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Biomedical subjects

C R Horsburgh

Publications and source records attributed to C R Horsburgh.

At least 73 records · Page 4Linked to original sources
PubMed1991

Survival of patients with acquired immune deficiency syndrome and disseminated Mycobacterium avium complex infection with and without antimycobacterial chemotherapy.

The contribution of disseminated Mycobacterium avium complex (DMAC) infection to the morbidity and mortality of patients with acquired immune deficiency syndrome (AIDS) is unclear. Previous studies that suggested the decreased survival of patients with AIDS and DMAC had incomplete information on patient immunologic status and follow-up. We studied patients with AIDS and DMAC and compared their survival with that of AIDS patients without DMAC but with other comparable risk factors for survival. Case and control subjects were similar in terms of CD4 cell count, prior AIDS status, history of antiretroviral therapy, history of Pneumocystis carinii prophylaxis, and year of diagnosis. A group of 39 patients with untreated DMAC had significantly shorter survival, mean of 5.6 +/- 1.1 months (median 4 months), than 39 matched patients with AIDS but without DMAC, mean 10.8 +/- 1.3 months (median 11 months, p less than 0.0001). The survival of 16 additional patients with DMAC who received antimycobacterial therapy, mean of 9.5 +/- 1.4 months (median 8 months), was not significantly shorter than that of an additional 16 matched control subjects, mean 11.7 +/- 1.9 months (median 11 months, p = 0.58). Patients with treated DMAC survived significantly longer than those with untreated DMAC (p less than 0.01). We conclude that untreated DMAC significantly shortens survival. Moreover, these results indicate that patients with DMAC who receive antimycobacterial therapy do not experience the shortened survival seen in untreated DMAC.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Complement levels in patients with hepatic dysfunction.

Total hemolytic complement activity and serum complement protein concentrations were compared in 17 hospitalized patients with normal hepatic function and 16 patients with liver disease due to alcohol (15 patients) or acetaminophen toxicity (one patient). In contrast to the control patients, individuals with hepatic dysfunction had decreased total CH50 levels and low concentrations of total C3, C4, C5, factor B, and the regulatory proteins factor I and beta-1H. These patients also had increased C4d/C4 ratios, indicating classical pathway activation. The level of complement deficiency appears to correlate with either prolongation of the prothrombin time or depression of serum albumin concentration. These results indicate that patients with hepatic disease have severe complement depletion that is probably multifactorial in origin. This impairment in complement function will contribute to the impaired antibacterial host defense of the patient with chronic hepatic disease.

Complement System Proteins↗
PubMed1990

Concordance of polymerase chain reaction with human immunodeficiency virus antibody detection.

To evaluate the correlation of detection of human immunodeficiency virus (HIV) by polymerase chain reaction (PCR) with detection of HIV antibody, 271 simultaneous serum and peripheral blood mononuclear cell samples were examined from 242 persons whose activities placed them at increased risk for HIV infection: 142 from homosexual men, 86 from hemophilic men, and 43 from heterosexual partners of HIV-infected persons. PCR was performed using the gag region primer pair SK38/39 and the env region primer pairs SK68/69 and CO71/72. Amplified HIV DNA was detected using specific oligomer probes. Of 63 HIV antibody-positive samples, 58 (92%) had HIV DNA by PCR. Of 208 HIV antibody-negative samples, 7 (3.4%) had HIV DNA by PCR. On follow-up, 4 of the latter persons were seropositive when next tested; 2 were well and antibody- and PCR-negative; 1 had died of a stroke before retesting. Thus, PCR detects HIV in most antibody-positive persons; detection is increased by use of multiple primer pairs. PCR-positive antibody-negative specimens may indicate HIV infection in which antibody has not yet developed or may be false-positive PCR results. When PCR is discordant with HIV antibody, testing of additional specimens and clinical follow-up are necessary to assess HIV infection status.

Bisexuality↗
PubMed1990

Seroconversion to human immunodeficiency virus in prison inmates.

We evaluated the prevalence and incidence of human immunodeficiency virus (HIV) infection in 3,837 inmates of a state prison system. Ninety-two (2.4 percent) were HIV-seropositive. The highest proportion of HIV-seropositive inmates was found among Blacks (5.4 percent), females, and those 30 years of age or older. HIV-seropositivity of entering inmates was also 2.4 percent and was unchanged over the three years of the study. Seroconversion occurred in two inmates while in prison, a rate of one conversion per 604 person-years, but HIV infection could have occurred before entry. Seroconversion to HIV was rare in inmates in this correctional facility.

Adult↗
PubMed1989

Duration of human immunodeficiency virus infection before detection of antibody.

To estimate the duration and frequency of the period of HIV infection without detectable antibody, modelling techniques were applied to results of detection of HIV DNA by means of the polymerase chain reaction (PCR) and to data from cases in published reports. PCR was carried out with gag and env region primers on samples from 27 homosexual and 12 haemophilic men for whom stored samples were available from before and after seroconversion; serum was also tested for p24 antigen by antigen-capture enzyme immunoassay. HIV DNA was detectable before seroconversion in 4 men; in all 4 PCR was positive only in the seronegative sample taken closest to the time of seroconversion. In 3 men antigen was detected before seroconversion; in each case HIV DNA was also detected. By a Markov model, the time from infection with HIV (as assessed by detection of HIV DNA) to first detection of HIV antibody was estimated to be 2.4 (SE 2.1) months for the median individual. Modelling of cases of HIV infection with known exposure in published reports gave a median estimate of 2.1 (0.1) months from exposure to antibody detection, and 95% of cases would be expected to seroconvert within 5.8 (0.6) months. HIV infection for longer than 6 months without detectable antibody seems uncommon.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Infectiousness of HIV between male homosexual partners.

To estimate the risk of transmission of HIV per receptive anal sexual contact, 329 homosexually-active men, representing 155 sexual partnerships, were enrolled into a study. Information on HIV infection status and sexual behavior within and outside the primary relationship was collected. Of these 329 men, 24 had AIDS and 31 had ARC. Of the 155 couples, 35 consisted of partners that were both HIV +; 62 of partners that were both HIV-; and 58 were discordant. A binomial model was fit to data obtained in the first visit to estimate per contact risk of HIV transmission. Assuming a constant risk of transmission per sexual contact between infected and uninfected partners, the estimated risk is about 5 to 30 per 1000 receptive anal exposures to ejaculate. Although the average risk of HIV transmission per sexual contact appears to be low, there appears to be great variability in infectivity. To model this variability over time and across individuals, more complex models must be fit to longitudinal studies of sexual partners.

AIDS-Related Complex↗
PubMed1989

Increased incidence of infections in intravenous drug users.

To ascertain the incidence of infections in intravenous users of illicit drugs, we performed a retrospective study of 270 intravenous drug users (IVDUs) and 562 controls who did not use drugs over a seven-year period from 1978-1985. IVDUs had an increased overall incidence of infections (P less than 0.001) compared to controls, which was explained to a large degree by an increased incidence of hepatitis. Endocarditis and disseminated gonococcal infection were seen with increased frequency in IVDUs (P less than 0.05), but abscess and cellulitis were not. Neither acquired immunodeficiency syndrome (AIDS), tuberculosis, Pneumocystis pneumonia, nor disseminated viral or fungal infection were seen in IVDUs or controls. Heroin users, but not other IVDUs, had an increased incidence of infections not thought to be associated with needle use, suggesting impaired immunity. This study demonstrates that IVDUs have an increased incidence of infection compared to control subjects, but the kinds of infections have changed substantially over the past two decades. The presence of opportunistic pathogens in these patients should suggest concurrent infection with human immunodeficiency virus (HIV).

Adult↗
PubMed1989

Biologic factors in the sexual transmission of human immunodeficiency virus.

The probability that any single episode of genital-genital or anogenital sexual intercourse will result in transmission of HIV may be determined by multiple biologic factors of the infectious person, the virus itself, and the exposed susceptible person. Some of these factors are known or suspected (figure 1), and they may explain observed differences in the sexual transmission of HIV in different parts of the world, notably in Africa, where genital ulcerative disease is probably influencing the epidemiology of HIV. Several studies have shown that infection in partners of HIV-infected persons is not determined solely by numbers of sexual encounters; on the contrary, HIV-infected partners have usually had fewer sexual encounters with infectious mates than have noninfected partners. Thus, sexually active persons should be cautioned that, to our knowledge, there are no nonsusceptible persons and that any single unprotected sexual encounter may lead to HIV transmission. Research into biologic factors that modulate HIV transmission continues to be hampered by difficulties in identifying HIV transmitters and nontransmitters, infective and noninfective variants of HIV (if the latter exist in vivo), and persons relatively more or less susceptible to HIV infection. However, as the number of partner studies and the number of those enrolled in them increase, a progressively clearer idea of the biologic determinants of sexual transmission of HIV should emerge.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The epidemiology of disseminated nontuberculous mycobacterial infection in the acquired immunodeficiency syndrome (AIDS).

We analyzed cases of disseminated nontuberculous mycobacterial infection (DNTM) in patients with AIDS reported to the Centers for Disease Control. Between 1981 and 1987, 2,269 cases were reported. In 96% of cases, infection was caused by M. avium complex (MAC). The number of cases has risen steadily since 1981, but the rate as a percentage of AIDS cases has remained stable at 5.5%. DNTM was seen less frequently in AIDS cases with Kaposi's sarcoma than in other AIDS cases (p less than 0.01). Rates of DNTM were lower in Hispanics and declined with age but were not significantly different by patient sex or means of acquiring HIV infection. Rates of disseminated MAC varied by geographic region from 3.9% to 7.8% (p less than 0.0001). As assessed by helper/suppressor T-cell ratios, AIDS patients with DNTM were not more immunologically impaired than those with other opportunistic infections. Life table analysis revealed that AIDS patients with DNTM survived a shorter time (median, 7.4 months) than did other AIDS patients (median, 13.3 months; p less than 0.0001). We conclude that DNTM is acquired by unpreventable environmental exposures. Because DNTM adversely affects survival of AIDS patients, effective therapeutic agents must be vigorously sought.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Increased suppressor T cells in probable transmitters of human immunodeficiency virus infection.

To evaluate behavioral and immunologic factors related to transmission of human immunodeficiency virus (HIV) by homosexual intercourse, we studied a population of 329 homosexual/bisexual men (155 partner-pairs) seen in a community health center and medical outpatient clinic. Logistic regression analysis showed that behavioral risk factors for infection in the 130 HIV-infected men included: receptive anal intercourse (OR 4.6, 95% CI-1.8, 12.1); receptive fisting (OR 2.5, CI-1.1, 7.0); nitrite use (OR 2.3, CI-1.2, 4.6); history of gonorrhea or syphilis (OR 2.3, CI-1.4, 3.9); and history of sexual contact with men from areas with many AIDS cases (OR 1.9, CI-1.0, 3.5). Comparing seven men who were probable transmitters of HIV and 11 men who had not transmitted HIV to their uninfected partners despite unprotected insertive anal intercourse, we found no differences in HIV isolation from peripheral blood mononuclear cells, circulating HIV antigen detection, or presence of neutralizing antibody to HIV. Helper T-cell numbers were not significantly different between the two groups, but transmitters had more suppressor T-cells than did nontransmitters.

AIDS-Related Complex↗
PubMed1989

Immunologic evaluation of persons infected with human immunodeficiency virus.

Persons infected with HIV show changes in all aspects of immunity. Cellular immunity is affected most markedly, with decreased numbers of CD4+ (helper) and CD8+ (suppressor) T cells. Cellular immune function in vitro is frequently abnormal, as assessed by ability of T cells to proliferate in response to antigens or mitogens. Impaired humoral immunity is manifested in polyclonal B-cell activation and in impaired antibody responses to soluble antigens in vivo and in vitro. Numerous functional defects of macrophages have also been reported. The most valuable clinical laboratory tests for evaluation of the immune status of the HIV-infected individual are enumeration of circulating CD4+ and CD8+ cells and quantitation of circulating immunoglobulins. The results of these tests can help differentiate the immunosuppression caused by HIV from other causes of immunodeficiency. Helper T-cell counts are also important for selecting appropriate treatment regimens. Combinations of the results of these tests with those of virus culture or antigen detection assays provide additional prognostic information. Future research may help us recognize other patterns of immunodeficiency with specific clinical implications. It is hoped that new therapies, both antiviral and immune reconstitutive, will soon become available; at such time immunologic testing will be able to chart the return to normal immune function.

Antibody Formation↗
PubMed1989

Evaluation of an atypical HIV type 1 antibody. Serologic pattern leading to detection of HIV type 2 infection in North America.

The variability and discordance of human immunodeficiency virus type 1 (HIV-1) antibody enzyme immunoassay determinations on serial specimens derived, to our knowledge, from the first documented case of HIV-2 infection in North America are described. The initial specimen was weakly reactive, but two subsequent serum specimens were both nonreactive by enzyme immunoassay. All specimens were indeterminate for HIV-1 antibody by HIV-1 Western blot analysis. Serum HIV-2 antibody was demonstrated by enzyme immunoassay using whole virus lysate, HIV-2-specific synthetic peptide assays, and HIV-2 Western blot analysis. Human immunodeficiency virus type 2 genomic sequences were demonstrated in peripheral blood mononuclear cells using gene amplification technology. Human immunodeficiency virus type 2, isolated from peripheral blood lymphocytes, had typical morphologic features of lenti-virus by electron microscopy. Western blot analysis and other specific assays should be considered in individuals with clinical evidence suggesting HIV infection who are nonreactive for HIV-1 antibody by enzyme immunoassay or who have atypical reactivity patterns.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Hepatic inflammation, hepatitis B replication, and cellular immune function in homosexual males with chronic hepatitis B and antibody to human immunodeficiency virus.

We measured serum aspartate transaminase (AST) concentration and serum hepatitis B virus (HBV) DNA concentration in homosexual men with chronic HBV infection and a spectrum of immune deficiency as a result of exposure to human immunodeficiency virus (HIV). Serum AST and HBV DNA concentrations were similar in patients with varying immune function as indicated by in vivo criteria (diagnosis and skin tests reactivity) and in vitro criteria (lymphocyte transformation responses to mitogens and Candida and tetanus antigens) and were unrelated to the number of circulating T cells, suppressor/cytotoxic cells, helper cells, natural killer cells, and the helper:suppressor ratio. Serum AST concentration and indices of cellular immune function were similar in patients with varying HBV replicative activity (high and low HBV DNA concentrations). The observed lack of relationship between serum AST concentration and indices of cellular immune function and HBV replication suggests either that other factors determine the severity of hepatic inflammation in chronic HBV infection, or that currently available tests of cellular immune function and HBV replicative activity do not accurately reflect processes in the liver.

Adult↗
PubMed1988

Lack of evidence of prolonged human immunodeficiency virus infection before antibody seroconversion.

Recently, considerable concern has been raised regarding the possibility that antibody-based screening tests for the human immunodeficiency virus (HIV) may fail to detect certain high-risk individuals for prolonged periods of time. It has been proposed that testing for HIV-related antigen may be a necessary procedure to detect such individuals. To address this issue, we longitudinally studied two groups of homosexual men: direct sexual partners of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) patients and individuals who ultimately sero-converted. There was no evidence of prolonged infection with HIV in the absence of detectable antibody in these two groups. It appears at this time that, even among subjects at very high risk for HIV infection, currently available antibody-based assays are sufficient to identify infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Preventive strategies in sexually transmitted diseases for the primary care physician. US Preventive Services Task Force.

This study provides the background recommendations of the US Preventive Services Task Force for interventions by primary care physicians to prevent sexually transmitted diseases. Rationale for and data supporting use of barrier methods, epidemiologic treatment, contact tracing, patient education, prophylactic antibiotics, and disease reporting are discussed. Specific recommendations include those for gonorrhea, syphilis, human immunodeficiency virus infection, enteric infections, human papillomavirus infection, herpes simplex virus infection, and Chlamydia trachomatis infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Lymphokines and platelets promote human monocyte adherence to fibrinogen and fibronectin in vitro.

Monocytes must accumulate in areas of tissue injury and inflammation to effect phagocytosis, antigen presentation, and monokine production. Fibrinogen/fibronectin matrices have been demonstrated in healing wounds and in delayed-type hypersensitivity skin reactions. We have developed an in vitro system for investigation of the ability of fibrinogen and fibronectin matrices to serve as substrata for human peripheral blood monocyte adherence. Monocyte adherence was greatest on matrices of both fibrinogen and fibronectin, less to fibrinogen alone, and least to fibronectin alone. Lymphokines increased adherence of monocytes to all three surfaces but not to albumin-coated surfaces. Addition of platelets also caused a dose-dependent increase in monocyte adherence to all three surfaces. This increased adherence was not a simple function of arachidonic acid metabolites, stable platelet products, nor monocyte binding sites on the platelet membrane. The effect of platelets was not additive to the effect of lymphokines. We conclude that fibrinogen and fibronectin provide a framework for monocyte adherence and that factors present in areas of inflammation and wound healing, such as lymphokines and platelets, can augment this adherence. Such adherence facilitates the transformation of monocytes into macrophages in vitro and may also foster such transformation in vivo.

Blood Platelets↗
PubMed1987

The significance of antilymphocyte antibodies in patients with acquired immune deficiency syndrome (AIDS) and their sexual partners.

Antilymphocyte antibodies have been demonstrated in autoimmune diseases, acute viral infections, and acquired immune deficiency syndrome (AIDS) by using either the conventional microlymphocytotoxicity or the double fluorescence technique. In the present study, we used both methods to detect the antilymphocyte antibodies and to characterize further their immunologic significance in patients with AIDS and their sexual partners. The results using the conventional microlymphocytotoxicity method demonstrated that 8 of 10 patients with AIDS and 6 of 10 partners had significant levels of antilymphocyte antibodies which were reactive with B and T cells at cold and warm temperatures. A significant loss in antibody activity following absorption with B, T, and Daudi cells and Staphylococcus aureus, but not platelets or red cells, indicated that these antibodies are not directed to HLA class I antigens but, rather, to antigens that are common to both groups of lymphocytes. There is a close association between antilymphocyte antibodies and lymphopenia in patients but not in partners. Antibodies against lymphocyte subclasses [helper (T4) and suppressor (T8)] were detected by the double fluorescence staining technique, which employs C6-deficient serum as a nonlytic source of complement, and demonstrated the binding of antibodies to target cells, in contrast to lysing of the target cells as in the microlymphocytotoxicity method. The results of this assay showed that antibodies were directed to both populations, and there was no correlation or association between the absolute numbers of peripheral T4 and T8 cells and the percentage of antibody binding. Taken together, there appear to be at least two kinds of antilymphocyte antibodies: lymphocytotoxic antibodies detected by the conventional microlymphocytotoxicity assay and noncytotoxic antibodies detected by the double fluorescence staining technique. The former may be responsible in part for the lymphopenia. The latter may alter lymphocyte function. The patients and partners who had antilymphocyte antibodies also had anti-HTLV-III antibodies, although there was not any close correlation between titers. These findings support the possibility that both types of antibodies occur as part of a generalized immune response, possibly stimulated by the same viral agent.

Acquired Immunodeficiency Syndrome↗