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)

Spontaneous bacterial peritonitis (SBP) and varices bleeding are the most dangerous complications of liver cirrhosis. Symptoms of SBP are often nonspecific. SBP is diagnosed in the presence of more than 250 granulocytes/ml ascites and/or positive ascites cultures. Antibiotic prophylactic therapy is indicated after the first episode of SBP or primarily if ascites proteins is low (< 10 g/l). The varices bleeding should by treated endoscopically. In case of bleeding portal venous pressure can be lowered by infusion of somatostatin or vasopressin long-active analogues. In long-term therapy of portal hypertension non-selective betablockers or nitrates are effective.
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PMID:[Therapy of acute variceal hemorrhage and spontaneous bacterial peritonitis in liver cirrhosis]. 978 69

In healthy subjects octreotide is largely metabolised by the liver suggesting that the plasma half-life of the somatostatin analogue may be prolonged in patients with hepatic dysfunction. The aim of this study was therefore (a) to determine the pharmacokinetics of octreotide following its subcutaneous injection in 6 patients with cirrhosis and portal hypertension and (b) compare the magnitude and duration of the effects of intravenous administration of 250 micrograms somatostatin and 50 micrograms octreotide on corrected wedged hepatic venous pressure (WHVP) and to relate the findings to the plasma levels of the analogue 1 h after administration in 13 patients with cirrhosis and portal hypertension. Following subcutaneous administration of 50 micrograms octreotide the circulating half life (range 2.4 to 4.79 h) was prolonged whereas the clearance (range 2.101 to 4.775 L/h) was decreased compared to healthy controls. Intravenous bolus administration of 250 micrograms somatostatin or 50 micrograms octreotide resulted in a reduction in WHVP of approximately the same magnitude and duration despite appreciable quantities of the analogue in the blood 1 h after administration (1944 +/- 226 pg/ml). These results indicate that the circulating half-life of octreotide is prolonged in cirrhotics suggesting that the dosage regimens should be modified in such patients to avoid accumulation of the analogue in the blood which may result in undesirable side-effects or toxicity. Furthermore, since the magnitude and duration of the reduction in WHVP elicited by IV octreotide is similar to that observed with somatostatin, the analogue, like the native hormone, must be administered by continuous IV infusion to produce a sustained response and hence a therapeutic effect in the management of acute variceal bleeding.
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PMID:Pharmacokinetics of octreotide in patients with cirrhosis and portal hypertension; relationship between the plasma levels of the analogue and the magnitude and duration of the reduction in corrected wedged hepatic venous pressure. 983 May 76

In patients with cirrhosis, somatostatin or octreotide administration is followed by a transient decrease in the hepatic venous pressure gradient and azygos blood flow. Although no clear-cut changes in variceal pressure are observed and the exact mechanisms of acute hemodynamic changes induced by somatostatin or its derivatives are still unknown, this provided the rationale for its use in patients with variceal hemorrhage. The only known sustained hemodynamic effect of octreotide is to prevent increases in hepatic venous gradient or azygos blood flow in response to food intake. Somatostatin infusion can be as effective as sclerotherapy in the initial control of bleeding esophageal varices in patients with cirrhosis and is associated with fewer complications. Octreotide also seems to be as effective as endoscopic therapy in the control of acute variceal bleeding, although larger studies should be performed before its efficacy and safety profile can be fully evaluated. The combination of somatostatin or long-acting analogues to endoscopic therapy has recently been delineated as one of the most promising approaches in these patients. Early somatostatin administration with repeat boluses, starting several hours before sclerotherapy is combined, eases the endoscopic procedure and reduces bleeding control failure rate. Although two studies also showed that octreotide, when started at the time of sclerotherapy or variceal banding, also improves bleeding control, a conclusion on octreotide use in these patients is premature. Optimal administration schedules and doses of somatostatin or octreotide are still unknown. The safety of octreotide in patients with variceal bleeding, which has recently been challenged, should be assessed in larger trials. Recent data suggesting that octreotide combination to beta-blockers or sclerotherapy may represent a useful approach for long-term prevention of rebleeding in these patients will have to be confirmed.
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PMID:Somatostatin or octreotide in acute variceal bleeding. 1020 29

We examined the effect of a new long-acting release formula (LAR) of the somatostatin analogue, octreotide, on development of sodium retention and functional and structural changes in the thick ascending limb of Henle's loop (TAL) in rats with cirrhosis induced by common bile duct ligation (CBL). CBL and sham-operated control rats were treated with octreotide-LAR (10 mg/kg body weight subcutaneously, as a single dose) or vehicle at the time of CBL or sham-CBL. The rats were instrumented with chronic catheters, and sodium balance and renal function were examined 4 weeks after CBL or sham operation. Octreotide-LAR treatment significantly inhibited sodium retention in CBL rats and prevented renal vasodilatation without changes in glomerular filtration rate (GFR). The natriuretic response to a test dose of furosemide (7.5 mg/kg body weight intravenously) was significantly increased in CBL rats, and when expressed in terms of natriuretic efficiency (mmol Na/mg furosemide in urine), the natriuretic response was increased by 57% relative to sham-operated controls. Stereological examination of kidneys demonstrated a 53% increase in the volume of the inner stripe of the outer medulla and a 108% increase in the volume of TAL epithelium in cirrhotic rats relative to controls. The increased natriuretic efficiency of furosemide as well as the hypertrophy of the inner stripe and the TAL in this renal zone were absent in CBL rats treated with octreotide-LAR. These results suggest that octreotide-LAR treatment inhibits sodium retention in cirrhotic rats, partly by inhibition of increased furosemide-sensitive sodium reabsorption in the TAL.
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PMID:Effects of chronic octreotide treatment on renal changes during cirrhosis in rats. 1021 20

Hepatocellular carcinoma is responsible in France for approximately 5,500 deaths per year. Incidence rates are growing and the general status of patients is improving mainly because of earlier diagnosis and improvement in the treatment of complications of liver cirrhosis. In most of the cases the severity of the underlying liver disease is the prominent prognostic factor. Its treatment remains a difficult challenge for oncologists. Unfortunately surgery is usually contraindicated. Most trials of systemic chemotherapy are disappointing with poor response rates and severe side effects; new drugs and direct delivery in the hepatic artery appear to be of interest. Results with interferon are interesting but requires more studies. The lack of efficacy of antiandrogenic and antiestrogenic treatments were recently demonstrated; a recent randomized study showing the interest of somatostatin requires confirmation. Reports on radiotherapy are anecdotals. A lot of studies using liver directed therapies were conducted worldwide. Percutaneous ethanol injections (PEI) are well tolerated and are highly effective in small solitary tumors (> 70% of complete necrosis) but less in larger tumors; recurrences are frequent. No randomized trial have been performed concerning PEI but survival rates seem similar to those of surgery. A randomized controlled trial recently demonstrates that injection of acetic acid is more effective than injection of ethanol. Chemoembolization was extensively studied because of the demonstration of objective responses but all trials failed to demonstrate an improvement in survival. Intraarterial injection of radioactive Lipiodol achieves the same response rate and the same survival than chemoembolization but is significantly best tolerated. This treatment is superior to best supportive cares in patients with portal vein thrombosis. In conclusion, despite the fact that this disease is very frequent we have currently too many treatment options and are lacking of simple rules. The best treatment remains prevention, and the efficacy of hepatitis B vaccination was recently demonstrated in Taiwan.
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PMID:[Nonsurgical treatment of hepatocellular carcinoma]. 1041 27

Recent trials have shown that somatostatin (SMT) is as effective as sclerotherapy in the treatment of acute variceal bleeding and that the combination of both treatments is more effective than sclerotherapy alone. To assess whether the addition of sclerotherapy improves the efficacy of SMT alone, all patients admitted to our unit with gastrointestinal bleeding and with suspected cirrhosis received a continuous infusion of SMT (250 micrograms/h). Endoscopy was performed between 1 and 5 hours later, and patients with esophageal variceal bleeding were randomized to receive or not to receive sclerotherapy. In both groups, SMT infusion was continued for 5 days. Fifty patient admissions were allocated to each group. Therapeutic failure occurred in 21 cases of the SMT group and in 7 cases of the combined-therapy group (P =.002). Failure to control the acute episode occurred in 24% vs. 8% (P =.03) and early rebleeding in 24% vs. 7% (P =.03), respectively. Transfusional requirements were significantly higher in the SMT group, while the incidence of complications was lower (8% vs. 24%; P =.029). In the multivariate analysis, the presence of shock at admission and active bleeding during endoscopy were the variables that better predicted the failure of therapy with SMT alone. Mortality at 6 weeks was similar. These data demonstrate that the addition of sclerotherapy significantly improves the efficacy of SMT alone for the treatment of acute variceal bleeding, although it also increases the rate of complications. Patients with shock and those with active bleeding are more likely to benefit from this combined therapy.
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PMID:Somatostatin alone or combined with emergency sclerotherapy in the treatment of acute esophageal variceal bleeding: a prospective randomized trial. 1042 44

Peripheral vasodilation initiates the hyperdynamic circulation in cirrhosis. Somatostatin and its analogues, such as octreotide, have a vasoconstrictive effect in cirrhotic patients and experimental animals with portal hypertension. The exact mechanism of octreotide-induced vasoconstriction remains unknown. To investigate whether octreotide produces vasoconstriction through suppression of vasodilatory peptides, such as glucagon, or through a local effect, we evaluated the effect of an intra-arterial dose on forearm blood flow (FBF), while measuring systemic glucagon levels. FBF was measured in 10 cirrhotic patients by venous occlusion plethysmography. The brachial artery of the nondominant arm was catheterized, and vasoactive drugs were administered: methacholine 4 microg/min; octreotide 20 microg/h, and octreotide 20 microg/h + methacholine 4 microg/min. Each infusion, lasting 5 minutes, was followed by saline for washout. FBF was measured in both arms during the last minute of each infusion and at the end of washout, with the uninfused arm acting as the control. Nitrates and nitrites, octreotide, and glucagon blood levels were determined at baseline and after each infusion. Percent change in flow (%triangle up) was obtained by comparing the flow during drug administration to that during the preceding saline infusion. Saline infusion did not alter FBF, but octreotide infusion resulted in a 34% +/- 7.7 (P <.005) reduction in FBF in the infused arm. FBF in the control arm was unchanged despite a significant decrease in systemic glucagon levels. Methacholine infusion increased FBF around 300%, which was not altered by the concomitant infusion of octreotide. Octreotide has a local vasoconstrictive effect that seems nitric oxide (NO)-independent. Octreotide probably has a facilitating effect over vasoconstrictors increased in chronic liver diseases.
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PMID:Local arterial vasoconstriction induced by octreotide in patients with cirrhosis. 1070 44

High gastrointestinal hemorrhage represents the more frequent (12-71.1%) and heavy complication of hepatic cirrhosis and correlates to portal hypertension; it is weighed by global mortality which sways from 30 to 50%. High gastrointestinal hemorrhage gives, therefore, a serious of diagnostic and therapeutic problems not easy to guide for at least 3 reasons: numerous causes of bleeding; hepatic failure; the marigold possible therapies. Aim of this work is to clarify some diagnostic and therapeutic features about high gastrointestinal hemorrhage in cirrhotic patient, because such eventuality often presents dramatic aspects, which endangers the patient's life. Our experience shows a casuistry referred to the period of time which goes from 1987 to 1998 and that comprehend 143 examined patients: 91 of theme have been submitted to medical treatment (endoscopic sclerotherapy, glupressin e/o somatostatin); in 52 cases it has been possible to realize a surgical treatment, different from the elective therapy (33 pz) and emergency therapy. Immediate hemostatic effect obtained in both the conditions, has been satisfying with best results at a distance of three years and five years given by devascularization. As matter stands our preference of the devascularization surgical treatment, it seems appropriate to pay attention to the operation of mesocaval anastomosis which, either in Our very brief experience (3 cases) or by international literature, seems to offer encouraging results.
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PMID:[Emergencies in gastroesophageal varices hemorrhage in the patient with portal hypertension]. 1092 Apr 90

High gastrointestinal hemorrhage represents the more frequent (12-71.1%) and heavy complication of hepatic cirrhosis and correlates to portal hypertension; it is weighed by global mortality which sways from 30 to 50%. High gastrointestinal hemorrhage gives, therefore, a serious of diagnostic and therapeutic problems not easy to guide for at least 3 reasons: numerous causes of bleeding; hepatic failure; the marigold possible therapies. Aim of this work is to clarify some diagnostic and therapeutic features about high gastrointestinal hemorrhage in cirrhotic patient, because such eventuality often presents dramatic aspects, which endangers the patient's life. Our experience shows a casuistry referred to the period of time which goes from 1987 to 1998 and that comprehend 143 examined patients: 91 of them have been submitted to medical treatment (endoscopic sclerotherapy, glupressin e/o somatostatin); in 52 cases it has been possible to realize a surgical treatment, different from the elective therapy (33 pz) and emergency therapy. Immediate hemostatic effect obtained in both the conditions, has been satisfying with best results at a distance of three years and five years given by devascularization. As matter stands our preference of the devascularization surgical treatment, it seems appropriate to pay attention to the operation of mesocaval anastomosis which, either in our very brief experience (3 cases) or by international literature, seems to offer encouraging results.
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PMID:[Hemorrhagic emergency due to esophagogastric varices in the portal hypertension patient]. 1110 69

In the liver, the autonomic nervous system plays an important role in degenerative and inflammatory changes. The aim of the present study was to investigate the distribution of neuronal fibres containing neuropeptides in livers of 5 patients with cirrhosis by immunocytochemical localization at the light and electron microscopical level of substance P (SP), neuropeptide Y (NPY), somatostatin (SOM), and calcitonin gene-related peptide (CGRP). In patients with alcoholic cirrhosis, a decreased number of neuronal fibres was found in the portal tract and fibrous septa as well as in the sinusoids of regenerative nodules. NPY- and SP-immunoreactive neuronal fibres were more numerous than CGRP-containing fibres. They were located mainly in portal tracts. These findings led to the conclusion that peptidergic innervation plays a role in inflammatory and fibrotic changes in cirrhotic liver.
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PMID:Immunocytochemical study on the liver innervation in patients with cirrhosis. 1114 32


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