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Biomedical subjects

C R Horsburgh

Publications and source records attributed to C R Horsburgh.

At least 55 records · Page 3Linked to original sources

Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin.

BACKGROUND AND METHODS: The frequency of infection with multidrug-resistant Mycobacterium tuberculosis is increasing. We reviewed the clinical courses of 171 patients with pulmonary disease due to M. tuberculosis resistant to rifampin and isoniazid who were referred to our hospital between 1973 and 1983. The patients' records were analyzed retrospectively. Their regimens were selected individually and preferably included three medications that they had not been given previously and to which the strain was fully susceptible. RESULTS: The 171 patients (median age, 46 years) had previously received a median of six drugs and shed bacilli that were resistant to a median of six drugs. Thus, their regimens were frequently not optimal. Of 134 patients with sufficient follow-up data, 87 (65 percent) responded to chemotherapy (as indicated by negative sputum cultures for at least three consecutive months); 47 patients (35 percent) had no response, as shown by continually positive cultures. The median stay in the hospital was more than seven months. In a multivariate analysis, an unfavorable response was significantly associated with a greater number of drugs received before the current course of therapy (odds ratio, 4.0; 95 percent confidence interval, 1.6 to 9.9; P < 0.001) and with male sex (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 6.2; P < 0.03). Twelve of the patients with responses subsequently had relapses. The overall response rate was 56 percent over a mean period of 51 months. Of the 171 patients, 63 (37 percent) died, and 37 of these deaths were attributed to tuberculosis. CONCLUSIONS: For patients with pulmonary tuberculosis that is resistant to rifampin and isoniazid, even the best available treatment is often unsuccessful. Only about half of such patients eventually have negative sputum cultures despite carefully selected regimens administered for extended periods. Failure to control this resistant infection is associated with high mortality and ominous implications for the public health.

Adolescent↗

A prospective evaluation of Mycobacterium avium complex colonization of the respiratory and gastrointestinal tracts of persons with human immunodeficiency virus infection.

To describe the natural history of Mycobacterium avium complex (MAC) in the respiratory or gastrointestinal tract of persons with human immunodeficiency virus (HIV) infection, 67 HIV-infected patients with CD4+ cell counts < 200/mm3 and initial negative MAC blood cultures were followed prospectively. Patients were screened every 3 months with cultures and smears of sputum, rectal swab, and blood for mycobacteria. Fourteen patients (20.9%) developed positive blood cultures for MAC (23.4%/year). Sputum cultures revealed MAC in 3 (21%) of the 14 patients at 1, 2, and 8 months before dissemination; no smears were positive. No rectal swab cultures or smears were positive before dissemination. Colonization of the respiratory and gastrointestinal tracts in persons with HIV infection and < 200/mm3 CD4+ cells is infrequently detected with currently available techniques. Screening cultures and smears of sputum and stool do not appear to be sensitive methods for detection of early MAC infection.

Antigens, CD↗

Low serum levels of oral antimycobacterial agents in patients with disseminated Mycobacterium avium complex disease.

Twenty-seven human immunodeficiency virus-infected patients with disseminated Mycobacterium avium complex disease who were treated with oral antimycobacterial agents (clofazimine, ciprofloxacin, ethambutol, and rifampin) were studied to evaluate the usefulness of monitoring serum drug concentrations and testing in vitro susceptibility of M. avium complex (MAC) isolates. Twenty patients tolerated treatment with three or four antimycobacterial agents for at least 8 weeks; mycobacteremia was eradicated in 7 (35%). The in vitro susceptibilities of MAC isolates to antimycobacterial agents were similar for these 7 and for the 13 who did not respond to antimycobacterial treatment. Serum drug levels were below the expected range in 6 of the 7 whose mycobacteremia was cleared and in 9 of the 13 nonresponders (P = .41). These low serum concentrations of antimycobacterial drugs may be due to impaired drug absorption in patients with AIDS and disseminated MAC disease.

AIDS-Related Opportunistic Infections↗

Epidemiology of disseminated nontuberculous mycobacterial disease in children with acquired immunodeficiency syndrome.

Between 1981 and 1991, disseminated nontuberculous mycobacterial infection (DNTM) was reported in 199 (5.7%) of 3472 children less than 13 years of age with acquired immunodeficiency syndrome (AIDS) in the United States. More than 85% of DNTM cases were caused by infection with Mycobacterium avium complex. The proportion of AIDS cases with DNTM was higher in those with hemophilia or transfusion-associated human immunodeficiency virus (HIV) infection than in those with perinatally acquired HIV infection (12.9% and 13.8% vs. 4.6%; P < 0.001). The proportion of AIDS cases with DNTM did not differ significantly by sex (6.1% in males and 5.3% in females) or race (7.4% in whites, 5.0% in blacks and 5.5% in Hispanics) when stratified by HIV transmission category. An active HIV infection surveillance project in 6 geographic areas revealed that the median age at diagnosis of DNTM was 3.3 years for perinatally acquired HIV infection but 8.7 years for DNTM in children with hemophilia or AIDS associated with transfusion, presumably because many of the latter acquired HIV at an older age. Among children with DNTM who had CD4 counts performed within 6 months of the date of DNTM, the median was 17 cells/mm3 and 70% of cases of DNTM occurred in children with fewer than 50 CD4 cells. We conclude that clinicians should have a high index of suspicion for DNTM in children with lower CD4 counts and a longer duration of HIV infection and that preventive strategies, such as prophylactic antimycobacterial therapy, should be focused on this group of children.

AIDS-Related Opportunistic Infections↗

Comparison of four decontamination methods for recovery of Mycobacterium avium complex from stools.

The presence of Mycobacterium avium complex (MAC) in stool specimens may be a predictor of disseminated MAC infection, yet the methods for decontaminating stools have not been evaluated for their usefulness in recovering MAC organisms. In the present study, four decontamination methods commonly used to recover acid-fast bacteria from respiratory specimens were compared for their utility in recovering MAC from stool specimens. Ten strains of MAC were used at a level of 10(4) to 10(6) CFU to seed the stool specimens. Specimens were divided into four portions and were decontaminated by using the following treatments: (i) N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH), (ii) cetylpyridinium chloride-sodium chloride (CPC-NaCl), (iii) oxalic acid, or (iv) benzalkonium chloride-trisodium phosphate (BC-TSP). The specimens were then plated onto a total of five pieces of selective and nonselective egg- and agar-based media. The oxalic acid method yielded the greatest number of MAC CFU from seeded stool samples; this was followed by NALC-NaOH, BC-TSP, and CPC-NaCl. The difference between the oxalic acid method and each of the other methods was statistically significant (analysis of variance at the 95% significance level). Although more MAC CFU was recovered from seeded stool samples by using oxalic acid than NALC-NaOH, no difference in culture positivity rates was observed when the two methods were used to test 368 clinical stool specimens processed with either oxalic acid (164 specimens) or NALC-NaOH (204 specimens) (P = 0.07) or 67 specimens processed by both methods (P = 0.77). The oxalic acid and NALC-NaOH decontamination methods both appear to be useful for the recovery of MAC organisms from stool specimens.

AIDS-Related Opportunistic Infections↗

Survival prognosis of HIV-infected patients.

Previous studies of survival after a diagnosis of acquired immunodeficiency syndrome (AIDS) have reported variation in temporal trends in association with age, gender, race, mode of transmission, lymphadenopathy, antiretroviral therapy, and presence of specific opportunistic infections at diagnosis. We used a logistic regression model to assess the effect of these factors while controlling for other potential predictors of time from initial CD4 cell count to death in 839 HIV-infected patients at a public hospital in Atlanta, Georgia. Our study found that a CD4 level of < 200 cells/microliters [odds ratio (OR) = 1.71; 95% confidence interval (CI) of 1.58, 1.85] and the presence of an AIDS-indicating condition (initial diagnosis OR = 2.50 and CI of 1.93, 3.24; diagnosis of a second AIDS condition OR = 3.02 and CI of 2.08, 4.40) are independently predictive of survival in HIV-infected persons. Furthermore, specific clinical manifestations of AIDS vary in their contribution to progression from diagnosis of AIDS to death. Therefore, changes in survival of AIDS patients must take into account changes over time in the relative frequency of specific AIDS-indicating diagnoses.

AIDS-Related Opportunistic Infections↗

Effects of disease stage and zidovudine therapy on the detection of human immunodeficiency virus type 1 in semen.

OBJECTIVE: To determine the prevalence and temporal expression of infectious human immunodeficiency virus type 1 (HIV-1) in the semen of HIV-1 seropositive men and to determine whether the detection of HIV-1 in semen is associated with disease stage, zidovudine treatment status, or other clinical factors. DESIGN: A microculture technique was used to detect infectious HIV-1 in semen from a cohort of 95 seropositive men. In addition, semen cultures were performed monthly for at least 6 months for 14 of the men. Information was obtained by interview and extracted from medical records to identify clinical variables associated with HIV-1 in semen. PATIENTS: Sixty HIV-1 seropositive homosexual men participating in clinical studies at the Fenway Community Health Center, Boston, Mass, and 35 HIV seropositive bisexual or heterosexual men participating in the California Partner Study of the University of California, San Francisco. MAIN OUTCOME MEASURES: Semen HIV-1 culture results, seminal leukocyte counts, Centers for Disease Control (CDC) disease stage, peripheral CD4+ cell counts, zidovudine therapy, HIV risk category. RESULTS: In the cross-sectional study, HIV-1 was cultured from the semen of nine (9%) of 95 men. Factors associated with detection of HIV-1 in semen were peripheral CD4+ cell counts of 0.20 x 10(9)/L (200/microL) or less (adjusted odds ratio [OR], 23.33; 95% confidence interval [Cl], 2.89 to 175.63); symptomatic (CDC class IV) disease (adjusted OR, 6.56; 95% Cl, 1.02 to 66.76); and seminal leukocytosis (greater than 1 x 10(9) white blood cells per liter of semen) (adjusted OR, 7.02; 95% Cl, 1.28 to 39.29). Zidovudine therapy was associated with decreased detection of HIV-1 in semen (adjusted OR, 0.04; 95% Cl, 0.00 to 0.63). In the longitudinal study of 14 men who had neither peripheral CD4+ cells counts of 0.20 x 10(9)/L or less nor seminal leukocytosis, seminal HIV-1 was detected in at least one sample from six men (43%). CONCLUSION: HIV-1 is more commonly found in semen from men with advanced HIV-1 infection and seminal leukocytosis but can also be cultured from semen of men with neither of these conditions. Zidovudine therapy may decrease the prevalence and/or titer of seminal HIV-1. However, all HIV-1-infected persons should continue to assume that they are potentially infectious through sexual contact.

CD4-Positive T-Lymphocytes↗

The relation between nitrite inhalants, unprotected receptive anal intercourse, and the risk of human immunodeficiency virus infection.

The role of nitrite was evaluated between 1985 and 1988 in a study of sexual transmission of the human immunodeficiency virus (HIV) among homosexual male couples in Boston, Massachusetts. Initial enrollment data suggested that a history of unprotected receptive anal intercourse (odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.4-3.6) and a history of nitrite use (OR = 1.7, 95% CI 1.1-2.5) were independent risk factors for HIV infection. In addition, interaction between nitrite use and unprotected receptive anal intercourse was observed (OR = 5.5, 95% CI 2.8-11.1) after controlling for number of unprotected receptive anal sex partners and history of sexually transmitted diseases. Since it was felt that nitrite use might be a marker for unprotected receptive anal sexual activity, a supplemental questionnaire was administered to obtain information on simultaneous nitrite use and unprotected receptive anal intercourse. The supplemental data suggested a strong interaction between nitrite use and unprotected receptive anal intercourse in increasing the risk of HIV infection. In the adjusted analyses, the odds ratio for HIV infection was considerably greater among men who always used nitrites during unprotected receptive anal intercourse (OR = 31.8, 95% CI 12.9-76.7) compared with men who sometimes (OR = 7.1, 95% CI 2.1-23.6) or never (OR = 9.0, 95% CI 2.5-32.1) used them. These findings have preventive public health implications and may add insight into our understanding of the mechanism by which HIV infection spread rapidly among homosexual men in the early 1980s.

Adult↗

Corroboration of sexual histories among male homosexual couples.

Using data from a study of human immunodeficiency virus transmission among homosexual male partners from Boston, Massachusetts, the authors compared self-reported sexual histories among 155 index-partner pairs during 1985-1988. Overall, high levels of agreement were observed for all reported sexual activities. Agreement on anal sex was very high (Spearman's r = 0.78-0.79, p less than or equal to 0.001; kappa = 0.76-0.88, p less than or equal to 0.001). Level of agreement did vary significantly by a couple's drug and alcohol use; the heavier substance user generally reported fewer sexual encounters than the lighter user. These results have important implications in sexual behavior research and show that among homosexual men, self-reports of sexual behavior may be reasonably valid.

Acquired Immunodeficiency Syndrome↗

Disseminated Mycobacterium avium complex infection: clinical identification and epidemiologic trends.

To evaluate the incidence of disseminated Mycobacterium avium complex infection (DMAC) and to define the association between signs and symptoms and development of DMAC in patients with human immunodeficiency virus (HIV) infection, all cases of DMAC at Grady Memorial Hospital Infectious Disease Clinic (Atlanta) between 1985 and 1990 were reviewed, and a prospective study of the association of symptoms with DMAC was done. Between 1985 and 1990, DMAC occurred in 16% of patients with AIDS. Incidence increased from 5.7% in 1985-1988 to 23.3% in 1989-1990 (P less than .001). Median time from AIDS diagnosis to diagnosis of DMAC increased from 4.5 months in 1985-1988 to 8 months in 1989-1990 (P less than .02). In the prospective study, DMAC was seen only in persons with a CD4+ count less than 100 cells/mm3 and was associated with fever (P less than .03), anemia (P less than .001), weight loss (P less than .01), diarrhea (P less than .01), and elevated alkaline phosphatase (P less than .01). It is recommended that all such HIV-infected persons have mycobacterial blood cultures done.

Acquired Immunodeficiency Syndrome↗

Changes in the spectrum of AIDS-defining conditions and decrease in CD4+ lymphocyte counts at AIDS manifestation in Germany from 1986 to 1991.

OBJECTIVES: Analysis of changes in the spectrum of AIDS-defining conditions and their correlation with CD4+ lymphocyte counts in different risk groups associated with HIV transmission. METHODS: Review of data from all adult AIDS cases reported in Germany between 1986 and 1991. RESULTS: Among AIDS cases diagnosed between 1986 and 1991, the proportion of cases with lymphoma and wasting syndrome increased, while the proportion of Kaposi's sarcoma decreased. Homosexual men, but not intravenous drug users, showed a decrease in the proportion of cases in Pneumocystis carinii pneumonia and an increase in the proportions with toxoplasmosis and cytomegalovirus infection. The median CD4+ lymphocyte count at time of AIDS diagnosis decreased from 73 x 10(6)/l in 1986 (25 and 75 percentiles, 28 and 212) to 47 x 10(6)/l in 1990 (25 and 75 percentiles, 20 and 120; P less than 0.01). This decrease was the result of reduced CD4+ lymphocyte counts of individuals presenting with opportunistic infections; there was no corresponding change for individuals with non-infectious AIDS-defining conditions. CONCLUSIONS: AIDS diagnosis is now occurring at a later time in the natural history of HIV infection than in 1986, and the relative frequency of specific AIDS-defining conditions has changed. Most pronounced is a decrease of Pneumocystis carinii pneumonia. Changes in the natural history of HIV infection due to therapeutic and prophylactic interventions must be considered when interpreting epidemiological data in the course of the AIDS epidemic. These changes also have implications for the planning and execution of medical care.

Acquired Immunodeficiency Syndrome↗

A comparison of HIV-1 antibody classes, titers, and specificities in paired semen and blood samples from HIV-1 seropositive men.

Twenty-eight paired blood and semen samples obtained from human immunodeficiency virus type 1 (HIV-1) seropositive men at various stages of disease progression were evaluated for titer and immunoglobulin (Ig) class by an enzyme-linked immunosorbent assay (ELISA). Blood antibody titers ranged from 40,000 to 4,000,000 with a median of 40,000. Semen titers ranged from 400 to 40,000 with a median of 400. HIV-1 antibody titers in matched semen and blood samples showed a strong positive correlation (r = 0.963). The ratio of semen:blood titers ranged from 1:1000 to 1:10 with a median of 1:100. There was no correlation between blood or semen antibody titer and stage of disease of the patients. However, there was a trend toward higher (greater than or equal to 4000) semen antibody titers in men with evidence of genital tract inflammation greater than 10(6) white blood cells/ml semen; 3/5 versus 5/23, p greater than 0.1 Fisher exact test). All HIV-1 antibodies detected were of the IgG class; no IgA or IgM class antibodies of titers greater than or equal to 40 were found in either blood or semen. Thirteen paired blood and semen samples from individual patients were analyzed for antibody specificity by Western blot. In some cases antibody profiles in semen were different from those in blood; strong antibody reactivity against the gp160 viral coat antigen band was consistently detected in semen and blood, whereas the prevalence of detectable antibody reactivity against the p55 and p17 HIV-1 antigen bands was significantly reduced in semen.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗

Human T lymphotropic virus type II (HTLV-II) infection in a cohort of New York intravenous drug users: an old infection?

To identify risk factors for human T lymphotropic virus type II (HTLV-II) infection in intravenous drug users (IVDUs), participants in a longitudinal study of human immunodeficiency virus (HIV) infection in a New York methadone maintenance program were studied. Of 270 participants tested for HTLV-I/II, 21 (8%) were seropositive. Of those, 15 (71%) had HTLV-II-specific sequences by polymerase chain reaction (PCR) and 1 (5%) had both HTLV-I- and -II-specific sequences; 3 persons with indeterminate serologic results were also PCR-positive for HTLV-II. HTLV-II infection was significantly associated with older age but was not predicted by sex, race, socioeconomic status, transfusion history, or HIV infection status. Behavioral factors since 1978, such as duration and frequency of intravenous drug use, needle sharing, visits to shooting galleries, or number of sex partners, were also not associated with HTLV-II infection. These findings are in contrast with the association of these risk factors with HIV in this group and suggest that, among IVDUs, HTLV-II is an older endemic infection that is less efficiently transmitted than HIV.

Adult↗