<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 Mitral regurgitation and can you explain it in depth? [/INST] Mitral regurgitation (MR), also known as mitral insufficiency or mitral incompetence, is a form of valvular heart disease in which the mitral valve is insufficient and does not close properly when the heart pumps out blood. It is the abnormal leaking of blood backwards – regurgitation from the left ventricle, through the mitral valve, into the left atrium, when the left ventricle contracts. Mitral regurgitation is the most common form of valvular heart disease.

Definition
Mitral regurgitation, also known as mitral insufficiency or mitral incompetence, is the backward flow of blood from the left ventricle, through the mitral valve, and into the left atrium, when the left ventricle contracts, resulting in a systolic murmur radiating to the left armpit.

Signs and symptoms
Mitral regurgitation may be present for many years before any symptoms appear. The symptoms associated with MR are dependent on which phase of the disease process the individual is in. Individuals with acute MR are typically severely symptomatic and will have the signs and symptoms of acute decompensated congestive heart failure (i.e. shortness of breath, pulmonary edema, orthopnea, and paroxysmal nocturnal dyspnea). In acute cases, a murmur and tachycardia may be the only distinctive signs.Individuals with chronic compensated MR may be asymptomatic for long periods of time, with a normal exercise tolerance and no evidence of heart failure. Over time, however, there may be decompensation and patients can develop volume overload (congestive heart failure). Symptoms of entry into a decompensated phase may include fatigue, shortness of breath particularly on exertion, and leg swelling. Also, there may be development of an irregular heart rhythm known as atrial fibrillation.Findings on clinical examination depend on the severity and duration of MR. The mitral component of the first heart sound is usually soft and with a laterally displaced apex beat, often with heave. The first heart sound is followed by a high-pitched holosystolic murmur at the apex, radiating to the back or clavicular area. Its duration is, as the name suggests, the whole of systole. The loudness of the murmur does not correlate well with the severity of regurgitation. It may be followed by a loud, palpable P2, heard best when lying on the left side. A third heart sound is commonly heard.Patients with mitral valve prolapse may have a holosystolic murmur or often a mid-to-late systolic click and a late systolic murmur. Cases with a late systolic regurgitant murmur may still be associated with significant hemodynamic consequences.Mitral regurgitation as a result of papillary muscle damage or rupture may be a complication of a heart attack and lead to cardiogenic shock.

Cause
The mitral valve apparatus comprises two valve leaflets, the mitral annulus, which forms a ring around the valve leaflets, and the papillary muscles, which tether the valve leaflets to the left ventricle and prevent them from prolapsing into the left atrium. The chordae tendineae is also present and connects the valve leaflets to the papillary muscles. Dysfunction of any of these portions of the mitral valve apparatus can cause regurgitation.The most common cause of MR in developing countries is mitral valve prolapse. It is the most common cause of primary mitral regurgitation in the United States, causing about 50% of cases. Myxomatous degeneration of the mitral valve is more common in women as well as with advancing age, which causes a stretching of the leaflets of the valve and the chordae tendineae. Such elongation prevents the valve leaflets from fully coming together when the valve closes, causing the valve leaflets to prolapse into the left atrium, thereby causing MR.Ischemic heart disease causes MR by the combination of ischemic dysfunction of the papillary muscles, and the dilatation of the left ventricle. This can lead to the subsequent displacement of the papillary muscles and the dilatation of the mitral valve annulus.Rheumatic fever (RF), Marfans syndrome and the Ehlers–Danlos syndromes are other typical causes. Mitral valve stenosis (MVS) can sometimes be a cause of mitral regurgitation (MR) in the sense that a stenotic valve (calcified and with restricted range of movement) allows backflow (regurgitation) if it is too stiff and misshapen to close completely. Most MVS is caused by RF, so one can say that MVS is sometimes the proximal cause of MI/MR (that is, stenotic MI/MR) and that RF is often the distal cause of MVS, MI/MR, or both. MR and mitral valve prolapse are also common in Ehlers–Danlos syndromes.Secondary mitral regurgitation is due to the dilatation of the left ventricle that causes stretching of the mitral valve annulus and displacement of the papillary muscles. This dilatation of the left ventricle can be due to any cause of dilated cardiomyopathy including aortic insufficiency, nonischemic dilated cardiomyopathy, and noncompaction cardiomyopathy. Because the papillary muscles, chordae, and valve leaflets are usually normal in such conditions, it is also called functional mitral regurgitation.Acute MR is most often caused by endocarditis, mainly S. aureus. Rupture or dysfunction of the papillary muscle are also common causes in acute cases, dysfunction, which can include mitral valve prolapse.

Pathophysiology
The pathophysiology of MR can be broken into three phases of the disease process: the acute phase, the chronic compensated phase, and the chronic decompensated phase.

Acute phase
Acute MR (as may occur due to the sudden rupture of the chordae tendinae or papillary muscle) causes a sudden volume overload of both the left atrium and the left ventricle. The left ventricle develops volume overload because with every contraction it now has to pump out not only the volume of blood that goes into the aorta (the forward cardiac output or forward stroke volume) but also the blood that regurgitates into the left atrium (the regurgitant volume). The combination of the forward stroke volume and the regurgitant volume is known as the total stroke volume of the left ventricle.In the acute setting, the stroke volume of the left ventricle is increased (increased ejection fraction); this happens because of more complete emptying of the heart. However, as it progresses the LV volume increases and the contractile function deteriorates, thus leading to dysfunctional LV and a decrease in ejection fraction. The increase in stroke volume is explained by the Frank–Starling mechanism, in which increased ventricular pre-load stretches the myocardium such that contractions are more forceful.The regurgitant volume causes a volume overload and a pressure overload of the left atrium and the left ventricle. The increased pressures in the left side of the heart may inhibit drainage of blood from the lungs via the pulmonary veins and lead to pulmonary congestion.

Chronic phase
Compensated
If the MR develops slowly over months to years or if the acute phase cannot be managed with medical therapy, the individual will enter the chronic compensated phase of the disease. In this phase, the left ventricle develops eccentric hypertrophy in order to better manage the larger than normal stroke volume. The eccentric hypertrophy and the increased diastolic volume combine to increase the stroke volume (to levels well above normal) so that the forward stroke volume (forward cardiac output) approaches the normal levels.In the left atrium, the volume overload causes enlargement of the left atrium, allowing the filling pressure in the left atrium to decrease. This improves the drainage from the pulmonary veins, and signs and symptoms of pulmonary congestion will decrease.These changes in the left ventricle and left atrium improve the low forward cardiac output state and the pulmonary congestion that occur in the acute phase of the disease. Individuals in the chronic compensated phase may be asymptomatic and have normal exercise tolerances.

Decompensated
An individual may be in the compensated phase of MR for years, but will eventually develop left ventricular dysfunction, the hallmark for the chronic decompensated phase of MR. It is currently unclear what causes an individual to enter the decompensated phase of this disease. However, the decompensated phase is characterized by calcium overload within the cardiac myocytes.In this phase, the ventricular myocardium is no longer able to contract adequately to compensate for the volume overload of mitral regurgitation, and the stroke volume of the left ventricle will decrease. The decreased stroke volume causes a decreased forward cardiac output and an increase in the end-systolic volume. The increased end-systolic volume translates to increased filling pressures of the left ventricle and increased pulmonary venous congestion. The individual may again have symptoms of congestive heart failure.The left ventricle begins to dilate during this phase. This causes a dilatation of the mitral valve annulus, which may worsen the degree of MR. The dilated left ventricle causes an increase in the wall stress of the cardiac chamber as well.While the ejection fraction is less in the chronic decompensated phase than in the acute phase or the chronic compensated phase, it may still be in the normal range (i.e.: > 50 percent), and may not decrease until late in the disease course. A decreased ejection fraction in an individual with MR and no other cardiac abnormality should alert the physician that the disease may be in its decompensated phase.

Diagnosis
There are many diagnostic tests that have abnormal results in the presence of MR. These tests suggest the diagnosis of MR and may indicate to the physician that further testing is warranted. For instance, the electrocardiogram (ECG) in long-standing MR may show evidence of left atrial enlargement and left ventricular dilatation. Atrial fibrillation may also be noted on the ECG in individuals with chronic mitral regurgitation. The ECG may not show any of these findings in the setting of acute MR.
The quantification of MR usually employs imaging studies such as echocardiography or magnetic resonance angiography of the heart.

Chest X-ray
The chest X-ray in individuals with chronic MR is characterized by enlargement of the left atrium and the left ventricle, and then maybe calcification of the mitral valve.

Echocardiogram
An echocardiogram is commonly used to confirm the diagnosis of MR. Color doppler flow on the transthoracic echocardiogram (TTE) will reveal a jet of blood flowing from the left ventricle into the left atrium during ventricular systole. Also, it may detect a dilated left atrium and ventricle and decreased left ventricular function. A transesophageal echocardiogram can give clearer images if needed as the back of the heart can also be viewed.

Electrocardiography
P mitrale is a broad, bifid notched P wave in several or many leads with a prominent late negative component to the P wave in lead V1, and may be seen in MR, but also in mitral stenosis, and, potentially, any cause of overload of the left atrium.

Quantification of mitral regurgitation
The degree of severity of MR can be quantified by the regurgitant fraction, which is the percentage of the left ventricular stroke volume that regurgitates into the left atrium.
regurgitant fraction   =

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    {\displaystyle {\frac {V_{mitral}-V_{aortic}}{V_{mitral}}}\times 100\%}
  where Vmitral and Vaortic are, respectively, the volumes of blood that flow forward through the mitral valve and aortic valve during a cardiac cycle.
Methods that have been used to assess the regurgitant fraction in mitral regurgitation include echocardiography, cardiac catheterization, fast CT scan, and cardiac MRI.The echocardiographic technique to measure the regurgitant fraction is to determine the forward flow through the mitral valve (from the left atrium to the left ventricle) during ventricular diastole, and comparing it with the flow out of the left ventricle through the aortic valve in ventricular systole. This method assumes that the aortic valve does not have aortic insufficiency.Another way to quantify the degree of MR is to determine the area of the regurgitant flow at the level of the valve. This is known as the regurgitant orifice area and correlates with the size of the defect in the mitral valve. One particular echocardiographic technique used to measure the orifice area is measurement of the proximal isovelocity surface area (PISA). The flaw of using PISA to determine the mitral valve regurgitant orifice area is that it measures the flow at one moment in time in the cardiac cycle, which may not reflect the average performance of the regurgitant jet.

Treatment
The treatment of MR depends on the acuteness of the disease and whether there are associated signs of hemodynamic compromise. In general, medical therapy is non-curative and is used for mild-to-moderate regurgitation or in patients unable to tolerate surgery.In acute MR secondary to a mechanical defect in the heart (i.e., rupture of a papillary muscle or chordae tendineae), the treatment of choice is mitral valve surgery. If the patient is hypotensive prior to the surgical procedure, an intra-aortic balloon pump may be placed in order to improve perfusion of the organs and to decrease the degree of MR.

Medicine
If the individual with acute MR is normotensive, vasodilators may be of use to decrease the afterload seen by the left ventricle and thereby decrease the regurgitant fraction. The vasodilator most commonly used is nitroprusside.Individuals with chronic MR can be treated with vasodilators as well to decrease afterload. In the chronic state, the most commonly used agents are ACE inhibitors and hydralazine. Studies have shown that the use of ACE inhibitors and hydralazine can delay surgical treatment of MR. The current guidelines for treatment of MR limit the use of vasodilators to individuals with hypertension, however. Any hypertension is treated aggressively, e.g. by diuretics and a low sodium diet. In both hypertensive and normotensive cases, digoxin and antiarrhythmics are also indicated. Also, chronic anticoagulation is given where there is concomitant mitral valve prolapse or atrial fibrillation.

Surgery
Surgery is curative of mitral valve regurgitation. There are two surgical options for the treatment of MR: mitral valve replacement and mitral valve repair. Mitral valve repair is preferred to mitral valve replacement where a repair is feasible as bioprosthetic replacement valves have a limited lifespan of 10 to 15 years, whereas synthetic replacement valves require ongoing use of blood thinners to reduce the risk of stroke. There are two general categories of approaches to mitral valve repair: resection of the prolapsed valvular segment (sometimes referred to as the "Carpentier" approach) and installation of artificial chordae to "anchor" the prolapsed segment to the papillary muscle (sometimes referred to as the "David" approach). With the resection approach, any prolapsing tissue is resected, in effect removing the hole through which the blood is leaking </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 Pyridoxine-dependent epilepsy and can you explain it in depth? [/INST] Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder characterized by intractable seizures in the prenatal and neonatal period.  The disorder was first recognized in the 1950s, with the first description provided by Hunt et al. in 1954. More recently, pathogenic variants within the ALDH7A1 gene have been identified to cause PDE.

Genetics
PDE is inherited in an autosomal recessive manner and is estimated to affect around 1 in 400,000 to 700,000 births, though one study conducted in Germany estimated a prevalence of 1 in 20,000 births. The ALDH7A1 gene encodes for the enzyme antiquitin or α-aminoadipic semialdehyde dehydrogenase, which is involved with the catabolism of lysine.

Treatment
Patients with PDE do not respond to anticonvulsant medications, but seizures rapidly cease with therapeutic intravenous doses of vitamin B6 and remission from seizures are often maintained on daily therapeutic doses of vitamin B6. An optimal dose has not yet been established, but doses of 50–100 mg/day or 15–30 mg/kg/day have been proposed </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 Hypotension and can you explain it in depth? [/INST] Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the diastolic blood pressure (the bottom number), which are the maximum and minimum blood pressures, respectively. A systolic blood pressure of less than 90 millimeters of mercury (mmHg) or diastolic of less than 60 mmHg is generally considered to be hypotension. Different numbers apply to children. However, in practice, blood pressure is considered too low only if noticeable symptoms are present. Primary symptoms generally include dizziness and lightheadedness. Other symptoms include fatigue, shortness of breath, headaches, shakiness, increased thirst, irregular heartbeat, chest pain, confusion.Hypotension is the opposite of hypertension, which is high blood pressure. It is best understood as a physiological state rather than a disease. Severely low blood pressure can deprive the brain and other vital organs of oxygen and nutrients, leading to a life-threatening condition called shock. Shock is classified based on the underlying cause, including hypovolemic shock, cardiogenic shock, distributive shock, and obstructive shock.Hypotension can be caused by strenuous exercise, excessive heat, low blood volume (hypovolemia), hormonal changes, widening of blood vessels, anemia, vitamin B12 deficiency, anaphylaxis, heart problems, or endocrine problems. Some medications can also lead to hypotension. There are also syndromes that can cause hypotension in patients including orthostatic hypotension, vasovagal syncope, and other rarer conditions.For many people, excessively low blood pressure can cause dizziness and fainting or indicate serious heart, endocrine or neurological disorders.For some people who exercise and are in top physical condition, low blood pressure could be normal. A single session of exercise can induce hypotension and water-based exercise can induce a hypotensive response.Treatment of hypotension may include the use of intravenous fluids or vasopressors. When using vasopressors, trying to achieve a mean arterial pressure (MAP) of greater than 70 mmHg does not appear to result in better outcomes than trying to achieve a MAP of greater than 65 mmHg in adults.

Signs and symptoms
The primary symptoms of hypotension are lightheadedness or dizziness.If the blood pressure is sufficiently low, fainting (syncope) may occur.Low blood pressure is sometimes associated with certain symptoms, many of which are related to causes rather than effects of hypotension:

Causes
Low blood pressure can be caused by low blood volume, hormonal changes, widening of blood vessels, medicine side effects, severe dehydration, anemia, vitamin B12 deficiency, anaphylaxis, heart problems or endocrine problems.Reduced blood volume, hypovolemia, is the most common cause of hypotension. This can result from hemorrhage; insufficient fluid intake, as in starvation; or excessive fluid losses from diarrhea or vomiting. Hypovolemia can be induced by excessive use of diuretics. Low blood pressure may also be attributed to heat stroke which can be indicated by absence of perspiration, light headedness and dark colored urine.Other medications can produce hypotension by different mechanisms. Chronic use of alpha blockers or beta blockers can lead to hypotension. Beta blockers can cause hypotension both by slowing the heart rate and by decreasing the pumping ability of the heart muscle.Decreased cardiac output despite normal blood volume, due to severe congestive heart failure, large myocardial infarction, heart valve problems, or extremely low heart rate (bradycardia), often produces hypotension and can rapidly progress to cardiogenic shock. Arrhythmias often result in hypotension by this mechanism.Excessive vasodilation, or insufficient constriction of the blood vessels (mostly arterioles), causes hypotension.  This can be due to decreased sympathetic nervous system output or to increased parasympathetic activity occurring as a consequence of injury to the brain or spinal cord. Dysautonomia, an intrinsic abnormality in autonomic system functioning, can also lead to hypotension.  Excessive vasodilation can also result from sepsis, acidosis, or medications, such as nitrate preparations, calcium channel blockers, or AT1 receptor antagonists (Angiotensin II acts on AT1 receptors).  Many anesthetic agents and techniques, including spinal anesthesia and most inhalational agents, produce significant vasodilation.Lower blood pressure is a side effect of certain herbal medicines, which can also interact with several medications.  An example is the theobromine in Theobroma cacao, which lowers blood pressure through its actions as both a vasodilator and a diuretic, and has been used to treat high blood pressure.

Syndromes
Orthostatic hypotension
Orthostatic hypotension, also called postural hypotension, is a common form of low blood pressure. It occurs after a change in body position, typically when a person stands up from either a seated or lying position. It is usually transient and represents a delay in the normal compensatory ability of the autonomic nervous system. It is commonly seen in hypovolemia and as a result of various medications. In addition to blood pressure-lowering medications, many psychiatric medications, in particular antidepressants, can have this side effect.  Simple blood pressure and heart rate measurements while lying, seated, and standing (with a two-minute delay in between each position change) can confirm the presence of orthostatic hypotension. Taking these measurements is known as orthostatic vitals. Orthostatic hypotension is indicated if there is a drop of 20 mmHg in systolic pressure (and a 10 mmHg drop in diastolic pressure in some facilities) and a 20 beats per minute increase in heart rate.

Vasovagal syncope
Vasovagal syncope is a form of dysautonomia characterized by an inappropriate drop in blood pressure while in the upright position. Vasovagal syncope occurs as a result of increased activity of the vagus nerve, the mainstay of the parasympathetic nervous system. Patients will feel sudden, unprovoked lightheadedness, sweating, changes in vision, and finally a loss of consciousness. Consciousness will often return rapidly once patient is lying down and the blood pressure returns to normal.

Other
Another, but rarer form, is postprandial hypotension, a drastic decline in blood pressure that occurs 30 to 75 minutes after eating substantial meals.  When a great deal of blood is diverted to the intestines (a kind of "splanchnic blood pooling") to facilitate digestion and absorption, the body must increase cardiac output and peripheral vasoconstriction to maintain enough blood pressure to perfuse vital organs, such as the brain. Postprandial hypotension is believed to be caused by the autonomic nervous system not compensating appropriately, because of aging or a specific disorder.Hypotension is a feature of Flammer syndrome, which is characterized by cold hands and feet and predisposes to normal tension glaucoma.Hypotension can be a symptom of relative energy deficiency in sport, sometimes known as the female athlete triad, although it can also affect men.

Pathophysiology
Blood pressure is continuously regulated by the autonomic nervous system, using an elaborate network of receptors, nerves, and hormones to balance the effects of the sympathetic nervous system, which tends to raise blood pressure, and the parasympathetic nervous system, which lowers it. The vast and rapid compensation abilities of the autonomic nervous system allow normal individuals to maintain an acceptable blood pressure over a wide range of activities and in many disease states. Even small alterations in these networks can lead to hypotension.

Diagnosis
For most adults, the optimal blood pressure is below 120/80 mmHg. If the systolic blood pressure is <90 mmHg or the diastolic blood pressure is <60 mmHg, it would be classified as hypotension. However, occasional blood pressure readings below 90/60 mmHg are not infrequent in the general population,  and, in the absence of some pathological cause, hypotension appears to be a relatively benign condition in most people.  The diagnosis of hypotension is usually made by measuring blood pressure, either non-invasively with a sphygmomanometer or invasively with an arterial catheter (mostly in an intensive care setting). Another way to diagnose low blood pressure is by using the mean arterial pressure (MAP) measured using an arterial catheter  or by continuous, non-invasive hemodynamic monitoring which measures intra-operative blood pressure beat-by-beat throughout surgery. A MAP <65 mmHg is considered hypotension. Intra-operative hypotension <65 mmHg can lead to an increased risk of acute kidney injury, myocardial injury  or post-operative stroke. While an incidental finding of hypotension during a routine blood pressure measurement may not be particularly worrying, a substantial drop in blood pressure following standing, exercise or eating can be asssociated with symptoms and may have implications for future health. A drop in blood pressure after standing, termed postural or othostatic hypotension, is defined as a decrease in supine-to-standing BP >20 mm Hg systolic or >10 mm Hg diastolic within 3 minutes of standing. Orthostatic hypotension is associated with increased risk of future cardiovascular events and mortality. Orthostatic vitals are frequently measured to assist with the diagnosis of orthostatic hypotension, and may involve the use of a tilt table test to evaluate vasovagal syncope.

Treatment
The treatment for hypotension depends on its cause. Chronic hypotension rarely exists as more than a symptom. Asymptomatic hypotension in healthy people usually does not require treatment. Adding electrolytes to a diet can relieve symptoms of mild hypotension. A morning dose of caffeine can also be effective. In mild cases, where the patient is still responsive, laying the person in dorsal decubitus (lying on the back) position and lifting the legs increases venous return, thus making more blood available to critical organs in the chest and head. The Trendelenburg position, though used historically, is no longer recommended.Hypotensive shock treatment always follows the first four following steps. Outcomes, in terms of mortality, are directly linked to the speed that hypotension is corrected. Still-debated methods are in parentheses, as are benchmarks for evaluating progress in correcting hypotension </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 Attenuated familial adenomatous polyposis 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 Coccidioidomycosis and can you explain it in depth? [/INST] Coccidioidomycosis (, kok-SID-ee-oy-doh-my-KOH-sis), commonly known as cocci, Valley fever, as well as California fever, desert rheumatism, or San Joaquin Valley fever, is a mammalian fungal disease caused by Coccidioides immitis or Coccidioides posadasii. Coccidioidomycosis is endemic in certain parts of the United States in Arizona, California, Nevada, New Mexico, Texas, Utah, and northern Mexico.C. immitis is a dimorphic saprophytic fungus that grows as a mycelium in the soil and produces a spherule form in the host organism. It resides in the soil in certain parts of the southwestern United States, most notably in California and Arizona. It is also commonly found in northern Mexico, and parts of Central and South America. C. immitis is dormant during long dry spells, then develops as a mold with long filaments that break off into airborne spores when it rains.  The spores, known as arthroconidia, are swept into the air by disruption of the soil, such as during construction, farming, low-wind or singular dust events, or an earthquake. Windstorms may also cause epidemics far from endemic areas.  In December 1977, a windstorm in an endemic area around Arvin, California led to several hundred cases, including deaths, in non-endemic areas hundreds of miles away.Coccidioidomycosis is a common cause of community-acquired pneumonia in the endemic areas of the United States. Infections usually occur due to inhalation of the arthroconidial spores after soil disruption. The disease is not contagious. In some cases the infection may recur or become chronic.
It was reported in 2022 that valley fever had been increasing in Californias Central Valley for years (1,000 cases in Kern county in 2014, 3,000 in 2021); experts said that cases could rise across the American west as the climate crisis makes the landscape drier and hotter.

Classification
After Coccidioides infection, coccidioidomycosis begins with Valley fever, which is its initial acute form. Valley fever may progress to the chronic form and then to disseminated coccidioidomycosis. Therefore, coccidioidomycosis may be divided into the following types:
Acute coccidioidomycosis, sometimes described in literature as primary pulmonary coccidioidomycosis
Chronic coccidioidomycosis
Disseminated coccidioidomycosis, which includes primary cutaneous coccidioidomycosisValley fever is not a contagious disease.

Signs and symptoms
An estimated 60% of people infected with the fungi responsible for coccidioidomycosis have minimal to no symptoms, while 40% will have a range of possible clinical symptoms. Of those who do develop symptoms, the primary infection is most often respiratory, with symptoms resembling bronchitis or pneumonia that resolve over a matter of a few weeks. In endemic regions, coccidioidomycosis is responsible for 20% of cases of community-acquired pneumonia. Notable coccidioidomycosis signs and symptoms include a profound feeling of tiredness, loss of smell and taste, fever, cough, headaches, rash, muscle pain, and joint pain. Fatigue can persist for many months after initial infection.  The classic triad of coccidioidomycosis known as "desert rheumatism" includes the combination of fever, joint pains, and erythema nodosum.A minority (3–5%) of infected individuals do not recover from the initial acute infection and develop a chronic infection. This can take the form of chronic lung infection or widespread disseminated infection (affecting the tissues lining the brain, soft tissues, joints, and bone). Chronic infection is responsible for most of the morbidity and mortality. Chronic fibrocavitary disease is manifested by cough (sometimes productive of mucus), fevers, night sweats and weight loss. Osteomyelitis, including involvement of the spine, and meningitis may occur months to years after initial infection. Severe lung disease may develop in HIV-infected persons.

Complications
Serious complications may occur in patients who have weakened immune systems, including severe pneumonia with respiratory failure and bronchopleural fistulas requiring resection, lung nodules, and possible disseminated form, where the infection spreads throughout the body. The disseminated form of coccidioidomycosis can devastate the body, causing skin ulcers, abscesses, bone lesions, swollen joints with severe pain, heart inflammation, urinary tract problems, and inflammation of the brains lining, which can lead to death.

Cause
Rain starts the cycle of initial growth of the fungus underneath the soil.  In soil (and in agar media), Coccidioides exist in filament form. It forms hyphae in both horizontal and vertical directions. Over a prolonged dry period, cells within hyphae degenerate to form alternating barrel-shaped cells (arthroconidia) which are light in weight and carried by air currents. This happens when the soil is disturbed, often by clearing trees, construction or  farming.  As the population grows, so do all these activities, causing a potential cascade effect.  The more land that is cleared and the more arid the soil, the riper the environment for Coccidioides.  These spores can be easily inhaled unknowingly. On reaching alveoli they enlarge in size to become spherules, and internal septations develop. This division of cells is made possible by the optimal temperature inside the body.  Septations develop and form endospores within the spherule. Rupture of spherules release these endospores, which in turn repeat the cycle and spread the infection to adjacent tissues within the body of the infected individual.  Nodules can form in lungs surrounding these spherules. When they rupture, they release their contents into bronchi, forming thin-walled cavities. These cavities can cause symptoms including characteristic chest pain, coughing up blood, and persistent cough. In individuals with a weakened immune system, the infection can spread through the blood. The fungus can also, rarely, enter the body through a break in the skin and cause infection.

Diagnosis
Coccidioidomycosis diagnosis relies on a combination of an infected persons signs and symptoms, findings on radiographic imaging, and laboratory results.
The disease is commonly misdiagnosed as bacterial community-acquired pneumonia. The fungal infection can be demonstrated by microscopic detection of diagnostic cells in body fluids, exudates, sputum and biopsy tissue by methods of Papanicolaou or Grocotts methenamine silver staining. These stains can demonstrate spherules and surrounding inflammation.With specific nucleotide primers, C. immitis DNA can be amplified by polymerase chain reaction (PCR). It can also be detected in culture by morphological identification or by using molecular probes that hybridize with C. immitis RNA. C. immitis and C. posadasii cannot be distinguished on cytology or by symptoms, but only by DNA PCR.An indirect demonstration of fungal infection can be achieved also by serologic analysis detecting fungal antigen or host IgM or IgG antibody produced against the fungus. The available tests include the tube-precipitin (TP) assays, complement fixation assays, and enzyme immunoassays. TP antibody is not found in cerebrospinal fluid (CSF). TP antibody is specific and is used as a confirmatory test, whereas ELISA is sensitive and thus used for initial testing.If the meninges are affected, CSF will show abnormally low glucose levels, an increased level of protein, and lymphocytic pleocytosis. Rarely, CSF eosinophilia is present.

Imaging
Chest X-rays rarely demonstrate nodules or cavities in the lungs, but these images commonly demonstrate lung opacification, pleural effusions, or enlargement of lymph nodes associated with the lungs. Computed tomography scans of the chest are more sensitive than chest X-rays to detect these changes.

Prevention
Preventing Valley fever is challenging because it is difficult to avoid breathing in the fungus should it be present; however, the public health effect of the disease is essential to understand in areas where the fungus is endemic. Enhancing surveillance of coccidioidomycosis is key to preparedness in the medical field in addition to improving diagnostics for early infections.  Currently there are no completely effective preventive measures available for people who live or travel through Valley fever-endemic areas. Recommended preventive measures include avoiding airborne dust or dirt, but this does not guarantee protection against infection. People in certain occupations may be advised to wear face masks. The use of air filtration indoors is also helpful, in addition to keeping skin injuries clean and covered to avoid skin infection.In 1998–2011, there were 111,117 cases of coccidioidomycosis in the U.S. that were logged into the National Notifiable Diseases Surveillance System (NNDSS). Since many U.S. states do not require reporting of coccidioidomycosis, the actual numbers may be higher. The United States Centers for Disease Control and Prevention (CDC) called the disease a "silent epidemic" and acknowledged that there is no proven anticoccidioidal vaccine available. A 2001 cost-effectiveness analysis indicated that a potential vaccine could improve health as well as reducing total health care expenditures among infants, teens, and immigrant adults, and more modestly improve health but increase total health care expenditures in older age groups.Raising both surveillance and awareness of the disease while medical researchers are developing a human vaccine can positively contribute towards prevention efforts. Research demonstrates that patients from endemic areas who are aware of the disease are most likely to request diagnostic testing for coccidioidomycosis. Presently, Meridian Bioscience manufactures the so-called EIA test to diagnose the Valley fever, which however is known for producing a fair quantity of false positives. Currently, recommended prevention measures can include type-of-exposure-based respirator protection for persons engaged in agriculture, construction and others working outdoors in endemic areas. Dust control measures such as planting grass and wetting the soil, and also limiting exposure to dust storms are advisable for residential areas in endemic regions.

Treatment
Significant disease develops in fewer than 5% of those infected and typically occurs in those with a weakened immune system. Mild asymptomatic cases often do not require any treatment. Those with severe symptoms may benefit from antifungal therapy, which requires 3–6 months or more of treatment depending on the response to the treatment. There is a lack of prospective studies that examine optimal antifungal therapy for coccidioidomycosis.On the whole, oral fluconazole and intravenous amphotericin B are used in progressive or disseminated disease, or in immunocompromised individuals. Amphotericin B was originally the only available treatment, but alternatives, including itraconazole and ketoconazole, became available for milder disease. Fluconazole is the preferred medication for coccidioidal meningitis, due to its penetration into CSF. Intrathecal or intraventricular amphotericin B therapy is used if infection persists after fluconazole treatment. Itraconazole is used for cases that involve treatment of infected persons bones and joints. The antifungal medications posaconazole and voriconazole have also been used to treat coccidioidomycosis.  Because the symptoms of coccidioidomycosis are similar to the common flu, pneumonia, and other respiratory diseases, it is important for public health professionals to be aware of the rise of coccidioidomycosis and the specifics of diagnosis. Greyhound dogs often get coccidioidomycosis; their treatment regimen involves 6–12 months of ketoconazole taken with food.A particular severe case of meningitis caused by valley fever initially received several incorrect diagnoses such as sinus infections and cluster headaches. The patient became unable to work during diagnosis and original search for treatments. Eventually the right treatment was found—albeit with severe side effects—requiring four pills a day and medication administered directly into the brain every 16 weeks.

Toxicity
Conventional amphotericin B desoxycholate (AmB: used since the 1950s as a primary agent) is known to be associated with increased drug-induced nephrotoxicity impairing kidney function. Other formulations have been developed such as lipid-soluble formulations to mitigate side-effects such as direct proximal and distal tubular cytotoxicity. These include liposomal amphotericin B, amphotericin B lipid complex such as Abelcet (brand) amphotericin B phospholipid complex also as AmBisome Intravenous, or Amphotec Intravenous (Generic; Amphotericin B Cholesteryl Sul), and amphotericin B colloidal dispersion, all shown to exhibit a decrease in nephrotoxicity. The latter was not as effective in one study as amphotericin B desoxycholate which had a 50% murine (rat and mouse) morbidity rate versus zero for the AmB colloidal dispersion.The cost of the nephrotoxic AmB deoxycholate, in 2015, for a patient of 70 kilograms (150 lb) at 1 mg/kg/day dosage, was approximately US$63.80, compared to $1318.80 for 5 mg/kg/day of the less toxic liposomal AmB.

Epidemiology
Coccidioidomycosis is endemic to the western hemisphere between 40°N and 40°S. The ecological niches are characterized by hot summers and mild winters with an annual rainfall of 10–50 cm.
The species are found in alkaline sandy soil, typically 10–30 cm below the surface. In harmony with the mycelium life cycle, incidence increases with periods of dryness after a rainy season; this phenomenon, termed "grow and blow", refers to growth of the fungus in wet weather, producing spores which are spread by the wind during succeeding dry weather. While the majority of cases are observed in the endemic region, cases reported outside the area are generally visitors, who contact the infection and return to their native areas before becoming symptomatic.

North America
In the United States, C. immitis is endemic to southern and central California with the highest presence in the San Joaquin Valley. C. posadassi is most prevalent in Arizona, although it can be found in a wider region spanning from Utah, New Mexico, Texas, and Nevada. An estimated 150,000 infections occur annually, with 25,000 new infections occurring every year. The incidence of coccidioidomycosis in the United States in 2011 (42.6 per 100,000) was almost ten times higher than the incidence reported in 1998 (5.3 per 100,000). In area where it is most prevalent, the infection rate is 2-4%.Incidence varies widely across the west and southwest. In Arizona, for instance, in 2007, there were 3,450 cases in Maricopa County, which in 2007 had an estimated population of 3,880,181 for an incidence of approximately 1 in 1,125. In contrast, though southern New Mexico is considered an endemic region, there were 35 cases in the entire state in 2008 and 23 in 2007, in a region that had an estimated 2008 population of 1,984,356, for an incidence of approximately 1 in 56,695.
Infection rates vary greatly by county, and although population density is important, so are other factors that have not been proven yet. Greater construction activity may disturb spores in the soil. In addition, the effect of altitude on fungi growth and morphology has not been studied, and altitude can range from sea level to 10,000 feet or higher across California, Arizona, Utah and New Mexico.In California from 2000 to 2007, there were 16,970 reported cases (5.9 per 100,000 people) and 752 deaths of the 8,657 people hospitalized. The highest incidence was in the San Joaquin Valley with 76% of the 16,970 cases (12,855) occurring in the area. Following the 1994 Northridge earthquake, there was a sudden increase of cases in the areas affected by the quake, at a pace of over 10 times baseline.There was an outbreak in the summer of 2001 in Colorado, away from where the disease was considered endemic. A group of archeologists visited Dinosaur National Monument, and eight members of the crew, along with two National Park Service workers were diagnosed with Valley fever.California state prisons, beginning in 1919, have been particularly affected by coccidioidomycosis. In 2005 and 2006, the Pleasant Valley State Prison near Coalinga and Avenal State Prison near Avenal on the western side of the San Joaquin Valley had the highest incidence in 2005, of at least 3,000 per 100,000. The receiver appointed in Plata v. Schwarzenegger issued an order in May 2013 requiring relocation of vulnerable populations in those prisons.
The incidence rate has been increasing, with rates as high as 7% during 2006–2010. The cost of care and treatment is $23 million in California prisons. A lawsuit was filed against the state in 2014 on behalf of 58 inmates stating that the Avenal and Pleasant valley state prisons did not take necessary steps to prevent infections.

Population risk factors
There are several populations that have a higher risk for contracting coccidioidomycosis and developing the advanced disseminated version of the disease. Populations with exposure to the airborne arthroconidia working in agriculture and construction have a higher risk. Outbreaks have also been linked to earthquakes, windstorms and military training exercises where the ground is disturbed. Historically, an infection is more likely to occur in males than females, although this could be attributed to occupation rather than being sex-specific. Women who are pregnant and immediately postpartum are at a high risk of infection and dissemination. There is also an association between stage of pregnancy and severity of the disease, with third trimester women being more likely to develop dissemination. Presumably this is related to highly elevated hormonal levels, which stimulate growth and maturation of spherules and subsequent release of endospores. Certain ethnic populations are more susceptible to disseminated coccidioidomycosis. The risk of dissemination is 175 times greater in Filipinos and 10 times greater in African Americans than non-Hispanic whites. Individuals with a weakened immune system are also more susceptible to the disease. In particular, individuals with HIV and diseases that impair T-cell function. Individuals with pre-existing conditions such as diabetes are also at a higher risk. Age also affects the severity of the disease, with more than one-third of deaths being in the 65-84 age group.

History
The first case of what was later named coccidioidomycosis was described in 1892 in Buenos Aires by Alejandro Posadas, a medical intern at the Hospital de Clínicas "José de San Martín". Posadas established an infectious character of the disease after being able to transfer it in laboratory conditions to lab animals. In the U.S., Dr. E. Rixford, a physician from a San Francisco hospital, and T. C. Gilchrist, a pathologist at Johns Hopkins Medical School, became early pioneers of clinical studies of the infection. They decided that the causative organism was a Coccidia-type protozoan and named it Coccidioides immitis (resembling Coccidia, not mild).Dr. William Ophüls, a professor at Stanford University Hospital (San Francisco), discovered that the causative agent of the disease that was at first called Coccidioides infection and later coccidioidomycosis was a fungal pathogen, and coccidioidomycosis was also distinguished from Histoplasmosis and Blastomycosis. Further, Coccidioides immitis was identified as the culprit of respiratory disorders previously called San Joaquin Valley fever, desert fever, and Valley fever, and a serum precipitin test was developed by Charles E. Smith that was able to detect an acute form of the infection. In retrospect, Smith played a major role in both medical research and raising awareness about coccidioidomycosis, especially when he became dean of the School of Public Health at the University of California at Berkeley in 1951.
Coccidioides immitis was considered by the United States during the 1950s and 1960s as a potential biological weapon. The strain selected for investigation was designated with the military symbol OC, and initial expectations were for its deployment as a human incapacitant. Medical research suggested that OC might have had some lethal effects on the populace, and Coccidioides immitis started to be classified by the authorities as a threat to public health. However, Coccidioides immitis was never weaponized to the publics knowledge, and most of the military research in the mid-1960s was concentrated on developing a human vaccine. Currently, it is not on the U.S. Department of Health and Human Services or Centers for Disease Control and Preventions list of select agents and toxins.
In 2002, Coccidioides posadasii was identified as genetically distinct from Coccidioides immitis despite their morphologic similarities and can also cause coccidioidomycosis.

Research
As of 2013, there is no vaccine available to prevent infection with  Coccidioides immitis or Coccidioides posadasii, but efforts to develop such a vaccine are underway.

Other animals
Valley fever is not contagious.
In dogs, the most common symptom of coccidioidomycosis is a chronic cough, which can be dry or moist. Other symptoms include fever (in approximately 50% of cases), weight loss, anorexia, lethargy, and depression. The disease can disseminate throughout the dogs body, most commonly causing osteomyelitis (infection of the bone), which leads to lameness. Dissemination can cause other symptoms, depending on which organs are infected. If the fungus infects the heart or pericardium, it can cause heart failure and death.In cats, symptoms may include skin lesions, fever, and loss of appetite, with skin lesions being the most common.Other species in which Valley fever has been found include livestock such as cattle and horses; llamas; marine mammals, including sea otters; zoo animals such as monkeys and apes, kangaroos, tigers, etc.; and wildlife native to the geographic area where the fungus is found, such as cougars, skunks, and javelinas.

Additional images
In Popular Culture
Everything in Between, a 2022 Australian feature film, contains references to coccidioidomycosis.

See also
Coccidioides
Coccidioides immitis
Coccidioides posadasii
Zygomycosis
Medical geology
List of cutaneous conditions
Thunderhead, a 1998 novel by Douglas Preston and Lincoln Child which uses the fungus and illness as a central plot point.

References
Further reading
Twarog M, Thompson GR (2015). "Coccidioidomycosis: Recent Updates". Seminars in Respiratory and Critical Care Medicine. 36 (5): 746–755 </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 Filippi syndrome and can you explain it in depth? [/INST] Filippi syndrome, also known as Syndactyly Type I with Microcephaly and Mental Retardation, is a very rare autosomal recessive genetic disease. Only a very limited number of cases have been reported to date. Filippi Syndrome is associated with diverse symptoms of varying severity across affected individuals, for example malformation of digits, craniofacial abnormalities, intellectual disability, and growth retardation. The diagnosis of Filippi Syndrome can be done through clinical observation, radiography, and genetic testing. Filippi Syndrome cannot be cured directly as of 2022, hence the main focus of treatments is on tackling the symptoms observed on affected individuals. It was first reported in 1985.

Signs and symptoms
The symptoms of Filippi Syndrome can be congenital (apparent as an infant). The occurrence and severity of such symptoms are variable across affected individuals. The progression of symptoms over ones lifetime has not been thoroughly studied due to the small number of people with Filippi Syndrome globally.

Malformations of digits
Malformations of digits are expressed among people with Filippi Syndrome. One of the most common malformations is the webbing or fusion of digits, which is termed syndactyly. In particular, syndactyly of the third and fourth fingers or the second, third and fourth toes is termed "syndactyly type 1". The degree of syndactyly may differ across affected individuals, with some exhibiting syndactyly of soft tissues and skin only, and more severe cases exhibiting syndactyly of digital bones.Other malformations of digits include clinodactyly (curving) of the fifth fingers and brachydactyly (abnormal shortening) of digits. Brachydactyly is believed to be largely due to abnormalities arising from the bones inside the hands and feet, specifically the metacarpals and metatarsals.

Craniofacial abnormalities
Furthermore, most people with Filippi Syndrome exhibit craniofacial abnormalities. Craniofacial abnormalities are birth defects observed at the head or face region of affected individuals. Some of the craniofacial abnormalities present in people with Filippi Syndrome include microcephaly (having a skull that is smaller than normal), prominent/ elevated nasal bridge, hypertelorism (having ones pair of eyes further apart from each other than normal), and underdeveloped nasal alae (underdeveloped tissues surrounding the nostril). Less common craniofacial abnormalities include having a broad forehead, thin vermilion border (having a thin upper lip), and frontal hirsutism (having a hairy forehead).

Mental retardation
People with Filippi Syndrome may also demonstrate varying degrees of intellectual disability. Affected individuals may experience defective speech development, aphasia (experiencing difficulty in finding the appropriate words to use), vision impairment, and an inability to speak.

Growth retardation
Another characteristic symptom of people with Filippi Syndrome is the occurrence of growth retardation, which is also referred to as growth delay. Such growth delays may be either prenatal or postnatal, meaning that they can occur both before and after birth. In particular, delayed bone maturation can be observed in patients with Filippi Syndrome.

Other symptoms
People with Filippi Syndrome may exhibit some other physical abnormalities. Examples of such abnormalities include dwarfism (having a severely short stature), dislocated elbows, decreased joint mobility, muscular hypotonia (having weak muscle tone), and involuntary muscle stiffness.They may also exhibit abnormal conditions at their skin and teeth. Moreover, a portion of affected males may demonstrate cryptorchidism (a condition in which the testes fail to descend into the scrotum).

Causes
Filippi syndrome is a genetic disease with an autosomal recessive inheritance pattern at the Cytoskeleton Associated Protein 2 Like (CKAP2L) gene.

Inheritance pattern
An autosomal recessive inheritance pattern means that the disease trait is exhibited on an individual only when both copies of the disease gene in the individual demonstrate a specific pathogenic mutation. This happens when the individual inherits one copy of the mutated gene from each of their parents. In the case of Filippi Syndrome, both copies of the CKAP2L gene of an individual have to be mutated in order for them to demonstrate symptoms of the disorder.

CKAP2L gene
The CKAP2L gene is the human ortholog of the mouse CKAP2I (Radmis) gene. It contains 10 exons and is located on chromosome 2q14.1. It is a protein-coding gene that is associated with microtubules and some cellular structures involved in mitosis. The CKAP2L gene is essential for the proper formation of mitotic spindles during mitosis and the progression of the cell cycle of human cells. The expression pattern of the CKAP2L gene can explain the occurrence of syndactyly in Filippi Syndrome.

Mutations
Multiple mutations at the CKAP2L gene can cause Filippi Syndrome. Some of these mutations include a 1-base pair duplication in exon 4, a 2-base pair insertion in exon 2, a 1-base pair deletion in exon 4, and a 329-base pair deletion in exon 4 of the gene. The above mutations cause a frameshift in the gene. A frameshift mutation refers to a condition in which the reading frame of the gene is disrupted by the insertion or deletion of base pairs from the gene (if the number of inserted or deleted base pairs is not divisible by three). This frameshift mutation ultimately results in a premature termination codon (the formation of a termination codon at a position more "forward" than normal). Other mutations include a base pair transition in the start codon, which is the starting site of translation of the gene. A transition mutation occurring at this codon disrupts the codon sequence and abolishes the site. This prevents the cell from carrying out translation of the gene.

Diagnosis
The diagnosis of Filippi Syndrome is mostly done postnatally. Initial diagnosis of the disease relies on clinical observation of symptoms, including different degrees of syndactyly and craniofacial abnormalities, exhibited by affected individuals. Diagnosis can also be done through radiography, which checks for malformation of digits.Confirmation of diagnosis requires the use of genetic testing. Specifically, it can be done through detecting mutations in the CKAP2L gene, of which a total of eight causative variants having been identified.Genetic testing of Filippi Syndrome makes use of three major techniques:

Whole Exome Sequencing, which focuses on sequencing the exons in the region of the genome coding for proteins.
Next-generation Sequencing, which is a high-throughput genomic sequence analysis method that make use of flow cytometry, and is able to analyze gigabases of sequences in one instrument run.
Array Based Techniques, which makes use of microarray applications to determine chromosomal abnormalities with greater precision compare to the conventional karyotyping tests.

Treatment
Currently, Filippi Syndrome has no direct cure. It is treated according to observed symptoms on affected individuals.

Syndactyly release surgery
Syndactyly exhibit varying degrees of severity in individuals. Hence not all affected individuals with this condition must undergo surgical intervention. For example, syndactyly that occurs at the proximal end of the digits may have limited effect on the normal functioning of the hand and foot, and correction through surgery is optional.Simple syndactyly is the condition of cutaneous fusion between two digits, and can be treated by surgically rebuilding the hourglass shape web space between digits. During surgery, incision is first carried out to separate the fused fingers. It is followed by reconstruction of the web spaces side walls using dorsal advancement flaps or skin grafts obtained from the affected individuals groin. After reconstruction, additional fingerpulp flaps are required for rebuilding of the nailfold between the nail bed and the surrounding skin if there is the occurrence of syndactyly at the tip of the fingers.Treatment for complex syndactyly, which refers to the bony fusion between two digits, has a higher degree of complexity. It involves the reconstruction of web space as well as highly specific surgical procedures with accordance to different types of bony fusion. It may also require separation and relocation of the flexor digitorum profundus or tendon-diverted transplantation if the structure of the tendons in the fused digits are also affected by syndactyly.Professionals usually advice that affected individuals receive surgical treatment during the first two years of life to avoid hindrance to motor ability development.

Craniofacial surgery
Craniofacial abnormalities can be corrected through surgical methods.
Affected individuals with severe hypertelorism may undergo orbital osteotomy </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 Endometrial stromal tumour 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 Aerosinusitis and can you explain it in depth? [/INST] Aerosinusitis, also called barosinusitis, sinus squeeze or sinus barotrauma is a painful inflammation and sometimes bleeding of the membrane of the paranasal sinus cavities, normally the frontal sinus. It is caused by a difference in air pressures inside and outside the cavities.

Presentation
Typically, sinus barotrauma is preceded by an upper respiratory tract infection or allergy. The affected person has a sudden sharp facial pain or headache during descent, which increases as the aircraft approaches ground level. The pain can ultimately become disabling unless the ambient pressure is reversed.
The pressure difference causes the mucosal lining of the sinuses to become swollen and submucosal bleeding follows with further difficulties ventilating the sinus, especially if the orifices are involved. Ultimately fluid or blood will fill the space.
In most cases of sinus barotrauma, localized pain to the frontal area is the predominant symptom. This is due to pain originating from the frontal sinus, it being above the brow bones.  Less common is pain referred to the temporal, occipital, or retrobulbar region. Epistaxis or serosanguineous secretion from the nose may occur. Neurological symptoms may affect the adjacent fifth cranial nerve and especially the infraorbital nerve.

Pathology
The pathology of sinus barotrauma is directly related to Boyles law, which states that the volume of a gas is inversely proportional to the pressure on it, when temperature is constant (P1 × V1 = P2 × V2). Two types of acute barotrauma are observed: squeeze and reverse squeeze.
On ascent, the air in the paranasal sinuses will expand according to Boyles law, contracting during descent. Normally, the sinuses drain into the nasal cavity through small ostia, which permit mucociliary clearance and ventilation that equilibrates pressure. However, when the opening is obstructed due to inflammation, polyps, mucosal thickening, anatomical abnormalities, or other lesions, pressure equilibration is impossible. Squeeze is produced on descent when trapped air in the sinuses contracts and produces negative pressure. The pressure differentials are directed to the center of the sinuses producing mucosal edema, transudation, and mucosal-or submucosal-hematoma, leading to further occlusion of the sinus ostium. The sinus will fill with fluid or blood unless the pressure differential is neutralized.If the outlet is blocked during ascent, the situation is reversed and "reverse squeeze" appears. Pressure inside the sinus increases, affecting the walls of the sinus and producing pain or epistaxis.

Location
The majority of episodes of sinus barotrauma occur in the frontal sinuses with pain localized over the frontal area. Possible explanations for this might be the relatively long and delicate nasofrontal duct that connects the narrow frontal recess with the frontal sinuses.
Barotrauma located in the maxillary, ethmoidal, or sphenoid sinuses is observed less frequently and appears when the ostia are blocked; the majority of cases are probably caused by an acute upper respiratory tract infection </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 Chiari malformation and can you explain it in depth? [/INST] Chiari malformation (CM) is a structural defect in the cerebellum, characterized by a downward displacement of one or both cerebellar tonsils through the foramen magnum (the opening at the base of the skull). CMs can cause headaches, difficulty swallowing, vomiting, dizziness, neck pain, unsteady gait, poor hand coordination, numbness and tingling of the hands and feet, and speech problems. Less often, people may experience ringing or buzzing in the ears, weakness, slow heart rhythm, or fast heart rhythm, curvature of the spine (scoliosis) related to spinal cord impairment, abnormal breathing, such as central sleep apnea, characterized by periods of breathing cessation during sleep, and, in severe cases, paralysis.This can sometimes lead to non-communicating hydrocephalus as a result of obstruction of cerebrospinal fluid (CSF) outflow. The cerebrospinal fluid outflow is caused by phase difference in outflow and influx of blood in the vasculature of the brain. The malformation is named for Austrian pathologist Hans Chiari. A type II CM is also known as an Arnold–Chiari malformation in honor of Chiari and German pathologist Julius Arnold.

Signs and symptoms
Findings are due to brain stem and lower cranial nerve dysfunction. Onset of symptoms are less likely to be present during adulthood in most patients. Younger children generally have a substantially different presentation of clinical symptoms from older children. Younger children are more likely to have a more rapid neurological degeneration with profound brain stem dysfunction over several days.
Neurogenic dysphagia: Difficulty swallowing. Seen by poor feeding in patient.
Cyanosis: Bluish discoloration of skin while feeding.
Weak crying
Facial weakness
Aspiration
Headaches aggravated by Valsalva maneuvers, such as yawning, laughing, crying, coughing, sneezing or straining, bending over, or getting up suddenly
Tinnitus (ringing in the ears)
Lhermittes sign (electrical sensation that runs down the back and into the limbs)
Vertigo (dizziness)
Nausea
Schmahmann syndrome
Nystagmus (irregular eye movements; typically, so-called "downbeat nystagmus")
Facial pain
Muscle weakness
Impaired gag reflex
Dysphagia (difficulty swallowing)
Restless leg syndrome
Sleep apnea
Sleep disorders
Impaired coordination
Severe cases may develop all the symptoms and signs of a bulbar palsy
Paralysis due to pressure at the cervico-medullary junction may progress in a so-called "clockwise" fashion, affecting the right arm, then the right leg, then the left leg, and finally the left arm; or the opposite way around.
Papilledema on fundoscopic exam due to Increased intracranial pressure
Pupillary dilation
Dysautonomia: tachycardia (rapid heart), syncope (fainting), polydipsia (extreme thirst), chronic fatigue
Apnea: Sudden pause of breathing, usually during sleep.
Opisthotonos: Spasm of the head which causes head to arch backwards. More common in infants than adults.
StridorThe blockage of cerebrospinal fluid (CSF) flow may also cause a syrinx to form, eventually leading to syringomyelia. Central cord symptoms such as hand weakness, dissociated sensory loss, and, in severe cases, paralysis may occur.

Syringomyelia
Syringomyelia is a chronic progressive degenerative disorder characterized by a fluid-filled cyst located in the spinal cord. Its symptoms include pain, weakness, numbness, and stiffness in the back, shoulders, arms or legs. Other symptoms include headaches, the inability to feel changes in the temperature, sweating, sexual dysfunction, and loss of bowel and bladder control. It is usually seen in the cervical region but can extend into the medulla oblongata and pons or it can reach downward into the thoracic or lumbar segments. Syringomyelia is often associated with type I Chiari malformation and is commonly seen between the C-4 and C-6 levels. The exact development of syringomyelia is unknown but many theories suggest that the herniated tonsils in type I Chiari malformations cause a "plug" to form, which does not allow an outlet of CSF from the brain to the spinal canal. Syringomyelia is present in 25% of patients with type I Chiari malformations.

Pathophysiology
The most widely accepted pathophysiological mechanism by which Chiari type I malformations occur is by a reduction or lack of development of the posterior fossa as a result of congenital or acquired disorders. Congenital causes include hydrocephalus, craniosynostosis (especially of the lambdoid suture), hyperostosis (such as craniometaphyseal dysplasia, osteopetrosis, erythroid hyperplasia), X-linked vitamin D-resistant rickets, and neurofibromatosis type I. Acquired disorders include space occupying lesions due to one of several potential causes ranging from brain tumors to hematomas.
Traumatic brain injury may cause delayed acquired Chiari malformation, but the pathophysiology of this is unknown. Additionally, ectopia may be present but asymptomatic until a whiplash injury causes it to become symptomatic.Some neurological experts believe that Chiari malformation type I is developed as a result of Filum Disease, an abnormal traction of the spinal cord caused by an excessively tense Filum terminale. This theory was first introduced by Dr. Miguel B. Royo Salvador in 1993.

Diagnosis
Diagnosis is made through a combination of patient history, neurological examination, and medical imaging. Magnetic resonance imaging (MRI) is considered the preferred imaging modality for Chiari malformation. The MRI visualizes neural tissue such as the cerebellar tonsils and spinal cord as well as bone and other soft tissues. CT and CT myelography are other options and were used prior to the advent of MRI, unfortunately the resolution of CT based modalities do not characterize syringomyelia and other neural abnormalities as well.By convention, the cerebellar tonsil position is measured relative to the basion-opisthion line, using sagittal T1 MRI images or sagittal CT images. The selected cutoff distance for abnormal tonsil position is somewhat arbitrary, as not every person will be symptomatic at a certain amount of tonsil displacement, and the probability of symptoms and syrinx increases with greater displacement; however, greater than 5 mm is the most frequently cited cutoff number, though some consider 3–5 mm to be "borderline,"; pathological signs and syrinx may occur beyond that distance. One study showed little difference in cerebellar tonsil position between standard recumbent MRI and upright MRI for patients without a history of whiplash injury. Neuroradiological investigation is used to first rule out any intracranial condition that could be responsible for tonsillar herniation. Neuroradiological diagnostics evaluate the severity of crowding of the neural structures within the posterior cranial fossa and their pressure against the foramen magnum. Chiari 1.5 is a term used when both brainstem and tonsillar herniation through the foramen magnum are present.The diagnosis of a Chiari II malformation can be made prenatally, through ultrasound.

Classification
In the late 19th century, Austrian pathologist Hans Chiari described seemingly related anomalies of the hindbrain, the so-called Chiari malformations I, II and III. Later, other investigators added a fourth (Chiari IV) malformation. The scale of severity is rated I – IV, with IV being the most severe. Types III and IV are very rare. Since Dr. Chiaris original descriptions Chiari 0, 1.5, 3.5, and 5 have been described in the medical literature.

Types of Chiari malformation
Other conditions sometimes causally associated with Chiari malformation include hydrocephalus, syringomyelia, spinal curvature, tethered spinal cord syndrome, and connective tissue disorders such as Ehlers-Danlos syndrome and Marfan syndrome.
Chiari malformation is the most frequently used term for this set of conditions.  The use of the term "Arnold–Chiari malformation" has fallen somewhat out of favor over time, although it is used to refer to the type II malformation.  Current sources use "Chiari malformation" to describe its four specific types, reserving the term "Arnold-Chiari" for type II only. Some sources still use "Arnold-Chiari" for all four types.Chiari malformation or Arnold–Chiari malformation should not be confused with Budd-Chiari syndrome, a hepatic condition also named for Hans Chiari.
In Pseudo-Chiari Malformation, leaking of CSF may cause displacement of the cerebellar tonsils and similar symptoms sufficient to be mistaken for a Chiari I malformation.

Treatment
While there is no current cure, the treatments for Chiari malformation are surgery and management of symptoms, based on the occurrence of clinical symptoms rather than the radiological findings. The presence of a syrinx is known to give specific signs and symptoms that vary from dysesthetic sensations to algothermal dissociation to spasticity and paresis. These are important indications that decompressive surgery is needed for patients with Chiari Malformation Type II. Type II patients have severe brain stem damage and rapidly diminishing neurological response.Decompressive surgery involves removing the lamina of the first and sometimes the second or third cervical vertebrae and part of the occipital bone of the skull to relieve pressure. The flow of spinal fluid may be augmented by a shunt. Since this surgery usually involves the opening of the dura mater and the expansion of the space beneath, a dural graft is usually applied to cover the expanded posterior fossa.A small number of neurological surgeons believe that detethering the spinal cord as an alternate approach relieves the compression of the brain against the skull opening (foramen magnum), obviating the need for decompression surgery and associated trauma. However, this approach is significantly less documented in the medical literature, with reports on only a handful of patients. The alternative spinal surgery is also not without risk.Complications of decompression surgery can arise. They include bleeding, damage to structures in the brain and spinal canal, meningitis, CSF fistulas, occipito-cervical instability and pseudomeningeocele. Rare post-operative complications include hydrocephalus and brain stem compression by retroflexion of odontoid. Also, an extended CVD created by a wide opening and big duroplasty can cause a cerebellar "slump". This complication needs to be corrected by cranioplasty.In certain cases, irreducible compression of the brainstem occurs from in front (anteriorly or ventral) resulting in a smaller posterior fossa and associated Chiari malformation. In these cases, an anterior decompression is required. The most commonly used approach is to operate through the mouth (transoral) to remove the bone compressing the brainstem, typically the odontoid. This results in decompressing the brainstem and therefore gives more room for the cerebellum, thus decompressing the Chiari malformation. Arnold Menzes, MD, is the neurosurgeon who pioneered this approach in the 1970s at the University of Iowa. Between 1984 and 2008 (the MR imaging era), 298 patients with irreducible ventral compression of the brainstem and Chiari type 1 malformation underwent a transoral approach for ventral cervicomedullary decompression at the University of Iowa. The results have been excellent resulting in improved brainstem function and resolution of the Chiari malformation in the majority of patients.

Epidemiology
Congenital Chiari I malformation, defined as tonsilar herniations of 3 to 5 mm or greater, was previously believed to be in the range of one per 1000 births, but is likely much higher. Women are three times more likely than men to have a congenital Chiari malformation. Type II malformations are more prevalent in people of Celtic descent. A study using upright MRI found cerebellar tonsillar ectopia in 23% of adults with headache from motor-vehicle-accident head trauma. Upright MRI was more than twice as sensitive as standard MRI, likely because gravity affects cerebellar position.Cases of congenital Chiari malformation may be explained by evolutionary and genetic factors. Typically, an infants brain weighs around 400g at birth and triples to 1100-1400g by age 11. At the same time the cranium triples in volume from 500 cm3 to 1500 cm3 to accommodate the growing brain. During human evolution, the skull underwent numerous changes to accommodate the growing brain. The evolutionary changes included increased size and shape of the skull, decreased basal angle and basicranial length. These modifications resulted in significant reduction of the size of the posterior fossa in modern humans. In normal adults, the posterior fossa comprises 27% of the total intracranial space, while in adults with Chiari Type I, it is only 21%. H. neanderthalensis had platycephalic (flattened) skulls. Some cases of Chiari are associated with platybasia (flattening of the skull base).

History
The history of Chiari malformation is described below and categorized by the year:

1883: Cleland was the first to describe Chiari II or Arnold–Chiari malformation on his report of a child with spina bifida, hydrocephalus, and anatomical alterations of the cerebellum and brainstem.
1891: Hans Chiari, a Viennese pathologist, described the case of a 17-year-old female with elongation of the tonsils into cone shaped projections which accompany the medulla and are crammed into the spinal canal.
1907: Schwalbe and Gredig, pupils of German pathologist Julius Arnold, described four cases of meningomyelocele and alterations in the brainstem and cerebellum, and gave the name "Arnold-Chiari" to these malformations.
1932: Van Houweninge Graftdijk was the first to report the surgical treatment of Chiari malformations. All patients died from surgery or postoperative complications.
1935: Russell and Donald suggested that decompression of the spinal cord at the foramen magnum might facilitate the CSF circulation.
1940: Gustafson and Oldberg diagnosed Chiari malformation with syringomyelia.
1974: Bloch et al. described the tonsils position to be classified between 7 mm and 8 mm below cerebellum.
1985: Aboulezz used MRI for discovery of extension

Society and culture
The condition was brought to the mainstream on the series CSI: Crime Scene Investigation in the tenth-season episode "Internal Combustion" on February 4, 2010.
Chiari malformation was briefly mentioned on the medical drama House M.D. in the fifth-season episode "House Divided",  It was the focus of the sixth-season episode "The Choice." It is also the focus of Private Practice Season 4 episode 4, where a pregnant woman is diagnosed with it. It was the a cause of death on the reality television series Dr. G: Medical Examiner in the sixth-season episode "Bruised and Battered". It was also mentioned in the medical drama A Gifted Man, in the first-season episode "In Case of Separation Anxiety".
It is also featured in the 3rd and 4th episode of the 7th season of the series Rizzoli & Isles where Dr </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Stasis dermatitis 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 Cystocele and can you explain it in depth? [/INST] A cystocele, also known as a prolapsed bladder, is a medical condition in which a womans bladder bulges into her vagina. Some may have no symptoms. Others may have trouble starting urination, urinary incontinence, or frequent urination. Complications may include recurrent urinary tract infections and urinary retention. Cystocele and a prolapsed urethra often occur together and is called a cystourethrocele. Cystocele can negatively affect quality of life.Causes include childbirth, constipation, chronic cough, heavy lifting, hysterectomy, genetics, and being overweight. The underlying mechanism involves weakening of muscles and connective tissue between the bladder and vagina. Diagnosis is often based on symptoms and examination.If the cystocele causes few symptoms, avoiding heavy lifting or straining may be all that is recommended. In those with more significant symptoms a vaginal pessary, pelvic muscle exercises, or surgery may be recommended. The type of surgery typically done is known as a colporrhaphy. The condition becomes more common with age. About a third of women over the age of 50 are affected to some degree.

Signs and symptoms
The symptoms of a cystocele may include:

a vaginal bulge
the feeling that something is falling out of the vagina
the sensation of pelvic heaviness or fullness
difficulty starting a urine stream
a feeling of incomplete urination
frequent or urgent urination
fecal incontinence
frequent urinary tract infections
back and pelvic pain
fatigue
painful sexual intercourse
bleedingA bladder that has dropped from its normal position and into the vagina can cause some forms of incontinence and incomplete emptying of the bladder.

Complications
Complications may include urinary retention, recurring urinary tract infections and incontinence. The anterior vaginal wall may actually protrude though the vaginal introitus (opening). This can interfere with sexual activity. Recurrent urinary tract infections are common for those who have urinary retention. In addition, though cystocele can be treated, some treatments may not alleviate troubling symptoms, and further treatment may need to be performed. Cystocele may affect the quality of life, women who have cystocele tend to avoid leaving their home and avoid social situations. The resulting incontinence puts women at risk of being placed in a nursing home or long-term care facility.

Cause
A cystocele occurs when the muscles, fascia, tendons and connective tissues between a womans bladder and vagina weaken, or detach. The type of cystocele that can develop can be due to one, two or three vaginal wall attachment failures: the midline defect, the paravaginal defect, and the transverse defect. The midline defect is a cystocele caused by the overstretching of the vaginal wall; the paravaginal defect is the separation of the vaginal connective tissue at the arcus tendineus fascia pelvis; the transverse defect is when the pubocervical fascia becomes detached from the top (apex) of the vagina. There is some pelvic prolapse in 40–60% of women who have given birth. Muscle injuries have been identified in women with cystocele. These injuries are more likely to occur in women who have given birth than those who have not. These muscular injuries result in less support to the anterior vaginal wall.Some women with connective tissue disorders are predisposed to developing anterior vaginal wall collapse. Up to one third of women with Marfan syndrome have a history of vaginal wall collapse. Ehlers-Danlos syndrome in women is associated with a rate of 3 out of 4.

Risk factors
Risk factors for developing a cystocele are:

Connective tissue disorders predispose women to developing cystocele and other pelvic organ prolapse. The tissues tensile strength of the vaginal wall decreases when the structure of the collagen fibers change and become weaker.

Diagnosis
There are two types of cystocele. The first is distension. This is thought to be due to the overstretching of the vaginal wall and is most often associated with aging, menopause and vaginal delivery. It can be observed when the rugae are less visible or even absent. The second type is displacement. Displacement is the detachment or abnormal elongation of supportive tissue.The initial assessment of cystocele can include a pelvic exam to evaluate leakage of urine when the women is asked to bear down or give a strong cough (Valsalva maneuver), and the anterior vaginal wall measured and evaluated for the appearance of a cystocele. If a woman has difficulty emptying her bladder, the clinician may measure the amount of urine left in the womans bladder after she urinates called the postvoid residual. This is measured by ultrasound. A voiding cystourethrogram is a test that involves taking x-rays of the bladder during urination. This x-ray shows the shape of the bladder and lets the doctor see any problems that might block the normal flow of urine. A urine culture and sensitivity test will assess the presence of a urinary tract infection that may be related to urinary retention. Other tests may be needed to find or rule out problems in other parts of the urinary system. Differential diagnosis will be improved by identifying possible inflammation of the Skenes glands and Bartholin glands.

Grading
A number of scales exist to grade the severity of a cystocele.The pelvic organ prolapse quantification (POP-Q) assessment, developed in 1996, quantifies the descent of the cystocele into the vagina. The POP-Q provides reliable description of the support of the anterior, posterior and apical vaginal wall. It uses objective and precise measurements to the reference point, the hymen. Cystocele and prolapse of the vagina from other causes is staged using POP-Q criteria can range from good support (no descent into the vagina) reported as a POP-Q stage 0 or I to a POP-Q score of IV which includes prolapse beyond the hymen. It also used to quantifies the movement of other structures into the vaginal lumen and their descent.The Baden–Walker Halfway Scoring System is used as the second most used system and assigns the classifications as mild (grade 1) when the bladder droops only a short way into the vagina; (grade 2) cystocele, the bladder sinks far enough to reach the opening of the vagina; and (grade 3) when the bladder bulges out through the opening of the vagina.

Classifications
Cystocele can be further described as being apical, medial, lateral, or mediolateral.Apical cystocele is located upper third of the vagina. The structures involved are the endopelvic fascia and ligaments. The cardinal ligaments and the uterosacral ligaments suspend the upper vaginal-dome. The cystocele in this region of the vagina is thought to be due to a cardinal ligament defect.Medial cystocele forms in the mid-vagina and is related to a defect in the suspension provided by to a sagittal suspension system defect in the uterosacral ligaments and pubocervical fascia. The pubocervical fascia may thin or tear and create the cystocele. An aid in diagnosis is the creation of a shiny spot on the epithelium of the vagina. This defect can be assessed by MRI.Lateral cystocele forms when both the pelviperineal muscle and its ligamentous–fascial develop a defect. The ligamentous– fascial creates a hammock-like suspension and support for the lateral sides of the vagina. Defects in this lateral support system results in a lack of bladder support. Cystocele that develops laterally is associated with an anatomic imbalance between anterior vaginal wall and the arcus tendineus fasciae pelvis – the essential ligament structure.

Prevention
Cystocele may be mild enough not to result in symptoms that are troubling to a woman. In this case, steps to prevent it from worsening include:

smoking cessation
losing weight
pelvic floor strengthening
treatment of a chronic cough
maintaining healthy bowel habits
eating high fiber foods
avoiding constipation and straining

Treatment
Treatment options range from no treatment for a mild cystocele to surgery for a more extensive cystocele. If a cystocele is not bothersome, the clinician may only recommend avoiding heavy lifting or straining that could cause the cystocele to worsen. If symptoms are moderately bothersome, the doctor may recommend a pessary, a device placed in the vagina to hold the bladder in place and to block protrusion. Treatment can consist of a combination of non-surgical and surgical management. Treatment choice is also related to age, desire to have children, severity of impairment, desire to continue sexual intercourse and other diseases that a woman may have.

Non-surgical
Cystocele is often treated by non-surgical means:

Pessary – This is a removable device inserted into the vagina to support the anterior vaginal wall. Pessaries come in many different shapes and sizes. There are sometimes complications with the use of a pessary.
Pelvic floor muscle therapy – Pelvic floor exercises to strengthen vaginal support can be of benefit. Specialized physical therapy can be prescribed to help strengthen the pelvic floor muscles.
Dietary changes – Ingesting high fiber foods will aid in promoting bowel movements.
Estrogen – intravaginal administration helps to prevent pelvic muscle atrophy

Surgery
The surgery to repair the anterior vaginal wall may be combined with other procedures that will repair the other points of pelvic organ support such as anterior-posterior repair and anterior colporrhaphy. Treatment of cystocele often accompanies the more invasive hysterectomy. Since the failure rate in cystocele repair remains high, additional surgery may be needed. Women who have surgery to repair a cystocele have a 17% of needing another operation within the next ten years.The surgical treatment of cystocele will depend on the cause of the defect and whether it occurs at the top (apex), middle, or lower part of the anterior vaginal wall. The type of surgery will also depend on the type of damage that exists between supporting structures and the vaginal wall. One of the most common surgical repairs is colporrhaphy. This surgical procedure consists of making a longitudinal folding of the vaginal tissue, suturing it into place and creating a stronger point of resistance to the intruding bladder wall. Surgical mesh is sometimes used to strengthen the anterior vaginal wall. It has a 10–50% failure rate. In some cases a surgeon may choose to use surgical mesh to strengthen the repair.During surgery, the repair of the vaginal wall consists of folding over and then suturing the existing tissue between the vagina and bladder to strengthen it. This tightens the layers of tissue to promote the replacement of the pelvic organs into their normal place. The surgery also provides more support for the bladder. This surgery is done by a surgeon specializing in gynecology and is performed in a hospital. Anesthesia varies according to the needs of each woman. Recovery may take four to six weeks. Other surgical treatment may be performed to treat cystocele. Support for the vaginal wall is accomplished with the paravaginal defect repair. This is a surgery, usually laproscopic, that is done to the ligaments and fascia through the abdomen. The lateral ligaments and supportive structures are repaired, sometimes shortened to provide additional support to the vaginal wall.Sacrocolpopexy is a procedure that stabilizes the vaginal vault (the uppermost portion of the vagina) and is often chosen as the treatment for cystocele, especially if previous surgeries were not successful. The procedure consists of attaching the vaginal vault to the sacrum. It has a success rate of 90%. Some women choose not to have surgery to close the vagina. This surgery, called colpocleisis, treats cystocele by closing the vaginal opening. This can be an option for women who no longer want to have vaginal intercourse.If an enterocele/sigmoidocele, or prolapse of the rectum/colon, is also present, the surgical treatment will take this concurrent condition into account while planning and performing the repairs. Estrogen that is administered vaginally before surgical repair can strengthen the vaginal tissue providing a more successful outcome when mesh or sutures are used for the repair. Vaginal thickness increases after estrogen therapy. Another review on the surgical management of cystocele describes a more successful treatment that more strongly attaches the ligaments and fascia to the vagina to lift and stabilize it.Post surgical complications can develop. The complications following surgical treatment of cystocele are:

After surgery, a woman is instructed to restrict her activities and monitor herself for signs of infection such as an elevated temperature, discharge with a foul odor and consistent pain. Clinicians may recommend that sneezing, coughing, and constipation are to be avoided. Splinting the abdomen while coughing provides support to an incised area and decreases pain on coughing. This is accomplished by applying gentle pressure to the surgical site for bracing during a cough.Recurrent surgery on the pelvic organs may not be due to a failure of the surgery to correct the cystocele. Subsequent surgeries can be directly or indirectly relating to the primary surgery. Prolapse can occur at a different site in the vagina. Further surgery after the initial repair can be to treat complications of mesh displacement, pain, or bleeding. Further surgery may be needed to treat incontinence.One goal of surgical treatment is to restore the vagina and other pelvic organs to their anatomically normal positions. This may not be the outcome that is most important to the woman being treated who may only want relief of symptoms and an improvement in her quality of life. The International Urogynecological Association (IUGA) has recommended that the data collected regarding the success of cystocele and pelvic organ repairs include the presence or absence of symptoms, satisfaction and Quality of Life. Other measures of a successful outcome should include perioperative data, such as operative time and hospital stay. Standardized Healthcare Quality of Life should be part of the measure of a successful resolution of cystocele. Data regarding short- and long-term complications is included in the recommendations of the IUGA to better assess the risk–benefit ratio of each procedure. Current investigations into the superiority of using biological grafting versus native tissue or surgical mesh indicates that using grafts provides better results.

Epidemiology
A large study found a rate of 29% over the lifetime of a woman. Other studies indicate a recurrence rate as low as 3%.In the US, greater than 200,000 surgeries are performed each year for pelvic organ prolapse and 81% of these are to correct cystocele. Cystocele occurs most frequently compared to the prolapse of other pelvic organs and structure. Cystocele is found to be three times as common as vaginal vault prolapse and twice as often as posterior vaginal wall defects. The incidence of cystocele is around 9 per 100 women-years. The highest incidence of symptoms occurs between ages of 70 and 79 years. Based on population growth statistics, the number of women with prolapse will increase by a minimum of 46% by the year 2050 in the US. Surgery to correct prolapse after hysterectomy is 3.6 per 1,000 women-years.

History
Notable is the mention of cystocele in many older cultures and locations. In 1500 B.C. Egyptians wrote about the "falling of the womb". In 400 B.C. a Greek physician documented his observations and treatments:
"After the patient had been tied to a ladder-like frame, she was tipped upward so that her head was toward the bottom of the frame. The frame was then moved upward and downward more or less rapidly for approximately 3–5 min. As the patient was in an inverted position, it was thought that the prolapsing organs of the genital tract would be returned to their normal position by the force of gravity and the shaking motion."Hippocrates had his own theories regarding the cause of prolapse. He thought that recent childbirth, wet feet, sexual excesses, exertion, and fatigue may have contributed to the condition. Polybus, Hippocratess son-in-law, wrote: "a prolapsed uterus was treated by using local astringent lotions, a natural sponge packed into the vagina, or placement of half a pomegranate in the vagina." In 350 A.D., another practitioner named Soranus described his treatments which stated that the pomegranate should be dipped into vinegar before insertion. Success could be enhanced if the woman was on bed rest and reduced intake of fluid and food. If the treatment was still not successful, the womans legs were tied together for three days.In 1521, Berengario da Carpi performed the first surgical treatment for prolapse. This was to tie a rope around the prolapse, tighten it for two days until it was no longer viable and cut it off. Wine, aloe, and honey were then applied to the stump.In the 1700s, a Swiss gynecologist, Peyer, published a description of a cystocele. He was able to describe and document both cystocele and uterine prolapse. In 1730, Halder associated cystocele with childbirth. During this same time, efforts began to standardize the terminology that is still familiar today. In the 1800s, the surgical advancements of anesthesia, suturing, suturing materials and acceptance of Joseph Listers theories of antisepsis improved outcomes for women with cystocele. The first surgical techniques were practiced on female cadavers. In 1823, Geradin proposed that an incision and resection may provide treatment. In 1830, the first dissection of the vagina was performed by Dieffenbach on a living woman. In 1834, Mendé proposed that dissecting and repair of the edges of the tissues could be done. In 1859, Huguier proposed the amputation of the cervix was going to solve the problem for elongation.In 1866, a method of correcting a cystocele was proposed that resembled current procedures. Sim subsequently developed another procedure that did not require the full-thickness dissection of the vaginal wall. In 1888, another method of treating anterior vaginal wall Manchester combined an anterior vaginal wall repair with an amputation of the cervix and a perineorrhaphy. In 1909, White noted the high rate of recurrence of cystocele repair </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 Distal intestinal obstruction syndrome and can you explain it in depth? [/INST] Distal intestinal obstruction syndrome (DIOS) involves obstruction of the distal part of the small intestines by thickened intestinal content  and occurs in about 20% of mainly adult individuals with cystic fibrosis. DIOS was previously known as meconium ileus equivalent, a name which highlights its similarity to the intestinal obstruction seen in newborn infants with cystic fibrosis </s>