Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Continued haemorrhage from oesophageal varices despite adequate injection sclerotherapy and tamponade has a high mortality rate. Such patients are usually referred for surgery. Over a 10-year period, 30 patients (21 men and nine women of median age 52 (range 21-70) years) with acute variceal haemorrhage uncontrolled by initial treatment underwent early emergency oesophageal transection. Portal hypertension was caused by alcoholic cirrhosis in 22 patients; other forms of cirrhosis were present in seven and portal vein thrombosis in one. Hepatic function immediately before operation was Pugh grade A in two patients, B in six and C in 22. Deterioration between admission and transection from grade A to B occurred in one patient and from B to C in five. Oesophageal transection stopped variceal haemorrhage in 29 of the 30 patients. Rebleeding from gastric varices within 35 days of surgery occurred in five patients. Postoperative haemorrhage also occurred from perioesophageal vessels (two patients), a gastrotomy (one) and oesophageal ulceration (two). Hepatic failure developed in seven patients, renal failure in five and both hepatic and renal failure in four. Mortality at 30 days occurred in neither of the two patients with liver function of grade A, in one of six of grade B and in 18 of 22 of grade C. The overall 30-day mortality rate was thus 63 per cent. Mortality was related to the preoperative Pugh grade (hazard ratio 3.95 per grade; P = 0.013) and preoperative blood transfusion (hazard ratio 1.37 per unit; P = 0.035). Four of six patients with grade B liver function died within 3 months and 21 of 22 with grade C disease within 1 year. Oesophageal transection is effective at stopping variceal bleeding but does not modify the underlying disease. Caution is urged for patients with grade C hepatocellular impairment proceeding to acute oesophageal transection after initial sclerotherapy. Such patients may benefit more from treatment with somatostatin or an intrahepatic porta-systemic stent shunt while awaiting definitive therapy.
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PMID:Emergency oesophageal transection for uncontrolled variceal haemorrhage. 792 95

The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 microgram.min-1.kg-1), isosorbide dinitrate (10 micrograms.min-1.kg-1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21 +/- 4% and portal pressure 17 +/- 3%. Isosorbide dinitrate decreased portal venous inflow 20 +/- 4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14 +/- 2%. Portal venous resistance rose 7.6 +/- 3% with isosorbide dinitrate alone, but decreased 18 +/- 4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22 +/- 4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.
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PMID:Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats. 795 57

The ventilation-perfusion relationships of the lung (VA/Q) and central haemodynamics were studied in seven patients with cirrhosis before and 30 min after a bolus injection of a somatostatin analogue, octreotide (Sandostatin, 50 micrograms i.v.), to elucidate the role of this substance in the hepatopulmonary syndrome. In the basal state all patients had normal spirometry but reduced diffusing capacity. Three patients had various degrees of hypoxaemia (6.9-8.3 kPa) and three had clubbing of the fingers. In the basal state VA/Q distributions, determined by inert gas elimination technique, showed an intrapulmonary shunt of 7.9 +/- 2.2% of cardiac output (range 1.5 to 17.1) and perfusion of lung regions with "low VA/Q" of 4.4 +/- 2.2% of cardiac output (range 0 to 15.4). After octreotide, the amount of shunting increased (10.9 +/- 4.4% of cardiac output; non-significant), while "low VAQ" was unchanged (3.7 +/- 1.3% of cardiac output). Arterial oxygen tension decreased from 10.2 +/- 1.1 to 9.7 +/- 1.1 kPa (non-significant). The mean pulmonary arterial pressure increased from 14.5 +/- 1.9 to 16.3 +/- 1.8 mmHg (p < 0.01). No alterations were seen in heart rate, stroke volume, cardiac output, central pressures or vascular resistances. The results of the present study do not support the hypothesis that octreotide improves hypoxaemia and ventilation-perfusion relationships in patients with hepatopulmonary syndrome.
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PMID:Ventilation-perfusion relationships and central haemodynamics in patients with cirrhosis. Effects of a somatostatin analogue. 796 22

Somatostatin has been used to effectively control acute variceal haemorrhage, with conjectured mechanisms on portal hypertension. We, therefore, evaluated the effects of somatostatin on hepatic and systemic haemodynamics in 15 patients with hepatitis B-related cirrhosis and portal hypertension. All patients received an intravenous, continuous infusion of somatostatin 250 micrograms/h, following a bolus injection of 250 micrograms. In systemic haemodynamics, the mean arterial pressure (MAP) increased (P < 0.05), associated with a reflex bradycardia within 3 min following bolus injections, compared with basal values. The right atrial pressure, pulmonary capillary wedge pressure, inferior vena cava pressure, cardiac index, and systemic vascular resistance remained unaffected after drug infusion. In hepatic haemodynamics, the wedge hepatic vein pressure remained unchanged after drug administration. However, there was an increase in free hepatic vein pressure (FHVP; P < 0.05), and a trend toward a decrease in the hepatic vein pressure gradient (HVPG; P = 0.063), within 3 min after bolus injection. Furthermore, the hepatic blood flow decreased significantly at 10 and 30 min after somatostatin infusion (P < 0.05). The effective sinusoidal perfusion assessed by indocyanine green infusion also decreased progressively at 10 min (P = 0.057) and 30 min (P < 0.05). We concluded that somatostatin, at the dose used in this study, caused a transient and bolus-related vasoconstrictive effect, resulting in increases in MAP and FHVP, a decrease in heart rate, and a trend toward lower HVPG. In addition, somatostatin reduced the hepatic blood flow and effective sinusoidal perfusion which may be hazardous to cirrhotic patients during variceal haemorrhage.
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PMID:Changes of hepatic and systemic haemodynamics following somatostatin administration in patients with hepatitis B-related cirrhosis. 809 83

The site of impaired glucose uptake in cirrhosis is uncertain. We therefore performed hyperglycemic clamps (glucose 10 mmol/L) in 10 patients with compensated alcoholic cirrhosis and impaired glucose tolerance and in six control subjects. Muscle glucose uptake was estimated in patients and controls with the forearm technique. In the cirrhotic subjects splanchnic glucose uptake was measured with hepatic vein catheterization and primed continuous infusions of indocyanine green and [6-3H]glucose. To assess insulin-independent glucose uptake and the effects of elevated nonesterified fatty acid levels on glucose uptake, we repeated the study with somatostatin to induce insulin deficiency and a nicotinic acid analog, acipimox, to inhibit lipolysis. Substrate disposal was assessed on indirect calorimetry. Despite similar stimulated insulin levels, total glucose utilization was lower in the cirrhotic subjects (3.9 +/- 0.3 vs. 8.8 +/- 1.7 mg/kg/min, p = 0.006). This deficiency was accounted for by lower nonoxidative glucose disposal (1.2 +/- 0.2 vs. 5.8 +/- 1.6 mg/kg/min, p = 0.002). Forearm glucose uptake was lower in the cirrhotic subjects (0.39 +/- 0.06 vs. 1.21 +/- 0.3 mg/100 ml/min, p = 0.001). However, splanchnic glucose uptake at 1.59 +/- 0.14 mg/kg/min was similar to that reported in other studies of normal subjects. Insulin-independent glucose uptake was normal, and acipimox had no effect on total or forearm glucose utilization. Glucose intolerance in cirrhosis is characterized by impaired peripheral insulin-stimulated non-oxidative glucose disposal. The high nonesterified fatty acid levels seen in cirrhosis most likely do not contribute to this defect. Splanchnic glucose uptake is normal in cirrhosis.
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PMID:Normal splanchnic but impaired peripheral insulin-stimulated glucose uptake in cirrhosis. 810 Jul 99

We retrospectively studied 22 patients with hepatopulmonary syndrome (HPS) evaluated at the Mayo Medical Center from 1984 to 1991. All patients had hepatic cirrhosis with clinical evidence of portal hypertension; 13 (59 percent) had severe hypoxemia while breathing room air in the supine position (PaO2 < 60 mm Hg), and 14 of 16 (88 percent) had orthodeoxia breathing room air. On the basis of angiographic observations, we defined type 1 and type 2 patterns of pulmonary vascular abnormalities in HPS. Response to 100 percent oxygen and therapeutic regimens may differ in the angiographic patterns. Substantial deterioration in PaO2 associated with clinically stable hepatic dysfunction was documented in five of seven patients studied with sequential arterial blood gas testing; four subsequently died within 48 months. Overall mortality was 41 percent, occurring a mean of 2.5 years after diagnosis. In 7 of the 22 patients, we prospectively studied the effect of somatostatin analogue given subcutaneously for 4 consecutive days. No significant improvement in PaO2 was documented while breathing room air or 100 percent oxygen (p < 0.05). We conclude that in selected patients with clinically stable hepatic dysfunction and deteriorating oxygenation, the prognosis is poor. Our data in combination with recent surgical reports suggest that liver transplantation may be the treatment of choice in patients with HPS and worsening oxygenation.
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PMID:Hepatopulmonary syndrome. Clinical observations and lack of therapeutic response to somatostatin analogue. 810 97

Pharmacological management of acute variceal hemorrhage appears to be effective in patients with liver cirrhosis. Somatostatin and presumably its longer-acting analog, octreotide, are more efficient and safer than other vasoconstrictors like vasopressin, terlipressin or their combination with nitroglycerin. Drug treatment, however, usually represents only a valuable adjunct to other measures to stop bleeding such as endoscopic variceal sclerotherapy. Prophylaxis of first bleeding by beta-blockade appears justified in patients at a high risk of bleeding which still has to be defined more precisely. Prevention of recurrent hemorrhage can be effective in some but not in all of the patients with liver cirrhosis and a first bleeding episode. Treatment of patients with good liver function under direct control of the wedged hepatic vein pressure gradient presumably will reduce the failure rate of prophylaxis with beta-blockade.
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PMID:The role of drug treatment in variceal bleeding. 811 90

Insulin resistance is a characteristic feature of glucose-intolerant and diabetic cirrhotic patients. The pathogenic factors, however, that are responsible for the development of impaired glucose tolerance in cirrhosis, remain unclear. To examine whether the ability of hyperglycemia per se to enhance glucose uptake (by means of mass-action effect) is impaired in cirrhosis, we measured (insulin-independent) whole-body glucose disposal during hyperglycemia (hyperglycemic clamp studies, +125 mg/dl, in combination with an infusion of somatostatin (500 micrograms/hr), insulin (0.1 mU/kg min) and glucagon (0.5 ng/kg min) to "clamp" hormone levels at baseline), whole-body glucose oxidation (indirect calorimetry) and glucose turnover (prime-continuous infusion of [6,6-2H2-]glucose in a clinically homogeneous group of cirrhotic patients with glucose intolerance (n = 7) or frank diabetes mellitus (n = 7) and in control individuals (n = 7). Fasting plasma glucose concentrations were normal in glucose-intolerant patients but were significantly increased in diabetic patients (158 +/- 19 vs. 87 +/- 2 mg/dl in controls; p < 0.01). Plasma glucose concentrations were clamped at 214 +/- 4 mg/dl in controls, at 212 +/- 4 mg/dl in glucose-intolerant patients and at 287 +/- 19 mg/dl in diabetic patients; plasma insulin and glucagon concentrations were maintained at baseline levels. In the basal state, total-body glucose disposal (which equals basal hepatic glucose output) was normal in glucose-intolerant patients (2.25 +/- 0.11 mg/kg min) but was increased in diabetic patients compared with controls (3.32 +/- 0.26 mg/dl vs. 2.45 +/- 0.10 mg/dl; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose resistance contributes to diabetes mellitus in cirrhosis. 780 65

Somatostatin is used to treat variceal hemorrhage in patients with cirrhosis and portal hypertension. Its systemic hemodynamic effects, however, are not yet well defined. Since cardiomyopathy or pulmonary artery hypertension may occur in patients with cirrhosis, definition of the systemic hemodynamic effects of somatostatin or its analogue octreotide is of clinical importance. The aim of this study was to evaluate the effects of somatostatin, at different doses and under different conditions of administration, on the systemic hemodynamics in 17 patients with cirrhosis. Two sets of experiments were performed. In the first, eight patients received two different bolus doses (100 and 250 micrograms) of somatostatin. The second set of experiments was designed to study the hemodynamic effects of the combination of a bolus and an infusion of somatostatin. Nine other patients received one bolus of 250 micrograms of somatostatin, followed by a 250 micrograms/h infusion for 65 min. A second bolus of 250 micrograms of somatostatin was injected in these patients after 35 min of infusion. Before and for 30 min after each bolus, systemic hemodynamics were measured. Following a bolus of somatostatin, a dose-dependent decrease in heart rate (from 77 +/- 3 to 73 +/- 5 beats/min with 100 micrograms, and from 78 +/- 4 to 68 +/- 5 beats/min with 250 micrograms, p < 0.05) and increases in systemic and pulmonary artery pressures were observed. The combination of an infusion and a bolus of somatostatin significantly reduced the increases in systemic and pulmonary artery pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Short-term cardiovascular effects of somatostatin in patients with cirrhosis. 853 92

Bleeding from oesophageal and gastric varices is one of the most dramatic and important complications of cirrhosis. Non surgical options are favoured as first line treatment because the operative mortality in cirrhotic patients is high. These options include vasoactive drugs (terlipressin or somatostatin) and endoscopic treatment or a combination of these two treatments. Vasoactive drugs could be given before endoscopic treatment and perhaps even earlier during transfer to hospital to permit a therapeutic measure to be given at initial diagnostic endoscopy when bleeding is controlled and the patient stable. Balloon tamponade should be used only in patients with uncontrolled bleeding. Surgical portacaval shunt or transjugular intrahepatic portosystemic stent shunts is used as a second line treatment when all else has failed to control bleeding and because of an increased mortality risk surgery should never be too much delayed.
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PMID:[Treatment of digestive hemorrhages caused by rupture of esophagogastric varices in liver cirrhosis]. 857 31


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