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Biomedical subjects

F B Hollinger

Publications and source records attributed to F B Hollinger.

At least 73 records · Page 4Linked to original sources

Bleeding from a Meckel's diverticulum after the use of ibuprofen.

A Meckel's diverticulum is an unusual site of gastrointestinal bleeding in adults. Bleeding often results from ulceration of ileal mucosa that lies adjacent to ectopic gastric mucosa. We report on a 27-yr-old man who bled from a Meckel's diverticulum after receiving oral ibuprofen, a nonsteroidal antiinflammatory drug. Examination of the resected diverticulum revealed fundal-type gastric mucosa with inflammation, submucosal hemorrhages, erosions and ulceration in the absence of Helicobacter pylori. The ileal mucosa was spared in this patient. These features suggest that oral ibuprofen caused damage to the ectopic gastric mucosa, precipitating significant hemorrhage. This is the first report in the English literature of such an occurrence.

Adult↗

Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and second-generation assays.

BACKGROUND: The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to diagnose post-transfusion hepatitis caused by infected blood. METHODS: We used two first-generation enzyme-linked immunoassays (EIAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion. RESULTS: Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatitis developed in these 111 patients, the first-generation EIAs detected anti-HCV in 51 (46 percent), and the second-generation assay detected anti-HCV in an additional 16 (14 percent), for a total of 60 percent. Of 40 controls, 37 were anti-HCV-negative initially, and none seroconverted after hepatitis developed. If the 3 percent rate of non-A, non-B, non-C hepatitis among the controls (37 of 1235) was applied to the 1247 transfusion recipients, only 74 of the 111 cases of hepatitis were attributable to the transfusion. Thus, 91 percent (67 of 74) of the cases of post-transfusion hepatitis were caused by HCV. Of the 99 donors, 60 were HCV-positive (9 on second-generation tests only) and 39 were not. CONCLUSIONS: Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by HCV. Screening with a second-generation assay improves the rate of detection of HCV infection in patients with post-transfusion hepatitis and in blood donors. The use of this test showed a 3.6 percent risk of non-A, non-B, non-C hepatitis, which was not significantly different from the rate in the controls (3.0 percent).

Blood Donors↗

The incidence of HIV-1 and HHV-6 in corneal buttons.

Twenty pairs of corneas from asymptomatic carriers of HIV-1 and seven pairs from AIDS patients were analyzed for the presence of HIV-1 and HHV-6 antigens, viral transcripts, DNA sequences, and intact and infectious particles. Although serum from all donors was positive for both HIV-1 and HHV-6 antibody by Western blot analysis, only one cornea from an asymptomatic carrier of HIV-1 was positive for HIV-1 and HHV-6. The cornea was positive when tested by tissue culture, PCR, in situ hybridization, and electron microscopy. There was no tear film contamination. These results suggest that HIV-1 and HHV-6 may be capable of invading corneal tissue.

Acquired Immunodeficiency Syndrome↗

Non-A, non-B hepatitis and antibody to hepatitis C virus.

Stored serum samples from the Transfusion-transmitted Viruses Study in the 1970s were tested for the presence of antibody to hepatitis C virus (anti-HCV). Single specimens from five control subjects who did not receive transfusions tested negative for anti-HCV. Of four control subjects who did not receive transfusions and who developed non-A, non-B (NANB) hepatitis after hospitalization, three remained anti-HCV negative; the fourth person with postoperative NANB hepatitis tested anti-HCV positive before the operation. Five transfusion recipients with posttransfusion hepatitis B virus infection remained seronegative; a sixth with NANB hepatitis as well as hepatitis B virus infection had seroconversion for anti-HCV. Five of nine transfusion recipients with NANB hepatitis had anti-HCV seroconversion. These results show that present anti-HCV testing demonstrates an etiologic basis for approximately half of the cases of transfusion-associated NANB hepatitis, particularly those that develop chronicity. Although cases of NANB hepatitis without seroconversion may be explained otherwise, they may be caused by another, presently unidentified, virus.

Blood Transfusion↗

Controlling hepatitis B virus transmission in North America. The North American Regional Study Group.

In the US in 1988, 54,011 cases of viral hepatitis were reported to the Centers for Disease Control (CDC), 42% of which were categorized as hepatitis B. Because of incomplete reporting and subclinical disease, the CDC estimates that approximately 300,000 acute cases of hepatitis B are occurring in the US each year for an annual estimated incidence of 125 cases per 100,000 population. Since 1985, a gradual decrease in the reported incidence of hepatitis B has been observed which may be attributed partly to the availability of new hepatitis B vaccines. Comprehensive control of hepatitis B infection in North America has, however, been impeded by the diversity and mobility of high-risk groups who often are unaware of their potential to infect other individuals. Surveillance studies have indicated that the modes of transmission of hepatitis B may be changing in the US. A larger proportion of cases are seen in parenteral drug abusers and in active heterosexuals. It is believed that hepatitis B vaccine has been administered to only 7% of the population who are at risk of acquiring hepatitis B virus (HBV). To achieve maximum control, universal immunization of infants will therefore be necessary. A first programme, already inaugurated in the US, involves screening of all pregnant women and providing appropriate prophylaxis to neonates of hepatitis B surface antigen-positive mothers and to susceptible household contacts of these individuals. Along with mandatory guidelines, collaboration between the hepatitis community, vaccine manufacturers, the CDC and appropriate medical, legislative and health care organizations should be fostered to achieve successful control of HBV in North America.

Adolescent↗

A multicenter clinical trial of oral ribavirin in HIV-infected people with lymphadenopathy: virologic observations. Ribavirin-LAS Collaborative Group.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin (600 and 800 mg) and a placebo was performed at four medical centers geographically distributed throughout the USA. One hundred and sixty-four HIV-infected adult men with lymphadenopathy were enrolled over a 2-month period and received active treatment for 24 weeks followed by a 4-week interval during which they did not receive the study drug. A marked interlaboratory variation in HIV isolation from peripheral blood mononuclear cells was observed, underscoring the critical role of quality assurance in similar multicenter trials. Nevertheless, the combined data indicate that ribavirin did not significantly suppress HIV activity (on measurement of reverse transcriptase activity) after week 6 or reduce serum p24 antigenemia.

AIDS-Related Complex↗

Microculture assay for isolation of human immunodeficiency virus type 1 and for titration of infected peripheral blood mononuclear cells.

To define the optimal conditions for human immunodeficiency virus (HIV) detection in microcultures, experiments were conducted with different ratios of patient and donor peripheral blood mononuclear cells (PBMCs). Donor/patient PBMC ratios ranged from 1:1 to 1:125. Optimal results were obtained when 1,500,000 donor cells were cocultured with equal or smaller quantities of patient PBMCs. Thus, virologic endpoints could be achieved by diluting patient cells. Smaller numbers of donor cells, with or without larger numbers of patients cells, resulted in lower rates of HIV isolation. Similarly, the direct stimulation of patient PBMCs with phytohemagglutinin without the addition of normal donor cells lowered the sensitivity of the assay significantly. We suggest that a microculture procedure using a fixed quantity of donor cells with different dilutions of patient cells may be useful for monitoring changing HIV levels during antiviral therapy.

Cells, Cultured↗

Intradermal inoculation with Heptavax-B. Immune response and histologic evaluation of injection sites.

The high cost of hepatitis B vaccine has limited its widespread use. Low-dose, intradermal injections of vaccine represent one option for reducing the cost. In this study, 92 nonimmune medical students were given three 0.1-mL intradermal injections of Heptavax-B containing 2 micrograms of hepatitis B surface antigen (HBsAg) at 0, 1, and 6 months. By 6 months, 90% of the subjects had developed protective levels of antibody to HBsAg (greater than or equal to 10 mIU/mL). Follow-up at 1 year showed a geometric mean concentration of antibodies to HBsAg of 396 mIU/mL for the group, and 95% had levels of antibody to HBsAg greater than or equal to 10 mIU/mL. A level of antibody to HBsAg of greater than 100 mIU/mL also was observed in more than 75% of subjects. Side effects included induration of the inoculation site in 18% at 6 months, which disappeared by 12 months, and macules that persisted at 1 year in 63%. The administration of hepatitis B vaccine intradermally is an attractive, low-cost alternative in the United States, where universal vaccination of preschool children or adolescents is being contemplated, and where booster doses are being considered.

Adult↗

AIDS in Bulgaria.

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Acquired Immunodeficiency Syndrome↗

Factors influencing the immune response to hepatitis B vaccine, booster dose guidelines, and vaccine protocol recommendations.

The clinical course and immunodiagnosis of hepatitis B infection is discussed. Immunization is necessary to prevent the clinical disease, the development of carriers, and the transmission of the hepatitis B virus to susceptible persons. Host factors that can curtail the immune response include increasing age, obesity, smoking cigarettes, and having a medical condition that compromises the immune system. Increasing the dose of vaccine, administering the inoculations intramuscularly, and giving the vaccine more frequently can enhance the immune response. The duration of immunity following vaccination has not yet been defined, but booster dose guidelines for selected groups are provided. Finally, recommendations for developing and implementing hepatitis B immunization protocols are presented.

Hepatitis B↗

In vivo and in vitro ultrastructural alterations induced by human immunodeficiency virus in human lymphoid cells.

The ultrastructural alterations induced by human immunodeficiency virus (HIV) in human lymphoid cells have been evaluated. Electron microscopic examination of peripheral blood mononuclear cells (PBMC) from 14 male homosexuals with confirmed acquired immunodeficiency syndrome (AIDS) or AIDS-related complex revealed that tubuloreticular inclusions were present in 5-15% of the cell sections from each case. In 5 of 14 cases, cylindrical confronting lamellae were found in 1-2% of the cell sections. No retrovirus-like particles or surface membrane alterations were detected. Neither of these structural alterations was observed in control PBMC obtained from six HIV-seronegative, hepatitis B virus surface antigen (HBsAg)-positive carriers or in 11 healthy subjects. When primary cultures of CD4+-enriched lymphocytes were infected in vitro with HIV, tubuloreticular inclusions could be detected in 3-10% of the cell sections, but no cylindrical confronting lamellae-like structures were found. In contrast, neither of these alterations were seen in uninfected or HIV-infected H9-HT continuous cell lines. These in vivo and in vitro studies indicate that there is an association between the appearance of the tubuloreticular inclusions and cytopathic HIV infection, although no correlation between cytopathic changes and active viral replication was observed at the single cell level. Further studies will be required to establish the mechanism(s) of formation of the tubuloreticular inclusions and to determine their prognostic potential.

AIDS-Related Complex↗

Human immunodeficiency virus-induced pathology favored by cellular transmission and activation.

Epidemiological data suggest that transmission of human immunodeficiency virus (HIV) occurs primarily by transference of virally infected cells. However, the efficiency of lytic productive infection induced by HIV after transmission of cell-associated virus vs. free virus is difficult to assess. The present studies compare the extent of depletion of CD4+ (helper/inducer) T cells after mixing uninfected cells with either free HIV or irradiated HIV-infected allogeneic or autologous cells in vitro. Rapid CD4+ cellular depletion occurred only in cultures containing allogeneic infected cells or after addition of a nonspecific T cell activation signal to cultures with autologous infected cells. These in vitro observations strongly support the epidemiological implication that interactions between infected and uninfected cells are the most efficient means of transmission and HIV-induced cytopathology in vivo. They also provide direct support for the concept that immunological stimulation by foreign cells infected with HIV dramatically increases the likelihood of transmission. These in vitro observations suggest a model for the acquisition of HIV in vivo and the role of cellular activation in dissemination of the virus to uninfected cells in an infected individual.

Acquired Immunodeficiency Syndrome↗

A simple assay based on HIV infection preventing the reclustering of MT-4 cells.

This report confirms and extends the recent work of Pauwels et al. on a "reclustering" assay (a simple microtitration plate method) for the determination of human immuno-deficiency virus (HIV) infection of MT-4 cells. MT-4 cells, which are highly susceptible to and permissive for HIV, typically grow in clusters. In the absence of virus these cell aggregates, after dissociation by pipetting, reform into clusters within 2 to 3 hours. Growth of HIV results in an inhibition of reclustering, with an end-point some 4-5 days after initiation of infection. In cultures inoculated with 5 to 8 TCID(50) of HIV, only 2-4% of the cells remain viable after 4 days. Correspondingly, HIV antigens can be detected by immunofluorescence in more than 90% of the cells remaining in the culture. The sensitivity of the "reclustering" assay is only slightly less than that of the immunofluorescence test. A colorimetric assay is also described that employs a tetrazolium salt (designated as MTT) to measure the cytolytic effect of various dilutions of HIV; comparable virus titres were obtained. This reclustering assay now appears to offer the simplest method for titration of prototype HIV in virus stocks and when used in drug evaluation tests and for measurement of HIV neutralizing antibodies.

Cell Aggregation↗

Fusion as a mediator of cytolysis in mixtures of uninfected CD4+ lymphocytes and cells infected by human immunodeficiency virus.

We describe an unusual type of cytopathology in which uninfected CD4+ (helper/inducer) cells (cells expressing the human leukocyte antigen CD4) interact with cells persistently infected with the human immunodeficiency virus (HIV). Prior antigenic stimulation was not required, since CD4+ cells taken either from healthy persons without anti-HIV antibodies or from individuals with anti-HIV antibodies were capable of inducing cytolysis. Neither CD8+ (suppressor/cytotoxic) nor CD16+ (natural killer) cells mediated the reaction. Light microscopic and autoradiographic studies revealed that, prior to cytolysis, multinucleated giant cells were formed from fusions between HIV-infected cells and large numbers of uninfected CD4+ lymphocytes. These data may explain the paradox that exists in vivo in which a dramatic depletion of CD4+ lymphocytes occurs in the presence of a small number of HIV-infected CD4+ cells. These new insights into the pathogenesis of acquired immunodeficiency syndrome (AIDS) may lead to future therapeutic strategies.

Acquired Immunodeficiency Syndrome↗