<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 Shell shock and can you explain it in depth? [/INST] Shell shock is a term coined in World War I by the British psychologist Charles Samuel Myers to describe the type of post-traumatic stress disorder (PTSD) many soldiers were afflicted with during the war (before PTSD was termed). It is a reaction to the intensity of the bombardment and fighting that produced a helplessness appearing variously as panic and being scared, flight, or an inability to reason, sleep, walk or talk.During the war, the concept of shell shock was ill-defined. Cases of "shell shock" could be interpreted as either a physical or psychological injury, or as a lack of moral fibre. The term shell shock is still used by the United States’ Department of Veterans Affairs to describe certain parts of PTSD, but mostly it has entered into memory, and it is often identified as the signature injury of the war.
In World War II and thereafter, diagnosis of "shell shock" was replaced by that of combat stress reaction, a similar but not identical response to the trauma of warfare and bombardment.

Origin
During the early stages of World War I in 1914, soldiers from the British Expeditionary Force began to report medical symptoms after combat, including tinnitus, amnesia, headaches, dizziness, tremors, and hypersensitivity to noise. While these symptoms resembled those that would be expected after a physical wound to the brain, many of those reporting sick showed no signs of head wounds. By December 1914 as many as 10% of British officers and 4% of enlisted men were experiencing "nervous and mental shock".The term "shell shock" was coined during the Battle of Loos to reflect an assumed link between the symptoms and the effects of explosions from artillery shells. The term was first published in 1915 in an article in The Lancet by Charles Myers. Some 60–80% of shell shock cases displayed acute neurasthenia, while 10% displayed what would now be termed symptoms of conversion disorder, including mutism and fugue.The number of shell shock cases grew during 1915 and 1916 but it remained poorly understood medically and psychologically. Some physicians held the view that it was a result of hidden physical damage to the brain, with the shock waves from bursting shells creating a cerebral lesion that caused the symptoms and could potentially prove fatal. Another explanation was that shell shock resulted from poisoning by the carbon monoxide formed by explosions.At the same time, an alternative view developed describing shell shock as an emotional, rather than a physical, injury. Evidence for this point of view was provided by the fact that an increasing proportion of men with shell shock symptoms had not been exposed to artillery fire. Since the symptoms appeared in men who had no proximity to an exploding shell, the physical explanation was clearly unsatisfactory.In spite of this evidence, the British Army continued to try to differentiate those whose symptoms followed explosive exposure from others. In 1915 the British Army in France was instructed that:

Shell-shock and shell concussion cases should have the letter W prefixed to the report of the casualty, if it was due to the enemy; in that case the patient would be entitled to rank as wounded and to wear on his arm a wound stripe.  If, however, the mans breakdown did not follow a shell explosion, it was not thought to be due to the enemy, and he was to [be] labelled Shell-shock or S (for sickness) and was not entitled to a wound stripe or a pension.
However, it often proved difficult to identify which cases were which, as the information on whether a casualty had been close to a shell explosion or not was rarely provided.

Management
Acute
At first, shell-shock casualties were rapidly evacuated from the front line – in part because of fear of their unpredictable behaviour. As the size of the British Expeditionary Force increased, and manpower became in shorter supply, the number of shell shock cases became a growing problem for the military authorities. At the Battle of the Somme in 1916, as many as 40% of casualties were shell-shocked, resulting in concern about an epidemic of psychiatric casualties, which could not be afforded in either military or financial terms.Among the consequences of this were an increasing official preference for the psychological interpretation of shell shock, and a deliberate attempt to avoid the medicalisation of shell shock. If men were uninjured it was easier to return them to the front to continue fighting. Another consequence was an increasing amount of time and effort devoted to understanding and treating shell shock symptoms. Soldiers who returned with shell shock generally could not remember much because their brain would shut out all the traumatic memories.
By the Battle of Passchendaele in 1917, the British Army had developed methods to reduce shell shock. A man who began to show shell-shock symptoms was best given a few days rest by his local medical officer. Col. Rogers, Regimental Medical Officer,  4th Battalion Black Watch wrote:

You must send your commotional cases down the line.  But when you get these emotional cases, unless they are very bad, if you have a hold of the men and they know you and you know them (and there is a good deal more in the man knowing you than in you knowing the man) … you are able to explain to him that there is really nothing wrong with him, give him a rest at the aid post if necessary and a day or two’s sleep, go up with him to the front line, and, when there, see him often, sit down beside him and talk to him about the war and look through his periscope and let the man see you are taking an interest in him.
If symptoms persisted after a few weeks at a local Casualty Clearing Station, which would normally be close enough to the front line to hear artillery fire, a casualty might be evacuated to one of four dedicated psychiatric centres which had been set up further behind the lines, and were labelled as "NYDN – Not Yet Diagnosed Nervous" pending further investigation by medical specialists.
Although the Battle of Passchendaele generally became a byword for horror, the number of cases of shell shock were relatively few. 5,346 shell shock cases reached the Casualty Clearing Station, or roughly 1% of the British forces engaged. 3,963 (or just under 75%) of these men returned to active service without being referred to a hospital for specialist treatment. The number of shell shock cases reduced throughout the battle, and the epidemic of illness was ended.During 1917, "shell shock" was entirely banned as a diagnosis in the British Army, and mentions of it were censored, even in medical journals.

Chronic treatment
The treatment of chronic shell shock varied widely according to the details of the symptoms, the views of the doctors involved, and other factors including the rank and class of the patient.
There were so many officers and men with shell shock that 19 British military hospitals were wholly devoted to the treatment of cases. Ten years after the war, 65,000 veterans of the war were still receiving treatment for it in Britain. In France it was possible to visit aged shell shock victims in hospital in 1960.

Physical causes
2015 research by Johns Hopkins University has found that the brain tissue of combat veterans who have been exposed to improvised explosive devices (IEDs) exhibit a pattern of injury in the areas responsible for decision making, memory and reasoning.  This evidence has led the researchers to conclude that shell shock may not only be a psychological disorder, since the symptoms exhibited by affected individuals from the First World War are very similar to these injuries. Immense pressure changes are involved in shell shock. Even mild changes in air pressure from weather have been linked to changes in behavior.There is also evidence to suggest that the type of warfare faced by soldiers would affect the probability of shell shock symptoms developing. First-hand reports from medical doctors at the time note that rates of such conditions decreased once the war was mobilized again during the 1918 German offensive, following the 1916–1917 period where the highest rates of shell shock can be found.  This could suggest that it was trench warfare, and the experience of siege warfare specifically, that led to the development of these symptoms.

Cowardice
Some men with shell shock were put on trial, and even executed, for military crimes including desertion and cowardice.  While it was recognised that the stresses of war could cause men to break down, a lasting episode was likely to be seen as symptomatic of an underlying lack of character. For instance, in his testimony to the post-war Royal Commission examining shell shock, Lord Gort said that shell shock was a weakness and was not found in "good" units. The continued pressure to avoid medical recognition of shell shock meant that it was not, in itself, considered an admissible defence. Although some doctors or medics did take procedure to try to cure soldiers shell shock, it was first done in a brutal way. Doctors would provide electric shock to soldiers in hopes that it would shock them back to their normal, heroic, pre-war self. After almost a year of giving one of his patients electric shocks, putting cigarettes on his tongue, hot plates at the back of his throat, etc., a British clinician, Lewis Yealland, said to his patient, "You will not leave this room until you are talking as well as you ever did... You must behave as the hero I expected you to be."Executions of soldiers in the British Army were not commonplace. While there were 240,000 Courts Martial and 3080 death sentences handed down, in only 346 cases was the sentence carried out. 266 British soldiers were executed for "Desertion", 18 for "Cowardice", 7 for "Quitting a post without authority", 5 for "Disobedience to a lawful command" and 2 for "Casting away arms".  On 7 November 2006, the government of the United Kingdom gave them all a posthumous conditional pardon.

Committee of Enquiry report
The British government produced a Report of the War Office Committee of Enquiry into "Shell-Shock" which was published in 1922. Recommendations from this included:

In forward areas
No soldier should be allowed to think that loss of nervous or mental control provides an honourable avenue of escape from the battlefield, and every endeavour should be made to prevent slight cases leaving the battalion or divisional area, where treatment should be confined to provision of rest and comfort for those who need it and to heartening them for return to the front line.
In neurological centres
When cases are sufficiently severe to necessitate more scientific and elaborate treatment they should be sent to special Neurological Centres as near the front as possible, to be under the care of an expert in nervous disorders.  No such case should, however, be so labelled on evacuation as to fix the idea of nervous breakdown in the patient’s mind.
In base hospitals
When evacuation to the base hospital is necessary, cases should be treated in a separate hospital or separate sections of a hospital, and not with the ordinary sick and wounded patients.  Only in exceptional circumstances should cases be sent to the United Kingdom, as, for instance, men likely to be unfit for further service of any kind with the forces in the field.  This policy should be widely known throughout the Force.
Forms of treatment
The establishment of an atmosphere of cure is the basis of all successful treatment, the personality of the physician is, therefore, of the greatest importance.  While recognising that each individual case of war neurosis must be treated on its merits, the Committee are of opinion that good results will be obtained in the majority by the simplest forms of psycho-therapy, i.e., explanation, persuasion and suggestion, aided by such physical methods as baths, electricity and massage.  Rest of mind and body is essential in all cases.The committee are of opinion that the production of hypnoidal state and deep hypnotic sleep, while beneficial as a means of conveying suggestions or eliciting forgotten experiences are useful in selected cases, but in the majority they are unnecessary and may even aggravate the symptoms for a time.
They do not recommend psycho-analysis in the Freudian sense.In the state of convalescence, re-education and suitable occupation of an interesting nature are of great importance.  If the patient is unfit for further military service, it is considered that every endeavour should be made to obtain for him suitable employment on his return to active life.
Return to the fighting line
Soldiers should not be returned to the fighting line under the following conditions:(1) If the symptoms of neurosis are of such a character that the soldier cannot be treated overseas with a view to subsequent useful employment.
(2) If the breakdown is of such severity as to necessitate a long period of rest and treatment in the United Kingdom.
(3) If the disability is anxiety neurosis of a severe type.
(4) If the disability is a mental breakdown or psychosis requiring treatment in a mental hospital.
It is, however, considered that many of such cases could, after recovery, be usefully employed in some form of auxiliary military duty.
Part of the concern was that many British veterans were receiving pensions and had long-term disabilities.

By 1939, some 120,000 British ex-servicemen had received final awards for primary psychiatric disability or were still drawing pensions – about 15% of all pensioned disabilities – and another 44,000 or so … were getting pensions for ‘soldier’s heart’ or Effort Syndrome.  There is, though, much that statistics do not show, because in terms of psychiatric effects, pensioners were just the tip of a huge iceberg.
War correspondent Philip Gibbs wrote:

Something was wrong.  They put on civilian clothes again and looked to their mothers and wives very much like the young men who had gone to business in the peaceful days before August 1914.  But they had not come back the same men.  Something had altered in them.  They were subject to sudden moods, and queer tempers, fits of profound depression alternating with a restless desire for pleasure.  Many were easily moved to passion where they lost control of themselves, many were bitter in their speech, violent in opinion, frightening.
One British writer between the wars wrote:

There should be no excuse given for the establishment of a belief that a functional nervous disability constitutes a right to compensation.  This is hard saying.  It may seem cruel that those whose sufferings are real, whose illness has been brought on by enemy action and very likely in the course of patriotic service, should be treated with such apparent callousness.  But there can be no doubt that in an overwhelming proportion of cases, these patients succumb to ‘shock’ because they get something out of it.  To give them this reward is not ultimately a benefit to them because it encourages the weaker tendencies in their character.  The nation cannot call on its citizens for courage and sacrifice and, at the same time, state by implication that an unconscious cowardice or an unconscious dishonesty will be rewarded.

Development of psychiatry
At the beginning of World War II, the term "shell shock" was banned by the British Army, though the phrase "postconcussional syndrome" was used to describe similar traumatic responses.

Society and culture
Shell shock has had a profound impact in British culture and the popular memory of World War I. At the time, war writers like the poets Siegfried Sassoon and Wilfred Owen dealt with shell shock in their work. Sassoon and Owen spent time at Craiglockhart War Hospital, which treated shell shock casualties. Author Pat Barker explored the causes and effects of shell shock in her Regeneration Trilogy, basing many of her characters on real historical figures and drawing on the writings of the first world war poets and the army doctor W. H. R. Rivers.

Modern cases of shell shock
Although the term "shell shocked" is typically used in discussion of WWI to describe early forms of PTSD, its high-impact explosives-related nature provides modern applications as well. During their deployment in Iraq and Afghanistan, approximately 380,000 U.S. troops, about 19% of those deployed, were estimated to have sustained brain injuries from explosive weapons and devices. This prompted the U.S. Defense Advanced Research Projects Agency (DARPA) to open up a $10 million study of the blast effects on the human brain. The study revealed that, while the brain remains initially intact immediately after low level blast effects, the chronic inflammation afterwards is what ultimately leads to many cases of shell shock and PTSD.

See also
Combat stress reaction

References
Sources
Coulthart, Ross. The Lost Diggers, Sydney: HarperCollins Publishers, 2012. ISBN 978-0732294618
Jones, E, Fear, N and Wessely, S. "Shell Shock and Mild Traumatic Brain Injury:  A Historical Review". Am J Psychiatry 2007; 164:1641–1645
Hochschild, Adam. To End all Wars – a story of loyalty and rebellion, 1914–1918 Mariner Books, Houghton, Mifflin Harcourt, Boston & New York, 2011. ISBN 978-0547750316
Horrocks, J. (2018). The limits of endurance: Shell shock and dissent in World War one. The Journal of New Zealand Studies, (NS27). https://doi.org/10.26686/jnzs.v0ins27.5175
Leese, Peter. Shell Shock. Traumatic Neurosis and the British Soldiers of the First World War, Palgrave Macmillan, 2014. ISBN 978-1137453372.
MacLeod, A. D. (2004). "Shell shock, Gordon Holmes and the Great War". Journal of the Royal Society of Medicine. 97 (2): 86–89 </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 Bakers itch 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 List of autoimmune diseases 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 Acute monocytic leukemia and can you explain it in depth? [/INST] Acute monocytic leukemia (AMoL, or AML-M5) is a type of acute myeloid leukemia. In AML-M5 >80% of the leukemic cells are of monocytic lineage. This cancer is characterized by a dominance of monocytes in the bone marrow. There is an overproduction of monocytes that the body does not need in the periphery. These overproduced monocytes interfere with normal immune cell production which causes many health complications for the infected individual.

Causes
The pathology of AML involves abnormal proliferation and differentiation of a population of myeloid stem cells. Genetic mutations are identified in the majority of cases. A common genetic mutation identified in these cases are characterized as chromosomal translocations where information from one chromosome is exchanged to a non-homologous chromosome creating an unusual rearrangement of chromosomes. This translocation is often abbreviated as t(#of one chromosome involved, #of other chromosome involved). M5 is associated with characteristic chromosomal abnormalities, often involving chromosome 11, such as t(9;11), affecting the MLL (KMTA2) locus at 11q23; however MLL translocations are also found in other leukemia subtypes. The t(8;16) translocation in AMoL is associated with hemophagocytosis. These translocations yield the formation of chimeric proteins (RUNX1-RUNX1T1 and PML-RARA, respectively) which disrupt normal myeloid precursor development.
Secondary leukaemia, which may include AML-M5, has been associated with exposure to epipodophyllotoxins, such as etoposide.Many cases of AML-M5 are seen to have enhanced phosphorylation of the STAT3 protein due to increased induction of cytokines thus increasing cell proliferation and survival. Finally, genetic mutations involved in epigenetic regulation are associated with this leukemia, as they have downstream effects on cell differentiation and proliferation. Excessive cytokine release could be a byproduct of skewed epigenetic regulation.

Diagnosis
In order to fulfill World Health Organization (WHO) criteria for AML-5, a patient must have greater than 20% blasts in the bone marrow, and of these, greater than 80% must be of the monocytic lineage </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 Primitive neuroectodermal tumor and can you explain it in depth? [/INST] Primitive neuroectodermal tumor is a malignant (cancerous) neural crest tumor </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 Cocaine intoxication and can you explain it in depth? [/INST] Cocaine intoxication refers to the subjective, desired and adverse effects of cocaine on the mind and behavior of users. Both self-induced and involuntary cocaine intoxication have medical and legal implications (even in absence of relevant adverse effects).
Adverse effects can develop over time due to repeated use and so become chronic conditions. However, even a one-time intake of the substance can result in severe acute intoxication.
Recurrent cocaine use and dependence to the drug  inevitably leads to the reduction of the desired effects perceived by the users,  while the occurrence of adverse effects of intoxication increase. The last can sometimes be completely reversed without bearing consequences but they can also potentially kill the users (e.g., in cases of untreated or non-manageable overdoses).

Signs and symptoms
Cocaine increases alertness, feelings of well-being, euphoria, energy, sociability, and sexuality. The former are some of the desired effects of cocaine intoxication. Not having the normal use of mental faculties by reason of the introduction of cocaine is defined drug intoxication by the laws in America, Europe, and most of the rest of the World, and it is a serious crime in specific contexts (e.g., in drug-impaired driving).Mild adverse effects include anxiety, increased temperature, paranoia, restlessness, and teeth grinding.  With prolonged use, the drug can cause chronic complications like insomnia, weight loss, anorexia, persistent tachycardia, heart failure, kidney failure, hallucinations, and paranoid delusions.Depression with suicidal ideation may develop in heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long-term damage to dopamine neurons. Chronic intranasal usage can degrade the cartilage separating the nostrils (the nasal septum), which can eventually lead to its complete disappearance.Studies have shown that cocaine usage during pregnancy triggers premature labor and may lead to abruptio placentae.In cases of severe acute intoxication, potentially lethal adverse effects include prolonged episodes of arrhythmia (i.e., a group of abnormal heart rhythms that also include tachycardia), heavy hypoglycemia, tremors, convulsions, hyperthermia (i.e., markedly increased core temperature), untreated uremia, myocardial infarction, stroke, and sudden cardiac arrest.

Overdose
Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of body packing or stuffing with rupture in the gastrointestinal tract. Use of cocaine causes abnormally fast heart rhythms and a marked elevation of blood pressure (hypertension), which can be life-threatening. This can lead to death from acute myocardial infarction, acute respiratory failure (i.e., hypoxemia, with or without hypercapnia), stroke, cerebral hemorrhage, and sudden cardiac arrest. Cocaine overdose may result in hyperthermia as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced vasoconstriction. Cocaine and/or associated hyperthermia may cause muscle cell destruction (rhabdomyolysis) and myoglobinuria resulting in kidney failure. Individuals with cocaine overdose should be transported immediately to the nearest emergency department, preferably by ambulance in case cardiac arrest occurs en route. According to the National Institute on Drug Abuse, approximately 14,600 deaths occurred in the US in 2017 due to an overdose where cocaine was somehow involved in any capacity, defined or undefined. Because of the increase in heart rate, cocaine users can be prone to elevated body temperatures, tremors, chest pains, and subject to nausea and vomiting. Some psychological symptoms due to an overdose include paranoia, delirium, anxiety as well as panicked feelings. Some signs of an overdose of cocaine are difficulty breathing, loss of urine control, bluish color of the skin, loss of awareness or surroundings, and high blood pressure. Although not as common, death can be caused from an over intoxication of cocaine. Most severe overdoses occur when users combine cocaine with other substances like alcohol or heroin, which increase the effects and heighten the chances of having a dangerous overdose. Treating an overdose can be done by bringing back blood flow to the heart, and restoring the body with oxygen rich blood, especially for the brain to reduce the risk of stroke. Cocaine overdoses have fluctuated over the years. From 2006 to 2010 there has been a decline in the number of reported cases. Though, from 2010 to 2015 there has been an increase in the reported cases involving over cocaine Intoxication. Males appear to have a much higher chance of overdosing than females. The ratio of male to female cocaine overdoses is 3:1.

Withdrawal
Cocaine withdrawal is not as severe as the withdrawal from other substances. For example, substances like alcohol and benzodiazepines can involve severe physical withdrawal symptoms while cocaine results in mostly psychological symptoms. Physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia, hypersomnia, anger, increased appetite, weight gain, psychomotor retardation, agitation, depression, and anxiety.  According to a study done by Gawin and Kleber in 1986, there are three phases in the withdrawal process. They observed the behavior of 30 cocaine-dependent individuals. Phase one, the crash, is characterized by acute dysphoria, irritability and anxiety, increased desire for sleep, exhaustion, increased appetite, decreased craving to use. Phase two, withdrawal, is characterized by increasing craving to use, poor concentration, some irritability and some lethargy, which persisted for up to 10 weeks. Lastly, phase three is characterized by the intermittent craving to use in the context of external cues. Cocaine and its metabolites are eliminated from the body by 3 days.  There are not any FDA-approved medications that specifically help treat cocaine withdrawal, however, there are some useful medications that could possibly help individuals overcome their addiction. One example is propranolol. Propranolol is a beta blocker that has been approved to treat hypertension, angina, anxiety, and other related psychological problems. Buprenorphine and naltrexone are two substances that act as an effective treatment in the earlier stages of withdrawal.

Pathophysiology
Cocaine pharmacodynamics involve multiple complex mechanisms. Although it has a short half-life (~ 1 hour), cocaine metabolites, which rise in concentrations several hours after cocaine ingestion, persist in circulation for up to 24 hours, and may cause delayed or recurrent coronary vasoconstriction. This drug binds and blocks monoamine (dopamine, epinephrine, norepinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects. Cocaines acute effect in the central nervous system is to raise the amount of dopamine and serotonin in the nucleus accumbens (the pleasure center in the brain). When this effect ceases due to metabolism of cocaine, depletion of associated neurotransmitters, and receptor down-regulation (tachyphylaxis), the cocaine user may experience dysphoria, or a "crash" after the initial high. The principal actions of cocaine on the cardiovascular system are from alpha- and beta-1-adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand. Cocaine and its metabolites may cause arterial vasoconstriction hours after use. Epicardial coronary arteries are especially vulnerable to these effects, leading to decreased myocardial oxygen supply. Cocaine-induced platelet activation and thrombus formation is another deleterious effect, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation. Plasminogen activator inhibitor is also increased following cocaine use, thereby promoting thrombosis. Cocaine acts like a class I antiarrhythmic agent by blocking sodium and potassium channels, in a similar way of local anesthetics such as lidocaine, and interferes with action potential propagation. This Vaughn-Williams class IC effect increases the risk of conduction disturbance and tachyarrhythmias. Adding to its complex toxicity, cocaine targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors.

Management
There is no specific antidote for cocaine. Emergency treatment of cocaine-associated high body temperature consists of giving a benzodiazepine and physical cooling. Immediate administration of aspirin is required for patients reporting cocaine-associated chest pain. Cooling is best accomplished with tepid water misting and cooling with a fan. Antipyretics (e.g., paracetamol) have no effect in lowering high temperature because cocaine is an muscarinic receptor agonist.
The chest pain, high blood pressure, and increased heart rate caused by cocaine may be also treated with benzodiazepines. Multiple and escalating dose of benzodiazepines may be necessary to achieve effect, which increases risk of over-sedation and respiratory depression. A review of cocaine cardiovascular toxicity found benzodiazepines may not always reliably lower heart rate and blood pressure.
Lidocaine and intravenous lipid emulsion have been successfully used for serious ventricular tachyarrhythmias in several case reports.
People who are agitated are best treated with benzodiazepines, though antipsychotics such as haloperidol and olanzapine may also be useful. The alpha-2 agonist dexmedetomidine may also be useful for agitation, but effects on heart rate and blood pressure are variable based on several studies and case reports.

Vasodilators
Nitric-oxide mediated vasodilators, such as nitroglycerin and nitroprusside, are effective at lowering blood pressure and reversing coronary arterial vasoconstriction, but not heart rate </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 Hypercapnia and can you explain it in depth? [/INST] Hypercapnia (from the Greek hyper = "above" or "too much" and kapnos = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous product of the bodys metabolism and is normally expelled through the lungs. Carbon dioxide may accumulate in any condition that causes hypoventilation, a reduction of alveolar ventilation (the clearance of air from the small sacs of the lung where gas exchange takes place) as well as resulting from inhalation of CO2. Inability of the lungs to clear carbon dioxide, or inhalation of elevated levels of CO2, leads to respiratory acidosis. Eventually the body compensates for the raised acidity by retaining alkali in the kidneys, a process known as "metabolic compensation".
Acute hypercapnia is called acute hypercapnic respiratory failure (AHRF) and is a medical emergency as it generally occurs in the context of acute illness. Chronic hypercapnia, where metabolic compensation is usually present, may cause symptoms but is not generally an emergency. Depending on the scenario both forms of hypercapnia may be treated with medication, with mask-based non-invasive ventilation or with mechanical ventilation.
Hypercapnia is a hazard of underwater diving associated with breath-hold diving, scuba diving, particularly on rebreathers, and deep diving where it is associated with increased breathing gas density due to the high ambient pressure.

Signs and symptoms
Hypercapnia may happen in the context of an underlying health condition, and symptoms may relate to this condition or directly to the hypercapnia. Specific symptoms attributable to early hypercapnia are dyspnea (breathlessness), headache, confusion and lethargy. Clinical signs include flushed skin, full pulse (bounding pulse), rapid breathing, premature heart beats, muscle twitches, and hand flaps (asterixis). The risk of dangerous irregularities of the heart beat is increased. Hypercapnia also occurs when the breathing gas is contaminated with carbon dioxide, or respiratory gas exchange cannot keep up with the metabolic production of carbon dioxide, which can occur when gas density limits ventilation at high ambient pressures.In severe hypercapnia (generally

            P

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                      2

    {\displaystyle {P_{a_{CO_{2}}}}}
   greater than 10 kPa or 75 mmHg), symptomatology progresses to disorientation, panic, hyperventilation, convulsions, unconsciousness, and eventually death.

Causes
Carbon dioxide is a normal metabolic product but it accumulates in the body if it is produced faster than it is cleared. During strenuous exercise the production rate of carbon dioxide can increase more than tenfold over the production rate during rest. Carbon dioxide is dissolved in the blood and elimination is by gas exchange in the lungs during breathing. Hypercapnia is generally caused by hypoventilation, lung disease, or diminished consciousness. It may also be caused by exposure to environments containing abnormally high concentrations of carbon dioxide, such as from volcanic or geothermal activity, or by rebreathing exhaled carbon dioxide. In this situation the hypercapnia can also be accompanied by respiratory acidosis.Acute hypercapnic respiratory failure may occur in acute illness caused by chronic obstructive pulmonary disease (COPD), chest wall deformity, some forms of neuromuscular disease (such as myasthenia gravis, and obesity hypoventilation syndrome. AHRF may also develop in any form of respiratory failure where the breathing muscles become exhausted, such as severe pneumonia and acute severe asthma. It can also be a consequence of profound suppression of consciousness such as opioid overdose.

During diving
Normal respiration in divers results in alveolar hypoventilation resulting in inadequate CO2 elimination or hypercapnia. Lanphiers work at the US Navy Experimental Diving Unit answered the question, "Why dont divers breathe enough?":
Higher inspired oxygen (

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    {\displaystyle {P_{i_{O_{2}}}}}
  ) at 4 atm (400 kPa) accounted for not more than 25% of the elevation in end tidal CO2 (ETCO2) above values found at the same work rate when breathing air just below the surface.
Increased work of breathing accounted for most of the elevation of

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                      2

    {\displaystyle {P_{a_{CO_{2}}}}}
   (alveolar gas equation) in exposures above 1 atm (100 kPa), as indicated by the results when helium was substituted for nitrogen at 4 atm (400 kPa).
Inadequate ventilatory response to exertion was indicated by the fact that, despite resting values in the normal range,

            P

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                      2

    {\displaystyle {P_{et_{CO_{2}}}}}
   rose markedly with exertion even when the divers breathed air at a depth of only a few feet.A variety of reasons exists for carbon dioxide not being expelled completely when the diver exhales:

The diver is exhaling into a vessel that does not allow all the CO2 to escape to the environment, such as a long snorkel, full-face diving mask, or diving helmet, and the diver then reinhales from that vessel, causing increased dead space.
The carbon dioxide scrubber in the divers rebreather is failing to remove sufficient carbon dioxide from the loop (higher inspired CO2), or the breathing gas is contaminated with CO2.
The diver is overexercising, producing excess carbon dioxide due to elevated metabolic activity and respiratory gas exchange cannot keep up with the metabolic production of carbon dioxide.
Gas density limits ventilation at high ambient pressures. The density of the breathing gas is higher at depth, so the effort required to fully inhale and exhale increases, making breathing more difficult and less efficient (high work of breathing). Higher gas density also causes gas mixing within the lung to be less efficient, thus increasing the effective dead space.
The diver is deliberately hypoventilating, known as "skip breathing".

Skip breathing
Skip breathing is a controversial technique to conserve breathing gas when using open-circuit scuba, which consists of briefly holding ones breath between inhalation and exhalation (i.e., "skipping" a breath). It can lead to CO2 not being exhaled efficiently. The risk of burst lung (pulmonary barotrauma of ascent) is increased if the breath is held while ascending.  It is particularly counterproductive with a rebreather, where the act of breathing pumps the gas around the "loop", pushing carbon dioxide through the scrubber and mixing freshly injected oxygen.In closed-circuit rebreather diving, exhaled carbon dioxide must be removed from the breathing system, usually by a scrubber containing a solid chemical compound with a high affinity for CO2, such as soda lime. If not removed from the system, it may be reinhaled, causing an increase in the inhaled concentration.Under hyperbaric conditions, hypercapnia contributes to nitrogen narcosis and oxygen toxicity by causing cerebral vasodilation which increases the dosage of oxygen to the brain.

Mechanism
Hypercapnia normally triggers a reflex which increases breathing and access to oxygen (O2), such as arousal and turning the head during sleep. A failure of this reflex can be fatal, for example as a contributory factor in sudden infant death syndrome.Hypercapnia can induce increased cardiac output, an elevation in arterial blood pressure (higher levels of carbon dioxide stimulate aortic and carotid chemoreceptors with afferents -CN IX and X- to medulla oblongata with following chrono- and ino-tropic effects), and a propensity toward cardiac arrhythmias. Hypercapnia may increase pulmonary capillary resistance.

Physiological effects
A high arterial partial pressure of carbon dioxide (

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  ) causes changes in brain activity that adversely affect both fine muscular control and reasoning. EEG changes denoting minor narcotic effects can be detected for expired gas end tidal partial pressure of carbon dioxide (

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  ) increase from 40 torrs (0.053 atm) to approximately 50 torrs (0.066 atm). The diver does not necessarily notice these effects.Higher levels of

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   have a stronger narcotic effect: Confusion and irrational behaviour may occur around 72 torrs (0.095 atm), and loss of consciousness around 90 torrs (0.12 atm). High

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   triggers the fight or flight response, affects hormone levels and can cause anxiety, irritability and inappropriate or panic responses, which can be beyond the control of the subject, sometimes with little or no warning. Vasodilation is another effect, notably in the skin, where feelings of unpleasant heat are reported, and in the brain, where blood flow can increase by 50% at a

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   of 50 torrs (0.066 atm), Intracranial pressure may rise, with a throbbing headache. If associated with a high

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   the high delivery of oxygen to the brain may increase the risk of CNS oxygen toxicity at partial pressures usually considered acceptable.In many people a high

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   causes a feeling of shortness of breath, but the lack of this symptom is no guarantee that the other effects are not occurring. A significant percentage of rebreather deaths have been associated with CO2 retention. The effects of high

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   can take several minutes to hours to resolve once the cause has been removed.

Diagnosis
Blood gas tests may be performed, typically by radial artery puncture, in the setting of acute breathing problems or other acute medical illness. Hypercapnia is generally defined as an arterial blood carbon dioxide level over 45 mmHg (6 kPa). Since carbon dioxide is in equilibrium with carbonic acid in the blood, hypercapnia drives serum pH down, resulting in respiratory acidosis. Clinically, the effect of hypercapnia on pH is estimated using the ratio of the arterial pressure of carbon dioxide to the concentration of bicarbonate ion,

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  .

Tolerance
CO2 toxicity in animal models
Tests performed on mongrel dogs showed the physiological effect of carbon dioxide on the body of the animal: after inhalation of a 50% CO2 and 50% air mixture, respiratory movement increased for about 2 minutes, and then, it decreased for 30 to 90 minutes </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 Caroli disease and can you explain it in depth? [/INST] Caroli disease (communicating cavernous ectasia, or congenital cystic dilatation of the intrahepatic biliary tree) is a rare inherited disorder characterized by cystic dilatation (or ectasia) of the bile ducts within the liver. There are two patterns of Caroli disease: focal or simple Caroli disease consists of abnormally widened bile ducts affecting an isolated portion of liver. The second form is more diffuse, and when associated with portal hypertension and congenital hepatic fibrosis, is often referred to as "Caroli syndrome". The underlying differences between the two types are not well understood. Caroli disease is also associated with liver failure and polycystic kidney disease. The disease affects about one in 1,000,000 people, with more reported cases of Caroli syndrome than of Caroli disease.Caroli disease is distinct from other diseases that cause ductal dilatation caused by obstruction, in that it is not one of the many choledochal cyst derivatives.

Signs and symptoms
The first symptoms typically include fever, intermittent abdominal pain, and an enlarged liver. Occasionally, yellow discoloration of the skin occurs. Caroli disease usually occurs in the presence of other diseases, such as autosomal recessive polycystic kidney disease, cholangitis, gallstones, biliary abscess, sepsis, liver cirrhosis, kidney failure, and cholangiocarcinoma (7% affected). People with Caroli disease are 100 times more at risk for cholangiocarcinoma than the general population. After recognizing symptoms of related diseases, Caroli disease can be diagnosed.Morbidity is common and is caused by complications of cholangitis, sepsis, choledocholithiasis, and cholangiocarcinoma. These morbid conditions often prompt the diagnosis. Portal hypertension may be present, resulting in other conditions including enlarged spleen, hematemesis, and melena. These problems can severely affect the patients quality of life. In a 10-year period between 1995 and 2005, only 10 patients were surgically treated for Caroli disease, with an average patient age of 45.8 years.After reviewing 46 cases of Caroli disease before 1990,  21.7% of the cases were the result of an intrahepatic cyst or nonobstructive biliary tree dilation, 34.7% were linked with congenital hepatic fibrosis, 13% were isolated choledochal cystic dilation, and the remaining 24.6% had a combination of all three.

Causes
The cause appears to be genetic; the simple form is an autosomal dominant trait, while the complex form is an autosomal recessive trait. Females are more prone to Caroli disease than males. Family history may include kidney and liver disease due to the link between Caroli disease and ARPKD. PKHD1, the gene linked to ARPKD, has been found mutated in patients with Caroli syndrome. PKHD1 is expressed primarily in the kidneys with lower levels in the liver, pancreas, and lungs, a pattern consistent with phenotype of the disease, which primarily affects the liver and kidneys. The genetic basis for the difference between Caroli disease and Caroli syndrome has not been defined.

Diagnosis
Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree.  Commonly, the disease is limited to the left lobe of the liver. Images taken by CT scan, X-ray, or MRI  show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an ultrasound, tubular dilation of the bile ducts can be seen. On a CT scan, Caroli disease can be observed by noting the many fluid-filled, tubular structures extending to the liver. A high-contrast CT must be used to distinguish the difference between stones and widened ducts. Bowel gas and digestive habits make it difficult to obtain a clear sonogram, so a CT scan is a good substitution. When the intrahepatic bile duct wall has protrusions, it is clearly seen as central dots or a linear streak. Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.

Treatment
The treatment depends on clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to remove the risk of malignancy. Good evidence suggests that malignancy complicates Caroli disease in roughly 7% of cases.Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid is used for hepatolithiasis. Ursodiol is given to treat cholelithiasis </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 Metabolic syndrome and can you explain it in depth? [/INST] Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).
Metabolic syndrome is associated with the risk of developing cardiovascular disease and type 2 diabetes. In the U.S., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial and ethnic minorities.Insulin resistance, metabolic syndrome, and prediabetes are closely related to one another and have overlapping aspects. The syndrome is thought to be caused by an underlying disorder of energy utilization and storage. The cause of the syndrome is an area of ongoing medical research.

Signs and symptoms
The key sign of metabolic syndrome is central obesity, also known as visceral, male-pattern or apple-shaped adiposity. It is characterized by adipose tissue accumulation predominantly around the waist and trunk. Other signs of metabolic syndrome include high blood pressure, decreased fasting serum HDL cholesterol, elevated fasting serum triglyceride level, impaired fasting glucose, insulin resistance, or prediabetes. Associated conditions include hyperuricemia; fatty liver (especially in concurrent obesity) progressing to nonalcoholic fatty liver disease; polycystic ovarian syndrome in women and erectile dysfunction in men; and acanthosis nigricans.

Complication
Metabolic syndrome can lead to several serious and chronic complications, including type-2 diabetes, cardiovascular diseases, stroke, kidney disease and nonalcoholic fatty liver disease.

Causes
The mechanisms of the complex pathways of metabolic syndrome are under investigation. The pathophysiology is very complex and has been only partially elucidated. Most people affected by the condition are older, obese, sedentary, and have a degree of insulin resistance. Stress can also be a contributing factor. The most important risk factors are diet (particularly sugar-sweetened beverage consumption), genetics, aging, sedentary behavior or low physical activity, disrupted chronobiology/sleep, mood disorders/psychotropic medication use, and excessive alcohol use. The pathogenic role played in the syndrome by the excessive expansion of adipose tissue occurring under sustained overeating, and its resulting lipotoxicity was reviewed by Vidal-Puig.There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or if they are consequences of a more far-reaching metabolic derangement. Markers of systemic inflammation, including C-reactive protein, are often increased, as are fibrinogen, interleukin 6, tumor necrosis factor-alpha (TNF-α), and others. Some have pointed to a variety of causes, including increased uric acid levels caused by dietary fructose.Research shows that Western diet habits are a factor in development of metabolic syndrome, with high consumption of food that is not biochemically suited to humans. Weight gain is associated with metabolic syndrome. Rather than total adiposity, the core clinical component of the syndrome is visceral and/or ectopic fat (i.e., fat in organs not designed for fat storage) whereas the principal metabolic abnormality is insulin resistance. The continuous provision of energy via dietary carbohydrate, lipid, and protein fuels, unmatched by physical activity/energy demand, creates a backlog of the products of mitochondrial oxidation, a process associated with progressive mitochondrial dysfunction and insulin resistance.

Stress
Recent research indicates prolonged chronic stress can contribute to metabolic syndrome by disrupting the hormonal balance of the hypothalamic-pituitary-adrenal axis (HPA-axis). A dysfunctional HPA-axis causes high cortisol levels to circulate, which results in raising glucose and insulin levels, which in turn cause insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension, with direct effects on the bone, causing "low turnover" osteoporosis. HPA-axis dysfunction may explain the reported risk indication of abdominal obesity to cardiovascular disease (CVD), type 2 diabetes and stroke. Psychosocial stress is also linked to heart disease.

Obesity
Central obesity is a key feature of the syndrome, being both a sign and a cause, in that the increasing adiposity often reflected in high waist circumference may both result from and contribute to insulin resistance. However, despite the importance of obesity, affected people who are of normal weight may also be insulin-resistant and have the syndrome.

Sedentary lifestyle
Physical inactivity is a predictor of CVD events and related mortality. Many components of metabolic syndrome are associated with a sedentary lifestyle, including increased adipose tissue (predominantly central); reduced HDL cholesterol; and a trend toward increased triglycerides, blood pressure, and glucose in the genetically susceptible. Compared with individuals who watched television or videos or used their computers for less than one hour daily, those who carried out these behaviors for greater than four hours daily have a twofold increased risk of metabolic syndrome.

Aging
Metabolic syndrome affects 60% of the U.S. population older than age 50. With respect to that demographic, the percentage of women having the syndrome is higher than that of men. The age dependency of the syndromes prevalence is seen in most populations around the world.

Diabetes mellitus type 2
The metabolic syndrome quintuples the risk of type 2 diabetes mellitus. Type 2 diabetes is considered a complication of metabolic syndrome. In people with impaired glucose tolerance or impaired fasting glucose, presence of metabolic syndrome doubles the risk of developing type 2 diabetes. It is likely that prediabetes and metabolic syndrome denote the same disorder, defining it by the different sets of biological markers.The presence of metabolic syndrome is associated with a higher prevalence of CVD than found in people with type 2 diabetes or impaired glucose tolerance without the syndrome. Hypoadiponectinemia has been shown to increase insulin resistance and is considered to be a risk factor for developing metabolic syndrome.

Coronary heart disease
The approximate prevalence of the metabolic syndrome in people with coronary artery disease (CAD) is 50%, with a prevalence of 37% in people with premature coronary artery disease (age 45), particularly in women. With appropriate cardiac rehabilitation and changes in lifestyle (e.g., nutrition, physical activity, weight reduction, and, in some cases, drugs), the prevalence of the syndrome can be reduced.

Lipodystrophy
Lipodystrophic disorders in general are associated with metabolic syndrome. Both genetic (e.g., Berardinelli-Seip congenital lipodystrophy, Dunnigan familial partial lipodystrophy) and acquired (e.g., HIV-related lipodystrophy in people treated with highly active antiretroviral therapy) forms of lipodystrophy may give rise to severe insulin resistance and many of metabolic syndromes components.

Rheumatic diseases
There is research that associates comorbidity with rheumatic diseases. Both psoriasis and psoriatic arthritis have been found to be associated with metabolic syndrome.

Chronic obstructive pulmonary disease
Metabolic syndrome is seen to be a comorbidity in up to 50 percent of those with chronic obstructive pulmonary disease (COPD). It may pre-exist or may be a consequence of the lung pathology of COPD.

Pathophysiology
It is common for there to be a development of visceral fat, after which the adipocytes (fat cells) of the visceral fat increase plasma levels of TNF-α and alter levels of other substances (e.g., adiponectin, resistin, and PAI-1). TNF-α has been shown to cause the production of inflammatory cytokines and also possibly trigger cell signaling by interaction with a TNF-α receptor that may lead to insulin resistance. An experiment with rats fed a diet with 33% sucrose has been proposed as a model for the development of metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance. The progression from visceral fat to increased TNF-α to insulin resistance has some parallels to human development of metabolic syndrome. The increase in adipose tissue also increases the number of immune cells, which play a role in inflammation. Chronic inflammation contributes to an increased risk of hypertension, atherosclerosis and diabetes.The involvement of the endocannabinoid system in the development of metabolic syndrome is indisputable. Endocannabinoid overproduction may induce reward system dysfunction and cause executive dysfunctions (e.g., impaired delay discounting), in turn perpetuating unhealthy behaviors. The brain is crucial in development of metabolic syndrome, modulating peripheral carbohydrate and lipid metabolism.Metabolic syndrome can be induced by overfeeding with sucrose or fructose, particularly concomitantly with high-fat diet. The resulting oversupply of omega-6 fatty acids, particularly arachidonic acid (AA), is an important factor in the pathogenesis of metabolic syndrome. Arachidonic acid (with its precursor – linoleic acid) serves as a substrate to the production of inflammatory mediators known as eicosanoids, whereas the arachidonic acid-containing compound diacylglycerol (DAG) is a precursor to the endocannabinoid 2-arachidonoylglycerol (2-AG) while fatty acid amide hydrolase (FAAH) mediates the metabolism of anandamide into arachidonic acid. Anandamide can also be produced from N-acylphosphatidylethanolamine via several pathways. Anandamide and 2-AG can also be hydrolized into arachidonic acid, potentially leading to increased eicosanoid synthesis.

Diagnosis
A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity published a guideline to harmonize the definition of the metabolic syndrome. This definition recognizes that the risk associated with a particular waist measurement will differ in different populations. Whether it is better at this time to set the level at which risk starts to increase or at which there is already substantially increased risk will be up to local decision-making groups. However, for international comparisons and to facilitate the etiology, it is critical that a commonly agreed-upon set of criteria be used worldwide, with agreed-upon cut points for different ethnic groups and sexes. There are many people in the world of mixed ethnicity, and in those cases, pragmatic decisions will have to be made. Therefore, an international criterion of overweight may be more appropriate than ethnic specific criteria of abdominal obesity for an anthropometric component of this syndrome which results from an excess lipid storage in adipose tissue, skeletal muscle and liver.The previous definitions of the metabolic syndrome by the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program (NCEP) are very similar, and they identify individuals with a given set of symptoms as having metabolic syndrome. There are two differences, however: the IDF definition states that if body mass index (BMI) is greater than 30 kg/m2, central obesity can be assumed, and waist circumference does not need to be measured.  However, this potentially excludes any subject without increased waist circumference if BMI is less than 30. Conversely, the NCEP definition indicates that metabolic syndrome can be diagnosed based on other criteria. Also, the IDF uses geography-specific cut points for waist circumference, while NCEP uses only one set of cut points for waist circumference regardless of geography.

IDF
The International Diabetes Federation consensus worldwide definition of metabolic syndrome (2006) is:
Central obesity (defined as waist circumference# with ethnicity-specific values) AND any two of the following:

Raised triglycerides: > 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality
Reduced HDL cholesterol:  < 40 mg/dL (1.03 mmol/L) in males, < 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality
Raised blood pressure (BP): systolic BP > 130 or diastolic BP >85 mm Hg, or treatment of previously diagnosed hypertension
Raised fasting plasma glucose (FPG): >100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetesIf FPG is >5.6 mmol/L or 100 mg/dL, an oral glucose tolerance test is strongly recommended, but is not necessary to define presence of the syndrome.
# If BMI is >30 kg/m2, central obesity can be assumed and waist circumference does not need to be measured

WHO
The World Health Organization (1999)  requires the presence of any one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, AND two of the following:

Blood pressure ≥ 140/90 mmHg
Dyslipidemia: triglycerides (TG) ≥ 1.695 mmol/L  and HDL cholesterol ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female)
Central obesity: waist:hip ratio > 0.90 (male); > 0.85 (female), or BMI > 30 kg/m2
Microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g

EGIR
The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following:
Central obesity: waist circumference ≥ 94 cm or 37 inches (male), ≥ 80 cm or 31.5 inches (female)
Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia
Blood pressure ≥ 140/90 mmHg or antihypertensive medication
Fasting plasma glucose ≥ 6.1 mmol/L

NCEP
The U.S. National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following:
Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female)
Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dl)
Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
Blood pressure ≥ 130/85 mmHg (or treated for hypertension)
Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl)

American Heart Association
There is confusion as to whether, in 2004, the American Heart Association and National Heart, Lung, and Blood Institute intended to create another set of guidelines or simply update the National Cholesterol Education Program definition.
Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female)
Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dL)
Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
Blood pressure ≥ 130/85 mmHg (or treated for hypertension)
Fasting plasma glucose ≥ 5.6 mmol/L (100 mg/dL), or use of medication for hyperglycemia

Other
High-sensitivity C-reactive protein has been developed and used as a marker to predict coronary vascular diseases in metabolic syndrome, and it was recently used as a predictor for nonalcoholic fatty liver disease (steatohepatitis) in correlation with serum markers that indicated lipid and glucose metabolism. Fatty liver disease and steatohepatitis can be considered manifestations of metabolic syndrome, indicative of abnormal energy storage as fat in ectopic distribution.
Reproductive disorders (such as polycystic ovary syndrome in women of reproductive age), and erectile dysfunction or decreased total testosterone (low testosterone-binding globulin) in men can be attributed to metabolic syndrome.

Prevention
Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day), and a healthy, reduced calorie diet.  Many studies support the value of a healthy lifestyle as above. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily because of a lack of compliance with lifestyle and diet changes. The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.The Caerphilly Heart Disease Study followed 2,375 male subjects over 20 years and suggested the daily intake of an Imperial pint (~568 mL) of milk or equivalent dairy products more than halved the risk of metabolic syndrome. Some subsequent studies support the authors findings, while others dispute them. A systematic review of four randomized controlled trials said that, in the short term, a paleolithic nutritional pattern improved three of five measurable components of the metabolic syndrome in participants with at least one of the components.

Management
Medications
Generally, the individual disorders that compose the metabolic syndrome are treated separately </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 Anomic aphasia and can you explain it in depth? [/INST] Anomic aphasia  (also known as dysnomia, nominal aphasia, and amnesic aphasia) is a mild, fluent type of aphasia where individuals have word retrieval failures and cannot express the words they want to say (particularly nouns and verbs). Anomia is a deficit of expressive language. Anomia is a symptom of all forms of aphasia, but patients whose primary deficit is word retrieval are diagnosed with anomic aphasia. Individuals with aphasia who display anomia can often describe an object in detail and maybe even use hand gestures to demonstrate how the object is used, but cannot find the appropriate word to name the object. Patients with anomic aphasia have relatively preserved speech fluency, repetition, comprehension, and grammatical speech.

Types
Word selection anomia is caused by damage to the posterior inferior temporal area. This type of anomia occurs when the patient knows how to use an object and can correctly select the target object from a group of objects, and yet cannot name the object. Some patients with word selection anomia may exhibit selective impairment in naming particular types of objects, such as animals or colors.  In the subtype known as color anomia, the patient can distinguish between colors but cannot identify them by name or name the color of an object. The patients can separate colors into categories, but they cannot name them.
Semantic anomia is caused by damage to the angular gyrus. This is a disorder in which the meaning of words becomes lost. In patients with semantic anomia, a naming deficit is accompanied by a recognition deficit. Thus, unlike patients with word selection anomia, patients with semantic anomia are unable to select the correct object from a group of objects, even when provided with the name of the target object.
Disconnection anomia results from the severing of connections between sensory and language cortices. Patients with disconnection anomia may exhibit modality-specific anomia, where the anomia is limited to a specific sensory modality, such as hearing. For example, a patient who is perfectly capable of naming a target object when it is presented via certain sensory modalities like audition or touch, may be unable to name the same object when the object is presented visually. Thus, in such a case, the patients anomia arises as a consequence of a disconnect between their visual cortex and language cortices.Patients with disconnection anomia may also exhibit callosal anomia, in which damage to the corpus callosum prevents sensory information from being transmitted between the two hemispheres of the brain. Therefore, when sensory information is unable to reach the hemisphere that is language-dominant (typically the left hemisphere in most individuals), the result is anomia. For instance, if patients with this type of disconnection anomia hold an object in their left hand, this somatosensory information about the object would be sent to the right hemisphere of the brain, but then would be unable to reach the left hemisphere due to callosal damage. Thus, this somatosensory information would fail to be transmitted to language areas in the left hemisphere, in turn resulting in the inability to name the object in the left hand. In this example, the patient would have no problem with naming, if the test object were to be held in the right hand. This type of anomia may also arise as a consequence of a disconnect between sensory and language cortices.
Articulatory initiation anomia results from damage to the frontal area. Characteristics of this anomia are non-fluent output, word-finding pauses, deficient word lists. Patients perform better at confrontation naming tasks, the selection of a label for a corresponding picture, than word list tasks. Patients are aided in word selection by prompting, unlike those with word selection anomia.
Phonemic substitution anomia results from damage to the inferior parietal area. Patients maintain fluent output but exhibit literal and neologistic paraphasia. Literal paraphasia is the incorrect substitution of phonemes, and neologistic paraphasia is the use of non-real words in the place of real words. Patients naming ability is contaminated by paraphasia.
Modality-specific anomia is caused by damage to the sensory cortex, pathways to the dominant angular gyrus, or both. In these patients, word-finding is worst in one sensory modality, for example visual or tactile.

Causes
Anomic aphasia occurring by itself may be caused by damage to almost anywhere in the left hemisphere and in some cases can be seen in instances of right hemisphere damage. Anomia can be genetic or caused by damage to various parts of the parietal lobe or the temporal lobe of the brain due to traumatic injury, stroke, or a brain tumor. While anomic aphasia is primarily caused by structural lesions, they may also originate in Alzheimers disease (anomia may be the earliest language deficit in posterior cortical atrophy variant of Alzheimers) or other neurodegenerative diseases.Although the main causes are not specifically known, many researchers have found factors contributing to anomic aphasia. People with damage to the left hemisphere of the brain are more likely to have anomic aphasia. Brocas area, the speech production center in the brain, was linked to being the source for speech execution problems, with the use of functional magnetic resonance imaging (fMRI), now commonly used to study anomic patients. Other experts believe that damage to Wernickes area, which is the speech comprehension area of the brain, is connected to anomia because the patients cannot comprehend the words that they are hearing.Although many experts have believed that damage to Brocas area or Wernickes area are the main causes of anomia, current studies have shown that damage in the left parietal lobe is the cause of anomic aphasia. One study was conducted using a word repetition test as well as fMRI in order to see the highest level of activity as well as where the lesions are in the brain tissue. Fridrikkson, et al. saw that damage to neither Brocas area nor Wernickes area were the sole sources of anomia in the subjects. Therefore, the original anomia model, which theorized that damage occurred on the surface of the brain in the grey matter was debunked, and it was found that the damage was in the white matter deeper in the brain, on the left hemisphere. More specifically, the damage was in a part of the nerve tract called the arcuate fasciculus, for which the mechanism of action is unknown, though it is known to connect the posterior (back) of the brain to the anterior (front) and vice versa.While anomic aphasia is associated with lesions throughout the left hemisphere, severe and isolated anomia has been considered a sign of deep temporal lobe or lateral temporo-occipital damage. Damage to these areas is seen in patients showing infarction limited to regions supplied by the dominant posterior cerebral artery (PCA) and is referred to as posterior cerebral artery syndrome.

Diagnosis
The best way to see if anomic aphasia has developed is by using verbal and imaging tests. The combination seems to be most effective, since either test done alone may give false positives or false negatives. For example, the verbal test is used to see if a speech disorder presents, and whether the problem is in speech production or comprehension.  Patients with Alzheimers disease have speech problems linked to dementia or progressive aphasias, which can include anomia. The imaging test, mostly done using MRI scans, is ideal for lesion mapping or viewing deterioration in the brain. However, imaging cannot diagnose anomia on its own because the lesions may not be located deep enough to damage the white matter or the arcuate fasciculus. However, anomic aphasia is very difficult to associate with a specific lesion location in the brain. Therefore, the combination of speech tests and imaging tests has the highest sensitivity and specificity.Picture-naming tests, such as the Philadelphia Naming Test (PNT), are also utilized in diagnosing aphasias. Analysis of picture-naming is compared with reading, picture categorizing, and word categorizing. There is a considerable similarity among aphasia syndromes in terms of picture-naming behavior, however anomic aphasiacs produced the fewest phonemic errors and the most multiword circumlocutions. These results suggest minimal word-production difficulty in anomic aphasia relative to other aphasia syndromes.Anomic aphasia has been diagnosed in some studies using the Aachen Aphasia Test (AAT), which tests language functioning after brain injury. This test aims to: identify the presence of aphasia; provide a profile of the speakers language functioning according to different language modalities (speaking, listening, reading, writing) and different levels of linguistic description (phonology, morphology, semantics, and syntax); give a measure of severity of any breakdown. This test was administered to patients participating in a study in 2012, and researchers found that on the naming subtest of the AAT patients showed relevant naming difficulties and tended to substitute the words they could not produce with circumlocutions.The Western Aphasia Battery is another test that is conducted with the goal of classifying aphasia subtypes and rating the severity of the aphasiac impairment. The test is composed of four language and three performance domains. Syndrome classification is determined by the pattern of performance on the four language subtests, which assess spontaneous speech, comprehension, repetition, and naming.Doing a hearing test first is important, in case the patient cannot clearly hear the words or sentences needed in the speech repetition test. In the speech tests, the person is asked to repeat a sentence with common words; if the person cannot identify the word, but he or she can describe it, then the person is highly likely to have anomic aphasia. However, to be completely sure, the test is given while a test subject is in an fMRI scanner, and the exact location of the lesions and areas activated by speech are pinpointed. Few simpler or cheaper options are available, so lesion mapping and speech repetition tests are the main ways of diagnosing anomic aphasia.

Definition
Anomic aphasia (anomia) is a type of aphasia characterized by problems recalling words, names, and numbers. Speech is fluent and receptive language is not impaired in someone with anomic aphasia. Subjects often use circumlocutions (speaking in a roundabout way) to avoid a name they cannot recall or to express a certain word they cannot remember. Sometimes, the subject can recall the name when given clues. Additionally, patients are able to speak with correct grammar; the main problem is finding the appropriate word to identify an object or person.Sometimes, subjects may know what to do with an object, but still not be able to give a name to the object. For example, if a subject is shown an orange and asked what it is called, the subject may be well aware that the object can be peeled and eaten, and may even be able to demonstrate this by actions or even verbal responses; however, they cannot recall that the object is called an "orange". Sometimes, when a person with this condition is multilingual, they might confuse the language they are speaking in trying to find the right word (inadvertent code-switching).

Management
No method is available to completely cure anomic aphasia. However, treatments can help improve word-finding skills.
Although a person with anomia may find recalling many types of words to be difficult, such as common nouns, proper nouns, verbs, etc., many studies have shown that treatment for object words, or nouns, has shown promise in rehabilitation research. The treatment includes visual aids, such as pictures, and the patient is asked to identify the object or activity. However, if that is not possible, then the patient is shown the same picture surrounded by words associated with the object or activity. Throughout the process, positive encouragement is provided. The treatment shows an increase in word finding during treatment; however, word identifying decreased two weeks after the rehabilitation period. Therefore, it shows that rehabilitation effort needs to be continuous for word-finding abilities to improve from the baseline. The studies show that verbs are harder to recall or repeat, even with rehabilitation.Other methods in treating anomic aphasia include circumlocution-induced naming therapy (CIN), wherein the patient uses circumlocution to assist with his or her naming rather than just being told to name the item pictured after given some sort of cue. Results suggest that the patient does better in properly naming objects when undergoing this therapy because CIN strengthens the weakened link between semantics and phonology for patients with anomia, since they often know what an object is used for, but cannot verbally name it.Anomia is often challenging for the families and friends of those affected by it. One way to overcome this is computer-based treatment models, effective especially when used with clinical therapy. Leemann et al. provided anomic patients with computerized-assisted therapy (CAT) sessions, along with traditional therapy sessions using treatment lists of words. Some of the patients received a drug known to help relieve symptoms of anomia (levodopa), while others received a placebo. The researchers found that the drug had no significant effects on improvement with the treatment lists, but almost all of the patients improved after the CAT sessions. They concluded that this form of computerized treatment is effective in increasing naming abilities in anomic patients.Additionally, one study researched the effects of using "excitatory (anodal) transcranial direct current stimulation" over the right temporoparietal cortex, a brain area that seems to correlate to language. The electrical stimulation seemed to enhance language training outcome in patients with chronic aphasia.Contextual repetition priming treatment is a technique which involves repeated repetition of names of pictures that are related semantically, phonologically, or are unrelated. Patients with impaired access to lexical-semantic representations show no long-term improvement in naming, but patients with good access to semantics show long-term benefits.Development of self-cueing strategies can also facilitate word retrieval. Patients identify core words that can be retrieved without struggle, and establish a relationship between cue words and words that begin with the same sound but cannot be retrieved. Patients then learn to use the cue word to facilitate word retrieval for the target object.

Epidemiology
Many different populations can and do have anomia. For instance, deaf patients who have had a stroke can demonstrate semantic and phonological errors, much like hearing anomic patients </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 Otomycosis and can you explain it in depth? [/INST] Otomycosis  is a fungal ear infection, a superficial mycotic infection of the outer ear canal </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 Navicular syndrome and can you explain it in depth? [/INST] Navicular syndrome, often called navicular disease, is a syndrome of lameness problems in horses.  It most commonly describes an inflammation or degeneration of the navicular bone and its surrounding tissues, usually on the front feet. It can lead to significant and even disabling lameness.

Description of the navicular area
Knowledge of equine forelimb anatomy is especially useful for understanding navicular syndrome. The navicular bone lies behind the coffin bone and under the small pastern bone. The deep digital flexor (DDF) tendon runs down the back of the cannon and soft tissue in that area and under the navicular bone before attaching to the back of the coffin bone. The DDF tendon flexes the coffin joint, and the navicular bone acts as a fulcrum that the DDF tendon runs over.The navicular bone is supported by several ligaments above, below, and on the side. One of these ligaments is the impar ligament, which attaches the navicular bone to the coffin bone (distal phalanx). Cartilage lies between the navicular bone and the coffin joint, as well as between the navicular bone and the DDF tendon. The navicular bursa - a small sac that protects the DDF and navicular bone from abrasion as the tendon slides over the area - lies between the navicular bone and the DDF tendon.

Causes and contributing factors
There is no single known cause of navicular syndrome, although there are many theories, and several primary factors.
The first factor is compression of the navicular bone under the DDF tendon and the back of the small pastern bone. Repeated compression in this area can cause cartilage degeneration, with the cartilage flattening and gradually becoming less springy and shock-absorbing. It may also begin to erode. Cartilage degeneration is common in navicular horses, usually along the flexor surface. This finding, and the associated biochemical changes, have led some researchers to conclude that there are elements in navicular disease common to osteoarthritis, and to suggest similar therapeutic regimes.Cartilage erosion may progress to the point that the bone underneath will become exposed. With the cartilage no longer present to protect it, the navicular bursa and DDF tendon may become damaged by the constant rubbing against the navicular bone. Navicular bursitis (inflammation of the navicular bursa) may occur, even if cartilage damage is not severe. This is probably due to the friction between the navicular bone and the DDF tendon from compression.
Constant compression can also increase the bone density directly under the cartilage surfaces, especially on the flexor side. This tends to make the bone more brittle, and thus more likely to break.
Another main factor is the tension placed on the ligaments that support the navicular bone. Some experts believe that the degenerative process begins with excess tension placed on these ligaments, causing strain and inflammation. Inflammation from strain of the impar ligament can decrease blood flow to and from the navicular bone, as the major blood vessels supplying the bone run up and down this area. If the ligament continues to be strained, it can thicken and permanently reduce blood flow to the navicular bone.
Because veins are more easily compressed than arteries, blood flow to the bone would be less obstructed than blood flow from the bone. This would cause a buildup of pressure within the navicular bone. The navicular bone, in response to both the increased pressure and overall decreased blood supply, would absorb mineral from its center.
Excess tension can also cause exostoses where the ligaments attach to the navicular bone, giving the bone a "canoe" shape. If tension is extreme, the ligaments may actually tear.
Recent research has found correlations between "toe-first landing" of the hooves and navicular problems, due to excessive strain put on the deep digital flexor tendon, as a consequence of misalignment of the lower joints.
Toe-first landing, usually seen as a consequence of navicular disease, may actually be a cause or at least a contributing factor to the onset of tendon inflammation and bone modifications.
Toe-first landing is often caused by frog and heel overtrimming, long toes, and/or poor shoeing.

Contributing factors
Conformation
Certain conformational defects may contribute to navicular syndrome, especially defects that promote concussion. These include upright pasterns, small feet, narrow and upright feet, significant downhill build (commonly seen in American Quarter Horses), and long toes with low heels (commonly seen in Thoroughbreds).
The long toe, low heel conformation places constant stress on the navicular bone, even as the horse is standing.  Upright feet increase concussion, especially in the heel region of the hoof where the navicular bone is located. Excess concussion cannot be absorbed as well by the structures designed to do so (the frog, heels, and digital cushion), so more impact is transmitted to the structures within the foot.
Poor hoof shape is usually inherited, although poor shoeing and trimming can contribute to these shapes.
With the long toe, low heel conformation can come contracted heels (narrowing of the heel) which further compresses the navicular bone along with sheared heels adding more stress to the tendons and navicular bones.

Shoeing
Poor trimming, shoe selection, or inappropriate shoe attachment are well-known causes of lameness, and navicular disease is fairly common in the modern-day domesticated horse. However, it is also seen in wild horse populations. Those who advocate "barefoot trimming" of domestic horses propose that in nature, a horses hoof is designed to expand and contract as the horse moves. This expanding and contracting acts as an auxiliary blood pump, and aids the circulation of blood to the lower extremities. When an inflexible metal shoe is improperly attached to the hoof, the hoof can no longer work as designed, and blood flow is inhibited. However, evidence of navicular degeneration has been established in the fossil record of early horses. Mary Thompson, a vertebrate paleontologist at Idaho Museum of Natural History, has found evidence in many species of early horses and concludes, "The results of this study strongly suggest that man’s intervention (whether by increased usage or improper breeding practices) may not be the sole cause of the syndrome", although she cautions that her results are preliminary.

Work
Working on steep hills, galloping, and jumping all contribute to navicular syndrome, as they place greater stress on the DDF tendons, and may cause overextension of the pastern and coffin joints.
Regular exercise on hard or irregular ground increases concussion on the hoof, thus increasing the risk of navicular syndrome.
It is possible that standing can also increase the chance of navicular disease (such as a horse that spends most of the day in a stall with little turnout, as with some racehorses and show horses). Blood flow to the hoof decreases when the horse is not in motion. The horse is also constantly applying pressure to the navicular bones (which is intermittent as the horse moves).

Body weight
Horses with a high weight-to-foot-size ratio may have an increased chance of exhibiting symptoms of navicular syndrome, since the relative load on the foot increases. This might explain why the syndrome is seen more frequently in Thoroughbreds, American Quarter Horses, and Warmbloods as opposed to ponies and Arabians.

Signs
Heel pain is very common in horses with navicular syndrome. Lameness may begin as mild and intermittent, and progress to severe. This may be due to strain and inflammation of the ligaments supporting the navicular bone, reduced blood flow and increased pressure within the hoof, damage to the navicular bursa or DDF tendon, or from cartilage erosion.
Affected horses display a "tiptoe" gait - trying to walk on the toes due to heel pain. They may stumble frequently. The lameness may switch from one leg to another, and may not be consistent. Lameness usually occurs in both front feet, although one foot may be more sore than the other.
Lameness is usually mild (1–2 on a scale of 5). It can be made worse when the horse is worked on a hard surface or on a circle.
After several months of pain, the feet may begin to change shape, especially the foot that has been experiencing the most pain, which tends to become more upright and narrow.

Treatment and prognosis
No single treatment works for all cases, probably because there is no single cause for all cases. The degenerative changes are usually quite advanced by the time the horse is consistently lame, and these changes are believed to be non-reversible. At this time, it is best to manage the condition and focus on alleviating pain and slowing the degeneration.

Trimming
Putting the foot into proper neurological and biomechanical balance is crucial.  Often navicular horses have long toes and underrun heels with very little inner wall depth or strength.  Exposing the horse to proper stimulus to improve hoof form and structure is also vital.

Hoof care
The issue of hoof care is a subject of great debate. Corrective shoeing can be beneficial to horses suffering from navicular disease, although sometimes the effects are only temporary. Others believe that removing the shoes altogether is the best way to manage this disease, as it allows increased circulation to the hoof.  People on both sides agree that proper hoof shape and angle are an important long-term management plan for a horse with navicular disease.  As with laminitis, different horses may respond in different ways to a given technique, so the farrier, owner, and veterinarian should work as a team to formulate a plan and to adapt if the initial plan is not effective.
People who choose to treat navicular disease through shoeing may use a shoe designed to lift and support the heels.  This can sometimes be accomplished with a flat shoe and trimming alone. Wedge pads or wedged shoes are often used, but can amplify heel-related problems if present. Another strategy is to use a bar type shoe. Often, an egg-bar shoe, or straight bar shoe.  Some horses benefit from shoes that change the breakover of their foot (like a rolled toe). With or without shoes, the hoof must be trimmed in such a way as to restore the balance and angle that may have been lost. Horses with long toe-low heel conformation need careful trimming to counter this. Horses with upright feet may need their heels lowered and a shoe that will allow their heels to spread. Early intervention is key; in one study, shoeing was successful in 97% of horses treated within ten months of the onset of signs, while only 54% of horses lame for over a year responded.Advocates of barefoot trimming cite recent studies which show that removing the shoes can help alleviate the symptoms of navicular disease, and in some cases, reverse some of the damage done to the hoof. Because navicular disease can be caused, or at least exacerbated by shoeing, removing the cause is the first step in this strategy toward the management of pain in the animal. Successive carefully applied trims help to restore the natural angle and shape of the hoof, while walking helps to stimulate circulation to the hoof. It is not uncommon to find horses whose navicular disease is completely manageable through corrective barefoot trimming.  However, this may require a transition period lasting from weeks to years where the horse may remain lame, or may never become sound.If there is significant degeneration in the bone, a flexor cortex cyst, adhesions to the deep digital flexor tendon, or avulsion fractures, relief is typically incomplete no matter what foot care technique is used.

Exercise
Horses with navicular syndrome need a less intense work schedule. Their fitness can be maintained through slow long-distance work or swimming, as opposed to being worked at high speeds, up steep hills, or on hard surfaces, irregular terrain, or deep footing. Reducing the frequency of jumping is also important.  Some veterinarians and hoof care practitioners recommend exercising the horse on varied terrain to stimulate and strengthen the caudal hoof structures.

Medication
Vasodilators improve the blood flow into the vessels of the hoof. Examples include isoxsuprine (currently unavailable in the UK) and pentoxifylline.
Anticoagulants can also improve blood flow. The use of warfarin has been proposed, but the extensive monitoring required makes it unsuitable in most cases.
Anti-inflammatory drugs are used to treat the pain, and can help the lameness resolve sometimes if shoeing and training changes are made. Include Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and other joint medications. The use of intramuscular glycosaminoglycans has been shown to decrease pain in horses with navicular disease, but this effect wanes after discontinuation of therapy.  Oral glycosaminoglycans may have a similar effect.Bisphosphonates can be useful in cases where bone remodeling is causing pain.Gallium nitrate (GaN) has been hypothesized as a possible treatment for navicular disease, but its benefits have not been confirmed by formal clinical studies. One pilot study examined horses given gallium nitrate in their feed rations. While it was absorbed slowly, it did stay in the animals system, providing a baseline dosage for future studies.

Surgery
Palmar digital neurectomy (or "nerving" or "denerving") is not without adverse side effects and should therefore be used as a last resort. In this procedure, the palmar digital nerves are severed, so the horse loses sensation in the back of the foot. This procedure should only be performed if it will eliminate the lameness associated with navicular syndrome, and only after all other options have been explored. The procedure is usually performed on both front feet. Complications can include infection of the wound, continuation of the lameness (if the nerves regrow or if small branches of the nerves are not removed), neuromas, and rupture of the deep digital flexor tendon. After the neurectomy, if the horse becomes injured in the area the injury may go undetected for a long period of time, which risks the animals health. Due to this, the feet should be cleaned and inspected regularly. Neurectomy tends to lower the market value of a horse, and may even make the horse ineligible for competition. Neurectomy is controversial.   The most common misconception about "nerving" a horse is that it will permanently solve the lameness/pain issue.  In fact, though the time periods vary based on the individual horse and surgical method utilized, these nerves often regenerate and return sensation to the afflicted region within two to three years.
In navicular suspensory desmotomy, the ligaments supporting the navicular bone are severed. This makes the navicular bone more mobile, and thus reduces the tension of the other ligaments. It is successful about half of the time.

Prognosis
The prognosis for a horse with navicular syndrome is guarded </s>