Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The management of both acute and recurrent variceal bleeding continues to be a significant challenge to the clinician. The cause and pathogenesis of portal hypertension has been described. Alcoholic cirrhosis is the most common cause of intrahepatic sinusoidal and postsinusoidal obstruction in the United States. Long term survival depends on rapid institution of an established protocol of surgical management for variceal hemorrhage. A patient who presents with variceal bleeding must be rapidly stabilized with fluid resuscitation, and specific measures, such as the use of vasopressin and balloon tamponade, must be instituted to control hemorrhage so that endoscopy can be used to establish the diagnosis. Sclerotherapy achieves a high rate of success in the acute situation, but if hemorrhage cannot be controlled, percutaneous transhepatic embolization or emergent shunting must be performed, depending on the condition of the patient. Angiography, prior to surgical treatment, is necessary to define venous anatomy and determine portal hemodynamics, both of which provide information vital in choosing the type of shunt. If bleeding is massive and the patient is unstable, H-grafts are most appropriate, for they are technically easier and give excellent short term results. In a stable Child's A or B patient with minor ascites as well as suitable anatomy and hepatopedal flow, DSRS is the procedure of choice because it produces the smallest degree of HE postoperatively and increases the survival rate for nonalcoholics. If this is not feasible or if the surgeon lacks the technical expertise to perform DSRS, PCS is the logical alternative. In view of the data from the series observed in the United States, ablative procedures cannot be recommended at the present for the treatment of variceal bleeding. In the Child's C poor-risk patient, the operative mortality rate is prohibitive, and only nonsurgical means should be used to establish control of bleeding. In the elective situation, the surgical options change. The efficacy of ES as a definitive procedure to control recurrent variceal bleeding is unproved, and rebleeding can be significant; therefore, it cannot be recommended. H-grafts have a prohibitively high rate of long term thrombosis and are also not recommended, and the Linton or proximal splenorenal shunt offers no advantages over conventional portacaval shunting. Moreover, arterialization of the hepatic stumps of the portal vein does not prevent hepatic encephalopathy or alter the survival rate. Both PCS and DSRS prevent rebleeding, yet neither alters the survival rate for alcoholic patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Portal hypertension. 240 26

To investigate whether paracentesis could be an alternative therapy for ascites, 117 cirrhotics with tense ascites were randomly allocated into two groups. Fifty-eight patients (group 1) were treated with paracentesis (4-6 L/day until disappearance of ascites) and intravenous albumin infusion (40 g after each tap). Fifty-nine patients (group 2) were treated with spironolactone (200-400 mg/day) plus furosemide (40-240 mg/day). Patients from group 2 not responding to diuretics were treated with a LeVeen shunt. After disappearance of ascites, patients from both groups were discharged from hospital and were instructed to take diuretics. Patients developing tense ascites during follow-up were readmitted to hospital and treated according to their initial schedule. Paracentesis was effective in eliminating the ascites in 56 patients from group 1 (96.5%) and did not induce significant changes in renal and hepatic function, plasma volume, cardiac index, peripheral resistance, plasma renin activity, plasma norepinephrine and antidiuretic hormone concentration, and urinary excretion of prostaglandin E2 and 6-keto-prostaglandin F1 alpha. Diuretics were effective in eliminating the ascites in 43 patients from group 2 (72.8%) (p less than 0.05). Ten patients in group 1 and 36 in group 2 developed complications during their first hospital stay (p less than 0.001). This difference was due to the significantly higher incidence of hepatic encephalopathy, renal impairment, and electrolyte disturbances occurring in patients treated with diuretics. The duration of hospital stay was 11.7 +/- 1.5 days for patients from group 1 and 31 +/- 2.8 days for patients from group 2 (p less than 0.001). The two groups did not differ significantly with respect to the probability of requiring readmission to hospital during follow-up, reasons for readmission, survival probability after entry into the study, and causes of death. These results indicate that paracentesis associated with intravenous albumin infusion is a fast, effective, and safe therapy for ascites in patients with cirrhosis.
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PMID:Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study. 329 7

Bleeding from esophageal varices remains a difficult clinical problem, carrying a high likelihood both of rebleeding and of mortality. The initial approach requires adequate but not overly vigorous volume replacement with blood and other fluids. Once the patient is resuscitated, upper gastrointestinal endoscopy should be performed to establish the source of bleeding. Both endoscopic variceal sclerotherapy and balloon tamponade appear to be effective in achieving temporary control of acute ongoing hemorrhage from esophageal varices. The value of intravenous vasopressin remains controversial. Rebleeding can be prevented in most patients by shunt surgery. However, surgery carries both considerable early morbidity and mortality (related mainly to the severity of the underlying liver disease) and substantial longer-term morbidity and mortality from hepatic encephalopathy and liver failure. The role of pharmacologic agents (eg, propranolol) intended to prevent variceal hemorrhage by reducing portal pressure remains to be established. At present, we recommend use of endoscopic variceal sclerotherapy for the control of active variceal bleeding, with employment of balloon tamponade and intravenous vasopressin if sclerotherapy is successful. Emergency shunt surgery should be reserved only for those patients whose bleeding cannot be controlled by these other means. For prevention of rebleeding in Child class C patients, we attempt to obliterate the varices by repeated endoscopic sclerotherapy. Patients who have two to three episodes of rebleeding despite this approach are considered for shunt surgery. For better-risk patients who do not have ascites, which is difficult to control, we are currently recommending a distal splenorenal shunt. Alternatively, repeated endoscopic variceal sclerotherapy is used for these better-risk patients (Child class A or B) in some centers, with shunt surgery reserved for patients who continue to rebleed. Which approach to preventing rebleeding in the better-risk patient is more effective, as well as the role of pharmacologic therapy with propranolol or other agents, remains to be settled by well-controlled randomized clinical trials.
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PMID:Management of the patient with hemorrhaging esophageal varices. 352 43

Chronic liver disease may be accompanied by disturbed sodium and water homeostasis. There is usually sodium retention and ascites. However, spontaneous natriuresis has also been reported in humans and experimental animals with liver cirrhosis. Chronic hypercortisolism, which may occur in dogs with advanced liver disease, is known to induce the inhibition of the osmostimulation of vasopressin (AVP) release. We have therefore investigated the osmoregulation of AVP release in 11 dogs with chronic hypercortisolism associated with advanced liver dysfunction and hepatic encepahlopathy and in 10 control dogs. Basal pituitary-adrenocortical activity was investigated by measuring the concentration in multiple plasma samples of adrenocorticotropin (ACTH), alpha-melanocyte-stimulating hormone (MSH), and cortisol and the cortisol:creatinine ratio in 24-hr urine. Urine specific gravity was also measured. The feedback regulation of the system was investigated by measuring these hormones in plasma after an intravenous (iv) injection of 0.01 mg/kg of dexamethasone. The osmoregulation of the release of AVP was investigated by the intravenous infusion of a 20% NaCl solution at a flow rate of 0.03 ml/kg for 2 hr and the measurement of AVP in plasma sampled at 20-min intervals. The AVP release was analyzed in terms of the threshold osmolality at which it commenced and the sensitivity, which reflects the magnitude of the response. All dogs had highly increased urinary cortisol:creatinine ratios, ranging from 21 to 210 x 10(-6) (normally < 10 x 10(-6)). The mean basal plasma concentrations of the three pituitary-adrenocortical hormones were significantly increased. ACTH values were 35 to 146 ng/l (normally, 14 to 68), MSH values were 26 to 118 ng/l (normally, 10 to 36), and cortisol values were 88 to 194 nmol/l (normally, 23 to 112). The feedback inhibition of the secretion of ACTH and cortisol in response to dexamethasone was unaffected. Urine specific gravity was significantly decreased. The regulation of AVP release was found to be abnormal in all dogs with hepatic encephalopathy. The osmotic threshold at which the release of AVP was induced was abnormally high in seven of the dogs with liver disease and in the normal range in one. It could not be determined in three dogs. The sensitivity of AVP release in response to increasing plasma hypertonicity was normal in two dogs and decreased in nine. In three dogs, there was no increase in AVP release. None of the dogs had normal values for both the sensitivity and the threshold.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic glucocorticoid excess and impaired osmoregulation of vasopressin release in dogs with hepatic encephalopathy. 762 76

Hepatorenal syndrome (HRS) is a complex syndrome. In addition to severe reduction of renal function due to renal vasoconstriction, there is impairment in systemic haemodynamics, activation of the renin-angiotensin and sympathetic nervous systems and antidiuretic hormone, vasoconstriction of the brain, muscle and skin, and dilutional hyponatraemia. Treatment in patients with type 2 HRS, the most frequent form of HRS, is directed towards managing refractory ascites. Paracentesis is the treatment of choice. TIPS is also effective but is more expensive, is associated with higher incidence of hepatic encephalopathy, and does not increase survival. Although a rapidly progressive renal failure is the most characteristic manifestation of type 1 HRS, there is failure in other organs such as the liver and the brain. A decrease in cardiac output develops in these patients, associated with a decrease in cardiopulmonary pressures. Since type 1 HRS mainly occurs in patients with spontaneous bacterial peritonitis and massive release of cytokines within the peritoneal cavity, it may be considered as a special form of multiorgan failure of circulatory origin. Not surprisingly, the treatment of choice in type 1 HRS is the combination of vasoconstrictors to reduce arterial vasodilation and plasma volume expansion with albumin to increase cardiac preload. TIPS is also effective in these patients and the combination of pharmacological treatment followed by TIPS may be the most effective approach.
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PMID:Review article: hepatorenal syndrome--how to assess response to treatment and nonpharmacological therapy. 1533 2

The management of children with end-stage chronic liver disease and acute liver failure mandates a multidisciplinary approach and intense monitoring. In recent years, considerable progress has been made in developing specific and supportive medical measures, but studies and publications have mainly concerned adult patients. Therapeutic approaches to complications of end-stage chronic liver disease and acute liver failure (e.g. refractory ascites, hepatorenal syndrome, encephalopathy, and cerebral edema) that may be applied to children are reviewed in this article.Mild-to-moderate ascites should be managed by modest salt restriction and oral diuretic therapy in the first instance. Large volume paracentesis associated with colloid volume expansion and diuretic therapy may be effective for acute relief. Treatment of hepatorenal syndrome type 1 with vasopressin analogs (terlipressin) is recommended prior to liver transplantation in order to improve renal function. Prevention and treatment of chronic hepatic encephalopathy are directed primarily at controlling the events that may precipitate hepatic encephalopathy and at reducing ammonia generation and increasing its detoxification or removal. In addition to reduction of gut ammonia production using non-absorbable disaccharides such as lactulose and/or antibacterials such as neomycin, sodium benzoate may be used on a long-term basis to prevent, stabilize, or improve hepatic encephalopathy. The management of hepatic encephalopathy in acute liver failure is considerably more unsatisfactory; treatment is aimed at preventing brain edema and intracranial hypertension. Extracorporeal liver support devices are now used commonly in critically ill children with acute renal failure, advanced hepatic encephalopathy, cerebral edema, intracranial hypertension, and severe coagulopathy. Continuous renal replacement therapy could potentially help support patients until liver transplantation is performed or liver regeneration occurs. The Molecular Adsorbent Recirculating System (MARS or albumin dialysis) is the liver support system most frequently used worldwide in adults and appears to offer distinct advantages over hepatocyte-based systems. There are no specific medical therapies or devices that can correct all of the functions of the liver. Apart from a few metabolic diseases presenting with severe liver dysfunction for which specific medical therapies may preclude the need for liver transplantation, liver transplantation still remains the only definitive therapy in most instances of end-stage chronic liver disease and acute liver failure. Future research should focus on gaining a better understanding of the mechanisms responsible for liver cell death and liver regeneration, as well as developments in hepatocyte transplantation and liver-directed gene therapy.
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PMID:New management options for end-stage chronic liver disease and acute liver failure: potential for pediatric patients. 1649 8

Primary prophylaxis is advisable for all patients with moderate-sized or large esophageal varices. After the first episode of bleeding, secondary prophylaxis should be initiated to prevent rebleeding. Multiple treatment modalities are available for each circumstance. Optimal regimens have not yet been established but are under investigation. At present, nonselective beta-blockers are the drugs of choice for primary prophylaxis. In patients with actively bleeding varices, octreotide or, in rare cases, a combination of vasopressin and nitroglycerin is used in conjunction with endoscopic band ligation of the varices. Either a beta-blocker, band ligation, or a combination of the two is appropriate for secondary prophylaxis. The combination is often the better choice for patients for whom primary prophylaxis with beta-blockers has failed. As in any treatment situation, the specific approach must be tailored to clinical circumstances. The patient's preferences and willingness or ability to comply with the therapy must be taken into account as well as the physician's expertise. Interventions for hepatic encephalopathy predominantly focus on reducing the amount of ammonia absorbed or endogenously generated in the body. They include correction of precipitating factors, bowel cleansing, and lactulose therapy. In difficult cases, a combination of lactulose and neomycin, metronidazole, or rifaximin is recommended. Because the prognosis for patients with hepatic encephalopathy is generally poor, orthotopic liver transplantation should be considered.
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PMID:Management of portal hypertension. 1712 40

Hyponatremia is a frequent complication of advanced cirrhosis related to an impairment in the renal capacity to eliminate solute-free water that causes a retention of water that is disproportionate to the retention of sodium, thus causing a reduction in serum sodium concentration and hypo-osmolality. The main pathogenic factor responsible for hyponatremia is a nonosmotic hypersecretion of arginine vasopressin (or antidiuretic hormone) from the neurohypophysis related to circulatory dysfunction. Hyponatremia in cirrhosis is associated with increased morbidity and mortality. There is evidence suggesting that hyponatremia may affect brain function and predispose to hepatic encephalopathy. Hyponatremia also represents a risk factor for liver transplantation as it is associated with increased frequency of complications and impaired short-term survival after transplantation. The current standard of care based on fluid restriction is unsatisfactory. Currently, a new family of drugs, known as vaptans, which act by antagonizing specifically the effects of arginine vasopressin on the V2 receptors located in the kidney tubules, is being evaluated for their role in the management of hyponatremia. The short-term treatment with vaptans is associated with a marked increase in renal solute-free water excretion and improvement of hyponatremia. Long-term administration of vaptans seems to be effective in maintaining the improvement of serum sodium concentration, but the available information is still limited. Treatment with vaptans represents a novel approach to improving serum sodium concentration in cirrhosis.
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PMID:Hyponatremia in cirrhosis: pathogenesis, clinical significance, and management. 1867 3

Ascites and hyponatremia are frequent complications of advanced liver cirrhosis. Over 50 % of cirrhotic patients develop ascites and about one third gets hyponatremic. The development of ascites is due to an increased sodium retention in the kidneys, leading to expansion of extracellular volume and accumulation of fluid in the peritoneum. Hyponatremia is related to an impairment in the renal capacity to eliminate solute-free water that causes water retention that is disproportionate to the sodium retention, thus causing a reduction in serum sodium concentration. The exact pathogenesis of sodium retention is not clear, yet. The main pathogenic factor responsible for hyponatremia is a nonosmotic hypersecretion of vasopressin from the neurohypophysis. There is evidence suggesting that hyponatremia predisposes to hepatic encephalopathy. Impairment in glomerular filtration rate in hepatorenal syndrome is due to renal vasoconstriction. Treatment of ascites consists of potassium sparing diuretics, loop diuretics, and/or paracentesis. The current standard of care of hyponatremia based on fluid restriction is unsatisfactory. Currently, a new family of drugs, known as vaptans, which act by specifically antagonizing the effects of vasopressin on the V2 receptors located in the kidney, is evaluated for their role in the management of hyponatremia. Because data on long-term administration are still incomplete, they cannot be used routinely, yet. Liver transplantation is the treatment of choice for hepatorenal syndrome. As bridge to transplantation long-term administration of intravenous albumin and vasoconstrictors can be used.
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PMID:[Treatment of ascites, hyponatremia and hepatorenal syndrome in liver cirrhosis]. 1988 92

Sepsis is physiologically viewed as a proinflammatory and procoagulant response to invading pathogens. There are three recognized stages in the inflammatory response with progressively increased risk of end-organ failure and death: sepsis, severe sepsis, and septic shock. Patients with cirrhosis are prone to develop sepsis, sepsis-induced organ failure, and death. There is evidence that in cirrhosis, sepsis is accompanied by a markedly imbalanced cytokine response ("cytokine storm"), which converts responses that are normally beneficial for fighting infections into excessive, damaging inflammation. Molecular mechanisms for this excessive proinflammatory response are poorly understood. In patients with cirrhosis and severe sepsis, high production of proinflammatory cytokines seems to play a role in the worsening of liver function and the development of organ/system failures such as shock, renal failure, acute lung injury or acute respiratory distress syndrome, coagulopathy, or hepatic encephalopathy. In addition, these patients may have sepsis-induced hyperglycemia, defective arginine-vasopressin secretion, adrenal insufficiency, or compartmental syndrome. In patients with cirrhosis and spontaneous bacterial peritonitis (SBP), early use of antibiotics and intravenous albumin administration decreases the risk for developing renal failure and improves survival. There are no randomized studies that have been specifically performed in patients with cirrhosis and severe sepsis to evaluate treatments that have been shown to improve outcome in patients without cirrhosis who have severe sepsis or septic shock. These treatments include recombinant human activated C protein and protective-ventilation strategy for respiratory failure. Other treatments should be evaluated in the cirrhotic population with severe sepsis including the early use of antibiotics in "non-SBP" infections, vasopressor therapy, hydrocortisone, renal-replacement therapy and liver support systems, and selective decontamination of the digestive tract or oropharynx.
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PMID:Severe sepsis in cirrhosis. 2037 75


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