Gastric endoscopic features in portal hypertension: final report of a consensus conference, Milan, Italy, September 19, 1992.
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Canada↗
Biomedical subjects
J Bosch
Publications and source records attributed to J Bosch.
Shunt surgery and beta-blockers.
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Adrenergic beta-Antagonists↗
Effect of cyclosporine A on normal human osteoblasts in vitro.
UNLABELLED: Cyclosporin-A (CsA) inhibits in vitro proliferation of non-human tumour-cloned osteoblasts. Our aims were to study the direct effect of CsA on proliferation of normal human osteoblast (NHOb) cultures and to ascertain whether CsA-treated patients' sera (CsATPS) may exert effects on the osteoblast which differ from the direct effects of CsA. We studied tritiated thymidine ([3H]thymidine) incorporation in NHOb cultures incubated with (a) increasing CsA concentrations (1.2 to 4800 ng/ml), (b) the same concentrations as in the previous experiment but with the addition of 20% fetal calf serum (FCS) or 20% normal human serum (NHS), (c) 40% NHS or 40% CsATPS. Results at 96 h in (a) CsA inhibited uptake from 300 ng/ml, in (b) CsA inhibited [3H]thymidine uptake from 2400 ng/ml for cultures with FCS and 4800 ng/ml for cultures with NHS, in (c) CsATPS produced [3H]thymidine uptake inhibition compared with NHS. CONCLUSION: CsA alone inhibited [3H]thymidine incorporation in NHOb from concentrations similar to therapeutic concentrations. With FCS or NHS, inhibition was produced at higher concentrations. CsATPS inhibited at CsA concentrations lower than those of the two previous experiments.
Blood↗
Rolling review: the treatment of major complications of cirrhosis.
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Adrenergic beta-Antagonists↗
Effects of continued NO inhibition on portal hypertensive syndrome after portal vein stenosis in rat.
The present study investigated whether chronic nitric oxide (NO) inhibition prevents the hyperdynamic circulatory syndrome that appears in rats after partial portal vein ligation (PPVL). N omega-nitro-L-arginine methyl ester (L-NAME; 30 micrograms.kg-1.min-1, n = 17), a NO biosynthesis inhibitor, or vehicle (n = 17) was infused continuously from PPVL through subcutaneously osmotic pumps. Studies were performed, in ketamine-anesthetized Sprague-Dawley rats, in one-half of the animals at 4 days and in the remaining one-half at 8 days from PPVL. At 4 days, PPVL rats treated with L-NAME had higher mean arterial pressure (MAP), systemic vascular resistance (SVR), and splanchnic arteriolar resistance (SAR) and lower cardiac output and portal venous inflow (PVI) than PPVL rats treated with vehicle (P < 0.05). Similarly, at 8 days PPVL rats treated with L-NAME had higher MAP and SVR and lower cardiac output (P < 0.05) than PPVL rats treated with vehicle. In contrast, PVI and SAR were similar. At 4 days plasma volume and mesenteric-systemic shunting were lower, although nonsignificantly, in PPVL rats treated with L-NAME. This trend completely disappeared at 8 days. L-NAME did not change portal pressure at either 4 or 8 days. After 4 days of continuous treatment with L-NAME, nonportal hypertensive control rats had a significantly higher MAP, lower cardiac index and PVI, and higher SVR and SAR than nonportal hypertensive rats treated with vehicle. Contrary to PPVL rats, these effects were maintained after 8 days of treatment. The present study shows that NO contributes to the systemic disturbances of portal hypertension. However, NO inhibition delayed but did not prevent the splanchnic vasodilation that appears after PPVL, suggesting that other factors could also be involved.
Animals↗
Measurement of kinetic parameters for urea in end-stage renal disease patients using a two-compartment model.
Urea kinetic modeling depends critically on the parameters of the model used. When urea is removed during hemodialysis, the kinetic model is quite complex. This experiment describes for the first time the use of injected stable isotope-labeled urea to define kinetics in ESRD patients and compares the magnitude of the two urea compartments in these patients with those of control subjects. Such an experimental approach provides the kinetic data in the most direct manner. A gas chromatograph/mass spectrometer-based assay provided quantitation to as little as 0.2 mol% excess urea. The rapidly equilibrating fraction of the two urea compartments is quantified as 41.2% in ESRD patients and 33.4% in controls (P = 0.24). The rest is in a more slowly equilibrating pool. The urea clearances between these two compartments were near 1 L/min for both sets of subjects. The elimination of urea was due to the metabolic removal of the 15N label in both groups of subjects as well as renal elimination in the controls. The nearly threefold larger clearance (Cl) of labeled urea removal in controls (Cl = 74.6 mL/min) than in ESRD patients (Cl = 25.4 mL/min; P = 0.015) shows the extent to which renal clearance is more important than metabolism. These direct analyses of the fractional volumes and intercompartmental clearances for urea agree closely with previous measurements during high-efficiency hemodialysis and indicate that ESRD patients do not differ significantly from control subjects in these parameters.
Adult↗
A global scale factor in brain topography.
In this paper statistical resampling techniques are used to support the presence of an equiangular first principal component in EEG log spectra and therefore the existence of a global scale factor in EEG recordings. the Log transformed spectra from a normal sample (n = 211, age 5-97) were analyzed. To reach this conclusion a method for estimating the scale factor is introduced. It is also shown that this factor remains constant in each individual for all derivations and frequencies and across functional states. The contribution of this scale factor to the overall variance of the normal EEG reaches 42% of the total variance of age corrected data. Part of the variance of the scale factor exhibits age dependency. Scale factor correction of EEG spectra data improves the diagnostic accuracy for detecting pathological EEG spectra from an almost random level (Area under the ROC curve = .6) to .84.
Adolescent↗
Effect of bolus injection and continuous infusion of somatostatin on gastric perfusion in cirrhotic patients with portal-hypertensive gastropathy.
Gastric perfusion has been found to be increased in cirrhotic patients with portal-hypertensive gastropathy. This phenomenon may contribute to gastric bleeding from these lesions. Therefore drugs reducing gastric mucosal perfusion may be beneficial in the treatment of bleeding portal-hypertensive gastropathy. In this study, gastric mucosal perfusion was assessed, by means of laser-Doppler flowmetry and reflectance spectrophotometry, in 36 cirrhotic patients with portal-hypertensive gastropathy in basal conditions and after double-blind administration of placebo or somatostatin. Intravenous bolus injection of 250 micrograms somatostatin induced a rapid, marked decrease in gastric perfusion (-31.6% +/- 7.9%, p < 0.05), as assessed on laser-Doppler flowmetry, that lasted for only 6 min. Changes in the hemoglobin content of the gastric mucosa paralleled those of laser-Doppler signal. The oxygen content of the gastric mucosa was mildly reduced (-6.9% +/- 1.1%, p < 0.05). When the bolus injection was followed by a continuous infusion of somatostatin, the reduction in gastric perfusion, as assessed by means of laser-Doppler flowmetry, was maintained, although the magnitude of the reduction (-17% +/- 7%) was significantly lower than that observed immediately after the bolus (p < 0.05); the hemoglobin content of the gastric mucosa was also significantly reduced (-8% +/- 1%), but no changes were observed in the oxygen content. Placebo administration had no effect on any of these parameters. We conclude that the increased gastric perfusion in cirrhotic patients with portal-hypertensive gastropathy can be effectively decreased by somatostatin administration.
Double-Blind Method↗
Hemodynamic effects of alpha-adrenergic blockade with prazosin in cirrhotic patients with portal hypertension.
This study was aimed at investigating whether the blockade of alpha 1-adrenergic receptors could reduce portal pressure in cirrhosis. Splanchnic and systemic hemodynamics were measured in 12 cirrhotic patients with esophageal varices at baseline and 1 hr after oral administration of 2 mg of prazosin (acute study). Measurements were repeated in 10 of these 12 patients after a 3-mo course of 5 mg/12 hr of prazosin (long-term study). Short-term prazosin significantly lowered the hepatic venous pressure gradient from 20.1 +/- 1.3 to 14.4 +/- 0.9 mm Hg (-25.7%) (p < 0.01), and chronic prazosin reduced it to 16.5 +/- 1.3 mm Hg (-19.1%) (p < 0.01). Hepatic blood flow was increased, thus changes in the hepatic venous pressure gradient resulted from a reduction in the estimated hepatic vascular resistance. Reductions in hepatic venous pressure gradient achieved after short-term and long-term prazosin were not significantly different. Reductions in mean arterial pressure and systemic vascular resistance were significantly greater after short-term than after long-term prazosin. Long-term prazosin was associated with significant increases in hepatic and intrinsic hepatic clearances of indocyanine green. This therapy also led to an increase in pulmonary capillary pressure (+ 28.6%, p < 0.05) and body weight (+ 3.06%, p < 0.01) and a decrease in hematocrit (-6.1%, p < 0.05) and urinary sodium excretion (-22.6%, p < 0.05). In contrast, there were no hemodynamic changes in a group of six cirrhotic patients receiving placebo. In cirrhotic patients, short-term prazosin lowers portal pressure by decreasing hepatic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic alpha-Antagonists↗
Impaired function of pancreatic islets from rats with portal hypertension resulting from cirrhosis and partial portal vein ligation.
Increased circulating insulin and glucagon levels are a common observation in patients with cirrhosis, as well as in portal hypertensive models. Hyperinsulinemia and hyperglucagonemia may be caused either by increased beta- and alpha-cell secretion or by defective hepatic clearance of these hormones. To elucidate whether an abnormal endocrine pancreatic function might contribute to the hyperinsulinism or to the hyperglucagonism observed in chronic portal hypertension, insulin and glucagon secretion were measured in vitro in isolated pancreatic islets from rats with partial portal vein ligated and rats with cirrhosis caused by carbon tetrachloride poisoning. Both rats with partial portal vein ligation and rats with cirrhosis caused by carbon tetrachloride poisoning exhibited hyperinsulinism and hyperglucagonism as compared with control rats. Isolated pancreatic islets from both experimental portal hypertensive models showed an impaired insulin secretion after glucose stimulation. On the contrary, glucagon secretion was significantly increased, and there was a markedly enhanced response to arginine. This increased in vitro glucagon production could not be corrected, even in the presence of high glucose concentrations in the incubation medium. Therefore our data show that although hyperglucagonism in rats with partial portal vein ligation and in rats with cirrhosis caused by carbon tetrachloride poisoning is promoted by an enhanced alpha-cell secretion, hyperinsulinism is associated with impaired beta-cell secretion.
Animals↗
Effects of propranolol on gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy.
This study investigated the effects of the short-term administration of propranolol on gastric blood perfusion in cirrhotic patients with portal hypertensive gastropathy. Portal hypertensive gastropathy is a common cause of nonvariceal bleeding in cirrhosis, which is associated with increased gastric mucosal perfusion and is favorably influenced by propranolol therapy. Gastric mucosal perfusion was evaluated with laser-Doppler flowmetry and reflectance spectrophotometry. Measurements were performed under basal conditions and after the double-blind administration of propranolol (0.15 mg/kg intravenously) or placebo. Propranolol administration significantly reduced (p < 0.001) the laser-Doppler signal (2.93 +/- 0.23 vs. 2.25 +/- 0.22 V) and the hemoglobin content of the gastric mucosa (99.2 +/- 3.8 vs. 89.3 +/- 3.1 arbitrary units), whereas the oxygen content remained unchanged (37.4 +/- 1.2 vs. 36.9 +/- 1.0 arbitrary units). Placebo administration had no effect in any of these parameters. Changes in gastric perfusion after propranolol administration were associated with a significant decrease in hepatic venous pressure gradient and azygos blood flow. We conclude that short-term propranolol administration, in addition to lowering portal pressure, reduces the increased gastric blood perfusion in cirrhotic patients with portal hypertensive gastropathy, an effect that may contribute to prevention of bleeding from these lesions.
Female↗
On the reliability of clinical criteria for the diagnosis of hepatic veno-occlusive disease.
Among 217 patients who received an allogeneic (136 cases) or autologous (81 cases) bone marrow transplant, the diagnosis of hepatic veno-occlusive disease (VOD) was established in 38 according to Seattle clinical criteria. Thirty-two underwent a transjugular liver biopsy and measurement of the hepatic venous pressure gradient (HVPG). The study was completed in 30 patients with no serious complications. Hepatic VOD was histologically confirmed in 18 patients (60%); the remaining 12 were classified as non-VOD. An increased HVPG discriminated well between VOD and non-VOD cases. Thus, hemodynamic data can considerably reinforce the accuracy of histological diagnosis. The predictive value of two vs. three clinical data of the Seattle criteria was analyzed. Among the 19 cases fulfilling two clinical data VOD was confirmed in only eight (42%), whereas VOD was proved in ten of 11 cases (91%) (p = 0.02) suspected on the basis of three clinical data. When reliability of the Baltimore clinical criteria was analyzed, the result was identical to that observed when three Seattle clinical data were present. The specificity of the latter classification was high (92%) while its sensitivity was relatively low (56%). In conclusion, clinical criteria are not reliable for either recognizing or excluding the diagnosis of VOD. Thus, a transjugular liver biopsy, associated with hemodynamic evaluation, is strongly recommended when VOD is clinically suspected.
Adolescent↗
Propranolol versus sclerotherapy in preventing variceal rebleeding: a randomized controlled trial.
BACKGROUND: Sclerotherapy has been widely recommended as initial treatment for prevention of variceal rebleeding. The present study was aimed at comparing the efficacy of endoscopic sclerotherapy and long-term administration of propranolol in the prevention of rebleeding and long-term survival in patients who had bled from varices. METHODS: One hundred sixteen consecutive cirrhotic patients admitted because of variceal bleeding were randomly allocated to either continuous administration of propranolol to reduce the resting heart rate by 25% (58 patients) or weekly intravariceal sclerotherapy sessions using 5% ethanolamide oleate until varices disappeared (58 patients). Results were analyzed on an intention-to-treat basis. RESULTS: Rebleeding occurred in 37 patients of the propranolol group and in 26 patients of the sclerotherapy group (RR = 1.45; 95% CI, 1.03-2.03). The actuarial probability of rebleeding was lower in the sclerotherapy group (P = 0.02). No differences were found in rebleeding index, hospitalization requirements, survival, and causes of death. Complications were significantly more frequent and severe in the sclerotherapy group. CONCLUSIONS: Despite the higher efficacy of sclerotherapy decreasing the probability of rebleeding when compared with propranolol, no beneficial effects were observed on other parameters also reflecting the efficacy of therapy. Moreover, complications of sclerotherapy were more frequent and severe than those of propranolol, which probably shall restrict the use of long-term elective sclerotherapy.
Aged↗
Hemodynamic effects of acute changes in intra-abdominal pressure in patients with cirrhosis.
BACKGROUND: Changes in intra-abdominal pressure (IAP) have significant circulatory effects. However, whether this may influence the gastroesophageal collateral blood flow in patients with cirrhosis has not been studied. METHODS: In 14 portal hypertensive cirrhotics, serial hemodynamic measurements were obtained in baseline conditions 30 minutes after the mechanical increase of IAP by 10 mm Hg and 30 minutes after returning IAP to baseline levels. RESULTS: Increasing IAP caused similar increases in free and wedged hepatic venous pressures (+10.3 mm Hg and +11.0 mm Hg, respectively; P < 0.005), without changing the hepatic venous pressure gradient (HVPG). However, there were significant decreases in cardiac output (-18%; P < 0.005) and hepatic blood flow (-20%; P < 0.05), whereas azygos blood flow, an index of gastroesophageal collateral blood flow, increased markedly (+23%; P < 0.005). The opposite occurred after releasing the high IAP. CONCLUSION: In portal hypertensive cirrhotics, acute changes in IAP did not change HVPG but markedly modified splanchnic and systemic hemodynamics. Brief elevations of IAP may have deletereous effects, as shown by the increase in azygos blood flow and the decrease in cardiac output and hepatic blood flow, whereas reduction of a high IAP causes the opposite changes and may be beneficial.
Abdomen↗
New approaches in the pharmacologic treatment of portal hypertension.
To alleviate the risk of variceal bleeding, the portal pressure gradient--usually evaluated as the hepatic venous pressure gradient (HVPG)--must be reduced to < or = 12 mmHg. Although beta-blocking agents are accepted therapy for preventing first or subsequent bleeding episodes, propranolol therapy decreases final HVPG to < or = 12 mmHg in only 12% of patients, while only 24% of patients have a > or = 20% reduction in HVPG and nearly 40% show no reduction in HVPG. This has stimulated research on alternative or additional treatments. Nitrates such as isosorbide dinitrate reduce portal pressure by decreasing resistance to portal and collateral blood flow and by promoting reflex splanchnic vasoconstriction. However, while nitrates are effective in the acute situation, tolerance leading to refractoriness develops over the long term unless they are combined with diuretics or other agents in the treatment of portal hypertension. Propranolol and isosorbide-5-mononitrate combined cause a substantially greater reduction in HVPG than monotherapy with either drug in both acute and long-term use. Presumably concomitant isosorbide-5-mononitrate administration opposes the increase in portal resistance induced by propranolol. Spironolactone, which has been shown to lower HVPG in patients with cirrhosis, produces a reduction in plasma volume that attenuates the increased cardiac output associated with cirrhosis and triggers vasoactive mechanisms that decrease splanchnic blood flow. Potentially, spironolactone may maintain and enhance the decrease in portal pressure achieved by nitrates or propranolol. Triple therapy with a beta-blocker, a nitrate and spironolactone may be feasible.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
Determinants of ethanol and acetaldehyde metabolism in chronic alcoholics.
We have studied the factors determining the rate of ethanol and acetaldehyde metabolism in a group of 25 alcoholics with varying degrees of liver lesion (from normal liver to cirrhosis) and in six nonalcoholic cirrhotics. In alcoholics the ethanol metabolic rate was related to hepatic function, estimated either by the aminopyrine breath test (r = 0.70, p < 0.001) or the indocyanine green clearance (r = 0.76, p < 0.01), and was independent of the activity of hepatic alcohol dehydrogenase and hepatic blood flow. In nonalcoholic cirrhotics blood acetaldehyde was always below the detection limit (0.5 microM), but elevated levels were found in 14 out of the 25 alcoholics. Alcoholics with elevated blood acetaldehyde showed a significantly higher ethanol metabolic rate than alcoholics with undetectable acetaldehyde (120 +/- 17 mg/kg/hr vs 104 +/- 11 mg/kg/hr, p < 0.02), but no differences were observed in the activities of alcohol and aldehyde dehydrogenases. Peak blood acetaldehyde levels were directly related to the ethanol metabolic rate (r = 0.48, p < 0.02), but not to activities of hepatic alcohol or aldehyde dehydrogenases. These results indicate that in chronic alcoholics the main determinant of the ethanol metabolic rate is hepatic function, while the rise of blood acetaldehyde is mainly dependent on the ethanol metabolic rate. Alcohol and aldehyde dehydrogenase activities do not seem to be rate-limiting factors in the oxidation of ethanol or acetaldehyde.
Acetaldehyde↗
Hyperintense globus pallidus on T1-weighted MRI in cirrhotic patients is associated with severity of liver failure.
Hyperintense globus pallidus on T1-weighted MRI is present in most patients with advanced liver disease. We evaluated the relationship between the signal intensity of the globus pallidus and clinical or laboratory data of 77 patients eligible for liver transplantation. There was a significant correlation between the intensity of the signal and the Child-Pugh score (as indication of severity of liver disease), presence of postural tremor, previous episodes of variceal bleeding or hepatic encephalopathy, prothrombin activity, serum aspartate and alanine aminotransferase, bilirubin, and the indocyanine green (ICG) hepatic clearance, a very sensitive marker of liver function. The multivariate analysis disclosed that the ICG hepatic clearance and previous episodes of variceal bleeding were independently associated with the signal intensity in the globus pallidus. MRI repeated in 21 patients 10 to 20 months after transplant showed a disappearance of the lesion in all cases. We conclude that the hyperintense globus pallidus is secondary to the severity of the liver disease, and is reversible when liver function returns to normal.
Adult↗
Sonographic diagnosis and hemodynamic correlation in veno-occlusive disease of the liver.
This study evaluated the role of duplex Doppler sonography in the diagnosis of VOD of the liver after bone marrow transplantation. Sixteen patients with clinical criteria of VOD were studied. The final diagnosis was achieved by transjugular liver biopsy, and the hepatic venous pressure gradient was measured during the procedure to estimate portal pressure. Nine patients (56.2%) had histologically proved VOD. Gallbladder wall thickening was present in 75% of patients with VOD, but in none of those without it (P = 0.01). Gallbladder wall thickening and ascites were present only in patients with portal hypertension. Nine patients (five with VOD and four without it) also were evaluated with duplex Doppler sonography, and no obvious flow abnormalities were detected in the portal vein and hepatic veins. These results suggest that sonography is useful in detecting early signs of portal hypertension pointing to the diagnosis of VOD in patients with bone marrow transplantation.
Adolescent↗