<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 Long QT syndrome and can you explain it in depth? [/INST] Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, drowning, seizures, or sudden death. These episodes can be triggered by exercise or stress. Some rare forms of LQTS are associated with other symptoms and signs including deafness and periods of muscle weakness.Long QT syndrome may be present at birth or develop later in life. The inherited form may occur by itself or as part of larger genetic disorder. Onset later in life may result from certain medications, low blood potassium, low blood calcium, or heart failure. Medications that are implicated include certain antiarrhythmics, antibiotics, and antipsychotics. LQTS can be diagnosed using an electrocardiogram (EKG) if a corrected QT interval of greater than 480–500 milliseconds is found, but clinical findings, other EKG features, and genetic testing may confirm the diagnosis with shorter QT intervals.Management may include avoiding strenuous exercise, getting sufficient potassium in the diet, the use of beta blockers, or an implantable cardiac defibrillator. For people with LQTS who survive cardiac arrest and remain untreated, the risk of death within 15 years is greater than 50%. With proper treatment this decreases to less than 1% over 20 years.Long QT syndrome is estimated to affect 1 in 7,000 people. Females are affected more often than males. Most people with the condition develop symptoms before they are 40 years old. It is a relatively common cause of sudden death along with Brugada syndrome and arrhythmogenic right ventricular dysplasia. In the United States it results in about 3,500 deaths a year. The condition was first clearly described in 1957.

Signs and symptoms
Many people with long QT syndrome have no signs or symptoms. When symptoms occur, they are generally caused by abnormal heart rhythms (arrhythmias), most commonly a form of ventricular tachycardia called Torsades de pointes (TdP). If the arrhythmia reverts to a normal rhythm spontaneously the affected person may experience lightheadedness (known as presyncope) or faint which may be preceded by a fluttering sensation in the chest. If the arrhythmia continues, the affected person may experience a cardiac arrest, which if untreated may lead to sudden death. Those with LQTS may also experience seizure-like activity (non-epileptic seizure) as a result of reduced blood flow to the brain during an arrhythmia. Epilepsy is also associated with certain types of long QT syndrome.The arrhythmias that lead to faints and sudden death are more likely to occur in specific circumstances, in part determined by which genetic variant is present. While arrhythmias can occur at any time, in some forms of LQTS arrhythmias are more commonly seen in response to exercise or mental stress (LQT1), in other forms following a sudden loud noise (LQT2), and in some forms during sleep or immediately upon waking (LQT3).Some rare forms of long QT syndrome affect other parts of the body, leading to deafness in the Jervell and Lange-Nielsen form of the condition, and periodic paralysis in the Andersen–Tawil (LQT7) form.

Risk for arrhythmias
While those with long QT syndrome have an increased risk of developing abnormal heart rhythms the absolute risk of arrhythmias is very variable. The strongest predictor of whether someone will develop TdP is whether they have experienced this arrhythmia or another form of cardiac arrest in the past. Those with LQTS who have experienced syncope without an ECG having been recorded at the time are also at higher risk, as syncope in these cases is frequently due to an undocumented self-terminating arrhythmia.In addition to a history of arrhythmias, the extent to which the QT is prolonged predicts risk. While some have QT intervals that are very prolonged, others have only slight QT prolongation, or even a normal QT interval at rest (concealed LQTS). Those with the longest QT intervals are more likely to experience TdP, and a corrected QT interval of greater than 500 ms is thought to represent those at higher risk. Despite this, those with only subtle QT prolongation or concealed LQTS still have some risk of arrhythmias. Overall, every 10 ms increase in the corrected QT interval is associated with a 15% increase in arrhythmic risk.As the QT prolonging effects of both genetic variants and acquired causes of LQTS are additive, those with inherited LQTS are more likely to experience TdP if given QT prolonging drugs or if they experience electrolyte problems such as low blood levels of low potassium (hypokalaemia). Similarly, those taking QT prolonging medications are more likely to experience TdP if they have a genetic tendency to a prolonged QT interval, even it this tendency is concealed. Arrhythmias occur more commonly in drug-induced LQTS if the medication in question has been rapidly given intravenously, or if high concentrations of the drug are present in the persons blood. The risk of arrhythmias is also higher if the person receiving the drug has heart failure, is taking digitalis, or has recently been cardioverted from atrial fibrillation. Other risk factors for developing torsades de pointes among those with LQTS include female sex, increasing age, pre-existing cardiovascular disease, and abnormal liver or kidney function.

Causes
There are several subtypes of long QT syndrome. These can be broadly split into those caused by genetic mutations which those affected are born with, carry throughout their lives, and can pass on to their children (inherited or congenital long QT syndrome), and those caused by other factors which cannot be passed on and are often reversible (acquired long QT syndrome).

Inherited
Inherited, or congenital long QT syndrome, is caused by genetic abnormalities.  LQTS can arise from variants in several genes, leading in some cases to quite different features.  The common thread linking these variants is that they affect one or more ion currents leading to prolongation of the ventricular action potential, thus lengthening the QT interval.  Classification systems have been proposed to distinguish between subtypes of the condition based on the clinical features (and named after those who first described the condition) and subdivided by the underlying genetic variant.  The commonest of these, accounting for 99% of cases, is Romano–Ward syndrome (genetically LQT1-6 and LQT9-16), an autosomal dominant form in which the electrical activity of the heart is affected without involving other organs. A less commonly seen form is Jervell and Lange-Nielsen syndrome, an autosomal recessive form of LQTS combining a prolonged QT interval with congenital deafness. Other rare forms include Anderson–Tawil syndrome (LQT7) with features including a prolonged QT interval, periodic paralysis, and abnormalities of the face and skeleton; and Timothy syndrome (LQT8) in which a prolonged QT interval is associated with abnormalities in the structure of the heart and autism spectrum disorder.

Romano–Ward syndrome
LQT1 is the most common subtype of Romano–Ward syndrome, responsible for 30 to 35% of all cases.  The gene responsible, KCNQ1, has been isolated to chromosome 11p15.5 and encodes the alpha subunit of the KvLQT1 potassium channel.  This subunit interacts with other proteins (in particular, the minK beta subunit) to create the channel, which carries the delayed potassium rectifier current IKs responsible for the repolarisation phase of the cardiac action potential. Variants in KCNQ1 that decrease IKs (loss of function variants) slow the repolarisation of the action potential.  This causes the LQT1 subtype of Romano–Ward syndrome when a single copy of the variant is inherited (heterozygous, autosomal dominant inheritance). Inheriting two copies of the variant (homozygous, autosomal recessive inheritance) leads to the more severe Jervell and Lange–Nielsen syndrome. Conversely, variants in KCNQ1 that increase IKs lead to more rapid repolarisation and the short QT syndrome.The LQT2 subtype is the second-most common form of Romano–Ward syndrome, responsible for 25 to 30% of all cases.  It is caused by variants in the KCNH2 gene (also known as hERG) on chromosome 7 which encodes the potassium channel that carries the rapid inward rectifier current IKr.  This current contributes to the terminal repolarisation phase of the cardiac action potential, and therefore the length of the QT interval.The LQT3 subtype of Romano–Ward syndrome is caused by variants in the SCN5A gene located on chromosome 3p21–24.  SCN5A encodes the alpha subunit of the cardiac sodium channel, NaV1.5, responsible for the sodium current INa which depolarises cardiac cells at the start of the action potential.  Cardiac sodium channels normally inactivate rapidly, but the mutations involved in LQT3 slow their inactivation leading to a small sustained late sodium current.  This continued inward current prolongs the action potential and thereby the QT interval. While some variants in SCN5A cause LQT3, other variants can cause quite different conditions.  Variants causing a reduction in the early peak current can cause Brugada syndrome and cardiac conduction disease, while other variants have been associated with dilated cardiomyopathy. Some variants which affect both the early and late sodium current can cause overlap syndromes which combine aspects of both LQT3 and Brugada syndrome.

Rare Romano–Ward subtypes (LQT4-6 and LQT9-16)
LQT5 is caused by variants in the KCNE1 gene responsible for the potassium channel beta subunit MinK. This subunit, in conjunction with the alpha subunit encoded by KCNQ1, is responsible for the potassium current IKs which is decreased in LQTS.  LQT6 is caused by variants in the KCNE2 gene responsible for the potassium channel beta subunit MiRP1 which generates the potassium current IKr.  Variants that decrease this current have been associated with prolongation of the QT interval.  However, subsequent evidence such as the relatively common finding of variants in the gene in those without long QT syndrome, and the general need for a second stressor such as hypokalaemia to be present to reveal the QT prolongation, has suggested that this gene instead represents a modifier to susceptibility to QT prolongation. Some therefore dispute whether variants in KCNE2 are sufficient to cause Romano-Ward syndrome by themselves.LQT9 is caused by variants in the membrane structural protein, caveolin-3. Caveolins form specific membrane domains called caveolae in which voltage-gated sodium channels sit. Similar to LQT3, these caveolin variants increase the late sustained sodium current, which impairs cellular repolarization.LQT10 is an extremely rare subtype, caused by variants in the SCN4B gene.  The product of this gene is an auxiliary beta-subunit (NaVβ4) forming cardiac sodium channels, variants in which increase the late sustained sodium current. LQT13 is caused by variants in GIRK4, a protein involved in the parasympathetic modulation of the heart. Clinically, the patients are characterized by only modest QT prolongation, but an increased propensity for atrial arrhythmias. LQT14, LQT15 and LQT16 are caused by variants in the genes responsible for calmodulin (CALM1, CALM2, and CALM3 respectively). Calmodulin interacts with several ion channels and its roles include modulation of the L-type calcium current in response to calcium concentrations, and trafficking the proteins produced by KCNQ1 and thereby influencing potassium currents.  The precise mechanisms by which means these genetic variants prolong the QT interval remain uncertain.

Jervell and Lange–Nielsen syndrome
Jervell and Lange–Nielsen syndrome (JLNS) is a rare form of LQTS inherited in an autosomal recessive manner.  In addition to severe prolongation of the QT interval, those affected are born with severe sensorineural deafness affecting both ears.  The syndrome is caused by inheriting two copies of certain variant in the KCNE1 or KCNQ1 genes.  The same genetic variants lead to the LQT1 and LQT5 forms of Romano-Ward syndrome if only a single copy of the variant is inherited. JLNS is generally associated with a higher risk of arrhythmias than most other forms of LQTS.

Andersen–Tawil syndrome (LQT7)
LQT7, also known as Andersen–Tawil syndrome, is characterised by a triad of features – in addition to a prolonged QT interval, those affected may experience intermittent weakness often occurring at times when blood potassium concentrations are low (hypokalaemic periodic paralysis), and characteristic facial and skeletal abnormalities such as a small lower jaw (micrognathia), low set ears, and fused or abnormally angled fingers and toes (syndactyly and clinodactyly). The condition is inherited in an autosomal-dominant manner and is caused by mutations in the KCNJ2 gene which encodes the potassium channel protein Kir2.1.

Timothy syndrome (LQT8)
LQT8, also known as Timothy syndrome combines a prolonged QT interval with fused fingers or toes (syndactyly).  Abnormalities of the structure of the heart are commonly seen including ventricular septal defect, tetralogy of Fallot, and hypertrophic cardiomyopathy. The condition presents early in life and the average life expectancy is 2.5 years with death most commonly caused by ventricular arrhythmias.  Many children with Timothy syndrome who survive longer than this have features of autism spectrum disorder.  Timothy syndrome is caused by variants in the calcium channel Cav1.2 encoded by the gene CACNA1c.

Table of associated genes
The following is a list of genes associated with Long QT syndrome:

Acquired
Although long QT syndrome is often a genetic condition, a prolonged QT interval associated with an increased risk of abnormal heart rhythms can also occur in people without a genetic abnormality, commonly due to a side effect of medications. Drug-induced QT prolongation is often a result of treatment by antiarrhythmic drugs such as amiodarone and sotalol, antibiotics such as erythromycin, or antihistamines such as terfenadine. Other drugs which prolong the QT interval include some antipsychotics such as haloperidol and ziprasidone,  and the antidepressant citalopram. Lists of medications associated with prolongation of the QT interval such as the CredibleMeds database can be found online.Other causes of acquired LQTS include abnormally low levels of potassium (hypokalaemia) or magnesium (hypomagnesaemia) within the blood. This can be exacerbated following a sudden reduction in the blood supply to the heart (myocardial infarction), low levels of thyroid hormone (hypothyroidism), and a slow heart rate (bradycardia).Anorexia nervosa has been associated with sudden death, possibly due to QT prolongation. The malnutrition seen in this condition can sometimes affect the blood concentration of salts such as potassium, potentially leading to acquired long QT syndrome, in turn causing sudden cardiac death.  The malnutrition and associated changes in salt balance develop over a prolonged period of time, and rapid refeeding may further disturb the salt imbalances, increasing the risk of arrhythmias. Care must therefore be taken to monitor electrolyte levels to avoid the complications of refeeding syndrome.Factors which prolong the QT interval are additive, meaning that a combination of factors (such as taking a QT-prolonging drug and having low levels of potassium) can cause a greater degree of QT prolongation than each factor alone. This also applies to some genetic variants which by themselves only minimally prolong the QT interval but can make people more susceptible to significant drug-induced QT prolongation.

Mechanisms
The various forms of long QT syndrome, both congenital and acquired, produce abnormal heart rhythms (arrhythmias) by influencing the electrical signals used to coordinate individual heart cells. The common theme is a prolongation of the cardiac action potential – the characteristic pattern of voltage changes across the cell membrane that occur with each heart beat. Heart cells when relaxed normally have fewer positively charged ions on the inner side of their cell membrane than on the outer side, referred to as the membrane being polarised. When heart cells contract, positively charged ions such as sodium and calcium enter the cell, equalising or reversing this polarity, or depolarising the cell. After a contraction has taken place, the cell restores its polarity (or repolarises) by allowing positively charged ions such as potassium to leave the cell, restoring the membrane to its relaxed, polarised state. In long QT syndrome it takes longer for this repolarisation to occur, shown in individual cells as a longer action potential while being marked on the surface ECG as a long QT interval.The prolonged action potentials can lead to arrhythmias through several mechanisms. The arrhythmia characteristic of long QT syndrome, Torsades de Pointes, starts when an initial action potential triggers further abnormal action potentials in the form of afterdepolarisations. Early afterdepolarisations, occurring before the cell has fully repolarised, are particularly likely to be seen when action potentials are prolonged, and arise due to reactivation of calcium and sodium channels that would normally switch off until the next heartbeat is due.  Under the right conditions, reactivation of these currents, facilitated by the sodium-calcium exchanger, can cause further depolarisation of the cell. The early afterdepolarisations triggering arrhythmias in long QT syndrome tend to arise from the Purkinje fibres of the cardiac conduction system.  Early afterdepolarisations may occur as single events, but may occur repeatedly leading to multiple rapid activations of the cell.Some research suggests that delayed afterdepolarisations, occurring after repolarisation has completed, may also play a role in long QT syndrome. This form of afterdepolarisation originates from the spontaneous release of calcium from the intracellular calcium store known as the sarcoplasmic reticulum, forcing calcium out of cell through the sodium calcium exchanger in exchange for sodium, generating a net inward current.While there is strong evidence that the trigger for Torsades de Pointes comes from afterdepolarisations, it is less certain what sustains this arrhythmia. Some lines of evidence suggest that repeated afterdepolarisations from many sources contribute to the continuing arrhythmia. However, some suggest that the arrhythmia sustains through a mechanism known as re-entry. According to this model, the action potential prolongation occurs to a variable extent in different layers of the heart muscle with longer action potentials in some layers than others. In response to a triggering impulse, the waves of depolarisation will spread through regions with shorter action potentials but block in regions with longer action potentials. This allows the depolarising wavefront to bend around areas of block, potentially forming a complete loop and self-perpetuating. The twisting pattern on the ECG can be explained by movement of the core of the re-entrant circuit in the form of a meandering spiral wave.

Diagnosis
Diagnosing long QT syndrome is challenging.  Whilst the hallmark of LQTS is prolongation of the QT interval, the QT interval is highly variable among both those who are healthy and those who have LQTS. This leads to overlap between the QT intervals of those with and without LQTS. 2.5% of those with genetically proven LQTS have a QT interval within the normal range.  Conversely, given the normal distribution of QT intervals, a proportion of healthy people will have a longer QT interval than any arbitrary cutoff. Other factors beyond the QT interval should therefore be taken into account when making a diagnosis, some of which have been incorporated into scoring systems.

Electrocardiogram
Long QT syndrome is principally diagnosed by measuring the QT interval corrected for heart rate (QTc) on a 12-lead electrocardiogram (ECG). Long QT syndrome is associated with a prolonged QTc, although in some genetically proven cases of LQTS this prolongation can be hidden, known as concealed LQTS. The QTc is less than 450 ms in 95% of normal males, and less than 460 ms in 95% of normal females. LQTS is suggested if the QTc is longer than these cutoffs.  However, as 5% of normal people also fall into this category, some suggest cutoffs of 470 and 480 ms for males and females respectively, corresponding with the 99th centiles of normal values.The major subtypes of inherited LQTS are associated with specific ECG features. LQT1 is typically associated with broad-based T-waves, whereas the T-waves in LQT2 are notched and of lower amplitude, whilst in LQT3 the T-waves are often late onset, being preceded by a long isoelectric segment.

Schwartz score
The Schwartz score has been proposed as a method of combining clinical and ECG factors to assess how likely an individual is to have an inherited form of LQTS. The table below lists the criteria used to calculate the score.

Other investigations
In cases of diagnostic uncertainty, other investigations may be helpful to unmask a prolonged QT.  In addition to prolonging the resting QT interval, LQTS may affect how the QT changes in response to exercise and stimulation by catecholamines such as adrenaline.  Provocation tests, in the form of exercise tolerance tests or direct infusion of adrenaline, can be used to detect these abnormal responses. These investigations are most useful for identifying those with concealed congenital Type 1 LQTS 1 (LQT1) who have a normal QT interval at rest.  While in healthy persons the QT interval shortens during exercise, in those with concealed LQT1 exercise or adrenaline infusion may lead to paradoxical prolongation of the QT interval, revealing the underlying condition.

Guideline cutoffs
International consensus guidelines differ on the degree of QT prolongation required to diagnose LQTS. The European Society of Cardiology recommends that, with or without symptoms or other investigations, LQTS can be diagnosed if the corrected QT interval is longer than 480ms.  They recommend that a diagnosis can be considered in the presence of a QTc of greater than 460 ms if unexplained syncope has occurred.  The Heart Rhythm Society guidelines are more stringent, recommending QTc cutoff of greater than 500 ms in the absence of other factors that prolong the QT, or greater than 480 ms with syncope.  Both sets of guidelines agree that LQTS can also be diagnosed if an individual has a Schwartz score of greater than 3 or if a pathogenic genetic variant associated with LQTS is identified, regardless of QT interval.

Treatment
Those diagnosed with LQTS are usually advised to avoid drugs that can prolong the QT interval further or lower the threshold for TDP, lists of which can be found in public access online databases. In addition to this, two intervention options are known for individuals with LQTS: arrhythmia prevention and arrhythmia termination.

Arrhythmia prevention
Arrhythmia suppression involves the use of medications or surgical procedures that attack the underlying cause of the arrhythmias associated with LQTS. Since the cause of arrhythmias in LQTS is early afterdepolarizations (EADs), and they are increased in states of adrenergic stimulation, steps can be taken to blunt adrenergic stimulation in these individuals. These include administration of beta receptor blocking agents, which decreases the risk of stress-induced arrhythmias. Nadolol, a powerful non-selective beta blocker, has been shown to reduce the arrhythmic risk in all three main genotypes (LQT1, LQT2, and LQT3).Genotype and QT interval duration are independent predictors of recurrence of life-threatening events during beta-blocker therapy. To be specific, the presence of QTc >500 ms and LQT2 and LQT3 genotype are associated with the highest incidence of recurrence. In these patients, primary prevention with use of implantable cardioverter-defibrillators can be considered.
Potassium supplementation: If the potassium content in the blood rises, the action potential shortens, so increasing potassium concentration could minimize the occurrence of arrhythmias. It should work best in LQT2, since the hERG channel is especially sensitive to potassium concentration, but the use is experimental and not evidence-based.
Sodium channel blocking drugs such as mexiletine have been used to prevent arrhythmias in long QT syndrome.  While the most compelling indication is for those whose long QT syndrome is caused by defective sodium channels producing a sustained late current (LQT3), mexiletine also shortens the QT interval in other forms of long QT syndrome including LQT1, LQT2 and LQT8. As the predominant action of mexiletine is on the early peak sodium current, there are theoretical reasons why drugs which preferentially suppress the late sodium current such as ranolazine may be more effective, although evidence that this is the case in practice is limited.
Amputation of the cervical sympathetic chain (left stellectomy). This therapy is typically reserved for LQTS caused by JLNS, but may be used as an add-on therapy to beta blockers in certain cases. In most cases, modern therapy favors ICD implantation if beta blocker therapy fails.
In patients considered at high risk of life-threatening arrhythmic events, ICD implantation may be considered as a preventive step.

Arrhythmia termination
Arrhythmia termination involves stopping a life-threatening arrhythmia once it has already occurred.  One effective form of arrhythmia termination in individuals with LQTS is placement of an implantable cardioverter-defibrillator (ICD). Also, external defibrillation can be used to restore sinus rhythm. ICDs are commonly used in patients with fainting episodes despite beta blocker therapy, and in patients having experienced a cardiac arrest. As mentioned earlier, ICDs may be used also in patients considered at high risk of life-threatening arrhythmic events.With better knowledge of the genetics underlying LQTS, more precise treatments hopefully will become available.

Outcomes
Genotype and QT interval duration are the strongest predictors of outcome for patients with LQTS. These have been combined to create an externally validated risk score calculator, estimating a 5-year risk for each individual patient, which can help physicians to identify patients at the highest risk of life-threatening arrhythmic events.For people who experience cardiac arrest or fainting caused by LQTS and who are untreated, the risk of death within 15 years is around 50%.  With careful treatment this decreases to less than 1% over 20 years. Those who exhibit symptoms before the age of 18 are more likely to experience a cardiac arrest.

Epidemiology
Inherited LQTS is estimated to affect between one in 2,500 and 7,000 people.

History
The first documented case of LQTS was described in Leipzig by Meissner in 1856, when a deaf girl died after her teacher yelled at her.  Soon after being notified, the girls parents reported that her older brother, also deaf, had previously died after a terrible fright. This was several decades before the ECG was invented, but is likely the first described case of Jervell and Lange-Nielsen syndrome </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 Nausea and can you explain it in depth? [/INST] Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.Over 30 definitions of nausea were proposed in a 2011 book on the topic.Nausea is a non-specific symptom, which means that it has many possible causes. Some common causes of nausea are gastroenteritis and other gastrointestinal disorders, food poisoning, motion sickness, dizziness, migraine, fainting, low blood sugar, anxiety, and lack of sleep. Nausea is a side effect of many medications including chemotherapy, or morning sickness in early pregnancy. Nausea may also be caused by disgust and depression.Medications taken to prevent and treat nausea and vomiting are called antiemetics. The most commonly prescribed antiemetics in the US are promethazine, metoclopramide, and the newer ondansetron. The word nausea is from Latin nausea, from Greek ναυσία – nausia, "ναυτία" – nautia, motion sickness, "feeling sick or queasy".

Causes
Gastrointestinal infections (37%) and food poisoning are the two most common causes of acute nausea and vomiting. Side effects from medications (3%) and pregnancy are also relatively frequent. There are many causes of chronic nausea. Nausea and vomiting remain undiagnosed in 10% of the cases. Aside from morning sickness, there are no sex differences in complaints of nausea. After childhood, doctor consultations decrease steadily with age. Only a fraction of one percent of doctor visits by those over 65 are due to nausea.

Gastrointestinal
Gastrointestinal infection is one of the most common causes of acute nausea and vomiting. Chronic nausea may be the presentation of many gastrointestinal disorders, occasionally as the major symptom, such as gastroesophageal reflux disease, functional dyspepsia, gastritis, biliary reflux, gastroparesis, peptic ulcer, celiac disease, non-celiac gluten sensitivity, Crohns disease, hepatitis, upper gastrointestinal malignancy, and pancreatic cancer. Uncomplicated Helicobacter pylori infection does not cause chronic nausea.

Food poisoning
Food poisoning usually causes an abrupt onset of nausea and vomiting one to six hours after ingestion of contaminated food and lasts for one to two days. It is due to toxins produced by bacteria in food.

Medications
Many medications can potentially cause nausea. Some of the most frequently associated include cytotoxic chemotherapy regimens for cancer and other diseases, and general anaesthetic agents. An old cure for migraine, ergotamine, is well known to cause devastating nausea in some patients; a person using it for the first time will be prescribed an antiemetic for relief if needed.

Pregnancy
Nausea or "morning sickness" is common during early pregnancy but may occasionally continue into the second and third trimesters. In the first trimester nearly 80% of women have some degree of nausea. Pregnancy should therefore be considered as a possible cause of nausea in any sexually active woman of child-bearing age. While usually it is mild and self-limiting, severe cases known as hyperemesis gravidarum may require treatment.

Disequilibrium
A number of conditions involving balance such as motion sickness and vertigo can lead to nausea and vomiting.

Gynecologic
Dysmenorrhea can cause nausea.

Psychiatric
Nausea may be caused by depression, anxiety disorders and eating disorders.

Potentially serious
While most causes of nausea are not serious, some serious conditions are associated with nausea. These include pancreatitis, small bowel obstruction, appendicitis, cholecystitis, hepatitis, Addisonian crisis, diabetic ketoacidosis, increased intracranial pressure, spontaneous intracranial hypotension, brain tumors, meningitis, heart attack, rabies carbon monoxide poisoning  and many others.

Comprehensive list
Inside the abdomen
Obstructing disorders

Gastric outlet obstruction
Small bowel obstruction
Colonic obstruction
Superior mesenteric artery syndromeEnteric infections

Viral infection
Bacterial infectionInflammatory diseases

Celiac disease
Cholecystitis
Pancreatitis
Appendicitis
HepatitisSensorimotor dysfunction

Gastroparesis
Intestinal pseudo-obstruction
Gastroesophageal reflux disease
Irritable bowel syndrome
Cyclic vomiting syndromeOther

Non-celiac gluten sensitivity
Biliary colic
Kidney stone
Cirrhosis
Abdominal irradiation

Outside the abdomen
Cardiopulmonary

Cardiomyopathy
Myocardial infarction (heart attack)
Paroxysmal coughInner-ear diseases

Motion sickness
Labyrinthitis
MalignancyIntracerebral disorders

Malignancy
Hemorrhage
Abscess
Hydrocephalus
Meningitis
Encephalitis
RabiesPsychiatric illnesses

Anorexia and bulimia nervosa
DepressionOther

Post-operative vomiting
Nociception

Medications and metabolic disorders
Drugs

Chemotherapy
Antibiotics
Antiarrhythmics
Digoxin
Oral hypoglycemic medications
Oral contraceptivesEndocrine/metabolic disease

Pregnancy
Uremia
Ketoacidosis
Thyroid and parathyroid disease
Adrenal insufficiencyToxins

Liver failure
Alcohol

Pathophysiology
Research on nausea and vomiting has relied on using animal models to mimic the anatomy and neuropharmacologic features of the human body. The physiologic mechanism of nausea is a complex process that has yet to be fully elucidated. There are four general pathways that are activated by specific triggers in the human body that go on to create the sensation of nausea and vomiting.
Central nervous system (CNS): Stimuli can affect areas of the CNS including the cerebral cortex and the limbic system. These areas are activated by elevated intracranial pressure, irritation of the meninges (i.e. blood or infection), and extreme emotional triggers such as anxiety. The supratentorial region is also responsible for the sensation of nausea.
Chemoreceptor trigger zone (CTZ): The CTZ is located in the area postrema in the floor of the fourth ventricle within the brain. This area is outside the blood brain barrier, and is therefore readily exposed to substances circulating through the blood and cerebral spinal fluid. Common triggers of the CTZ include metabolic abnormalities, toxins, and medications. Activation of the CTZ is mediated by dopamine (D2) receptors, serotonin (5HT3) receptors, and neurokinin receptors (NK1).
Vestibular system: This system is activated by disturbances to the vestibular apparatus in the inner ear. These include movements that cause motion sickness and dizziness. This pathway is triggered via histamine (H1) receptors and acetylcholine (ACh) receptors.
Peripheral Pathways: These pathways are triggered via chemoreceptors and mechanoreceptors in the gastrointestinal tract, as well as other organs such as the heart and kidneys. Common activators of these pathways include toxins present in the gastrointestinal lumen and distension of the gastrointestinal lumen from blockage or dysmotility of the bowels. Signals from these pathways travel via multiple neural tracts including the vagus, glossopharyngeal, splanchnic, and sympathetic nerves.Signals from any of these pathways then travel to the brainstem, activating several structures including the nucleus of the solitary tract, the dorsal motor nucleus of the vagus, and central pattern generator. These structures go on to signal various downstream effects of nausea and vomiting. The bodys motor muscle responses involve halting the muscles of the gastrointestinal tract, and in fact causing reversed propulsion of gastric contents towards the mouth while increasing abdominal muscle contraction. Autonomic effects involve increased salivation and the sensation of feeling faint that often occurs with nausea and vomiting.

Pre-nausea pathophysiology
It has been described that alterations in heart rate can occur as well as the release of vasopressin from the posterior pituitary.

Diagnosis
Patient history
Taking a thorough patient history may reveal important clues to the cause of nausea and vomiting. If the patients symptoms have an acute onset, then drugs, toxins, and infections are likely. In contrast, a long-standing history of nausea will point towards a chronic illness as the culprit. The timing of nausea and vomiting after eating food is an important factor to pay attention to. Symptoms that occur within an hour of eating may indicate an obstruction proximal to the small intestine, such as gastroparesis or pyloric stenosis. An obstruction further down in the intestine or colon will cause delayed vomiting. An infectious cause of nausea and vomiting such as gastroenteritis may present several hours to days after the food was ingested. The contents of the emesis is a valuable clue towards determining the cause. Bits of fecal matter in the emesis indicate obstruction in the distal intestine or the colon. Emesis that is of a bilious nature (greenish in color) localizes the obstruction to a point past the stomach. Emesis of undigested food points to an obstruction prior to the gastric outlet, such as achalasia or Zenkers diverticulum. If patient experiences reduced abdominal pain after vomiting, then obstruction is a likely etiology. However, vomiting does not relieve the pain brought on by pancreatitis or cholecystitis.

Physical exam
It is important to watch out for signs of dehydration, such as orthostatic hypotension and loss of skin turgor. Auscultation of the abdomen can produce several clues to the cause of nausea and vomiting. A high-pitched tinkling sound indicates possible bowel obstruction, while a splashing "succussion" sound is more indicative of gastric outlet obstruction. Eliciting pain on the abdominal exam when pressing on the patient may indicate an inflammatory process. Signs such as papilledema, visual field losses, or focal neurological deficits are red flag signs for elevated intracranial pressure.

Diagnostic testing
When a history and physical exam are not enough to determine the cause of nausea and vomiting, certain diagnostic tests may prove useful. A chemistry panel would be useful for electrolyte and metabolic abnormalities. Liver function tests and lipase would identify pancreaticobiliary diseases. Abdominal X-rays showing air-fluid levels indicate bowel obstruction, while an X-ray showing air-filled bowel loops are more indicative of ileus. More advanced imaging and procedures may be necessary, such as a CT scan, upper endoscopy, colonoscopy, barium enema, or MRI. Abnormal GI motility can be assessed using specific tests like gastric scintigraphy, wireless motility capsules, and small-intestinal manometry.

Treatment
If dehydration is present due to loss of fluids from severe vomiting, rehydration with oral electrolyte solutions is preferred. If this is not effective or possible, intravenous rehydration may be required. Medical care is recommended if: a person cannot keep any liquids down, has symptoms more than 2 days, is weak, has a fever, has stomach pain, vomits more than two times in a day or does not urinate for more than 8 hours.

Medications
Many pharmacologic medications are available for the treatment of nausea. There is no medication that is clearly superior to other medications for all cases of nausea. The choice of antiemetic medication may be based on the situation during which the person experiences nausea. For people with motion sickness and vertigo, antihistamines and anticholinergics such as meclizine and scopolamine are particularly effective. Nausea and vomiting associated with migraine headaches respond best to dopamine antagonists such as metoclopramide, prochlorperazine, and chlorpromazine. In cases of gastroenteritis, serotonin antagonists such as ondansetron were found to suppress nausea and vomiting, as well as reduce the need for IV fluid resuscitation. The combination of pyridoxine and doxylamine is the first line treatment for pregnancy-related nausea and vomiting </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 Polyarthritis 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 Persistent pupillary membrane 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 Synovial bursa and can you explain it in depth? [/INST] A synovial bursa (plural bursae or bursas) is a small fluid-filled sac lined by synovial membrane with an inner capillary layer of viscous synovial fluid (similar in consistency to that of a raw egg white). It provides a cushion between bones and tendons and/or muscles around a joint. This helps to reduce friction between the bones and allows free movement. Bursae are found around most major joints of the body.

Structure
There are four types of bursa: adventitious, subcutaneous, synovial, and sub-muscular. Among these, only adventitious is non-native </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 Trimester 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 Hypermagnesemia and can you explain it in depth? [/INST] Hypermagnesemia is an electrolyte disorder in which there is a high level of magnesium in the blood. Symptoms include weakness, confusion, decreased breathing rate, and decreased reflexes. Complications may include low blood pressure and cardiac arrest.It is typically caused by kidney failure or is treatment-induced such as from antacids that contain magnesium. Less common causes include tumor lysis syndrome, seizures, and prolonged ischemia. Diagnosis is based on a blood level of magnesium greater than 1.1 mmol/L (2.6 mg/dL). It is severe if levels are greater than 2.9 mmol/L (7 mg/dL). Specific electrocardiogram (ECG) changes may be present.Treatment involves stopping the magnesium a person is getting. Treatment when levels are very high include calcium chloride, intravenous normal saline with furosemide, and hemodialysis. Hypermagnesemia is uncommon. Rates among hospitalized patients in renal failure may be as high as 10%.

Signs and symptoms
Symptoms include weakness, confusion, decreased breathing rate, and decreased reflexes. As well as nausea, low blood pressure, low blood calcium, abnormal heart rhythms and asystole, dizziness, and sleepiness.
Abnormal heart rhythms and asystole are possible complications of hypermagnesemia related to the heart. Magnesium acts as a physiologic calcium blocker, which results in abnormalities of the electrical conduction system of the heart.
Consequences related to serum concentration:

4.0 mEq/L – Decreased reflexes
>5.0 mEq/L – Prolonged atrioventricular conduction
>10.0 mEq/L – Complete heart block
>13.0 mEq/L – Cardiac arrestThe therapeutic range for the prevention of the pre-eclamptic uterine contractions is: 4.0–7.0 mEq/L. As per Lu and Nightingale, serum magnesium concentrations associated with maternal toxicity (also neonate depression, hypotonia and low Apgar scores) are:

7.0–10.0 mEq/L – Loss of patellar reflex
10.0-13.0 mEq/L – Respiratory depression
15.0-25.0 mEq/L – Altered atrioventricular conduction and (further) complete heart block
>25.0 mEq/L – Cardiac arrest

Complications
Severe hypermagnesemia (levels greater than 12 mg/dL) can lead to cardiovascular complications (hypotension and arrhythmias) and neurological disorder (confusion and lethargy). Higher values of serum magnesium (exceeding 15 mg/dL) can induce cardiac arrest and coma.

Causes
Magnesium status depends on three organs: uptake in the intestine, storage in the bone, and excretion in the kidneys. Hypermagnesemia is therefore often due to problems in these organs, mostly the intestine or kidney.

Predisposing conditions
Hemolysis, magnesium concentration in red blood cells is approximately three times greater than in serum, therefore hemolysis can increase plasma magnesium. Hypermagnesemia is expected only in massive hemolysis.
Chronic kidney disease, excretion of magnesium becomes impaired when creatinine clearance falls below 30 ml/min. However, hypermagnesemia is not a prominent feature of chronic kidney disease unless magnesium intake is increased.
Magnesium toxicity from emergency pre-eclampsia treatment during labor and delivery.
Other conditions that can predispose to mild hypermagnesemia are diabetic ketoacidosis, adrenal insufficiency, hypothyroidism, hyperparathyroidism, and lithium intoxication.

Metabolism
For a detailed description of magnesium homeostasis and metabolism see hypomagnesemia.

Diagnosis
Hypermagnesemia is diagnosed by measuring the concentration of magnesium in the blood. Concentrations of magnesium greater than 1.1 mmol/L are considered diagnostic.

Treatment
People with normal kidney function (glomerular filtration rate (GFR) over 60 ml/min) and mild asymptomatic hypermagnesemia require no treatment except for the removal of all sources of exogenous magnesium. One must consider that the half-time of elimination of magnesium is approximately 28 hours.
In more severe cases, close monitoring of the ECG, blood pressure, and neuromuscular function and early treatment are necessary:
Intravenous calcium gluconate or calcium chloride since the actions of magnesium in neuromuscular and cardiac function become antagonized by calcium.
Severe clinical conditions require increasing renal magnesium excretion through:
Intravenous loop diuretics (e.g., furosemide), or hemodialysis, when kidney function is impaired, or the patient is symptomatic from severe hypermagnesemia. This approach usually removes magnesium efficiently (up to 50% reduction after a 3- to 4-hour treatment). Dialysis can, however, increase the excretion of calcium by developing hypocalcemia, thus possibly worsening the symptoms and signs of hypermagnesemia.
The use of diuretics must be associated with infusions of saline solutions to avoid further electrolyte disturbances (e.g., hypokalemia) and metabolic alkalosis. The clinician must perform serial measurements of calcium and magnesium </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 Lymphocytosis 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 Thrombosis and can you explain it in depth? [/INST] Thrombosis (from Ancient Greek θρόμβωσις thrómbōsis "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss.  Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus.Thrombosis may occur in veins (venous thrombosis) or in arteries (arterial thrombosis). Venous thrombosis (sometimes called DVT, deep vein thrombosis) leads to a blood clot in the affected part of the body, while arterial thrombosis (and, rarely, severe venous thrombosis) affects the blood supply and leads to damage of the tissue supplied by that artery (ischemia and necrosis). A piece of either an arterial or a venous thrombus can break off as an embolus, which could then travel through the circulation and lodge somewhere else as an embolism. This type of embolism is known as a thromboembolism. Complications can arise when a venous thromboembolism (commonly called a VTE) lodges in the lung as a pulmonary embolism. An arterial embolus may travel further down the affected blood vessel, where it can lodge as an embolism.

Signs and symptoms
Thrombosis is generally defined by the type of blood vessel affected (arterial or venous thrombosis) and the precise location of the blood vessel or the organ supplied by it.

Venous thrombosis
Deep vein thrombosis
Deep vein thrombosis (DVT) is the formation of a blood clot within a deep vein. It most commonly affects leg veins, such as the femoral vein. Three factors are important in the formation of a blood clot within a deep vein—these are the rate of blood flow, the thickness of the blood and qualities of the vessel wall. Classical signs of DVT include swelling, pain and redness of the affected area.

Paget-Schroetter disease
Paget-Schroetter disease or upper extremity DVT (UEDVT) is the obstruction of an arm vein (such as the axillary vein or subclavian vein) by a thrombus. The condition usually comes to light after vigorous exercise and usually presents in younger, otherwise healthy people. Men are affected more than women.

Budd-Chiari syndrome
Budd-Chiari syndrome is the blockage of a hepatic vein or of the hepatic part of the inferior vena cava. This form of thrombosis presents with abdominal pain, ascites and enlarged liver. Treatment varies between therapy and surgical intervention by the use of shunts.

Portal vein thrombosis
Portal vein thrombosis affects the hepatic portal vein, which can lead to portal hypertension and reduction of the blood supply to the liver. It usually happens in the setting of another disease such as pancreatitis, cirrhosis, diverticulitis or cholangiocarcinoma.

Renal vein thrombosis
Renal vein thrombosis is the obstruction of the renal vein by a thrombus. This tends to lead to reduced drainage from the kidney."Renal vein thrombosis: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 27 May 2019.</ref>

Cerebral venous sinus thrombosis
Cerebral venous sinus thrombosis (CVST) is a rare form of stroke which results from the blockage of the dural venous sinuses by a thrombus. Symptoms may include headache, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body and seizures. The diagnosis is usually made with a CT or MRI scan. The majority of persons affected make a full recovery. The mortality rate is 4.3%.

Jugular vein thrombosis
Jugular vein thrombosis is a condition that may occur due to infection, intravenous drug use or malignancy. Jugular vein thrombosis can have a varying list of complications, including: systemic sepsis, pulmonary embolism, and papilledema. Though characterized by a sharp pain at the site of the vein, it can prove difficult to diagnose, because it can occur at random.

Cavernous sinus thrombosis
Cavernous sinus thrombosis is a specialised form of cerebral venous sinus thrombosis, where there is thrombosis of the cavernous sinus of the basal skull dura, due to the retrograde spread of infection and endothelial damage from the danger triangle of the face. The facial veins in this area anastomose with the superior and inferior ophthalmic veins of the orbit, which drain directly posteriorly into the cavernous sinus through the superior orbital fissure. Staphyloccoal or Streptococcal infections of the face, for example nasal or upper lip pustules may thus spread directly into the cavernous sinus, causing stroke-like symptoms of double vision, squint, as well as spread of infection to cause meningitis."Guidelines Cavernous sinus thrombosis" (PDF).</ref>

Arterial thrombosis
Arterial thrombosis is the formation of a thrombus within an artery. In most cases, arterial thrombosis follows rupture of atheroma (a fat-rich deposit in the blood vessel wall), and is therefore referred to as atherothrombosis. Arterial embolism occurs when clots then migrate downstream and can affect any organ.Alternatively, arterial occlusion occurs as a consequence of embolism of blood clots originating from the heart ("cardiogenic" emboli). The most common cause is atrial fibrillation, which causes a blood stasis within the atria with easy thrombus formation, but blood clots can develop inside the heart for other reasons too as infective endocarditis.

Stroke
A stroke is the rapid decline of brain function due to a disturbance in the supply of blood to the brain. This can be due to ischemia, thrombus, embolus (a lodged particle) or hemorrhage (a bleed). In thrombotic stroke, a thrombus (blood clot) usually forms around atherosclerotic plaques. Since blockage of the artery is gradual, the onset of symptomatic thrombotic strokes is slower. Thrombotic stroke can be divided into two categories — large vessel disease or small vessel disease. The former affects vessels such as the internal carotids, vertebral and the circle of Willis. The latter can affect smaller vessels, such as the branches of the circle of Willis.

Myocardial infarction
Myocardial infarction (MI), or heart attack, is caused by ischemia (restriction in the blood supply), which is often due to the obstruction of a coronary artery by a thrombus. This restriction gives an insufficient supply of oxygen to the heart muscle which then results in tissue death (infarction). A lesion is then formed which is the infarct. MI can quickly become fatal if emergency medical treatment is not received promptly. If diagnosed within 12 hours of the initial episode (attack) then thrombolytic therapy is initiated.

Limb ischemia
An arterial thrombus or embolus can also form in the limbs, which can lead to acute limb ischemia.

Other sites
Hepatic artery thrombosis usually occurs as a devastating complication after liver transplantation.

Causes
Thrombosis prevention is initiated with assessing the risk for its development. Some people have a higher risk of developing thrombosis and its possible development into thromboembolism. Some of these risk factors are related to inflammation. "Virchows triad" has been suggested to describe the three factors necessary for the formation of thrombosis: stasis of blood, vessel wall injury, and altered blood coagulation. Some risk factors predispose for venous thrombosis while others increase the risk of arterial thrombosis. Newborn babies in the neonatal period are also at risk of a thromboembolism.

Mechanism
Pathogenesis
The main causes of thrombosis are given in Virchows triad which lists thrombophilia, endothelial cell injury, and disturbed blood flow. Generally speaking the risk for thrombosis increases over the life course of individuals, depending on life style factors like smoking, diet, and physical activity, the presence of other diseases like cancer or autoimmune disease, while also platelet properties change in aging individuals which is an important consideration as well.

Hypercoagulability
Hypercoagulability or thrombophilia, is caused by, for example, genetic deficiencies or autoimmune disorders. Recent studies indicate that white blood cells play a pivotal role in deep vein thrombosis, mediating numerous pro-thrombotic actions.

Endothelial cell injury
Any inflammatory process, such as trauma, surgery or infection, can cause damage to the endothelial lining of the vessels wall. The main mechanism is exposure of tissue factor to the blood coagulation system. Inflammatory and other stimuli (such as hypercholesterolemia) can lead to changes in gene expression in endothelium producing to a pro-thrombotic state. When this occurs, endothelial cells downregulate substances such as thrombomodulin, which is a key modulator of thrombin activity. The result is a sustained activation of thrombin and reduced production of protein C and tissue factor inhibitor, which furthers the pro-thrombotic state.Endothelial injury is almost invariably involved in the formation of thrombi in arteries, as high rates of blood flow normally hinder clot formation. In addition, arterial and cardiac clots are normally rich in platelets–which are required for clot formation in areas under high stress due to blood flow.

Disturbed blood flow
Causes of disturbed blood flow include stagnation of blood flow past the point of injury, or venous stasis which may occur in heart failure, or after long periods of sedentary behaviour, such as sitting on a long airplane flight. Also, atrial fibrillation, causes stagnant blood in the left atrium (LA), or left atrial appendage (LAA), and can lead to a thromboembolism. Cancers or malignancies such as leukemia may cause increased risk of thrombosis by possible activation of the coagulation system by cancer cells or secretion of procoagulant substances (paraneoplastic syndrome), by external compression on a blood vessel when a solid tumor is present, or (more rarely) extension into the vasculature (for example, renal cell cancers extending into the renal veins). Also, treatments for cancer (radiation, chemotherapy) often cause additional hypercoagulability. There are scores that correlate different aspects of patient data (comorbidities, vital signs, and others) to risk of thrombosis, such as the POMPE-C, which stratifies risk of mortality due to pulmonary embolism in patients with cancer, who typically have higher rates of thrombosis. Also, there are several predictive scores for thromboembolic events, such as Padua, Khorana, and ThroLy score.

Pathophysiology
Natural history
Fibrinolysis is the physiological breakdown of blood clots by enzymes such as plasmin.
Organisation: following the thrombotic event, residual vascular thrombus will be re-organised histologically with several possible outcomes. For an occlusive thrombus (defined as thrombosis within a small vessel that leads to complete occlusion), wound healing will reorganise the occlusive thrombus into collagenous scar tissue, where the scar tissue will either permanently obstruct the vessel, or contract down with myofibroblastic activity to unblock the lumen. For a mural thrombus (defined as a thrombus in a large vessel that restricts the blood flow but does not occlude completely), histological reorganisation of the thrombus does not occur via the classic wound healing mechanism. Instead, the platelet-derived growth factor degranulated by the clotted platelets will attract a layer of smooth muscle cells to cover the clot, and this layer of mural smooth muscle will be vascularised by the blood inside the vessel lumen rather than by the vasa vasorum.Ischemia/infarction: if an arterial thrombus cannot be lysed by the body and it does not embolise, and if the thrombus is large enough to impair or occlude blood flow in the involved artery, then local ischemia or infarction will result. A venous thrombus may or may not be ischemic, since veins distribute deoxygenated blood that is less vital for cellular metabolism. Nevertheless, non-ischemic venous thrombosis may still be problematic, due to the swelling caused by blockage to venous drainage. In deep vein thrombosis this manifests as pain, redness, and swelling; in retinal vein occlusion this may result in macular oedema and visual acuity impairment, which if severe enough can lead to blindness.

Embolization
A thrombus may become detached and enter circulation as an embolus, finally lodging in and completely obstructing a blood vessel, which unless treated very quickly will lead to tissue necrosis (an infarction) in the area past the occlusion. Venous thrombosis can lead to pulmonary embolism when the migrated embolus becomes lodged in the lung. In people with a "shunt" (a connection between the pulmonary and systemic circulation), either in the heart or in the lung, a venous clot can also end up in the arteries and cause arterial embolism.Arterial embolism can lead to obstruction of blood flow through the blood vessel that is obstructed by it, and a lack of oxygen and nutrients (ischemia) of the downstream tissue. The tissue can become irreversibly damaged, a process known as necrosis. This can affect any organ; for instance, arterial embolism of the brain is one of the causes of stroke.

Prevention
The use of heparin following surgery is common if there are no issues with bleeding. Generally, a risk-benefit analysis is required, as all anticoagulants lead to an increased risk of bleeding. In people admitted to hospital, thrombosis is a major cause for complications and occasionally death. In the UK, for instance, the Parliamentary Health Select Committee heard in 2005 that the annual rate of death due to thrombosis was 25,000, with at least 50% of these being hospital-acquired. Hence thromboprophylaxis (prevention of thrombosis) is increasingly emphasized. In patients admitted for surgery, graded compression stockings are widely used, and in severe illness, prolonged immobility and in all orthopedic surgery, professional guidelines recommend low molecular weight heparin (LMWH) administration, mechanical calf compression or (if all else is contraindicated and the patient has recently developed deep vein thrombosis) the insertion of a vena cava filter. In patients with medical rather than surgical illness, LMWH too is known to prevent thrombosis, and in the United Kingdom the Chief Medical Officer has issued guidance to the effect that preventative measures should be used in medical patients, in anticipation of formal guidelines.

Treatment
The treatment for thrombosis depends on whether it is in a vein or an artery, the impact on the person, and the risk of complications from treatment.

Anticoagulation
Warfarin and vitamin K antagonists are anticoagulants that can be taken orally to reduce thromboembolic occurrence. Where a more effective response is required, heparin can be given (by injection) concomitantly. As a side effect of any anticoagulant, the risk of bleeding is increased, so the international normalized ratio of blood is monitored. Self-monitoring and self-management are safe options for competent patients, though their practice varies. In Germany, about 20% of patients were self-managed while only 1% of U.S. patients did home self-testing (according to one 2012 study). Other medications such as direct thrombin inhibitors and direct Xa inhibitors are increasingly being used instead of warfarin.

Thrombolysis
Thrombolysis is the pharmacological destruction of blood clots by administering thrombolytic drugs including recombinant tissue plasminogen activator, which enhances the normal destruction of blood clots by the bodys enzymes. This carries an increased risk of bleeding so is generally only used for specific situations (such as severe stroke or a massive pulmonary embolism).

Surgery
Arterial thrombosis may require surgery if it causes acute limb ischemia.

Endovascular treatment
Mechanical clot retrieval and catheter-guided thrombolysis are used in certain situations.

Antiplatelet agents
Arterial thrombosis is platelet-rich, and inhibition of platelet aggregation with antiplatelet drugs such as aspirin may reduce the risk of recurrence or progression.

Targeting ischemia/reperfusion injury
With reperfusion comes ischemia/reperfusion (IR) injury (IRI), which paradoxically causes cell death in reperfused tissue and contributes significantly to post-reperfusion mortality and morbidity. For example, in a feline model of intestinal ischemia, four hours of ischemia resulted in less injury than three hours of ischemia followed by one hour of reperfusion. In ST-elevation myocardial infarction (STEMI), IRI contributes up to 50% of final infarct size despite timely primary percutaneous coronary intervention. This is a key reason for the continued high mortality and morbidity in these conditions, despite endovascular reperfusion treatments and continuous efforts to improve timeliness and access to these treatments. Hence, protective therapies are required to attenuate IRI alongside reperfusion in acute ischemic conditions to improve clinical outcomes. Therapeutic strategies that have potential to improve clinical outcomes in reperfused STEMI patients include remote ischemic conditioning (RIC), exenatide, and metoprolol. These have emerged amongst a multitude of cardioprotective interventions investigated with largely neutral clinical data. Of these, RIC has the most robust clinical evidence, especially in the context of STEMI, but also emerging for other indications such as acute ischemic stroke and aneurysmal subarachnoid hemorrhage.

Neonatal thrombosis
Treatment options for full-term and preterm babies who develop thromboembolism include expectant management (with careful observation), nitroglycerin ointment, pharmacological therapy (thrombolytics and/or anticoagulants), and surgery. The evidence supporting these treatment approaches is weak. For anticoagulant treatment, t is not clear if unfractionated and/or low molecular weight heparin treatment is effective at decreasing mortality and serious adverse events in this population.  There is also insufficient evidence to understand the risk of adverse effects associated with these treatment approaches in term or preterm infants.

See also
Blood clotting tests
Disseminated intravascular coagulation
Hepatic artery thrombosis
Thrombotic microangiopathy

References
Bibliography
Brunner, Lillian (2010). Brunner & Suddarths textbook of medical-surgical nursing. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 978-0781785907.
Copstead, Lee (2013). Pathophysiology. St. Louis, Mo: Elsevier </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 Nasal fracture and can you explain it in depth? [/INST] A nasal fracture, commonly referred to as a broken nose, is a fracture of one of the bones of the nose. Symptoms may include bleeding, swelling, bruising, and an inability to breathe through the nose. They may be complicated by other facial fractures or a septal hematoma.The most common causes include assault, trauma during sports, falls, and motor vehicle collisions. Diagnosis is typically based on the signs and symptoms and may occasionally be confirmed by plain X-ray.Treatment is typically with pain medication and cold compresses. Reduction, if needed, can typically occur after the swelling has come down. Depending on the type of fracture reduction may be closed or open. Outcomes are generally good. Nasal fractures are common, comprising about 40% of facial fractures. Males in their 20s are most commonly affected.

Signs and symptoms
Symptoms of a broken nose include bruising, swelling, tenderness, pain, deformity, and/or bleeding of the nose and nasal region of the face.  The patient may have difficulty breathing, or excessive nosebleeds (if the nasal mucosa are damaged) </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 Diffuse idiopathic skeletal hyperostosis and can you explain it in depth? [/INST] Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by abnormal calcification/bone formation (hyperostosis) of the soft tissues surrounding the joints of the spine, and also of the peripheral or appendicular skeleton. In the spine, there is bone formation along the anterior longitudinal ligament and sometimes the posterior longitudinal ligament, which may lead to partial or complete fusion of adjacent vertebrae. The facet and sacroiliac joints tend to be uninvolved. The thoracic spine is the most common level involved. In the peripheral skeleton, DISH manifests as a calcific enthesopathy, with pathologic bone formation at sites where ligaments and tendons attach to bone.

Signs and symptoms
The majority of people with DISH are not symptomatic, and the findings are an incidental imaging abnormality.
In some, the x-ray findings may correspond to symptoms of back stiffness with flexion/extension or with mild back pain. Back pain or stiffness may be worse in the morning.  Rarely, large anterior cervical spine osteophytes may affect the esophagus or the larynx and cause pain, difficulty swallowing or even dyspnea. Similar calcification and ossification may be seen at peripheral entheseal sites, including the shoulder, iliac crest, ischial tuberosity, trochanters of the hip, tibial tuberosities, patellae, and bones of the hands and/or feet.DISH can be a complicating factor when suffering from trauma involving the spine. It increases the risk of unstable fractures involving the intervertebral disc and the calcified/ossified ligaments which influences the need for surgical treatment.

Cause
The exact cause is unknown. Mechanical, dietary factors and use of some medications (e.g. isotretinoin, etretinate, acitretin and other vitamin A derivatives) may be of significance. There is a correlation between these factors but not a cause or effect. The distinctive radiological feature of DISH is the continuous linear calcification along the antero-medial aspect of the thoracic spine. DISH is usually found in people in their 60s and above, and is extremely rare in people in their 30s and 40s. The disease can spread to any joint of the body, affecting the neck, shoulders, ribs, hips, pelvis, knees, ankles, and hands </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 Premature ejaculation and can you explain it in depth? [/INST] Premature ejaculation (PE) occurs when a man expels semen (and most likely experiences orgasm) soon after beginning sexual activity, and with minimal penile stimulation. It has also been called early ejaculation, rapid ejaculation, rapid climax, premature climax and (historically) ejaculatio praecox. There is no uniform cut-off defining "premature", but a consensus of experts at the International Society for Sexual Medicine endorsed a definition of around one minute after penetration. The International Classification of Diseases (ICD-10) applies a cut-off of 15 seconds from the beginning of sexual intercourse.Although men with premature ejaculation describe feeling that they have less control over ejaculating, it is not clear if that is true, and many or most average men also report that they wish they could last longer. Mens typical ejaculatory latency is approximately 4–8 minutes. The opposite condition is delayed ejaculation.Men with PE often report emotional and relationship distress, and some avoid pursuing sexual relationships because of PE-related embarrassment. Compared with men, women consider PE less of a problem, but several studies show that the condition also causes female partners distress.

Cause
The causes of premature ejaculation are unclear. Many theories have been suggested, including that PE was the result of masturbating quickly during adolescence to avoid being caught, performance anxiety, passive-aggressiveness or having too little sex; but there is little evidence to support any of these theories.Several physiological mechanisms have been hypothesized to contribute to causing premature ejaculation, including serotonin receptors, a genetic predisposition, elevated penile sensitivity and nerve conduction atypicalities. Scientists have long suspected a genetic link to certain forms of premature ejaculation. However, studies have been inconclusive in isolating the gene responsible for lifelong PE.
The nucleus paragigantocellularis of the brain has been identified as having involvement in ejaculatory control. Other researchers have noted that men who have premature ejaculation have a faster neurological response in the pelvic muscles.PE may be caused by prostatitis or as a medication side effect.
PE has been classified into four subtypes - lifelong, acquired, variable and subjective PE. The pathophysiology of lifelong PE is mediated by a complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and epigenetic factors. Acquired PE may occur due to psychological problems - such as sexual performance anxiety, and psychological or relationship problems - and/or co-morbidity, including Erectile dysfunction, prostatitis and hyperthyroidism.

Mechanism
The physical process of ejaculation requires two actions: emission and expulsion. The emission is the first phase. It involves deposition of fluid from the ampullary vas deferens, seminal vesicles and prostate gland into the posterior urethra. The second phase is the expulsion phase. It involves closure of bladder neck, followed by the rhythmic contractions of the urethra by pelvic-perineal and bulbospongiosus muscle and intermittent relaxation of external urethral sphincters.Sympathetic motor neurons control the emission phase of ejaculation reflex, and expulsion phase is executed by somatic and autonomic motor neurons. These motor neurons are located in the thoracolumbar and lumbosacral spinal cord and are activated in a coordinated manner when sufficient sensory input to reach the ejaculatory threshold has entered the central nervous system.

Intromission time
The 1948 Kinsey Report suggested that three-quarters of men ejaculate within two minutes of penetration in over half of their sexual encounters.Current evidence supports an average intravaginal ejaculation latency time (IELT) of six and a half minutes in 18- to 30-year-olds. If the disorder is defined as an IELT percentile below 2.5, then premature ejaculation could be suggested by an IELT of less than about two minutes. Nevertheless, it is possible that men with abnormally low IELTs could be satisfied with their performance and do not report a lack of control. Likewise, those with higher IELTs may consider themselves premature ejaculators, have detrimental side effects normally associated with premature ejaculation, and even benefit from treatment.

Diagnosis
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) defines premature ejaculation as "A persistent or recurrent pattern of ejaculation occurring during partnered sexual activity within approximately 1 minute following vaginal penetration and before the person wishes it," with the additional requirements that the condition occurs for a duration longer than 6 months, causes clinically significant distress, and cannot be better explained by relationship distress, another mental disorder, or the use of medications. These factors are identified by talking with the person, not through any diagnostic test. The DSM-5 allows for specifiers whether the condition is lifelong or acquired, applying in general or only to certain situations, and severity based on the time under one minute, however these subtypes have been criticised as lacking validity due to insufficient evidence.The 2007 ICD-10 defined PE as ejaculating without control, and within around 15 seconds.

Treatments
Several treatments have been tested for treating premature ejaculation. A combination of medication and non-medication treatments is often the most effective method.

Self-treatment
Many men attempt to treat themselves for premature ejaculation by trying to distract themselves, such as by trying to focus their attention away from the sexual stimulation. There is little evidence to indicate that it is effective and it tends to detract from the sexual fulfilment of both partners. Other self-treatments include thrusting more slowly, withdrawing the penis altogether, purposefully ejaculating before sexual intercourse, and using more than one condom. Using more than one condom is not recommended as the friction will often lead to breakage. Some men report these to have been helpful.A qualitative clinical trial, conducted by Kings College London medical school teaching hospitals, compared use of the Prolong device with cognitive behavioural therapy. Using the Climax Control Training program in 58 subjects was found to delay time to ejaculation from 48 seconds (0.8 minutes) to 8 minutes and 48 seconds (8.8 minutes) on average in 61% of men, compared to 2 minutes and 36 seconds (2.6 minutes) in 40% of men having cognitive behavioural therapy, with a difference on average of 6 minutes and 12 seconds (6.2 minutes) between the two groups.

Sex therapy
Several techniques have been developed and applied by sex therapists, including Kegel exercises (to strengthen the muscles of the pelvic floor) and Masters and Johnsons "stop-start technique" (to desensitize the mans responses) and "squeeze technique" (to reduce excessive arousal).: 27 To treat premature ejaculation, Masters and Johnson developed the "squeeze technique", based on the Semans technique developed by James Semans in 1956. Men were instructed to pay close attention to their arousal pattern and learn to recognize how they felt shortly before their "point of no return", the moment ejaculation felt imminent and inevitable. Sensing it, they were to signal their partner, who squeezed the head of the penis between thumb and index finger, suppressing the ejaculatory reflex and allowing the man to last longer.The squeeze technique worked, but many couples found it cumbersome. From the 1970s to the 1990s, sex therapists refined the Masters and Johnson approach, largely abandoning the squeeze technique and focused on a simpler and more effective technique called the "stop-start" technique. During intercourse, as the man senses he is approaching climax, both partners stop moving and remain still until the mans feelings of ejaculatory inevitability subside, at which point, they are free to resume active intercourse.These techniques appear to work for around half of people, in the short-term studies that had been done as of 2017.: 27

Medications
As of 2019, there are no drugs specifically approved for the treatment of PE. Selective serotonin reuptake inhibitors (SSRIs) are used to treat PE, including fluoxetine, paroxetine, citalopram, escitalopram  or dapoxetine and clomipramine. The opioid tramadol, an atypical oral analgesic is also used. Results have found PDE5 inhibitors to be effective in combination treatment with SSRIs. The full effects of these medications typically emerge after 2-3 weeks, with results indicating about ejaculatory delay varying between 6–20 times greater than before medication. Premature ejaculation can return upon discontinuation, and the side effects of these SSRIs can also include anorgasmia, erectile dysfunction, and diminished libido.Topical anesthetics such as lidocaine and benzocaine that are applied to the tip and shaft of the penis have also been used. They are applied 10–15 minutes before sexual activity and have fewer potential side effects as compared to SSRIs. However, this is sometimes disliked due to the reduction of sensation in the penis as well as for the partner (due to the medication rubbing onto the partner).

Surgical treatments
Two different surgeries, both developed in South Korea, are available to permanently treat premature ejaculation: selective dorsal neurectomy (SDN) and glans penis augmentation using a hyaluronan gel. Circumcision has shown no effect on PE. The International Society for Sexual Medicine guidelines do not recommend either surgical treatment due to the risk of permanent loss of sexual function and insufficient reliable data and on the basis of violating the medical principle of non-maleficence as the surgery can lead to complications, of which some might not yet be known. The most common complication of surgery is the recurrence of PE, reported to occur in about 10% of surgeries. Other sources consider SDN as a safe and efficient treatment and these surgeries are popular in Asian countries.

Epidemiology
Premature ejaculation is a prevalent sexual dysfunction in men; however, because of the variability in time required to ejaculate and in partners desired duration of sex, exact prevalence rates of PE are difficult to determine. In the "Sex in America" surveys (1999 and 2008), University of Chicago researchers found that between adolescence and age 59, approximately 30% of men reported having experienced PE at least once during the previous 12 months, whereas about 10 percent reported erectile dysfunction (ED). Although ED is mens most prevalent sex problem after age 60, and may be more prevalent than PE overall according to some estimates, premature ejaculation remains a significant issue that, according to the survey, affects 28 percent of men age 65–74, and 22 percent of men age 75–85. Other studies report PE prevalence ranging from 3 percent to 41 percent of men over 18, but the great majority estimate a prevalence of 20 to 30 percent—making PE a very common sex problem.There is a common misconception that younger men are more likely to develop premature ejaculation and that its frequency decreases with age. Prevalence studies have indicated, however, that rates of PE are constant across age groups.

History
Male mammals ejaculate quickly during intercourse, prompting some biologists to speculate that rapid ejaculation had evolved into mens genetic makeup to increase their chances of passing their genes.Ejaculatory control issues have been documented for more than 1,500 years. The Kamasutra, the 4th century BCE Indian marriage handbook, declares: "Women love the man whose sexual energy lasts a long time, but they resent a man whose energy ends quickly because he stops before they reach a climax."  Waldinger summarizes professional perspectives from early in the twentieth century.Sex researcher Alfred Kinsey did not consider rapid ejaculation a problem, but viewed it as a sign of "masculine vigor" that could not always be cured.  The belief that it should be considered a disease rather than a normal variation, has also been disputed by some modern researchers.

Psychoanalysis
Freudian theory postulated that rapid ejaculation was a symptom of underlying neurosis. It stated that the man has unconscious hostility toward women, so he ejaculates rapidly, which satisfies him but frustrates his lover, who is unlikely to experience orgasm that quickly. Freudians claimed that premature ejaculation could be cured using psychoanalysis. But even years of psychoanalysis accomplished little, if anything, in curing premature ejaculation.In 1974, there was no evidence found to suggest that men with premature ejaculation harbor unusual hostility toward women.

See also
Anorgasmia
Delayed ejaculation
Edging (sexual practice)
Pre-ejaculate
Retrograde ejaculation
Erectile dysfunction
Blue balls
Pull out method
Foreplay

References
Cited sources
Kaplan, Helen S. (1974). The New Sex Therapy. Psychology Press. ISBN 9780876300831.
Kaplan, Helen S. (1989). How to Overcome Premature Ejaculation. Routledge. ISBN 978-0876305423.

Further reading
Hamblin, James (2012). "When Is Ejaculation Premature, and When Should a Penis Be Made Numb?" </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 Incidents and can you explain it in depth? [/INST] Incidents is a 1987 collection of four essays by Roland Barthes </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 Ketonuria and can you explain it in depth? [/INST] Ketonuria is a medical condition in which ketone bodies are present in the urine.
It is seen in conditions in which the body produces excess ketones as an indication that it is using an alternative source of energy. It is seen during starvation or more commonly in type 1 diabetes mellitus. Production of ketone bodies is a normal response to a shortage of glucose, meant to provide an alternate source of fuel from fatty acids.

Pathophysiology
Ketones are metabolic end-products of fatty acid metabolism. In healthy individuals, ketones are formed in the liver and are completely metabolized so that only negligible amounts appear in the urine. However, when carbohydrates are unavailable or unable to be used as an energy source, fat becomes the predominant body fuel instead of carbohydrates and excessive amounts of ketones are formed as a metabolic byproduct. Higher levels of ketones in the urine indicate that the body is using fat as the major source of energy.
Ketone bodies that commonly appear in the urine when fats are burned for energy are acetoacetate and beta-hydroxybutyric acid. Acetone is also produced and is expired by the lungs. Normally, the urine should not contain a noticeable concentration of ketones to give a positive reading. As with tests for glucose, acetoacetate can be tested by a dipstick or by a lab. The results are reported as small, moderate, or large amounts of acetoacetate. A small amount of acetoacetate is a value under 20 mg/dL; a moderate amount is a value of 30–40 mg/dL, and a finding of 80 mg/dL or greater is reported as a large amount.
One 2010 study admits that though ketonurias relation to general metabolic health is ill-understood, there is a positive relationship between the presence of ketonuria after fasting and positive metabolic health.

Causes
Metabolic abnormalities such as diabetes, renal glycosuria, or glycogen storage disease.
Dietary conditions such as starvation, fasting, low-carbohydrate diets, prolonged vomiting, and anorexia including caused by hyperemesis gravidarum.
Conditions in which metabolism is increased, such as hyperthyroidism, fever, pregnancy or lactation.In non-diabetic persons, ketonuria may occur during acute illness or severe stress. Approximately 15% of hospitalized patients may have ketonuria, even though they do not have diabetes. In a diabetic patient, ketone bodies in the urine suggest that the patient is not adequately controlled and that adjustments of medication, diet, or both should be made promptly. In the non diabetic patient, ketonuria reflects a reduced carbohydrate metabolism and an increased fat metabolism.

Diagnosis
A wide variety of companies manufacture ketone screening strips </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 Hereditary fructose intolerance and can you explain it in depth? [/INST] Hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism caused by a deficiency of the enzyme aldolase B. Individuals affected with HFI are asymptomatic until they ingest fructose, sucrose, or sorbitol. If fructose is ingested, the enzymatic block at aldolase B causes an accumulation of fructose-1-phosphate which, over time, results in the death of liver cells. This accumulation has downstream effects on gluconeogenesis and regeneration of adenosine triphosphate (ATP). Symptoms of HFI include vomiting, convulsions, irritability, poor feeding as a baby, hypoglycemia, jaundice, hemorrhage, hepatomegaly, hyperuricemia and potentially kidney failure. While HFI is not clinically a devastating condition, there are reported deaths in infants and children as a result of the metabolic consequences of HFI. Death in HFI is always associated with problems in diagnosis.HFI is an autosomal recessive condition caused by mutations in the ALDOB gene, located at 9q31.1. HFI is typically suspected based on dietary history, especially in infants who become symptomatic after breast feeding. This suspicion is typically confirmed by molecular analysis Treatment of HFI involves strict avoidance of fructose in the diet. Older patients with HFI typically self-select a diet low in fructose, even before being diagnosed.

Presentation
The key identifying feature of HFI is the appearance of symptoms with the introduction of fructose to the diet. Affected individuals are asymptomatic and healthy, provided they do not ingest foods containing fructose or any of its common precursors, sucrose and sorbitol. In the past, infants often became symptomatic when they were introduced to formulas that were sweetened with fructose or sucrose. These sweeteners are not common in formulas used today. Symptoms such as vomiting, nausea, restlessness, pallor, sweating, trembling and lethargy can also first present in infants when they are introduced to fruits and vegetables. These can progress to apathy, coma and convulsions if the source is not recognized early.When patients are diagnosed with HFI, a dietary history will often reveal an aversion to fruit and other foods that contain large amounts of fructose. Most adult patients do not have any dental caries.

Fructose metabolism
After ingestion, fructose is converted to fructose-1-phosphate in the liver by fructokinase </s>