnosis of juvenile polyposis syndrome are one of either:

More than five juvenile polyps in the colon or rectum; or
Juvenile polyps throughout the gastrointestinal tract; or
Any number of juvenile polyps in a person with a family history of juvenile polyposis.

Signs and symptoms
Age of onset is variable. The term juvenile in the title of juvenile polyposis syndrome refers to the histological type of the polyps rather than the age of onset.
Affected individuals may present with rectal bleeding, abdominal pain, diarrhea or anemia. On colonoscopy or sigmoidoscopy polyps that vary in shape or size are present. The polyps can be sessile or pedunculated hamartomatous polyps.

Genetics
Juvenile polyposis syndrome can occur sporadically in families or be inherited in an autosomal dominant manner.Two genes associated with juvenile polyposis syndrome are BMPR1A and SMAD4. Gene testing may be useful when trying to ascertain which non-symptomatic family members may be at risk of developing polyps, however having a known familial mutation would be unlikely to change the course of treatment. A known mutation may also be of use for affected individuals when they decide to start a family as it allows them reproductive choices.While mutations in the gene PTEN were also thought to have caused juvenile polyposis syndrome, it is now thought that mutations in this gene cause a similar clinical picture to juvenile polyposis syndrome but are actually affected with Cowden syndrome or other phenotypes of the PTEN hamartoma tumor syndrome.

Screening
People with juvenile polyps may require yearly upper and lower endoscopies with polyp excision and cytology. Their siblings may also need to be screened regularly.

Treatment
Malignant transformation of polyps requires surgical colectomy.

Prognosis
Most juvenile polyps are benign; however, malignancy can occur </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Primary pigmented nodular adrenocortical disease and can you explain it in depth? [/INST] Primary pigmented nodular adrenocortical disease (PPNAD) was first coined in 1984 by Carney et al. it often occurs in association with Carney complex (CNC). CNC is a rare syndrome that involves the formation of abnormal tumours that cause endocrine hyperactivity.
PPNAD arises due to the enlargement of the cortex of the adrenal glands, resulting in Cushings syndrome that is independent of the pituitary hormone ACTH.

Signs and symptoms
PPNAD is a rare cause of high cortisol levels in the blood and often manifests as ACTH-independent Cushings syndrome. The effects of PPNAD can often be cyclical so the symptoms of Cushings syndrome will not always be as severe, which may complicate diagnosis. The classic symptoms of Cushings syndrome include rapid central weight gain, a puffy red face and a buffalo hump at the back of the neck due to fat deposits. Skin changes in Cushings syndrome include thinning and bruising easily, developing striae and hyperpigmentation at skin folds. The hormonal changes can lead to hirsutism, males developing breast tissue, females no longer having periods and both sexes may become infertile. High cortisol levels can lead to psychological disturbances such as anxiety or depression and insomnia. Bone health can deteriorate, leading to an increased fracture risk in people with Cushings syndrome. PPNAD is unique as it often causes Cushings at a young age, in children and adolescents. In addition to the other symptoms of Cushings syndrome, the patient may have a short stature due to interrupted growth because of ACTH  suppression.In 90% of people with PPNAD it is associated with Carney Complex. Carney Complex is usually inherited, however it can also occur sporadically. A visible sign of Carney complex is abnormal skin hyperpigmentation. There may also be myxomas which can appear as lumps in the skin and breast as well as often being present in the heart, which can lead to multiple cardiovascular problems. The majority of people with PPNAD will have some of these signs/symptoms due to the strong association between PPNAD and Carney Complex.

Causes
PPNAD, the endocrine manifestation that comes from Carney Complex (CNC), can be syndromic or isolated. The main cause of isolated PPNAD is a mutation of PRKAR1α, located at 17q22-24, which is the gene encoding the regulatory R1α subunit of protein kinase A. Germline heterozygous PRKAR1α inactivation mutations are present in 80% of CNC patients affected by Cushings syndrome. There are over 117 mutations of the PRKAR1α gene that can cause CNC, with many of these mutations producing premature stop codons, thus resulting in the complete loss of PRKAR1α protein. CNC patients have also been discovered with an unusually shortened PRKAR1α protein, detected in tumours and leukocytes, following a splice-site mutation, which causes exon-6 skipping. Therefore, both haploinsufficiency and the complete loss of PRKAR1α can lead to the increased PKA activity observed in PPNAD patients, due to the disruption of the cAMP signalling pathway.Sahut-Barnola et al. used a mouse model to cre-lox knockout the Prkar1a gene specifically from cells of the adrenal cortex and observed that the mice subsequently developed Cushing syndrome that is independent of the pituitary. They also observed that the mutation caused increased PKA activity.The R1α loss caused the adult adrenal gland became hyperactive and hyperplastic on both sides, as seemingly the foetal adrenal cells within it were not maintained and thus expanded. This established tumoral growths </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Blind loop syndrome and can you explain it in depth? [/INST] Blind loop syndrome (BLS), also known as stagnant loop syndrome, is a state that occurs when the normal bacterial flora of the small intestine proliferates to numbers that cause significant derangement to the normal physiological processes of digestion and absorption. In some cases of blind loop syndrome, overgrowth of pathogenic non-commensal bacteria has also been noted. It has long been understood that from birth, and throughout life, large amounts of bacteria reside symbiotically within animal gastrointestinal tracts such as the human gastrointestinal tract. The understanding of this gut flora has even led to novel treatments for bowel irregularity that utilize  so called "probiotics" or good bacteria that aid in normal digestion.
The problem of BLS arises when the bacterial colonies residing in the upper gastrointestinal tract begin to grow out of control or are altered in their makeup thereby creating a burden on the normal physiological processes occurring in the small intestine </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Unibrow and can you explain it in depth? [/INST] A unibrow (or jacco brow or monobrow; called synophrys in medicine) is a single eyebrow created when the two eyebrows meet in the middle above the bridge of the nose </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Erythema dyschromicum perstans and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Beaus lines and can you explain it in depth? [/INST] Beaus lines are deep grooved lines that run from side to side on the fingernail or the toenail. They may look like indentations or ridges in the nail plate.: 657   This condition of the nail was named by a French physician, Joseph Honoré Simon Beau (1806–1865), who first described it in 1846.

Signs and symptoms
Beaus lines are horizontal, going across the nailline, and should not be confused with vertical ridges going from the bottom (cuticle) of the nail out to the fingertip.  These vertical lines are usually a natural consequence of aging and are harmless.Beaus lines should also be distinguished from Muehrckes lines of the fingernails.  While Beaus lines are actual ridges and indentations in the nail plate, Muehrcke lines are areas of hypopigmentation without palpable ridges; they affect the underlying nail bed, and not the nail itself. Beaus lines should also be distinguished from Mees lines of the fingernails, which are areas of discoloration in the nail plate.
As the nail grows out, the ridge in the nail can be seen to move upwards until it reaches the fingertip </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Exanthem and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Early myoclonic encephalopathy and can you explain it in depth? [/INST] Early myoclonic encephalopathy (EME) is a rare  neonatal-onset epilepsy developmental and epileptic encephalopathy (DEE) with an onset at neonatal period or during the first 3 months of life. It is marked by the presence of myoclonic seizures but multiple seizure types may occur. The electroencephalographic recording is abnormal with eitherusually a suppression-burst pattern or other significantly abnormal patterns. On most occasions the seizures are drug-resistant. After several months, the seizure pattern may develop into infantile spasms syndrome (West syndrome). The neurological exam is abnormal with a significant risk of early death. Various genetic and metabolic disorders are responsible. At present, EME and Ohtahara syndrome are recorded as distinct patterns in the categorization of epilepsies but both neonatal-onset epilepsy syndromes are considered to be merged in one unique entity. It is a severe type of epilepsy syndrome associated with high level of resistance to treatment and a high risk for cognitive impairment. The myoclonic seizures could be seen in other epilepsy syndromes. Multiple types of childhood epilepsies are usually mentioned as myoclonic epilepsies when the myoclonic seizures are a predominant feature.

Signs and symptoms
It is characterized by early-onset myoclonic seizures that can vary from erratic movements of a single limb or a part of the face (focal) to bilateral myoclonic movement of the whole body. The myoclonus may occur at any time (sleep, wakefulneess) from few times per day to very frequent or even continuous myoclonus. The symptoms may start appearing as early as a few hours after birth and up to three months of age. Around three-fourths of affected children present with neonatal seizure. Other seizure types such as focal or generalized tonic seizures, epileptic  spasms or other epileptic manifestations may occur at the course of the disease. The distinctive feature of the phenotype is severe progressive encephalopathy with delay in development and abnormal neurological examination delay (hypotonia, lethargy, poor eye contact, difficulties in feeding) usually being present even before the onset of other symptoms. Head circumference is usually normal at onset but microcephaly may develop over time. Family history is usually normal.

Causes
There are varied etiologies related to EME that are mainly genetic abnormalities (mutations), brain structure abnormalities, or inborn metabolic defects. Another common reason rather than structural brain abnormality is inborn metabolic defects. Sometimes a metabolic disorder that affects how the brain works may lead to EME. While most of these metabolic disorders cannot be reversed, sometimes treating the underlying disorder can help. Vitamin-responsive epileptic encephalopathies are rare but significant reasons.

Genetics
A growing number of genetic aetiologies have been linked to the phenotype of EME and Otahara syndrome and diagnosis by genetic testing can nowadays be achieved in around 50 percent of cases. Some examples of well described genetic aetiologies include: KCNQ2- DEE. • SCN2A-DEE • STXBP1-DEE. • CDKL5-DEE• KCNT1-DEE and UBA5-DEE.

Acquired
No acquired aetiologies are known for EME although etiology remains unknown for a small percentage of patients after genetic, metabolic, and imaging workup. Some acquired conditions may share some features with EME and should be differentiated from it. These include hypoxic-ischaemic encephalopathy, central nervous system infections, acute metabolic disturbances or acute vascular events.

Mechanism
Pathology results in EME consist of multifocal changes in white matter, imperfect lamination of the deep cortical layers, astrocytic proliferation, and demyelination.

Diagnosis
Electroencephalogram (EEG) is usually characterized by a burst suppression pattern. Subsequently it may transition to hypsarrhythmia, a chaotic pattern on EEG, or other severely abnormal EEG patterns. Neuroimaging is useful in assessing a possible underlying structural causality that might cause EME. MRI findings depend on the underlying etiology and may be normal or not at diagnosis.

Prevention
Early identification of metabolism error defects is very essential in prevention as the traditional antiepileptic drug are usually not very effective, proper treatment aiming to the conditions can prevent neurological worsening. Genetic counselling is critical given the high prevalence of genetic mutations and early genetic testing also helps to avoid unnecessary procedures and unsuccessful treatment. The families who are at risk, prophylactic treatment is suggested as it may stop the seizure and help in recovering the neurodevelopmental consequences.

Management
Antiepileptic drugs are used to treat EME, but it is difficult to control seizures with anti-epileptic drugs alone. Phenobarbital, valproate, pyridoxine, zonisamide, and benzodiazepines have all been used but with inadequate usefulness in seizure control </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Neorickettsia helminthoeca and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Atopic dermatitis and can you explain it in depth? [/INST] Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens over time. While the condition may occur at any age, it typically starts in childhood, with changing severity over the years. In children under one year of age, much of the body may be affected. As children get older, the areas on the insides of the knees and elbows are most commonly affected. In adults, the hands and feet are most commonly affected. Scratching the affected areas worsens the symptoms, and those affected have an increased risk of skin infections. Many people with atopic dermatitis develop hay fever or asthma.The cause is unknown but believed to involve genetics, immune system dysfunction, environmental exposures, and difficulties with the permeability of the skin. If one identical twin is affected, the other has an 85% chance of having the condition. Those who live in cities and dry climates are more commonly affected. Exposure to certain chemicals or frequent hand washing makes symptoms worse. While emotional stress may make the symptoms worse, it is not a cause. The disorder is not contagious. A diagnosis is typically based on the signs and symptoms. Other diseases that must be excluded before making a diagnosis include contact dermatitis, psoriasis, and seborrheic dermatitis.Treatment involves avoiding things that make the condition worse, daily bathing with application of a moisturising cream afterwards, applying steroid creams when flares occur, and medications to help with itchiness. Things that commonly make it worse include wool clothing, soaps, perfumes, chlorine, dust, and cigarette smoke. Phototherapy may be useful in some people. Steroid pills or creams based on calcineurin inhibitors may occasionally be used if other measures are not effective. Antibiotics (either by mouth or topically) may be needed if a bacterial infection develops. Dietary changes are only needed if food allergies are suspected.Atopic dermatitis affects about 20% of people at some point in their lives. It is more common in younger children. Females are slightly more affected than males. Many people outgrow the condition. Atopic dermatitis is sometimes called eczema, a term that also refers to a larger group of skin conditions. Other names include "infantile eczema", "flexural eczema", "prurigo Besnier", "allergic eczema", and "neurodermatitis".

Signs and symptoms
People with AD often have dry and scaly skin that spans the entire body, except perhaps the diaper area, and intensely itchy red, splotchy, raised lesions to form in the bends of the arms or legs, face, and neck.AD commonly affects the eyelids, where signs such as Dennie-Morgan infraorbital fold, infra-auricular fissure, and periorbital pigmentation can be seen. Postinflammatory hyperpigmentation on the neck gives the classic "dirty neck" appearance. Lichenification, excoriation, and erosion or crusting on the trunk may indicate secondary infection. Flexural distribution with ill-defined edges with or without hyperlinearity on the wrist, finger knuckles, ankle, feet, and hands are also commonly seen.

Causes
The cause of AD is not known, although  some evidence indicates genetic, environmental, and immunologic factors.

Climate
Low humidity, and low temperature increase the prevalence and risk of flares in patients with atopic dermatitis.

Genetics
Many people with AD have a family history or a personal history of atopy. Atopy is an immediate-onset allergic reaction (type-1 hypersensitivity reaction mediated by IgE) that may manifest as asthma, food allergies, AD, or hay fever. Up to 80% of people with atopic dermatitis have elevated total or allergen-specific IgE levels.About 30% of people with atopic dermatitis have mutations in the gene for the production of filaggrin (FLG), which increase the risk for early onset of atopic dermatitis and developing asthma.

Hygiene hypothesis
According to the hygiene hypothesis, early childhood exposure to certain microorganisms (such as gut flora and helminth parasites) protects against allergic diseases by contributing to the development of the immune system. This exposure is limited in a modern "sanitary" environment, and the incorrectly developed immune system is prone to develop allergies to harmless substances.
Some support exists for this hypothesis with respect to AD. Those exposed to dogs while growing up have a lower risk of atopic dermatitis. Also, epidemiological studies support a protective role for helminths against AD. Likewise, children with poor hygiene are at a lower risk for developing AD, as are children who drink unpasteurized milk.

Allergens
In a small percentage of cases, atopic dermatitis is caused by sensitization to foods. Also, exposure to allergens, either from food or the environment, can exacerbate existing atopic dermatitis. Exposure to dust mites, for example, is believed to contribute to ones risk of developing AD. A diet high in fruits seems to have a protective effect against AD, whereas the opposite seems true for fast foods. Atopic dermatitis sometimes appears associated with celiac disease and nonceliac gluten sensitivity, and the improvement with a gluten-free diet (GFD) indicates that gluten is a causative agent in these cases.

Role of Staphylococcus aureus
Colonization of the skin by the bacterium S. aureus is extremely prevalent in those with atopic dermatitis.  Abnormalities in the skin barrier of persons with AD are exploited by S. aureus to trigger cytokine expression, thus aggravating the condition.

Hard water
Atopic dermatitis in children may be linked to the level of calcium carbonate or "hardness" of household water, when used to drink. So far, these findings have been supported in children from the United Kingdom, Spain, and Japan.

Pathophysiology
Excessive type 2 inflammation underlies the pathophysiology of atopic dermatitis.Disruption of the epidermal barrier is thought to play an integral role in the pathogenesis of AD. Disruptions of the epidermal barrier allows allergens to penetrate the epidermis to deeper layers of the skin. This leads to activation of epidermal inflammatory dendritic and innate lymphoid cells which subsequently attracts Th2 CD4+ helper T cells to the skin. This dysregulated Th2 inflammatory response is thought to lead to the eczematous lesions. The Th2 helper T cells become activated, leading to the release of inflammatory cytokines including IL-4, IL-13 and IL-31 which activate downstream Janus kinase (Jak) pathways. The active Jak pathways lead to inflammation and downstream activation of plasma cells and B lymphocytes which release antigen specific IgE contributing to further inflammation. Other CD4+ helper T-cell pathways thought to be involved in atopic dermatitis inflammation include the Th1, Th17, and Th22 pathways. Some specific CD4+ helper T-cell inflammatory pathways are more commonly activated in specific ethnic groups with AD (for example, the Th-2 and Th-17 pathways are commonly activated in Asian people) possibly explaining the differences in phenotypic presentation of atopic dermatitis in specific populations.Mutations in the filaggrin gene, FLG, also cause impairment in the skin barrier that contributes to the pathogenesis of AD. Filaggrin is produced by epidermal skin cells (keratinocytes) in the horny layer of the epidermis. Filaggrin stimulates skin cells to release moisturizing factors and lipid matrix material, which cause adhesion of adjacent keratinocytes and contributes to the skin barrier. A loss-of-function mutation of filaggrin causes loss of this lipid matrix and external moisturizing factors, subsequently leading to disruption of the skin barrier. The disrupted skin barrier leads to transdermal water loss (leading to the xerosis or dry skin commonly seen in AD) and antigen and allergen penetration of the epidermal layer. Filaggrin mutations are also associated with a decrease in natural antimicrobial peptides found on the skin; subsequently leading to disruption of skin flora and bacterial overgrowth (commonly Staphylococcus aureus overgrowth or colonization).Atopic dermatitis is also associated with the release of pruritogens (molecules that stimulate pruritus or itching) in the skin. Keratinocytes, mast cells, eosinophils and T-cells release pruritogens in the skin; leading to activation of Aδ fibers and Group C nerve fibers in the epidermis and dermis contributing to sensations of pruritus and pain. The pruritogens include the Th2 cytokines IL-4, IL-13, IL-31, histamine, and various neuropeptides. Mechanical stimulation from scratching lesions can also lead to the release of pruritogens contributing to the itch scratch cycle whereby there is increased pruritus or itch after scratching a lesion. Chronic scratching of lesions can cause thickening or lichenification of the skin or prurigo nodularis (generalized nodules that are severely itchy).

Diagnosis
AD is typically diagnosed clinically, meaning it is based on signs and symptoms alone, without special testing. Several different criteria developed for research have also been validated to aid in diagnosis. Of these, the UK Diagnostic Criteria, based on the work of Hanifin and Rajka, has been the most widely validated.

Treatments
No cure for AD is known, although treatments may reduce the severity and frequency of flares.

Humidity
A humidifier can be used to prevent low indoor humidity during winter (especially with indoor heating), and dry season. And a dehumidifier can be used during seasons with excessive humidity.
Applying moisturisers may prevent the skin from drying out and decrease the need for other medications. Affected persons often report that improvement of skin hydration parallels with improvement in AD symptoms.

Lifestyle
Health professionals often recommend that persons with AD bathe regularly in lukewarm baths, especially in salt water, to moisten their skin. Avoiding woolen clothing is usually good for those with AD. Likewise silk, silver-coated clothing may help. Dilute bleach baths have also been reported effective at managing AD.

Diet
The role of vitamin D on atopic dermatitis is not clear, but some evidence shows that vitamin D supplementation may improve its symptoms.Studies have investigated the role of long-chain polyunsaturated fatty acid (LCPUFA) supplementation and LCPUFA status in the prevention and treatment of AD, but the results are controversial. Whether the nutritional intake of n-3 fatty acids has a clear preventive or therapeutic role, or if n-6 fatty acids consumption promotes atopic diseases is unclear.Several probiotics seem to have a positive effect, with a roughly 20% reduction in the rate of AD. The best evidence is for multiple strains of bacteria.In people with celiac disease or nonceliac gluten sensitivity, a gluten-free diet improves their symptoms and prevents the occurrence of new outbreaks.

Medication
Topical corticosteroids, such as hydrocortisone, have proven effective in managing AD. If topical corticosteroids and moisturisers fail, short-term treatment with topical calcineurin inhibitors such as tacrolimus or pimecrolimus may be tried, although their use is controversial, as some studies indicate that they increase the risk of developing skin cancer or lymphoma. A 2007 meta-analysis showed that topical pimecrolimus is not as effective as corticosteroids and tacrolimus. A 2015 meta-analysis, though, indicated that topical tacrolimus and pimecrolimus are more effective than low-dose topical corticosteroids, and found no evidence for increased risk of malignancy or skin atrophy. In 2016, crisaborole, an inhibitor of PDE-4, was approved as a topical treatment for mild-to-moderate eczema.Other medications used for AD include systemic immunosuppressants such as ciclosporin, methotrexate, interferon gamma-1b, mycophenolate mofetil, and azathioprine. Antidepressants and naltrexone may be used to control pruritus (itchiness). Leukotriene inhibitors such as monteleukast are of unclear benefit as of 2018.In 2017, the monoclonal antibody(mAb) dupilumab under the trade name Dupixent was approved to treat moderate-to-severe eczema.
In 2021, an additional monoclonal antibody, tralokinumab, was approved in the EU & UK with the trade name Adtralza then later in the US as Adbry for similarly severe cases. Another monoclonal antibody treatment, lebrikizumab, is in phase 3 trials in the US; the drug has been granted Fast Track Designation by the FDA, and Eli Lilly and Company is expected to apply for FDA approval of the drug in the second half of 2022.Some JAK inhibitors such as abrocitinib, trade name Cibinquo, and upadacitinib, trade name Rinvoq, have been approved in the US for the treatment of moderate-to-severe eczema as of January 2022.
Tentative, low-quality evidence indicates that allergy immunotherapy is effective in AD. This treatment consists of a series of injections or drops under the tongue of a solution containing the allergen.Antibiotics, either by mouth or applied topically, are commonly used to target overgrowth of S. aureus in the skin of people with AD, but a 2019 meta-analysis found no clear evidence of benefit.

Light
A more novel form of treatment involves exposure to broad- or narrow-band ultraviolet (UV) light. UV radiation exposure has been found to have a localized immunomodulatory effect on affected tissues and may be used to decrease the severity and frequency of flares. In particular, the usage of UVA1 is more effective in treating acute flares, whereas narrow-band UVB is more effective in long-term management scenarios </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pityriasis rubra pilaris and can you explain it in depth? [/INST] Pityriasis rubra pilaris  refers to a group of chronic disorders characterized by reddish orange, scaling plaques and keratotic follicular papules.: 442   Symptoms may include reddish-orange patches (Latin: rubra) on the skin, severe flaking (Latin: pityriasis), uncomfortable itching, thickening of the skin on the feet and hands, and thickened bumps around hair follicles (Latin: pilus for hair). For some, early symptoms may also include generalized swelling of the legs, feet and other parts of the body. PRP has a varied clinical progression and a varied rate of improvement.  There is currently no known cause or cure for PRP.
It was first described by Marie-Guillaume-Alphonse Devergie in 1856, and the condition is also known as Devergies disease.

Diagnosis
Classification
Dr. W.A.D. Griffiths, from Great Britain, classified six forms of PRP in the early 1980s.  At this time, the causes of PRP are still unknown and symptoms can be difficult to diagnose.  Frequently, more than one medical professional will be consulted before an accurate PRP diagnosis is made.Dermatologists have identified both an acquired form and an inherited form (familial) of PRP and have described them in medical journals.  The acquired form usually shows a spontaneous or gradual remission of symptoms within several years although long-term symptoms may continue for years.  The inherited form starts early in childhood with persistent long-term symptoms into adulthood.Although most people who develop PRP are over age 50, individuals of any age, race, and nationality can be affected.  Women and men seem to be equally affected.

Treatment
Treatment with emollients is used to relieve symptoms of cracking and dryness. Application of lubricants under plastic occlusion before bedtime appears to aid removal of scales on hands and feet. Other topical options include: topical corticosteroids alone, or combined with keratolytics, such as urea and vitamin D3 analogues.
The most effective therapy is long term use of oral retinoids, such as acitretin and isotretinoin. Other effective systemic approaches include: methotrexate, cyclosporin and corticosteroids. There are also reports that the monoclonal antibody ustekinumab (which blocks IL-23/ IL-12) may be effective.

See also
List of cutaneous conditions

Footnotes
Further reading
Dr </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Purpura and can you explain it in depth? [/INST] Purpura () is a condition of  red or purple discolored spots on the skin that do not blanch on applying pressure </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Peritonsillar abscess and can you explain it in depth? [/INST] Peritonsillar abscess (PTA), also known as quinsy, is an accumulation of pus due to an infection behind the tonsil. Symptoms include fever, throat pain, trouble opening the mouth, and a change to the voice. Pain is usually worse on one side. Complications may include blockage of the airway or aspiration pneumonitis.PTA is typically due to infection by a number of types of bacteria. Often it follows streptococcal pharyngitis. They do not typically occur in those who have had a tonsillectomy. Diagnosis is usually based on the symptoms. Medical imaging may be done to rule out complications.Treatment is by removing the pus, antibiotics, sufficient fluids, and pain medication. Steroids may also be useful. Admission to hospital is generally not needed. In the United States about 3 per 10,000 people per year are affected. Young adults are most commonly affected.

Signs and symptoms
Physical signs of a peritonsillar abscess include redness and swelling in the tonsillar area of the affected side and swelling of the jugulodigastric lymph nodes. The uvula may be displaced towards the unaffected side.Unlike tonsillitis, which is more common in children, PTA has a more even age spread, from children to adults. Symptoms start appearing two to eight days before the formation of an abscess. A progressively severe sore throat on one side and pain during swallowing (odynophagia) usually are the earliest symptoms. As the abscess develops, persistent pain in the peritonsillar area, fever, a general sense of feeling unwell, headache, and a distortion of vowels informally known as "hot potato voice" may appear. Neck pain associated with tender, swollen lymph nodes, referred ear pain and foul breath are also common. While these signs may be present in tonsillitis itself, a PTA should be specifically considered if there is limited ability to open the mouth (trismus).

Complications
While most people recover uneventfully, there is a wide range of possible complications. These may include:
Retropharyngeal abscess
Extension of abscess in other deep neck spaces leading to airway compromise (see Ludwigs angina)
Airway obstruction
Aspiration pneumonitis
Lung abscess (following rupture)
Sepsis
Life-threatening hemorrhage (following erosion or septic necrosis into the carotid sheath of the neck)
Glomerulonephritis and rheumatic fever (chronic complications of strep throat)Difficulty swallowing can lead to decreased oral intake and dehydration.

Causes
PTA usually arises as a complication of an untreated or partially treated episode of acute tonsillitis. The infection, in these cases, spreads to the peritonsillar area (peritonsillitis).  This region comprises loose connective tissue and is hence susceptible to formation of an abscess.  PTA can also occur de novo. Both aerobic and anaerobic bacteria can be causative. Commonly involved aerobic pathogens include Streptococcus, Staphylococcus and Haemophilus. The most common anaerobic species include Fusobacterium necrophorum,  Peptostreptococcus, Prevotella species, and Bacteroides.

Diagnosis
Diagnosis is usually based on the symptoms. Medical imaging may be done to rule out complications. Medical imaging may include CT scan, MRI, or ultrasound is also useful in diagnosis.

Treatment
Medical treatment with antibiotics, volume repletion with fluids, and pain medication is usually adequate, although in cases where airway obstruction or systemic sepsis occurs, surgical drainage may be necessary </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Dens invaginatus and can you explain it in depth? [/INST] Dens invaginatus (DI), also known as tooth within a tooth, is a rare dental malformation where there is an infolding of enamel into dentine. The prevalence of condition is 0.3 - 10%, affecting more males than females. The condition is presented in two forms, coronal and radicular, with the coronal form being more common.
DI is a malformation of teeth most likely resulting from an infolding of the dental papilla during tooth development or invagination of all layers of the enamel organ in dental papillae. Affected teeth show a deep infolding of enamel and dentine starting from the foramen coecum or even the tip of the cusps and which may extend deep into the root. Teeth most affected are maxillary lateral incisors (80%), followed by maxillary canines (20%). Bilateral occurrence is not uncommon (25%).

Signs and symptoms
Tooth affected by this condition has a higher risk of developing caries and periradicular pathology. The thin layer of the infolding enamel could be chipped off easily, providing entrance for microorganisms into the tooth canal. This can cause abscess formation, displacement of dental structures (i.e. teeth). Preventive measures should be taken.

Cause
Cause of DI is unclear. However, there are several theories:

Infection
Trauma
Growth pressure of the dental arches during odontogenesis
Rapid proliferation of the internal enamel epithelium invades the underlying dental papilla

Diagnosis
During clinical examination, abnormally shaped tooth can be observed. Teeth with this condition can have a conical shape or deep pit on the lingual side or have an exaggerated talon cusp.
Although examination may reveal a fissure on the surface of anterior tooth, radiographic examination is the way. On a periapical radiograph, the invagination lesion will appear as a radiolucent pocket. It is usually seen beneath the cingulum or incisal edge. Larger lesions can appear as fissures. A radio-opaque could be shown. Pulp may be involved and the root canal could have complex anatomy. Two periapical radiographs are often required to make sure that it is not a masked lesion.
Cone beam computed tomography (CBCT) is useful in diagnosing DI. It provides clinicians a detailed 3D image and could aid treatment planning. Feasibility of root canal treatment or apical surgery or other procedures could be assessed.

Oehlers classification
Class I - Partial invagination </s>