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Biomedical subjects

R E Stauber

Publications and source records attributed to R E Stauber.

At least 37 records · Page 2Linked to original sources

Vasodilator responses to nitric oxide are enhanced in mesenteric arteries of portal hypertensive rats.

Nitric oxide (NO) is discussed as a mediator of the splanchnic hyperaemia in portal hypertension. We assessed the vasorelaxation by the NO-dependent vasodilator acetylcholine, the NO donor 3-morpholino-sydnonimine (SIN-1) and forskolin, a stimulator of the adenylate cyclase pathway in potassium-preconstricted isolated perfused mesenteric arteries of portal vein-ligated and sham-operated rats. Dilator responses to acetylcholine and SIN-1 were significantly enhanced in vessels of portal vein-ligated rats as compared to sham-operated rats, whereas no difference was found in forskolin-induced vasodilatation. This suggests enhanced reactivity of the vasculature to NO in experimental portal hypertension.

Acetylcholine↗

Increased carbohydrate-deficient transferrin during pregnancy: relation to sex hormones.

Controversy exists whether carbohydrate-deficient transferrin (CDT) is valuable as a screening tool for fetal alcohol syndrome. We evaluated serum CDT in 60 non-alcohol-abusing women at different stages of normal pregnancy. CDT was weakly related to week of pregnancy and to human placental lactogen. CDT did not correlate with iron oestradiol or progesterone. By contrast, good correlations were found between transferrin and week of pregnancy or either sex hormone. Using multiple linear regression analysis, only transferrin and week of pregnancy were important predictors of CDT. The diagnostic accuracy of CDT for detecting alcohol abuse may be limited in pregnant women and should be carefully assessed in relation to alcohol consumption.

Estradiol↗

Divergent effects of propranolol and nadolol in isolated mesenteric arteries from normal and portal hypertensive rats.

Propranolol, a non-selective beta-blocker, is used for treatment of portal hypertension as it is believed to diminish splanchnic blood flow both by reducing cardiac output (beta(1)-blockade) and by increasing splanchnic arteriolar resistance (beta(2)-blockade). However, possible vasodilatory properties of propranolol at higher concentrations may counteract splanchnic vasoconstriction. Nadolol, another nonselective beta-blocker, has also been suggested for treatment of portal hypertension. The aim of the present study was to investigate the effects of various concentrations of propranolol and nadolol on vascular resistance in isolated perfused mesenteric arterial beds from normal and portal hypertensive rats. At concentrations of 10(-7) mol L-1 to 10(-6) mol L-1 neither propranolol nor nadolol changed pressor responses to noradrenaline in normal rats. However, nadolol 10(-5) mol L-1 significantly increased, whereas propranolol 10(-5) mol L-1 reduced, noradrenaline-induced vasoconstriction both in normal and in portal hypertensive rats. This unexpected vasodilatory effect of propranolol at high concentrations was present in preparations stimulated by both noradrenaline and methoxamine but not vasopressin and thus may be due to competitive alpha-receptor blockade. In contrast, nadolol lacked this effect and produced splanchnic arteriolar vasoconstriction at high concentrations also.

Adrenergic beta-Antagonists↗

Carbohydrate-deficient transferrin in healthy women: relation to estrogens and iron status.

The determination of carbohydrate-deficient transferrin (CDT) in serum has been found useful as a marker of increased alcohol consumption of > 60 g/day. It is not clear why the reference range is different for women (0 to 26 units/liter) and men (0 to 20 units/liter). We evaluated serum CDT in 286 healthy subjects (209 women, 77 men) using a commercially available radioimmunoassay. Premenopausal women had higher CDT levels than postmenopausal women, whereas no age-related difference of CDT levels was found in men. In postmenopausal women, higher CDT levels were associated with estrogen replacement therapy. In premenopausal women, however, neither the phase of the menstrual cycle nor contraceptive steroid use showed a significant association with the increase in CDT levels. No significant correlations were found between CDT and either serum estradiol or serum iron. In conclusion, both premenopausal state and postmenopausal estrogen replacement therapy seem to increase serum levels of CDT. Therefore, menopausal status and exogenous estrogens should be considered when interpreting CDT values in women.

Adult↗

Propranolol stereoselectively inhibits alpha-adrenoceptor-mediated vasoconstriction in mesenteric arterial beds of rats.

1. The optical isomers of propranolol were compared for their effects on pressor responses to adrenergic and non-adrenergic vasoconstrictors in mesenteric arterial beds of rats. 2. R(+)-propranolol (10(-7)-10(-5) M) had no effect on vessel preparations stimulated with noradrenaline, methoxamine, or arginine-vasopressin. 3. S(-)-propranolol 10(-7) M did not alter pressor responses to noradrenaline. However, S(-)-propranolol 10(-6) and 10(-5) M inhibited vasoconstriction induced by noradrenaline. This effect was similar in the presence of indomethacin 3 x 10(-6) M. 4. S(-)-propranolol 10(-5) M also inhibited vasoconstriction induced by methoxamine, shifting the dose-response curves to the right, but did not affect pressor responses to arginine-vasopressin. 5. Schild analysis for equilibrium vasoconstrictor responses to methoxamine indicated stereoselective competitive alpha-adrenoceptor antagonism by propranolol. 6. These data suggest selective inhibition of alpha-adrenoceptor-mediated vasoconstriction by S(-)-propranolol at higher concentrations by competitive alpha-adrenoceptor antagonism.

Adrenergic alpha-Agonists↗

The role of inducible nitric oxide synthase in vascular hyporeactivity of endotoxin-treated and portal hypertensive rats.

The involvement of the inducible nitric oxide (NO) synthase in the vascular hyporeactivity in portal vein-ligated rats was assessed in isolated perfused mesenteric arterial beds. Aminoguanidine, a selective inhibitor of the inducible NO synthase, restored the pressor responses to methoxamine in arteries of endotoxin-treated rats, but was ineffective in hyporeactive portal vein-ligated vessels. NG-Nitro-L-arginine methyl ester enhanced the responsiveness both in portal vein-ligated and sham-operated rats, without changing the difference between the two groups. These results not only indicate that the inducible NO synthase is not involved in the hyporeactivity to methoxamine in mesenteric arteries of portal hypertensive rats, but also suggest a role for factors other than NO.

Amino Acid Oxidoreductases↗

Laparoscopic diagnosis of peritoneal serous papillary carcinoma.

Peritoneal serous papillary carcinoma is a rare primary tumor of the peritoneum. We report here a case diagnosed by laparoscopy, and summarize the clinicopathological features previously reported in patients with this tumor. Laparoscopy was performed in a 66-year-old woman with high-protein ascites and a three-month history of lower abdominal pain. Macroscopically, the parietal and visceral peritoneum was studded with prominent white nodules up to 5 mm in diameter. Multiple biopsies revealed a tubulopapillary serous adenocarcinoma. After exclusion of metastatic peritoneal carcinomatosis (especially ovarian cancer) and malignant mesothelioma, the diagnosis of peritoneal serous papillary carcinoma was established. The patient was placed on chemotherapy (first-line: 5-fluorouracil, adriamycin, and mitomycin C; second-line: paclitaxel). She died 22 months after diagnosis. The present case is also remarkable for the coexistence of granulomatous peritonitis overshadowing the malignant nature of the process. This case report emphasizes the importance of laparoscopy with multiple biopsies in the workup of undetermined exudative ascites.

Aged↗

Recurrent Salmonella enteritidis sepsis and hepatic tuberculosis.

A 33 year old woman with recurrent Salmonella enteritidis sepsis is described. Penicillins, ceftriaxone, ciprofloxacin, and chloramphenicol could not eradicate the salmonellas but a combination of high dose ciprofloxacin and ceftriaxone for the eighth episode successfully cured the infection. The combination of ciprofloxacin and ceftriaxone may be a valuable therapeutic regimen in patients with recurrent salmonella sepsis. Prolonged intrahepatic cholestasis resulting from granulomatous hepatitis in this patient improved considerably with empiric ursodeoxycholic acid treatment. A liver biopsy specimen showing non-caseating epitheloid granulomas was positive for mycobacterial DNA by polymerase chain reaction. Repeated bronchoscopy with multiple biopsies eventually revealed caseating granulomas with acid fast bacilli in the lung biopsy specimens. Therefore, tuberculosis was diagnosed as the underlying disease and the cause of granulomatous hepatitis in this patient and tuberculostatic treatment was started. Polymerase chain reaction for mycobacterial DNA may be helpful in the differential diagnosis of hepatic granulomas when routine histological examination and culture of biopsy specimens are not diagnostic. Tuberculosis should be considered as one of the diseases predisposing to recurrent salmonella sepsis.

Adult↗

Evaluation of carbohydrate-deficient transferrin for detection of alcohol abuse in patients with liver dysfunction.

The determination of carbohydrate-deficient transferrin (CDT) in serum has been suggested as a marker of alcohol abuse. We evaluated serum CDT in 199 patients admitted to our Department of Medicine using a commercially available radioimmunoassay kit for CDT. A history of alcohol consumption was obtained quantitatively by a self-administered questionnaire and qualitatively by the Munich Alcoholism Test. Using a cut-off level of 60 g ethanol per day according to the information from the questionnaire. CDT had a sensitivity of 70% and a specificity of 84%. False-positive values were primarily encountered in cases of hepatic malignoma, primary biliary cirrhosis and chronic hepatitis C. The sensitivity and specificity of CDT was superior to two other markers of chronic ethanol consumption, serum gamma-glutamyltransferase and mean cell volume, and thus proved to be the best single laboratory test for the detection of alcohol abuse.

Biomarkers↗

Glomerulonephritis as late manifestation of severe alpha 1-antitrypsin deficiency.

An association of alpha 1-antitrypsin deficiency with glomerulonephritis is rare and has so far been observed only in children or young adults. We report a 63-year-old man with severe alpha 1-antitrypsin deficiency associated with pulmonary emphysema, cirrhosis of the liver, and mesangioproliferative glomerulonephritis with nephrotic syndrome. Following initial presentation with nephropathy, further work-up revealed alpha 1-antitrypsin deficiency of proteinase inhibitor Z. In the absence of glomerular alpha 1-antitrypsin deposits the relationship between renal disease and alpha 1-antitrypsin deficiency remains unclear. alpha 1-Antitrypsin deficiency should be considered in adults with abnormal renal function and chronic liver disease.

Fatal Outcome↗

Effect of isolated portal hypertension on Kupffer cell function.

The increased incidence of infection in cirrhotics may in part be attributable to dysfunction of the reticuloendothelial system (RES) in removing pathogens from the circulation. The portosystemic shunting (PSS) that results from portal hypertension in cirrhotics may compromise RES function by allowing enteric pathogens to be shunted away from the Kupffer cells. A well-characterized model of portal hypertension induced by partial portal vein ligation (PVL), in which there is no hepatic parenchymal cell damage, was used. Kupffer cell function is unaltered and the effect of PSS alone on overall RES function can be evaluated. In addition to the usual immunologically inert [99mTc]sulfur colloid, an actual pathogen was also evaluated. PVL and sham-ligated rats were given either [99mTc]sulfur colloid or E. coli via the ileocolic vein. The right femurs, lungs, livers and spleens of the animals receiving 99mTc were excised and the radioactivity counted. The lungs, livers, and spleens of the animals receiving E. coli were liquefied and the bacteria were quantified. For both groups the ratios of 99mTc or E. coli in the lung, spleen, and femur to liver were calculated. PVL rats had significantly more 99mTc in the lung, spleen, and femur than the sham rats. There were also significantly more E. coli in the lungs for PVL rats but no significant difference in the spleen counts. These results imply that even in the absence of Kupffer cell dysfunction, PSS alters reticuloendothelial system function by causing a greater distribution of pathogens to the periphery. This altered distribution may contribute to an increased susceptibility to infection in cirrhotics.

Animals↗

Carcinoembryonic antigen, cytokeratin expression and mucin composition in hyperplastic and neoplastic polyps of the colorectum.

We examined the expression of carcinoembryonic antigen (CEA) and cytokeratin (CK) as well as the sialo- and sulphomucin content of 40 hyperplastic polyps (HPs), 6 mixed hyperplastic-adenomatous polyps, 30 adenomas and 40 adenocarcinomas of the colorectum. HPs showed a positive CEA expression in 95% of cases and a decreased sialo- and sulphomucin content compared with normal mucosa. Similar changes were observed in adenomas with low-grade dysplasia. The increase in CEA expression from HPs and adenomas to carcinomas was accompanied by a reduction of sialo- and sulphomucins with about three fourths of carcinomas being sialo- and sulphomucin negative. Oncofetal antigen expression concomitant with mucin changes observed in HPs may indicate impaired cellular maturation at a functional level before dysplastic changes become visible. CEA and CK positive macrophages were found in carcinomas predominantly at sites of tumor disruption and necrosis as well as within veins and lymphatic vessels. Our findings suggest that macrophages may play a role in CEA and CK release into the circulation and thus may be determinants of tumor marker serum levels.

Adenocarcinoma↗

Assessment of the estrogenic activity of phytoestrogens isolated from bourbon and beer.

Phytoestrogenic substances have previously been isolated and identified in two alcoholic beverages: bourbon and beer. To delineate the relative potencies of the estrogenic substances of plant origin thus far identified in these commonly consumed alcoholic beverages, we evaluated the ability of biochanin A, beta-sitosterol, genistein, and daidzein to bind to cytosolic estrogen receptor binding sites. The in vitro studies demonstrated that each of the contained substances was capable of effectively competing for cytosolic estrogen receptor binding sites of rat liver and uterus. Further, the two phytoestrogenic constituents of bourbon, beta-sitosterol and biochanin A, were less potent than those present in beer. Given the high concentration of beta-sitosterol in bourbon, we chose to evaluate the estrogenicity of beta-sitosterol in vivo using ovariectomized rats. beta-sitosterol was administered either daily or intermittently at 3 doses, based on amounts previously determined to be present in bourbon. The in vivo studies demonstrated that beta-sitosterol is capable of producing a weak estrogenic effect only at the lowest dose (6.2 micrograms/dl) administered intermittently. These responses suggest that beta-sitosterol may be weakly estrogenic at low doses, but is unable to maintain such an effect at higher doses.

Alcoholic Beverages↗

[Indications for liver transplantation in neoplasms of the liver].

Orthotopic liver transplantation for hepatic neoplasms is controversial. In the past, liver transplantation was utilized to treat various advanced hepatic neoplasms such as hepatocellular carcinoma including the fibrolamellar variant, cholangiocellular carcinoma, epithelioid hemangio-endothelioma, and liver metastases. In many cases, total hepatectomy with orthotopic liver replacement is the only treatment option with intent to cure because of reduced liver function in cirrhotic patients limiting resectability. On the other hand, results of transplantation are poor; for hepatocellular carcinoma, the 5-year-survival probability averages only 20%. Thus, hepatic neoplasms have to compete with benign liver diseases for a limited supply of donor organs. However, success rates of liver transplantation were higher for fibrolamellar carcinoma and for epithelioid hemangioendothelioma. New treatment strategies for hepatocellular carcinoma including neoadjuvant chemotherapy and chemoembolization are currently being investigated. Results of liver transplantation for cholangiocellular carcinoma or hepatic metastases have been disappointing. Single cases have been successfully treated with the "cluster operation" designed by Starzl in 1988.

Adenoma, Bile Duct↗

The use of quantitative scintigraphy in the measurement of portal-systemic shunting in rats.

Portal-systemic shunting was studied in 54 portal hypertensive rats both in vivo and in vitro using radioactive microspheres. The animals underwent partial portal vein ligation around needles of varying diameter to produce a wide range of shunting. Two to four weeks later, quantitative lung-liver scintigraphic and whole body images were obtained in vivo following ileocolic vein injection with 99mTc-MAA. After sacrifice, the lung and liver activities were determined by the gamma camera, a dose calibrator, and a well counter. Portal-systemic shunting ranged from 0.1-97.6%. When shunting was compared in vivo and in vitro, an excellent correlation was found (r = 0.99, p < 0.001). A subgroup of 24 animals had consecutive injections of 99mTc-MAA and 51Cr-labeled 15 microns microspheres, which, although different in size, yielded similar results (r = 0.89, p < 0.001). We conclude that in small laboratory animals a wide range of shunting can be measured accurately in vivo by quantitative scintigraphy.

Animals↗

Evaluation of portal-systemic shunting in rats from mesenteric and splenic beds.

In rats with partial portal vein ligation, 95 +/- 0.9% of the splenic blood flow is shunted from the portal to the systemic circulation when an intrasplenic injection of microspheres is used to determine the degree of shunting. Despite this magnitude of portal-systemic shunting, several biochemical and endocrine consequences of portal-systemic shunting occur at levels below what is expected for the degree of shunting found. In an effort to resolve these discordant findings, shunting from both the splenic and the mesenteric bed was studied in anesthetized portal hypertensive rats with various degrees and/or duration of portal vein stenosis. The shunting from the mesenteric bed averaged 66.7 +/- 29.9% (range 5.1-99.1%) and was influenced both by the degree and duration of portal vein stenosis. In contrast, shunting from the splenic bed averaged 97.3 +/- 4.0% (range 79-99.9%) and demonstrated no variation between groups determined by the degree of portal vein stenosis. The shunting from the splenic bed was consistently greater than that found from the mesenteric bed. Mesenteric but not splenic shunting correlated with serum bile acid levels. Mesenteric shunting was related inversely to the weight-adjusted liver mass and to serum testosterone levels. Based upon these data obtained in portal hypertensive rats, it is concluded that splenic injections of microspheres overestimate portal-systemic shunting. In contrast, mesenteric injections of microspheres yield values for shunting that correlate well with independently determined biochemical and endocrine consequences of shunting. These observations support the validity of the mesenteric shunting measurements obtained.

Animals↗

The effect of portal-systemic shunting on hepatic sex hormone receptors in male rats.

Signs of feminization are seen in men with cirrhosis of alcoholic but also of nonalcoholic origin even in the absence of markedly increased plasma estrogen levels. Recently identified alterations of hepatic sex hormone receptor levels have provided a hypothetical mechanism for the pathogenesis of the feminization seen in cirrhotic men. The aim of the present study was to determine the effect of experimental portal-systemic shunting in adult male rats on hepatic sex hormone receptor levels, plasma sex hormones, and two markers for sex hormone action in the liver. The following alterations were found in male rats with surgically created portacaval shunts compared with sham-operated controls: the hepatic content of cytosolic estrogen receptors was reduced by 35% and the cytosolic androgen receptors content by 59%; plasma levels of estradiol increased 6.7-fold while those of testosterone were reduced by 71%; the estrogen-responsive ceruloplasmin levels were decreased by 31% and the androgen-responsive male-specific estrogen binder by 72%. Based on these data, it can be concluded that portal-systemic shunting reduces the hepatic cytoplasmic content of several sex hormone related proteins. These changes are paralleled by a decreased estrogen responsiveness of the liver, as evidenced by the plasma ceruloplasmin level.

Animals↗

Orthotopic liver transplantation for alcoholic liver disease.

Alcohol abuse is the most common cause of end-stage liver disease in the United States, but many transplant centers are unwilling to accept alcoholic patients because of their supposed potential for recidivism, poor compliance with the required immunosuppression regimen and resulting failure of the allograft. There is also concern that alcohol-induced injury in other organs will preclude a good result. From July 1, 1982, to April 30, 1988, 73 patients received orthotopic liver transplants at the University of Pittsburgh for end-stage alcoholic liver disease. Fifty-two (71%) of these were alive at 25 +/- 9 mo (mean +/- S.D.) after transplantation, when a phone survey of these patients, their wives/husbands, and their physicians was performed to evaluate their subsequent use of alcohol, current medical condition and employment. Data obtained were compared with those for nonalcoholic patients selected as transplant controls. The recidivism rate has been 11.5%, with most patients drinking only socially. Fifty-four percent of the survivors are employed, 21% classify themselves as homemakers and only 11 (21%) are unable to work. Twenty-one patients died after transplantation; the most frequent cause of death was sepsis (43%), and intraoperative death was the next most common cause (28.6%). These data demonstrate that alcoholic patients can be transplanted successfully and achieve good health not significantly different from that of individuals transplanted for other causes. Thus orthotopic liver transplantation is a therapeutic option that should be considered for individuals with end-stage alcoholic liver disease who desire such therapy.

Alanine Transaminase↗