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Biomedical subjects

J S Gavaler

Publications and source records attributed to J S Gavaler.

At least 19 recordsLinked to original sources
PubMed1992

31P-NMR spectroscopy of perifused rat hepatocytes immobilized in agarose threads: application to chemical-induced hepatotoxicity.

A system consisting of isolated rat hepatocytes immobilized in agarose threads continuously perifused with oxygenated Krebs-Henseleit (KH) solution has been found to maintain cell viability with excellent metabolic activity for more than 6 h. The hepatocytes were monitored by phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy at 4.7 Tesla, by measurement of oxygen consumption and by the leakage of lactate dehydrogenase (LD) and alanine aminotransferase (ALT). The data obtained were comparable to those found for an isolated perfused whole liver in vitro. The effects of allyl alcohol (AA), ethanol, and 4-acetaminophenol (AP) were examined. A solution of 225 microM AA perifused for 90 min caused the disappearance of the beta-phosphate resonance of adenosine triphosphate (ATP) in the 31P-NMR spectra, a 7-fold increase in LD leakage and a 70% reduction in oxygen consumption. Ethanol (1.0 M) perifused for 90 min reduced the beta-ATP signal intensity ratio by 20%, the phosphomonoester (PME) signal by 50% and inorganic phosphate (Pi) by 33% (P less than 0.05). AP (10 mM) caused only mild liver-cell damage. The results demonstrate that perifused immobilized hepatocytes can be used as a liver model to assess the effects of a wide range of chemicals and other xenobiotics by NMR spectroscopy.

Animals↗
PubMed1992

Lack of increase in heterozygous alpha 1-antitrypsin deficiency phenotypes among patients with hepatocellular and bile duct carcinoma.

Homozygous alpha 1-antitrypsin deficiency (PiZZ phenotype) is known to be associated with increased risk of cirrhosis and primary liver cancer. Although a relationship between heterozygous alpha 1-antitrypsin deficiency and chronic liver disease was suggested recently, it is still a matter of controversy whether such patients are at increased risk of liver cancer. The goal of this study was to determine the prevalence of heterozygous alpha 1-antitrypsin deficiency of different phenotypes among patients with primary hepatobiliary cancers. We studied 82 patients with primary hepatobiliary cancer; 59 had hepatocellular carcinoma and 23 had bile duct carcinoma. alpha 1-Antitrypsin quantitation and phenotyping were performed in each patient using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds-ratio and chi 2 tests were used to measure the relative risk and the significance of association, respectively, between primary hepatobiliary cancers and heterozygous alpha 1-antitrypsin deficiency. Four patients in each of the cancer groups were heterozygous. Among the hepatocellular carcinoma patients, three had the PiMS phenotype and one had the PiMZ phenotype. Of these four heterozygous patients, only two had cirrhosis; one had cryptogenic cirrhosis and the other had hepatitis B virus-related cirrhosis. One noncirrhotic patient with a PiMZ phenotype had a fibrolamellar carcinoma. Of the four patients with bile duct carcinoma, three had the PiMS phenotype and one had the PiMZ phenotype. Of the four heterozygous patients, two had primary sclerosing cholangitis without associated inflammatory bowel disease and one patient had had previous biliary operations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Bile Duct↗
PubMed1992

Association between heterozygous alpha 1-antitrypsin deficiency and genetic hemochromatosis.

Primary hemochromatosis is a genetically determined autosomal recessive disorder characterized by the excessive accumulation of body iron, most of which is deposited in the parenchymal cells of various organs. alpha 1-Antitrypsin deficiency is characterized among others by defective secretion of alpha 1-antitrypsin from liver cells. Whereas the risk of cirrhosis is increased in homozygous patients (PI ZZ) and possible in heterozygous patients (non-PI MM) as well, a greater risk for hepatocellular carcinoma has been suggested only in homozygous patients. Because these two metabolic disorders are relatively common, it has been difficult to determine whether they are associated with each other. In this study, we tried to determine the relationship between these two disorders using the case material seen at the University of Pittsburgh during a 7-yr period. We studied 15 patients with genetic hemochromatosis. alpha 1-Antitrypsin quantitation and phenotyping were performed in each case using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds ratio and chi 2 tests were used to measure the relative risk and significance of association, respectively. Eleven patients (73%) were found to be PI M and four (27%) were identified as being heterozygotes: three (20%) were PI MZ, and one (7%) was PI MS. The prevalence of the PI MS phenotype was similar to that in the general population (7% vs. 6.4%; NS). The PI MZ phenotype, however, was statistically more common in patients with hemochromatosis than in the general population (20% vs. 2.2%; p less than 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Hormonal status of postmenopausal women with alcohol-induced cirrhosis: further findings and a review of the literature.

The derangements of levels of sex hormones and gonadotropins in alcoholic cirrhotic men are well delineated. The countersituation in alcoholic cirrhotic women has not yet been fully described. This study was performed in postmenopausal women among whom menstrual cycle variations in hormones no longer occur; with such a study population, it is possible to control for confounding factors and thus optimize detection of differences in levels of hormones and hormone interrelationships. Both estradiol levels and a rough estimate of aromatization of testosterone to estradiol, the estradiol to testosterone ratio, were significantly elevated in the 20 alcoholic subjects with alcohol-induced cirrhosis, as compared with the 27 normal controls; similarly, testosterone, luteinizing hormone and follicle-stimulating hormone were all significantly reduced in the alcoholic cirrhotic women. In addition, the normal relationships of estradiol with luteinizing hormone, follicle-stimulating hormone, body mass and the estradiol/testosterone ratio were detected in the control group but not in the group of cirrhotic women. Further, among the alcoholic cirrhotic postmenopausal women, testosterone, luteinizing hormone, follicle-stimulating hormone and the estradiol/testosterone ratio were all significantly correlated with the Child's liver disease severity score. That the hormone levels and their interrelationships differ markedly between normal and alcoholic cirrhotic women extends previous findings in both men and postmenopausal women; the correlations of hormone levels and markers of liver disease will require further investigation.

Body Mass Index↗
PubMed1992

Response to HBV vaccination in patients with severe liver disease. Absence of an HLA effect.

HLA antigen profiles have been used to identify individuals who are likely not to respond to HBV vaccination. The majority of these reports have included either normal individuals or individuals with severe abnormalities of their immune system. The present investigation assessed the rate of HBV vaccination seroconversion in 132 individuals with chronic advanced liver disease who were referred for possible liver transplantation. Each was vaccinated using a serum-derived vaccine administered intramuscularly at three consecutive monthly clinic visits. As part of their transplant evaluation, each subject also underwent HLA typing for class I and class II antigens. Of the 132 subjects vaccinated, only 47% seroconverted and became HBsAb positive. There was no difference between types of liver disease. As expected, individuals older than 55 years of age responded less well than those younger than this cutoff age. No difference between seroconverters and nonresponders was evident for gender or any individual or combination of HLA antigens. In conclusion, individuals with advanced chronic liver disease seroconvert less often in response to HBV vaccination than do normal individuals. Moreover, unlike normals and the experience with other disease groups, no difference in conversion rates was evident for gender. Similarly, no difference in seroconversion rates was evident for the two major pathophysiologic types of chronic liver disease. Age greater than 55 years was associated with a reduced rate of seroconversion.

Chronic Disease↗
PubMed1992

Response to hepatitis B vaccination by liver transplant candidates.

Liver transplantation (OLTx) is a procedure offered to individuals with advanced liver disease who are expected to live less than a year. Despite improvement in the care of transplant recipients, these patients are exposed to large volumes of blood and, as a result, are at risk to acquire hepatitis. Currently, the only vaccines available for the prevention of hepatitis are those that induce a response to HBsAg. In this study, 144 patients awaiting OLTx and 15 controls were vaccinated three times, once a month, intramuscularly in the deltoid using the Merck Hepatovax plasma-derived vaccine. This schedule was continued regardless of whether or not OLTx occurred before the series was completed. For the 15 controls, the response rate was 93% and for individuals with end-stage liver disease, it ranged from 44 to 54% (P less than 0.004). No difference in the percentage of those developing antibody was detected between groups based upon disease indication or whether the vaccination series was completed before or after OLTx. Of the following: WBC, lymphocytes (percent and number), CD3+ cells (percent and number), CD4+ cells (percent and number), CD8+ cells (percent and number), CD4+/CD8+ ratio, and B cells (percent and number), only the absolute WBC (P less than 0.05) distinguished between those who did and did not develop antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Prevalence of hepatitis C virus antibody in a liver transplantation population.

The development of a serologic assay to detect antibodies directed at an antigen (C-100-3) of the hepatitis C virus (anti-HCV) has been a major breakthrough in the long search for causative agents of non-A, non-B (NANB) hepatitis. The frequency of HCV in those who have end-stage liver disease is not known. Moreover, the rate of recurrence after liver transplantation (OLTx) and the rate of acquisition of new HCV infection as a result of the OLTx experience is as yet unknown. This study was performed in an attempt to answer these questions. The prevalence of HCV in 372 patients undergoing OLTx at the University of Pittsburgh was determined. Those transplanted for HBV-related liver disease with hepatoma had the highest rate of HCV antibody positivity (45.4%) followed by those with metabolic liver disease (42.5%), putative NANB liver disease (41.4%), and cryptogenic cirrhosis (20.9%); those with cholestatic liver disease exhibited the lowest rate (16.2%). HCV antibody was positive in only 26.3% of patients with hepatoma. Of those patients who were negative prior to transplantation, 12.2% acquired HCV antibody post-OLTx. In the putative NANB group, no difference was detected in the AST and ALT prior to transplantation in either the HCV antibody-positive or -negative patients. In patients with cryptogenic cirrhosis, those who were positive for HCV antibody had higher transaminase levels prior to transplantation than did those patients who were HCV antibody negative.

Blood Transfusion↗
PubMed1992

Incidence, prevalence, and clinical course of hepatitis C following liver transplantation.

Hepatitis C virus (HCV) is the agent responsible for posttransfusion hepatitis. The incidence, timing, and clinical course of HCV positive hepatitis in liver transplant recipients are unknown. Three hundred and seventeen donor-recipient liver transplant pairs were grouped on the basis of their pretransplant HCV antibody status. The biopsy findings were examined. Four distinct groups were identified on the basis of HCV serology: group I, both were negative; group II, donor was negative and recipient was positive; group III, donor was positive and recipient was negative; group IV, both were positive. The prevalence of anti-HCV positivity in recipients was 13.6%. The rate of seroconversion was 9.2%. Histologic hepatitis not ascribable to any specific cause other than non-A, non-B (NANB) hepatitis occurred in 13.8%. The incidence of histologic chronic active hepatitis was 1.6%, and none progressed to cirrhosis. The concordance rate for a positive anti-HCV serology and NANB hepatitis was 2.8%. Of the 35 patients (group II and IV) with positive anti-HCV serology pretransplant, only 17 were positive posttransplantation. Based on these data it can be concluded that posttransplant NANB hepatitis occurred in 13.8% of liver recipients. Twenty percent of these were anti-HCV positive. Progression to histologic chronic active hepatitis occurs over a period of 1-5 years in 1.6% of cases.

Adolescent↗
PubMed1992

Bacteriuria in patients with cirrhosis.

The prevalence and bacteriology of bacteriuria was studied in 140 patients with cirrhosis of the liver, referred to the University of Pittsburgh Medical Center for evaluation for liver transplantation (72 males and 68 females; mean age 46 years). Urine samples were obtained for cultures within 24 h after admission. Significant bacteriuria (SB) (> 10(5) bacteria/ml) was present in 25 patients (18%), the most common being E. coli (36%) and coagulase-negative staphylococcus (20%). SB was more common in females than in males (32 vs. 4%, p < 0.001), and was seen in every category of cirrhosis. The occurrence of bacteriuria did not correlate with the severity of the underlying liver disease or with the age of the patient. Based upon these results, it can be concluded that: (1) bacteriuria is common in patients with advanced liver disease and occurs in approximately 20% of the cases; (2) it is more common in females than in males; and (3) its prevalence in patients with primary biliary cirrhosis is similar to that in other types of chronic advanced liver disease.

Adult↗
PubMed1992

Preliminary experience with alpha-2b-interferon therapy of viral hepatitis in liver allograft recipients.

Currently, alpha interferon is the only recognized therapy for chronic viral hepatitis. As a result of its success in several multicenter trials, the agent was approved recently by the FDA for use in the clinical management of patients with chronic hepatitis C. FDA approval for its use in chronic hepatitis B is anticipated. Based upon this experience in nonimmunosuppressed individuals, the efficacy of alpha interferon therapy in patients who are recipients of liver allografts and are receiving chronic immunosuppression was assessed in a preliminary trial of the agent in 30 patients (13 with HBV, 11 with HCV, and 6 with hepatitis non A, non B, non C). Therapy was initiated at a dose of 3 X 10(6) units three times per week and continued for 6 months. Dose reduction in the amount of the alpha interferon administered was determined by a preestablished protocol. Nine percent of those with HCV and 18% of those with hepatitis non A, non B, non C experienced a full response to alpha interferon therapy. No full responses to alpha interferon therapy. No full responses were seen in those with HBV disease. Partial responses were common in all three groups but were most frequent in those with hepatitis non A, non B, non C and least frequent in those with HCV-related disease. This preliminary experience demonstrates the following: 1. Viral hepatitis following OLTx can be treated with alpha-2b-interferon. 2. The complications of alpha-2b-interferon therapy utilized prior to OLTx can be avoided by giving the therapy following successful OLTx. 3. The high rate of partial responses noted suggests that future studies should utilize either higher doses or longer durations of therapy or both. 4. The response rate was greatest for those having non A, non B, non C hepatitis and least for those with HCV hepatitis. 5. In this small preliminary series, no episodes of liver graft rejection could be ascribed to the use of alpha-2b-interferon in the patients so treated.

Hepatitis C↗
PubMed1992

Cytomegalovirus infection and gastric emptying.

Gastrointestinal infection due to cytomegalovirus occurs frequently in liver transplant recipients. Upper gastrointestinal cytomegalovirus infection is associated with subjective complaints of nausea, a sense of abdominal fullness, and occasionally emesis and/or dysphagia. In order to determine whether these symptoms reflect a disruption of the normal motility of the stomach, the following study was performed. Eleven individuals who were evaluated for liver transplantation were prospectively recruited and studied as follows: (1) upper gastrointestinal endoscopy with biopsy of the gastric antral mucosa; (2) viral culture of the gastric mucosa; (3) a histologic examination of the gastric mucosa; and (4) a radionuclide gastric emptying study was obtained before and 4-8 weeks following successful liver transplantation. Prior to liver transplantation, none had symptoms of nausea, vomiting, or epigastric fullness. All were culture-negative for cytomegalovirus. All had endoscopic and histologic evidence of portal hypertensive gastropathy but none had antral erosions or ulcers. All demonstrated normal gastric emptying of a liquid meal. Following liver transplantation, 6 remained free of gastric cytomegalovirus while 5 developed a culture-confirmed gastric cytomegalovirus infection. Those that developed a gastric cytomegalovirus infection also had more gastric symptoms, and more gastric histologic abnormalities. Moreover, those with a gastric cytomegalovirus infection demonstrated enhanced gastric retention of a liquid meal (P less than 0.01).

Adult↗
PubMed1992

The association of IgA deficiency but not IgG or IgM deficiency with a reduced patient and graft survival following liver transplantation.

Recipients of solid organ allografts require lifelong immunosuppression in order to prevent graft rejection and to maintain graft function. In general, such immunosuppression greatly impairs the cellular immune system, as this level of the immune system is principally responsible for self and non-self recognition. The consequences of allograft transplantation in terms of patient and graft survival when transplants are given to individuals who have a preexisting humoral immune deficiency characterized by a deficiency of the serum levels of one or more of the major Ig classes have not yet been reported. From February 1, 1981 through December 31, 1990, a total of 43 adult patients with a deficiency of 1 or more Ig classes received a ABO-matched liver allograft at this institution. This sample represents 2.5% of a total of 1684 adults transplanted during this interval. These 43 liver graft recipients could be divided into 3 major groups based upon the presence of an IgG, IgM, or IgA deficiency. IgG deficiencies were defined as levels less than 50 mg/dl. Patient and graft survival for the IgA-deficient group was significantly reduced (P less than 0.04 and P less than 0.009, respectively) compared with both the IgG- and IgM-deficient groups. The latter two groups did not differ from controls without an Ig deficiency for these same two endpoints. The major causes of death in the IgA-deficient group were sepsis and opportunistic infection. A third of the deaths in the IgA-deficient group occurred in the perioperative period (first 30 days) while greater than 50% of the deaths occurred within the first 3 months, and all deaths occurred before the first year. Based upon these data, the following conclusions can be made: (1) serum IgA deficiency but not IgG or IgM deficiency is associated with an increased post-OLTx death and graft loss rate; (2) the majority of these deaths are due to sepsis or an opportunistic infection; and (3) most of the deaths occur early. These data suggest that recognition of a deficiency of IgA prior to organ grafting necessitates meticulous attention to the prevention of infection in the immediate perioperative period if patient and graft survival of these patients is to be improved.

Adult↗
PubMed1992

The association between moderate alcoholic beverage consumption and serum estradiol and testosterone levels in normal postmenopausal women: relationship to the literature.

The major source of endogenous estrogens in postmenopausal women is the aromatization of androgens to estrogens; because alcohol is known to increase aromatization, the relationship between moderate alcoholic beverage consumption and serum estradiol levels was evaluated in 128 normal postmenopausal women. Alcohol intake was based on a composite of self-report and food record information. Among the 78.8% of women reporting alcohol use, weekly intake was 4.8 +/- 0.6 drinks. Among abstainers, estradiol levels were 100.8 +/- 12.1 pmol/liter, significantly lower than in alcohol users, 162.6 +/- 11.9 pmol/liter. Significant bivariate correlations were found between the logarithm of estradiol and total weekly drinks. In multiple linear regression analyses inclusion of alcohol as a variable increased the amount of explained variation in estradiol. Similar findings were demonstrable when the crude estimator of aromatization, the estradiol:testosterone ratio logarithm was the dependent variable. Together, these findings suggest that moderate alcohol use is an important factor for postmenopausal estrogen status and may offer a partial explanation for the reported protective effect of moderate alcohol consumption with respect to postmenopausal cardiovascular disease risk.

Alcohol Drinking↗
PubMed1992

Isolation and identification of phytoestrogens from beer.

Two estrogenic substances of plant origin have been identified in beer using gas chromatography/mass spectrometry. These phytoestrogens, daidzein and genistein, have previously been shown to be biologically active in animals. Confirming the presence of biologically active phytoestrogens in beer and their possible presence in other beverages, suggests that there may be clinically significant effects related to sustained exposure to phytoestrogens contained in alcoholic beverages.

Beer↗
PubMed1992

Detection of the relationship between moderate alcoholic beverage consumption and serum levels of estradiol in normal postmenopausal women: effects of alcohol consumption quantitation methods and sample size adequacy.

The purpose of this study was to evaluate the detectability of an effect of moderate alcoholic beverage consumption on the biologic correlate of postmenopausal estradiol levels. Total weekly consumption and beverage-specific intake were assessed using both self-reported usual consumption information and prospective food record data. In terms of total weekly drinks, discrepancies were observed in 35 of the 101 women who reported alcohol use; no consistent pattern of overreporting/underreporting was seen. Although the two alcohol estimates were highly correlated, the relationship between estradiol levels and total weekly alcohol intake was found to be detectable when alcohol consumption based on the food record data was analyzed, but not when the self-report data were examined in a two-tailed hypothesis-testing situation. Evaluating the association between postmenopausal estradiol levels and the two estimates of alcohol intake in random samples of varying sample sizes generated from the mother population of 128 normal postmenopausal women confirmed the finding that the prospectively obtained alcohol data better predict the relationship. Based on the results of this study, it must be concluded that self-reported usual alcohol consumption data must be used with caution when examining an association between alcohol intake and a biologic effect.

Alcohol Drinking↗
PubMed1992

Heatstroke: its clinical and pathological presentation, with particular attention to the liver.

Heatstroke is a potentially fatal disorder caused by an extreme elevation of body temperature. It is the most severe of the illnesses produced as a result of a high ambient temperature; however, it also may occur sporadically among individuals working or exercising in more favorable weather conditions, particularly early in their training before acclimatization occurs. The liver is a common site of tissue injury in cases of heatstroke and can be the site of fatal tissue injury in cases that survive the initial neurologic injury. Prompt early recognition of heatstroke as the entity responsible for a given patient's problems and effective early cooling with attention to expected complications can result in complete recovery in most cases. In a minority (< 10%) in whom neurologic injury has not resulted in an early death occurring within the first 2-3 days, the hepatic injury due to heatstroke can result in death that occurs a week or more after the onset of the heat stress, unless the liver is replaced. Recently, two such cases have been referred to the University of Pittsburgh for transplantation. On the basis of these two referrals and a review of the literature, we believe that this problem occurs more often than is currently appreciated, principally because of a lack of knowledge about the problem. In an attempt to correct this information deficit, this review was prepared.

Animals↗
PubMed1991

Ulcerative colitis disease activity as subjectively assessed by patient-completed questionnaires following orthotopic liver transplantation for sclerosing cholangitis.

To assess whether or not liver transplantation and subsequent immunosuppression with cyclosporine and prednisone affect ulcerative colitis symptomatology, we surveyed by questionnaire all 23 surviving patients with pretransplant colonoscopy-documented ulcerative colitis who were transplanted for primary sclerosing cholangitis between June 1982 and September 1985. At follow-up [89.8 +/- 7.6 weeks (mean +/- SEM], all six patients who had had asymptomatic colonoscopy-documented ulcerative colitis reported continued ulcerative colitis quiescence. Among the 17 patients who had had symptomatic colonoscopy-documented ulcerative colitis at time of liver transplantation, 88.2% reported improvement in overall ulcerative colitis severity (P less than 0.001), with significant improvement in the frequency of bowel movements reported by 100%, in crampy abdominal pain by 87.5%, in bowel urgency by 75%, in the occurrence of pus or mucus in stool by 87.5%, in the incidence of ulcerative colitis flares by 81.8%, and in the number of days unable to function normally due to ulcerative colitis symptoms by 78.6% (all at least P less than 0.01). These data demonstrate that ulcerative colitis symptom severity significantly improves following liver transplantation with immunosuppression with cyclosporine and prednisone.

Adult↗