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Biomedical subjects

E Donegan

Publications and source records attributed to E Donegan.

At least 37 records · Page 2Linked to original sources
PubMed1993

Hepatitis C and B in liver transplantation.

Hepatitis B recurrence remains a major problem facing liver transplantation programs. The risk of infection varies depending upon the HBV load. High doses of HBIg may reduce the risk of occurrence but it remains expensive. Finally, apparently new infections may occur posttransplantation, which may have been transmitted by organs or blood from HBsAg (-), HBcAb (+) donors, or may reflect reactivation of latent infections in patients who were HBsAg (-). HCV infections are common in patients undergoing liver transplantation, and HCV infection recurs in > 90% of patients; however, recurrent hepatitis C occurs in less than half of these patients. HCV is not an important cause of fulminant non-A, non-B hepatitis, but appears to be the most common cause of posttransplant hepatitis. So what is in the future? For hepatitis B, we still believe the efficacy of HBIg, and in which patients with hepatitis B HBIg should be used, remains to be defined. The effects of antivirals on posttransplant hepatitis B, as well as in prevention of HBV recurrence, also remain to be determined. In the United States, insurance companies are likely to play an important role in determining the future of transplantation for hepatitis B. Medicare recently excluded patients who were HBsAg (+) from coverage for liver transplantation, and a number of private insurers have subsequently followed suit. For HCV, newer screening tests for the virus are likely to decrease the rate of HCV acquisition following liver transplantation, from the current 35% incidence of HCV acquisition. The impact of antiviral treatment on posttransplant hepatitis remains to be determined and deserves study. Finally, the development of regimens that might allow prevention of recurrent HCV infections in patients undergoing liver transplantation also should be a matter of future study.

Hepatitis B↗
PubMed1992

Effect of age on human immunodeficiency virus type 1-induced changes in lymphocyte populations among persons with congenital clotting disorders. Transfusion Safety Study Group.

Children other than neonates infected with human immunodeficiency virus type 1 (HIV-1) have low rates of progression to acquired immunodeficiency syndrome (AIDS). Through 1989, 5.3% of 95 infected hemophiliacs aged 5 to 13 years developed AIDS, compared with 20.3% of 364 aged greater than or equal to 25 years. We asked whether the HIV-1 impact on peripheral blood mononuclear cell subpopulations differed with age using pairwise comparisons of uninfected and infected male children and adult hemophiliacs. Infected children had lesser reductions of total lymphocytes than adults, but proportionately lower numbers of CD2+, CD4+, CD2+CD26+, and CD4+CD29+ counts. CD4+CD45RA+ cell counts were greater than twofold higher in uninfected and infected children than adults; with infection, the CD4+CD45RA+/CD4+ proportion increased by 1.4-fold in adults, but was unchanged in children. Infected adults had highly significantly increased total CD8+ counts; both age groups had elevated CD8+HLA-DR+ counts. Infected children had significantly higher total B-cell counts than infected adults, with a disproportionately lower number of resting B cells (CD20+CD21+). During 2 years of follow-up, infected children and adults had lymphocyte changes in the same directions and these were proportionately equal. The lower rate of HIV-1 progression in children may be partly associated with differences in lymphocyte populations compared with adults; functional properties of immune cells may be equally or more important.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Hepatitis B virus and apparent fulminant non-A, non-B hepatitis.

While there is evidence that hepatitis C virus (HCV) does not cause fulminant non-A, non-B hepatitis, the causal agent remains unknown. To evaluate the role of hepatitis B virus (HBV) in this disease, we used a two-step polymerase chain reaction (PCR) to amplify the surface and core regions of HBV DNA in serum and liver samples taken prospectively from twenty-six patients (mean age 36 years, range 1 to 64) with acute hepatic failure undergoing liver transplantation. HBV DNA was absent from the serum of all patients before transplantation. Seventeen patients were diagnosed as having non-A, non-B hepatitis because they lacked serological evidence of hepatitis A virus or HBV infection. Liver samples were taken from twelve of these patients, and six samples were positive for HBV DNA. By contrast HBV DNA was not detected in liver from three patients with acute liver failure caused by hepatitis A or toxins. HCV RNA was not found in pretransplant samples by PCR. Four of the six patients with detectable HBV DNA in liver and presumptive non-A, non-B hepatitis had detectable HBV DNA in serum after transplantation. One additional patient who did not donate pretransplant liver had HBV DNA in a post-transplant serum sample. Thus, HBV DNA was present before or after transplantation in seven of seventeen patients with apparent non-A, non-B hepatitis. Three of five patients with detectable post-transplant serum HBV DNA were serologically positive for HBV surface antigen. These findings indicate that HBV may be a common cause of fulminant hepatic failure in patients lacking serological evidence of HBV infection.

Acute Disease↗
PubMed1992

Recurrent and acquired hepatitis C viral infection in liver transplant recipients.

To examine the postliver transplant recurrence of hepatitis C virus (HCV) infection in patients with pretransplant infection, as well as its acquisition in patients without prior infection, we used the polymerase chain reaction to amplify HCV RNA in serum and/or liver samples of 89 patients with alcoholic and cryptogenic cirrhosis undergoing liver transplantation. Results were correlated with histologic findings from posttransplant liver biopsies. Ninety-five percent of patients with pretransplant infection had posttransplant viremia. In contrast, 35% of patients without pretransplant infection acquired the virus (P less than 0.0001). Pretransplant HCV infection predisposed patients to hepatitis in the new graft. HCV RNA was present in serum of 96% of patients with posttransplant hepatitis. Fifty-six percent of patients with posttransplant HCV infection had no evidence of liver damage at least 1 year posttransplant. However, of those patients with histologic hepatitis, chronic active hepatitis was common. It is concluded that although HCV infection recurs posttransplant in almost all infected patients, acquisition of the HCV infection with transplant is common. Pretransplant HCV infection is an independent risk factor for the development of posttransplant hepatitis. HCV infection accounts for the majority of posttransplant hepatitis not due to cytomegalovirus, and although many patients with posttransplant viremia have little evidence of histologic hepatitis, significant hepatic damage may occur.

Base Sequence↗
PubMed1992

New developments in serologic screening of corneal donors for HIV-1 and hepatitis B virus infections.

PURPOSE: The authors evaluated different methods to serologically screen potential cadaveric corneal donors for human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) infections. METHODS: Three commercially available enzyme-linked immunosorbent assays (ELISAs) for antibodies against HIV-1, a supplemental ELISA test for HIV antigen, and a radioimmunoassay and two ELISAs for hepatitis B surface antigen were compared using serum from cadavers with acquired immune deficiency syndrome (AIDS), cadavers with high risk factors for HIV infection, and cadavers with no known risk of HIV infection, along with respective confirmatory testing. RESULTS: The ELISA tests for HIV antibodies from Abbott Laboratories, Electro-nucleonics, and Organon-Teknika showed sensitivities of 94.3%, 94.3%, and 97.1%, respectively, compared with the autopsy diagnosis of AIDS in 35 cadavers. The sensitivities of the HIV-1 antibody ELISAs ranged between 73% and 87% compared with positive Western blots in testing 118 sera from cadavers at high risk of HIV-infection, but not manifesting AIDS at the time of death. Supplemental ELISA testing for HIV-1 antigen, in an effort to close the seronegative window, failed to identify any HIV antigen-positive sera confirmed by neutralization that were not also positive for antibodies to HIV-1 by ELISA and Western blot. The ELISA for HBV surface antigen had an overall sensitivity of 92.9% and specificity of only 81.3% compared with radioimmunoassay in testing 409 sera. Monoclonal ELISAs for HIV-1 antigen and HBV surface antigen paradoxically had lower specificity than polyclonal ELISAs, with false positivity correlating with hemolysis and with increasing death to puncture time. CONCLUSION: ELISA testing for antibodies against HIV-1 is relatively but not absolutely effective, should be accompanied by historical screening for risk factors, and does not appear to benefit from supplemental ELISA testing for HIV-1 antigen. ELISA testing for HBV surface antigen has lower specificity in screening cadaveric sera when compared with radioimmunoassay.

AIDS Serodiagnosis↗
PubMed1992

Transmission of human T-lymphotropic virus type I by blood components from a donor lacking anti-p24: a case report. The Transfusion Safety Study Group.

The present criteria for confirmation of human T-lymphotrophic virus types I and II (HTLV-I/II) infection in blood donors are based on seroreactivity to p24 (gag) and gp46 and/or gp61 (env) on Western blot (WB) and radioimmunoprecipitation assays (WB/RIPA). Any single band and other combinations are classified as indeterminate. This case report documents infection in a donor with a repeatedly indeterminate pattern. The blood donor was anti-HTLV-I/II positive on enzyme-linked immunoassay, and two sera taken 5 years apart were WB/RIPA-indeterminate (p19 and gp68 only). His donations in the interval were associated with transmission of HTLV-I to four of the six recipients available for study. Other recipients of blood from donors whose WB/RIPA results were indeterminate by present criteria should be examined to determine if additional patterns are at least occasionally associated with transmission. The likelihood that such donors are infected is important to those who are counseling them and making decisions concerning recipients of their bloody.

Adult↗
PubMed1991

Hepatitis C in patients undergoing liver transplantation.

OBJECTIVE: To determine the prevalence of antibodies to hepatitis C virus (anti-HCV) among patients undergoing liver transplantation and the relation between anti-HCV and post-transplant hepatitis. DESIGN: Retrospective cohort. PATIENTS: Serum samples from 128 patients who underwent liver transplantation. Sixty-six patients who had 6 months of follow-up and for whom both pretransplant and post-transplant serum samples were available were included in a study to asses the relation between anti-HCV and post-transplant hepatitis. MEASUREMENTS: Sera were tested for anti-HCV using an enzyme-linked immunosorbent assay (ELISA) and, if positive, two confirmatory tests were done. Patients had a biopsy every week until two specimens showed no abnormal findings. MAIN RESULTS: Only patients with chronic non-A, non-B hepatitis (15 of 30; 50%), alcoholic cirrhosis (7 of 19; 37%), and chronic hepatitis B infection (3 of 11; 27%) were anti-HCV positive. No patient with another form of chronic liver disease or with acute liver failure due to non-A, non-B hepatitis was anti-HCV positive. After transplantation, loss of anti-HCV was frequent and acquisition rare. Hepatitis developed in the graft in 17% of patients, but the incidence was similar among anti-HCV negative and anti-HCV-positive patients. CONCLUSIONS: Hepatitis C virus is a common cause of chronic liver disease in patients requiring liver transplantation, but anti-HCV is rarely found in patients with acute liver failure. Previous HCV infection, based on detection of anti-HCV, is not an independent risk factor for post-transplant hepatitis.

Cohort Studies↗
PubMed1991

Hemolytic transfusion reaction following transfusion of frozen and washed autologous red cells.

A case of hemolytic transfusion reaction, accompanied by hypotension and followed by transient renal failure, occurred after the transfusion of 1 unit of previously frozen autologous red cells. Subsequent investigation revealed the probable cause of the hemolysis to be inadequate deglycerolization of the unit. The cause of the associated symptoms is unknown. Possibilities include nephrotoxic effects of hemoglobin or stroma, toxic effects of glycerol, or release of vasoactive or thrombogenic substances from lysed red cells. This case of a hemolytic reaction adds to the known risks of autologous transfusion.

Blood Preservation↗
PubMed1991

Lymphocyte immunophenotypes among anti-HTLV-I/II-positive blood donors and recipients. The Transfusion Safety Study Group.

The Transfusion Safety Study retrospectively screened a repository of serum specimens collected in late 1984-early 1985 to identify blood donors with antibody to human T-cell lymphotropic virus (HTLV) at that time. They and their recipients have been traced for additional HTLV studies. Immunophenotypic analyses of peripheral blood lymphocytes from nine anti-HTLV-positive recipients, assumed to be infected during or since late 1984, showed no significant changes from healthy controls. Evaluation of the immunophenotypes of the 48 donors, however, showed significant elevations in the absolute counts of the T-cell (CD2) and natural killer (CD56) populations, the T helper/inducer and suppressor/inducer subsets (CD4+ CD29+ and CD4+ CD45RA+), and changes in T-cell activation markers. Long-term but not recent HTLV infection appears to alter the T-cell immunophenotypic pattern. Both infection with HTLV and human immunodeficiency virus type 1 are associated with a decreased CD2+ CD26+ count.

Blood Donors↗
PubMed1991

Hepatitis C in liver transplant recipients.

HCV infection is commonly found in patients with chronic liver disease undergoing liver transplantation. However, the presence of antibody to HCV does not appear to be associated with the development of hepatitis posttransplant. No other risk factors were identified that appear to predispose patients to development of hepatitis in the posttransplant period, including amount of blood product exposure. The role of immunosuppression in the acquisition and expression of liver disease caused by HCV remains to be determined.

Hepacivirus↗
PubMed1990

Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations.

OBJECTIVE: To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients. DESIGN AND SUBJECTS: We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations. MEASUREMENTS AND MAIN RESULTS: Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipient's sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal. CONCLUSIONS: Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effects of counselling on knowledge about HIV-1 among transfusion recipients and their partners. Transfusion Safety Study Group.

The present study determined how much HIV-1-positive persons knew about AIDS, and HIV-1 transmission and prevention, in comparison with HIV-1-negative controls in a predominantly heterosexual cohort. The subjects were blood donors, blood recipients, hemophiliacs, and their sexual partners. A 16-item questionnaire about AIDS, HIV-1 transmission, and knowledge of safe sexual practices was administered to 228 subjects to determine background information. The HIV-1-positive cohort answered more questions correctly (mean = 8.5) than did the HIV-1-negative cohort (mean = 6.5), largely as a result of general information about AIDS among those with steady sexual partners. All persons, however, were poorly informed about HIV-1 transmission and safe sexual practices. Thus, there is a great need for effective counselling.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Epidemiologic background of blood donors with antibody to human T-cell lymphotropic virus. Transfusion Safety Study Group.

We interviewed 51 blood donors in four major US metropolitan areas subsequently found to have had antibodies to human T-cell lymphotropic virus (anti-HTLV) in late 1984-early 1985. Sixteen donors (31%) reported that they or a sexual contact had a history of blood transfusion. Twelve donors (24%) reported that they or a sexual contact used intravenous drugs. Ten donors (20%) were blacks born in the southeastern US. Four of the male donors (15%) reported homosexual contact. The most common characteristic was an association with Japan or the Caribbean basin (61%). These results show a broader variation of epidemiologic backgrounds than anticipated.

Adult↗
PubMed1987

Screening cornea donors for antibodies against human immunodeficiency virus. Efficacy of ELISA testing of cadaveric sera and aqueous humor.

Coded cadaveric sera from 35 patients with acquired immunodeficiency syndrome (AIDS), from 45 cadavers at high risk of human immunodeficiency virus (HIV) infection, and from 262 cadavers without known signs or risk of AIDS were assessed using three commercially available enzyme-linked immunosorbent assays (ELISA) kits and Western blot analysis. Greater than 94% sensitivity and 99% specificity was achieved with each of the ELISA test kits using cadaveric sera. The Western blot method gave 97.1% sensitivity compared with the autopsy-proven diagnosis of AIDS. Positive results were obtained on sera from AIDS cadavers even if the time of blood draw was delayed 35 hours from death and the time of sera preparation was delayed up to 176 days. False-negative or false-positive ELISA results did not appear to correlate with hemolysis or any parameter of sera preparation. In contrast to the high sensitivity in testing sera, only 16 to 26% of aqueous humor samples from AIDS cadavers were ELISA-positive and 79% were positive by Western blot. These results indicate that three commercially available ELISA test kits are an effective means of screening cadaveric sera for antibodies to HIV, but that aqueous humor cannot be reliably substituted for cadaveric sera to screen potential cornea donors by an ELISA assay.

Acquired Immunodeficiency Syndrome↗