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Biomedical subjects

S Govindarajan

Publications and source records attributed to S Govindarajan.

At least 91 records · Page 5Linked to original sources
PubMed1991

Nonviral risk factors for hepatocellular carcinoma in a low-risk population, the non-Asians of Los Angeles County, California.

We conducted interviews on 74 patients with histologically confirmed hepatocellular carcinoma. These patients, aged 18-74 years, were black or white residents of Los Angeles County. We also interviewed 162 population control subjects who were comparable to the case patients by age, sex, and race. Cigarette smoking was a significant risk factor for hepatocellular carcinoma [relative risk (RR) = 2.1; 95% confidence limits (CL) = 1.1, 4.0]; the effects were similar in men and in women. Heavy alcohol consumption was another risk factor for hepatocellular carcinoma in men; men who consumed 80 g or more of ethanol per day had an RR of 4.7 (95% CL = 1.4, 15.4) relative to those who had never drunk alcohol on a weekly basis. The level of alcohol intake was relatively low in women, and no significant effect on risk of hepatocellular carcinoma was observed. Use of oral contraceptives was significantly related to risk of hepatocellular carcinoma in women (RR = 3.0; 95% CL = 1.0, 8.8); those who were exposed for more than 5 years exhibited a 5.5-fold increased risk (95% CL = 1.2, 24.8). The effects of these three risk factors on hepatocellular carcinoma development were independent of each other and independent of serologically determined viral hepatitis. Our data suggest that cigarette smoking, alcohol consumption, and use of oral contraceptives are major risk factors for hepatocellular carcinoma among non-Asian residents of Los Angeles County. We also observed a significant association between a history of diabetes and hepatocellular carcinoma (RR = 3.3; 95% CL = 1.5, 7.2), especially among those who had received insulin treatment (RR = 18.5; 95% CL = 2.2, 156.0). This association may have etiological significance.

Adolescent↗
PubMed1991

Host dependent modulation of hepatitis delta virus replication in chronic delta hepatitis.

To determine whether host dependent differences modulated hepatitis delta virus replication in chronic delta hepatitis, we tested HDV RNA in homosexual and intravenous drug abuser populations. Overall, the seroprevalence of HDV RNA in the two groups with matching clinical characteristics was 72% (76/106 patient visits). A trend for greater prevalence of HDV RNA was noted at initial presentation in homosexuals (82%) compared to intravenous drug abusers (60%, P less than 0.05) and this trend appeared to be maintained during two years of sequential follow-up. The seroprevalence of co-appearing IgM and IgG anti-HD antibodies was similar in the two groups of patients. However, in HDV RNA positive homosexuals IgG anti-HD antibody was more prevalent, and additionally, assumed concordance with HDV RNA of 92% although the significance of this observation is unclear. The difference in prevalence of HIV in the two groups did not reach statistical significance. Prospective studies are required to confirm differences in HDV replication in various patient groups and to define underlying mechanisms.

Adult↗
PubMed1991

A double-blinded, randomized trial of hydrocortisone in acute hepatic failure. The Acute Hepatic Failure Study Group.

The Acute Hepatic Failure Study Group (AHFSG) has conducted a double-blinded, randomized evaluation of hydrocortisone in patients with acute hepatic failure. From July 1975 through August 1978, a 38-month period, 18 medical centers in the United States and one in Canada participated in this trial. A total of 64 patients were accessed and found eligible to participate in the study; two of them were subsequently eliminated from our analysis. Eighteen patients received placebo; 23 received 400 mg hydrocortisone per day, and 21 patients were administered 800 mg hydrocortisone per day. We did not observe any therapeutic effect of hydrocortisone, and the survival rates for placebo versus 400 mg and versus 800 mg hydrocortisone per day were 22%, 9%, and 24%, respectively. Fulminant hepatitis associated with drug hepatotoxicity or non-A, non-B hepatitis seemed to have a worse prognosis than fulminant B, although these differences were not significant. Serum alpha-fetoprotein had a modest prognostic value of survival and seemed to be limited to fulminant B. The AHFSG recommends, therefore, that corticosteroid use in acute hepatic failure with hepatic encephalopathy be discontinued.

Adult↗
PubMed1991

The molecular basis of heterogeneity of hepatitis delta virus.

HDV-RNA displays genetic heterogeneity at several different levels. This heterogeneity is likely reflected in the biological properties, such as pathogenicity and evolution, of HDV. The variation and progression of the clinical picture of delta hepatitis is likely associated with the heterogeneity of the virus. The mechanism of the generation of the heterogeneity remains largely to be studied.

Antigens, Viral↗
PubMed1991

Evaluation of a commercial anti-delta EIA kit for detection of antibodies to hepatitis delta virus.

Anti-hepatitis delta virus (anti-HDV) antibodies were measured by solid phase IgG and IgM capture radioimmunoassays (RIA) as well as by a competitive binding enzyme immunoassay (EIA) in both acute and chronic HDV infections. EIA anti-delta test measures total delta antibody without discriminating IgM from IgG anti-delta. Low titer IgG antibodies were detected by both techniques with equal sensitivity. High titer IgG antibodies reached the end point sooner with EIA than with RIA (10(-3) versus greater than 10(-6)). When IgM anti-HDV was present without accompanying IgG anti-HDV, EIA failed to identify the antibody. Presence of high titer rheumatoid factor in the serum and lipemic samples produced false-positive results by EIA. Usage of undiluted serum samples for EIA probably exaggerates the factors contributing to false-positive reaction.

Evaluation Studies as Topic↗
PubMed1991

Human immunodeficiency virus infection does not alter serum transaminases and hepatitis B virus (HBV) DNA in homosexual patients with chronic HBV infection.

The influence of human immunodeficiency virus (HIV) infection on the clinical course of chronic hepatitis B virus (HBV) infection is controversial. We followed a cohort of 64 homosexual men with persistent HBs antigenemia for a median of 24 months in the hepatitis clinic of a large urban public hospital. We divided the patients into three groups according to their immune status. Group 1 (n = 13) consisted of HIV-seropositive men with evidence of immunosuppression; group 2 (n = 17), HIV-positive patients without evidence of immunosuppression; and group 3 (n = 34), HIV-negative patients. We followed serum ALT and HBV DNA determinations. There was no difference in the demographic characteristics of the three groups. Group 1 had significantly lower levels of circulating T4 lymphocytes. We found no differences in the number and severity of episodes of HBV reactivation, serum ALT levels, or HBV DNA scores among the three groups. In each group, the percentage of patients with circulating HBV DNA was the same. We conclude that HIV infection apparently does not influence the markers of liver inflammation or HBV replication in homosexual men.

Adult↗
PubMed1991

Glycation of lysozyme in a restricted water environment.

Fast atom bombardment mass spectrometry (FAB) was used to determine the glycation sites of lysozyme in a restricted water environment. A 30-day incubation at 25 degrees C, and 65% relative humidity (R.H.) resulted in glycation at lysine-1 while a much shorter (3-day) incubation at 50 degrees C and 65% R.H. resulted in diglycation at lysine-1 as well as glycation at lysine-13 and lysine-33.

Amino Acid Sequence↗
PubMed1991

Acute delta hepatitis: serological diagnosis with particular reference to hepatitis delta virus RNA.

To evaluate serologic diagnosis of hepatitis delta virus, we tested HDV RNA in stored sera from 48 patients with acute delta hepatitis who were identified with anti-HD antibodies. Initial sera were positive for HDV RNA in 27 of 48 (56%) patients. In comparison, isolated IgM anti-HD was present in 18 (38%) patients, although IgM and IgG anti-HD were present concurrently in 16 (33%) additional patients. Overall, either HDV RNA or IgM anti-HD was present in 69% of the initial sera. The HDV infection was self-limiting in all except two patients who died of fulminant hepatitis and nine others in whom chronic delta hepatitis ensued. Patterns of HDV seropositivity during progression to chronicity induced variable persistence, disappearance or recrudescence of either HDV RNA or IgM and IgG anti-HD. Results of HDV RNA and IgM anti-HD tests were concordant in only 40-50% of instances. Our results indicate that serological testing for HDV RNA is direct and will demonstrate HDV replication in a large number of cases with acute delta hepatitis. Testing for IgM anti-HD could provide supplemental evidence for HDV infection. Sequential testing for these markers will facilitate assessment of the outcome of acute HDV infection.

Acute Disease↗
PubMed1991

Molecular cloning and characterization of an isolate of hepatitis delta virus from Taiwan.

The genomic RNA of an Asian isolate of hepatitis delta virus was cloned from a Chinese patient from Taiwan, using the polymerase chain reaction to amplify cDNA for cloning and sequencing. The sequence of this hepatitis delta virus isolate shares an 86% to 88% similarity with the three published hepatitis delta virus RNA sequences, suggesting heterogeneity of hepatitis delta viruses from different geographical areas. Four highly conserved, long stretches of sequence were found. These four regions corresponded to the sequences required for the autocatalytic cleavage activities of the genomic and antigenomic RNAs and the middle and the carboxyl terminal parts of the open reading frame for the delta antigen on the antigenomic strand. The conservation of nucleotide sequence in these four regions was further confirmed by sequencing additional hepatitis delta virus RNAs obtained from three patients with chronic delta hepatitis who lived in Los Angeles. These findings suggest that the conserved sequences are critical for viral replication. These conserved regions offer ideal sites for primer selection to carry out polymerase chain reactions to detect hepatitis delta virus RNA in patients with hepatitis delta virus infection.

Adult↗
PubMed1991

Interactions of HDV, HBV and HIV in chronic B and D infections and in reactivation of chronic D infection.

From this study, we can conclude that there is significant influence of HIV infection on the clinical course of chronic HDV as follows: In these patients, there is simultaneous replication of both HBV and HDV and the suppression of HBV by HDV is modified. There is decreased antibody response to HDV, however, the degree of liver injury is not altered. Although these patients tend to have "reactivation episodes" as frequently as the HIV negative group, no correlation of serum ALT to HDV-RNA could be found. The possibility of these episodes resulting from injury due to other viruses such as non-A, non-B cannot be excluded.

Alanine Transaminase↗
PubMed1990

Prevalence of hepatitis B and C viral markers in black and white patients with hepatocellular carcinoma in the United States.

The recent cloning of the genome of a non-A, non-B hepatitis agent, designated the hepatitis C virus (HCV), has led to the development of an immunoassay for circulating HCV antibodies (anti-HCV). We used this immunoassay to investigate the possible association between HCV infection and hepatocellular carcinoma in black and white residents of Los Angeles County, California. Serum samples from 51 patients (12 black and 39 white) in Los Angeles County with hepatocellular carcinoma and 128 control subjects (1 black and 127 white) were tested for the presence of anti-HCV. In addition, samples were tested for hepatitis B surface antigen (HBsAg), antibodies to the hepatitis B core antigen (anti-HBc), and antibodies to HBsAg (anti-HBs). Our results indicate that the presence of anti-HCV was a significant risk factor for hepatocellular carcinoma; the relative risk was 10.5 (95% confidence limits = 3.5, 31.3). Hepatocellular carcinoma risk was also significantly related to the presence of one or more of the hepatitis B virus (HBV) markers, primarily HBsAg and anti-HBc, and the relative risk was 7.0 (95% confidence limits = 3.1, 16.1). HCV and HBV independently contributed to hepatocellular carcinoma development. Significantly increased risk of hepatocellular carcinoma was demonstrated in individuals with HCV (relative risk = 4.8) or HBV (relative risk = 4.4) serologic markers alone. A synergistic effect on risk was observed when both hepatitis B and C viral markers were present in peripheral blood (10 cases vs. no controls). We estimate that approximately 47% of hepatocellular carcinoma occurring in black and white residents of Los Angeles County could be attributed to prior HCV and/or HBV infections: 9% were related to HCV alone, 20% to HBV alone, and 18% to occurrence of both HCV and HBV infections.

Antibodies, Viral↗
PubMed1990

Acute hepatic injury after the withdrawal of immunosuppressive chemotherapy in patients with hepatitis B.

Five patients with lymphoproliferative malignancies and chronic hepatitis B suffered severe acute hepatic injury after the withdrawal of multiagent chemotherapy that included high-dose corticosteroid. Four patients died of hepatic failure, three of whom received corticosteroid as treatment for the hepatic injury. We believe that the cause of this entity is massive immune-associated cytolysis of hepatitis B virus infected hepatocytes occurring after a period of immunosuppression and increased viral replication. The literature regarding this complication of chemotherapy and its pathophysiology is reviewed.

Adult↗
PubMed1990

Sexual transmission of hepatitis D virus infection in Taiwan.

Multivariate analysis of the risk factors for hepatitis D virus infection among 53 men with acute hepatitis D virus superinfection, 59 men with acute exacerbation of chronic hepatitis B and 54 asymptomatic male hepatitis B carriers revealed that sexual contact with prostitutes and use of nondisposable needles were the factors significantly associated with hepatitis D virus infection in Taiwan (odds ratio = 5.5, 95% confidence interval = 3.3 to 9.2; odds ratio = 2.4, 95% confidence interval = 1.3 to 4.4, respectively). The prevalence of antibody to hepatitis D virus antigen among hepatitis B virus carriers with histories of sexual exposure to prostitutes was 10.3% (14 of 136) and the prevalence of hepatitis D virus antigen among the female prostitutes who were hepatitis B virus carriers was 59% (24 of 51). Among those who admitted to sexual contact with prostitutes, testing for hepatitis D virus antigen revealed positive correlations with the frequency of such sexual contacts and with the frequency of history of venereal diseases. Among the female prostitutes, the prevalence of hepatitis D virus antigen had a positive correlation with the frequency of sexual contact and a negative correlation with age. Analysis of serum hepatitis D virus RNA among those with hepatitis D virus antigen revealed that 4 of the 9 with sexual exposure to prostitutes and 3 of the 24 prostitutes were positive. From these findings, we conclude that these two groups are not only at high risk for hepatitis D virus infection but also form a reservoir of this virus.

Adolescent↗
PubMed1990

Heterogeneity of hepatitis delta antigen.

Hepatitis delta antigen (HDAg) is the only known protein encoded by the hepatitis delta virus (HDV). Two HDAg species of different sizes have been detected in the sera and livers of the infected humans, chimpanzees, and woodchucks, even though only one RNA species was previously identified in most of the HDV strains. To study HDAg heterogeneity, we took advantage of the fact that a single base mutation at nucleotide 1015 (C to U), which results in an amber termination codon in the HDAg open reading frame (ORF), eliminates a unique Ncol restriction enzyme site. We screened various HDV cDNA clones and detected sequence heterogeneity of the HDAg-coding region on the basis of the presence or absence of the Ncol site. Five delta hepatitis patients were examined. In every patient, two types of HDAg-coding sequence were detected at nucleotide 1015: one which contains a C and results in an ORF encoding a delta antigen of 214 amino acids, and the other which possesses a U and results in an amber termination codon and a truncated HDAg species of 195 amino acids. The in vitro translation products of these two ORFs comigrated with the two HDAg species from the patient's plasma on SDS polyacrylamide gels. Polymerase chain reaction (PCR) amplification of the HDV RNA from some patients' sera and subsequent sequencing showed several additional mutations in the HDAg-coding region. These mutations are independent of the C or U nucleotide change at the site of the amber termination codon.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Viral↗
PubMed1990

Correlation of serum delta RNA with clinical course of acute hepatitis delta virus superinfection in Taiwan: a longitudinal study.

Twenty of 22 hepatitis delta virus (HDV)-superinfected chronic hepatitis B carriers who had detectable HDV RNA at the acute stage progressed to chronicity, while only 6 of 16 patients without HDV RNA did so (P less than .005). The poor outcome of patients with persistently positive or fluctuating HDV RNA has been indicated by the following findings: 24 of 38 patients suffered from prolonged hepatic inflammation complicated by three to eight episodes of exacerbations; among them, 5 developed cirrhosis and 2 died in a follow-up period of 4 years. For most patients, the replication of HBV was suppressed at acute stage; only 3 of the 38 cases had detectable HBV DNA in sera. While reactivation of HBV was found in another 8 patients in the follow-up period, for 5 it was in the presence of serum HDV RNA and 2 developed cirrhosis. Therefore, serial assays of serum HDV RNA and HBV DNA appeared to be of value in monitoring the clinical course and outcome of acute HDV superinfection and in the study of the long-term interactions between these two viruses.

Acute Disease↗
PubMed1990

Spontaneous reactivation in chronic hepatitis B: patterns and natural history.

We identified spontaneous reactivation of hepatitis B virus (HBV) retrospectively by utilizing serum alanine aminotransferase and HBV DNA in 19 men (79% homosexual), with an estimated annual incidence of 7.3%. In 11 patients, spontaneous reactivation occurred as a single episode and in eight patients, reactivation was recurrent, with two to five episodes each. The mean serum alanine aminotransferase level was elevated over 10-fold at the peak of reactivation. Serum anti-HBc IgM was detected during 73% of the reactivation episodes. Actuarial analysis revealed that reactivation was long lasting with 45% and nearly 20% of episodes continued after 6 and 24 months, respectively. The course of 24 chronic HBV carriers with a negative serum HBV DNA test and normal alanine aminotransferase levels at initial appearance was unremarkable. We could not identify clinical features predictive of reactivation or its resolution. Severe reactivation hepatitis occurred in three patients (10%), with two deaths (6%). None of the patients lost HBsAg. Spontaneous reactivation in chronic hepatitis B can appear variably, persist long term, recur, and be fatal. Therefore, accurate classification of chronic HBV infection requires prolonged observation, and spontaneous reactivation should be considered a variable in therapeutic trials for chronic hepatitis B.

Adult↗