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Biomedical subjects

K H Mayer

Publications and source records attributed to K H Mayer.

At least 19 recordsLinked to original sources

A genome-wide association study of methamphetamine use among people with HIV.

BACKGROUND: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors. METHODS: Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n&#x2009;=&#x2009;1,196 reported ever use, n&#x2009;=&#x2009;4,750 reported never use). RESULTS: No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p&#x2009;<&#x2009;5 * 10-8) in our study. Further, we did not replicate previously suggested genetic variants from other studies (all p&#x2009;>&#x2009;0.05 in our analysis). DISCUSSION: Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary.

Humans

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

Lomefloxacin: microbiologic assessment and unique properties.

In comparative studies, lomefloxacin, a new difluorinated quinolone, exhibits broad antibacterial activity in vitro, similar or superior to that of other quinolones (enoxacin, ofloxacin, pipemidic acid, nalidixic acid, and norfloxacin) but less than that of ciprofloxacin. Lomefloxacin inhibited Neisseria gonorrhoeae, Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus aureus, and the majority of aerobic gram-negative rods, including nosocomial isolates, at concentrations readily achievable in biologic fluids and tissues. Lomefloxacin was less active against obligate anaerobes and streptococci. Organisms resistant to methicillin, penicillin, or the aminoglycosides were susceptible to lomefloxacin. No significant lomefloxacin resistance was identified in 18 countries in which in vitro studies were conducted, with the exception of a small number of strains tested in France. The frequency with which spontaneous single-step resistance to lomefloxacin develops in vitro is low.

Anti-Infective Agents

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

Maintenance of behavioral change in a cohort of homosexually active men.

OBJECTIVES: To assess associations of perceptions of sexual behavior change with actual risk behaviors and psychosocial variables, and to determine whether perceptions of behavior change predict subsequent behavior. DESIGN: Cohort study of homosexually active men. SETTING: Community health center in Boston, Massachusetts, USA. PATIENTS, PARTICIPANTS: Two hundred and sixty-two cohort members who participated in follow-up in 1989 and who had at least one subsequent visit. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Composite risk behavior variable, based on unprotected anogenital contact and number of partners. RESULTS: Of the 96% who had effected behavior change, 47% perceived that they were able to maintain those changes consistently and 58% wanted to make more changes. Perceptions of consistent maintenance were associated with lower risk behavior, lower perceived riskiness of behaviors and susceptibility to AIDS, and fewer barriers to behavior change. Desire for more change was associated with increased behavioral effort, fewer barriers to condom use, and greater perceived riskiness of current behavior. Among those with lower risk behaviors, perceived inconsistent maintenance predicted relapse to more risky behavior at the following visit. CONCLUSIONS: Perceived maintenance of behavior change is potentially useful in identifying individuals at risk of relapse from safer sex.

Acquired Immunodeficiency Syndrome

[Conventional therapy exemplified by COPD].

Conventional therapies are those, that are generally agreed on and applied. With COPD these are strongly anti-inflammatory corticosteroids, bronchodilatant betamimetics, vagolytics and theophyllines, within certain indications antibiotics, secretolytics and secretomotorics, physical therapy and therapy of secondary effects. At present those measures, that might mitigate the status of patients importantly, e.g. patient training and beyond this early diagnosis and therapy to improve the prognosis are still unconventional. Prophylactic measures, importantly influencing pathogenesis and progression of the disease, would be of special importance. Prevention of cigarette smoking would show the greatest benefit. It would be desirable, that these unconventional measures would be more widespread in use than is presently the case.

Adrenal Cortex Hormones

Women and AIDS.

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Acquired Immunodeficiency Syndrome

An IgG human monoclonal antibody that reacts with HIV-1/GP120, inhibits virus binding to cells, and neutralizes infection.

A human mAb (HmAb) termed F105 was obtained by fusion of antibody-producing EBV-transformed cells with the HMMA2.11TG/O cell line. F105 is an IgG1 kappa antibody that binds to the surfaces of cells infected with all HIV-1 strains tested: MN, RF, IIIB, and SF2, but not uninfected cells. The HmAb immunoprecipitates GP120 from all four strains. F105 does not react with denatured GP120 on Western blots, but does react with viral lysates and purified GP120 dotted onto nitrocellulose filter paper under nondenaturing conditions. rGP120 from SF2 and soluble rCD4 inhibit antibody binding to infected cells in a dose-dependent manner. F105 inhibits the binding of free, infectious virions to uninfected HT-H9 cells with 50% of maximal (100%) inhibition at approximately 1 microgram/ml. F105 inhibits infection of HT-H9 cells by 100 tissue culture infective dose 50% units of MN and IIIB strains with 50% inhibition at concentrations of HmAb readily achievable in man. It appears that the F105 HmAb reacts with a conformationally defined epitope on HIV-1/GP120 that is exposed on the free virion and is important for binding to the cell surface by the virion. The epitope, which is immunogenic in humans, appears to be within, or topographically near, the CD4-binding site. F105 and the F105 epitope are potentially useful in therapy and in the design of peptide or anti-Id based vaccines; monitoring of the expression of the Id may prove useful in evaluating immune responses in infected individuals or vaccinated volunteers.

Antibodies, Monoclonal

Failure of ciprofloxacin to eradicate convalescent fecal excretion after acute salmonellosis: experience during an outbreak in health care workers.

OBJECTIVE: To determine the efficacy of ciprofloxacin therapy in eradicating convalescent fecal excretion of salmonellae after acute salmonellosis. DESIGN: Randomized, placebo-controlled, double-blind trial of ciprofloxacin, with prospective follow-up of nonparticipants. SETTING: An acute care community hospital experiencing an outbreak of salmonellosis. PATIENTS: Twenty-eight health care workers developed acute infection with Salmonella java; 15 participated in a placebo-controlled trial of ciprofloxacin, beginning on day 9 after infection. INTERVENTIONS: Eight patients were randomly assigned to receive ciprofloxacin, 750 mg, and 7 patients to receive placebo; both were administered orally twice daily for 14 days. Nonparticipants who received therapy were placed on the same ciprofloxacin regimen. MEASUREMENTS AND MAIN RESULTS: Study participants had follow-up stool cultures every 3 days initially and then weekly for 3 weeks; nonparticipants were followed until three consecutive cultures were negative. All eight ciprofloxacin recipients showed eradication of S. java from stool cultures within 7 days of beginning therapy (compared with 1 of 7 placebo recipients), and their stool cultures remained negative up to 14 days after discontinuing therapy (P less than 0.01). However, 4 of 8 relapsed; their stool cultures became positive between 14 and 21 days after therapy. In addition, 3 of 3 hospitalized patients treated with ciprofloxacin who did not participate in the controlled trial also relapsed. Thus, the total relapse rate was 7 of 11 (64%; 95% CI, 31% to 89%). In 4 of these 7 patients, relapse was associated with a longer duration of fecal excretion of salmonellae than that of the placebo group. Relapse could not be explained on the basis of noncompliance, development of resistance, or presence of biliary disease. CONCLUSIONS: Despite its excellent antimicrobial activity against salmonellae and its favorable pharmacokinetic profile, ciprofloxacin at a dosage of 750 mg orally twice daily had an unacceptably high failure rate in patients with acute salmonellosis and may have prolonged fecal excretion of salmonellae. The late occurrence of relapses indicates the need to obtain stool cultures up to 21 days after therapy to document fecal eradication in acute salmonellosis.

Acute Disease

Plasma adenosine deaminase2 is a marker for human immunodeficiency virus-1 seroconversion.

Plasma adenosine deaminase2 (ADA2) has recently been proposed to be a marker for human immunodeficiency virus-1 (HIV) infection. We measured ADA2 levels in plasma from two groups of white homosexual males at 6-month intervals for a total of 2.5 years. One group consisted of 6 subjects who seroconverted for HIV, and the other consisted of 8 HIV seropositive patients who progressed from asymptomatic (CDC Groups II/III) to symptomatic (CDC Group IV) disease. Seroconversion was associated with a significant increase in plasma ADA2 which persisted throughout follow-up of 1.5 years. However, disease progression in HIV seropositive patients was not associated with any significant change in plasma ADA2. In conclusion, ADA2 may represent a unique marker for HIV seroconversion which does not change with later progression to symptomatic disease.

Adenosine Deaminase

Combination therapy with ciprofloxacin plus azlocillin against Pseudomonas aeruginosa: effect of simultaneous versus staggered administration in an in vitro model of infection.

The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal beta-lactam with ciprofloxacin against P. aeruginosa.

Azlocillin

Human immunodeficiency virus infection in North American women: experience with 200 cases and a review of the literature.

This study was designed to define the epidemiology and natural history of human immunodeficiency virus (HIV) infection in women in Rhode Island. Two hundred women referred to Brown University physicians from 1986 through 1990 were evaluated at 3-to-6-month intervals for 12 to 60 months. All received antiretroviral therapy and prophylaxis against opportunistic infections when indicated on the basis of CD4 lymphocyte counts. Major findings included: 1) rapid shift of dominant mode of transmission from intravenous drug sharing to heterosexual route; 2) significant gender-specific differences in clinical presentation; 3) increased frequency of cervical dysplasia in women infected via intravenous needle sharing; 4) no definite gender-specific differences in progression of HIV infection; 5) enormous societal impact of HIV infection in women. Principal conclusions are: 1) rapid change to predominantly heterosexual HIV transmission can occur in North America, with serious societal impact; 2) gender-specific clinical features can lead to earlier diagnosis of HIV infection in women; 3) HIV infection in women does not pursue an inherently more rapid course than that observed in men.

Adolescent

Plasma adenosine deaminase2: a marker for human immunodeficiency virus infection.

Plasma concentrations of the two isoenzymes of adenosine deaminase (ADA, E.C. 3.5.4.4), adenosine deaminase1 (ADA1) and adenosine deaminase2 (ADA2), were measured in a cohort of ambulatory patients infected with the human immunodeficiency virus (HIV) and controls. A sensitive isoenzyme-specific radioisotopic assay system was developed for these studies. Among 22 HIV-infected patients, plasma ADA2 was significantly elevated as compared with 16 control subjects (p less than 0.01) and 6 uninfected subjects having a risk factor for HIV infection (p less than 0.01). Plasma ADA2 was not associated with the stage of disease as defined by clinical status (p greater than 0.05) or helper (CD4) lymphocyte count (p greater than 0.05). Available evidence suggests that elevated plasma ADA2 could be a useful surrogate marker for HIV infection that occurs early in the disease process.

Adenosine Deaminase

Hierarchical pattern of mucosal candida infections in HIV-seropositive women.

PURPOSE: Candida is the most common cause of opportunistic mucosal infections in human immunodeficiency virus (HIV)-positive women. We had observed an apparent correlation between the severity of immunodeficiency and the site of mucosal candida infection. The current study was designed to determine whether significant correlations existed between the sites of mucosal candida infection and the degree of immunodeficiency, as determined by subsets of lymphocyte populations. PATIENTS AND METHODS: The subjects in this study are 66 HIV-seropositive women evaluated by members of the Brown University Acquired Immunodeficiency Syndrome (AIDS) Program during the 3-year period, September 1, 1986, through August 30, 1989. All patients had thorough clinical evaluations and relevant laboratory studies at defined intervals. All patients with CD4 lymphocyte counts below 0.2 X 10(9)/L received zidovudine therapy as soon as it became available. After July 1988, all patients with CD4 counts below 0.2 X 10(9)/L received prophylaxis against Pneumocystis carinii pneumonia. All patients were counseled about HIV infection, its modes of transmission, and the early symptoms of opportunistic infections. RESULTS: The longitudinal data demonstrated that candida often infected vaginal mucosa when there was no significant reduction in CD4 lymphocyte counts. Candida infection of the oropharyngeal mucosa was associated with highly significant reductions in CD4 lymphocyte counts. Esophageal candidiasis occurred only with advanced immunodeficiency associated with CD4 counts below 0.1 X 10(9)/L. CONCLUSIONS: Candida mucosal infections occur in a hierarchical pattern in women with HIV infection. Determination of the basis for the differences in susceptibility to candida of the vaginal, oropharyngeal, and esophageal mucosal surfaces will require further studies.

Adolescent

Frequent acquisition of multiple strains of methicillin-resistant Staphylococcus aureus by healthcare workers in an endemic hospital environment.

Methicillin-resistant Staphylococcus aureus (MRSA) has been an endemic nosocomial pathogen at the VA medical center (VAMC) in Providence, Rhode Island since 1981. From 1985 to 1987, more than 30% of all unique S aureus isolates were methicillin resistant. To evaluate the frequency of acquisition of MRSA isolates by healthcare workers, we compared the antimicrobial susceptibility patterns, multilocus enzyme genotypes and plasmid profiles of isolates recovered from nasal and hand cultures from VAMC nurses and house staff on rotation at the VAMC with those of clinical isolates from patients at the VAMC and four other affiliated hospitals. Fifty-six percent of ward nurses cultured (n = 112) were colonized with S aureus, of which 65% was methicillin resistant. Six isolates of MRSA were identified on the initial culturing of house staff (n = 65); 16 MRSA isolates were recovered at the end of a four-week rotation (p less than .02). Phenotypic and genotypic analyses demonstrated that numerous distinct MRSA strains were recovered in the study period. The incidence of MRSA among clinical isolates at the VAMC and affiliated institutions was remarkably constant throughout the three-year study period. Moreover, despite regularly sharing resident physicians, interns and medical students, MRSA isolates were commonly recovered at the other university-affiliated hospitals. Our study failed to reveal evidence of significant interhospital transmission of MRSA isolates by healthcare workers. While healthcare workers may contribute to the dissemination of MRSA within institutions, they appear to be less important in spreading MRSA between institutions.

DNA, Bacterial

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