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Biomedical subjects

K H Mayer

Publications and source records attributed to K H Mayer.

At least 73 records · Page 4Linked to original sources
PubMed1996

Electronic compliance assessment of antifungal prophylaxis for human immunodeficiency virus-infected women.

Several prophylactic medications for opportunistic or recurrent infections are used in human immunodeficiency virus-infected individuals. Essential to the efficacy evaluation of these agents is the accurate reporting of medication compliance. We hypothesized that poor patient compliance with thrice-weekly fluconazole prophylaxis would correlate with the occurrence of clinical events. Fluconazole compliance was monitored electronically by using the Medication Event Monitoring Systems with 19 women receiving fluconazole at 50 mg thrice weekly for prophylaxis of recurrent mucocutaneous candidiasis. During 202 patient-months of follow-up, eight breakthrough episodes of mucocutaneous candidiasis developed in four women; compliance data were available for seven of these episodes. At 6 months of therapy, more women with greater than or equal to 80% compliance were disease free compared with women with less than 80% compliance (P < 0.05; the Fisher exact test). These data suggest that documentation of medication compliance is essential in studies of chronic prophylaxis in human immunodeficiency virus-infected patients to properly evaluate drug efficacy and to avoid erroneous conclusions concerning drug failure.

AIDS-Related Opportunistic Infections↗
PubMed1995

The data and safety monitoring board and acquired immune deficiency syndrome (AIDS) clinical trials.

The urgency of the Acquired immune deficiency syndrome (AIDS) epidemic has mandated that multiple therapeutic approaches be developed and that these approaches be evaluated through clinical trials. To oversee these trials, the National Institute of Allergy and Infectious Diseases (NIAID) has created three large clinical trial programs monitored by a Data and Safety Monitoring Board (DSMB). For each clinical trial, this Board uses a standardized approach employing contemporary biostatistical, medical, and ethical principles. The DSMB is responsible for reviewing interim data on clinical trial performance, treatment safety and efficacy, and overall study progress. If interim results provide convincing evidence of either excessive adverse effects or significant treatment benefit, the DSMB may recommend early termination of the trial to the NIAID and the study investigators. The responsibility, organization, and operating procedures of this DSMB are presented and illustrated through three clinical trials sponsored by NIAID and monitored by the Board. The rationale and operational model for the DSMB may be a useful example for the development of similar review processes in other HIV clinical trial settings.

Advisory Committees↗
PubMed1995

Opportunistic candidal infections in patients infected with human immunodeficiency virus: prevention issues and priorities.

Mucosal candidiasis (oropharyngeal, esophageal, and vulvovaginal candidiasis) has been among the most prominent opportunistic infections in persons infected with human immunodeficiency virus (HIV). Esophageal candidiasis, an AIDS-defining illness, accounted for 15% of the AIDS-defining illnesses in adults and adolescents diagnosed in the United States through 1992. The diagnosis of oropharyngeal and vaginal candidiasis is based on clinically consistent signs and symptoms and a positive culture or a positive gram, KOH, or calcofluor stain, whereas the diagnosis of esophageal and pulmonary candidiasis is based on histopathology. Although a prospective controlled trial showed that prophylaxis with fluconazole can reduce the risk of mucosal candidiasis in patients with advanced HIV disease, routine primary prophylaxis is not recommended because of the effectiveness of therapy for acute disease, the low mortality associated with mucosal candidiasis, the potential for development of drug-resistant candidal infection, and the cost of prophylaxis. The probability of recurrences increases as CD4 counts decline. Nonetheless, many experts do not recommend chronic prophylaxis to prevent recurrent oropharyngeal and vulvovaginal candidiasis, for the same reasons that primary prophylaxis is not recommended. However, if recurrences are frequent or severe following documented esophageal candidiasis, long-term suppressive therapy with fluconazole should be considered.

AIDS-Related Opportunistic Infections↗
PubMed1995

Population pharmacokinetics of stavudine (d4T) in patients with AIDS or advanced AIDS-related complex.

The population pharmacokinetics and bioavailability of oral stavudine (d4T; 2',3'-dideoxy-3'-deoxythymidine) was determined in 81 patients with AIDS or AIDS-related complex (ARC) enrolled in phase I and phase I/II dose-ranging trials. Each patient underwent inpatient pharmacokinetic studies following administration of the first oral stavudine dose; 59 patients were restudied after chronic therapy for an average of 19 days. Thirty-three of these patients also received a single intravenous stavudine dose prior to starting an oral regimen. A two-compartment model with first-order absorption and elimination was used as the structural pharmacokinetic model. A basic model provided the following population parameter estimates (interpatient variability expressed in parentheses as percent coefficient of variation): clearance/bioavailability = 30.9 (24.5%) liters/h; volume of distribution/bioavailability = 8.42 (not modeled) liters; volume of distribution at steady state/bioavailability = 68.9 (105%) liters; intercompartmental clearance/bioavailability = 12.4 (26%) liters/h; and first-order absorption rate constant = 1.32 (78.9%) liters/h. In the subset of 33 patients receiving both intravenous and oral doses, the bioavailability of stavudine was estimated to be 99.1% (18.5%). Total body weight, stage of disease (AIDS versus ARC), and an oral stavudine dose of > or = 200 mg were found to have a statistically significant but a clinically marginal effect on the estimate of the oral clearance of stavudine. This analysis shows the high degree of bioavailability of stavudine in patients with AIDS and ARC and the relatively low degree of interpatient variability in oral drug clearance compared with those of other nucleosides. Population pharmacokinetic analysis is a useful tool for assessing the combined effects of several patient variables on the pharmacokinetic properties of drugs in human immunodeficiency virus-infected patients.

AIDS-Related Complex↗
PubMed1995

Videoendoscopic procedures in thoracic surgery: technical aspects and report of removal of a mediastinal cyst.

Current videoendoscopic technology and percutaneous techniques of exposure and dissection have been successfully applied to abdominal surgery with favorable results. Application of this technology to our practice of thoracic surgery is the basis of this report. Video-assisted thoracic surgery was performed in 36 patients for the following indications: Raynaud's syndrome, undefined pulmonary nodule, persisting spontaneous pneumothorax, T1 bronchial carcinoma, and mediastinal cyst. Videoendoscopic surgical procedures were accomplished using double-lumen endotracheal anaesthesia and a percutaneous stapling device. Procedures performed using this technique include thoracic sympathectomy, wedge or keel excision, blebectomy, lung apex stapling, parietal pleurectomy, and dissection of the mediastinal cyst. Median operating time was 45 min (range, 15 to 90 min). Tissue diagnosis was obtained in all patients. Median diameter of excised nodules was 10 mm (range, 7 to 70 mm). There were no operative deaths. The single complication was a prolonged air leak. This new method of thoracic surgery appears to benefit the patients. For us it proved a secure way to perform thoracic surgery. Our case of removal of a benign cyst in the posterior mediastinum shows that video-assisted thoracic surgery has expanding applications in the field of general thoracic surgery.

Adult↗
PubMed1995

Heterosexual HIV transmission.

Most of the people now living with HIV acquired the infection through heterosexual intercourse. HIV transmission has been facilitated by (a) concomitant sexually transmitted diseases (STDs), (b) the presence of social conditions that create core groups who have frequent and numerous partners, (c) sexual practices associated with bleeding (i.e., trauma, sex during menses) as well as noncircumcision, (d) cervical ectopy, and (e) anal sex. HIV may be found both cell-free and as intracellular virus in genital tract secretion, and may be sexually transmitted through either mechanism. HIV titers in genital tract secretions vary by several logs between people and within individuals over time, being greatest just after seroconversion and with advanced immunosuppression, concomitant genital tract inflammation (including STDs), and decreasing (but not to zero) with antiretroviral therapy. The per-contact transmission efficiency rate is highly variable, ranging from > 3% to < 1 per thousand contacts, with male-to-female HIV transmission generally being more efficient than vice versa. Control of the heterosexual HIV epidemic will necessitate a multidisciplinary approach, utilizing direct biological approaches (e.g., culturally specific and behavioral interventions, as well as more fundamental community changes that decrease societal norms that augment unsafe practices.

Cervix Mucus↗
PubMed1994

Dysregulation of interleukin-7 receptor may generate loss of cytotoxic T cell response in human immunodeficiency virus type 1 infection.

Virus-specific cytotoxic T lymphocytes (CTL) play a crucial role in modulating an immune response against human immunodeficiency type 1 (HIV-1) infection. The generation of effector cytotoxic cells from CTL precursors involves intricate interactions with antigen via T cell receptors (TcR) and soluble cytokines. Interleukin (IL)-7 can affect T cell maturation and differentiation. Here we report on a group of five HIV-1-positive individuals who tested negative for env- and gag-specific CTL activity. When exogenous recombinant human IL-7 was added as a stimulus to the cultures, none (0/5) of the CTL-negative individuals exhibited a CTL response. Individuals that were negative for HIV-1-specific CTL activity were found to lack IL-7 receptor (IL-7R) on CD8+ cells with a comparable reduction on CD4+ cells. Increased shedding of IL-7R in the culture supernatant was observed. A significant reduction in receptor number was detected by binding of 125I-labeled IL-7 and Scatchard analysis. The lack of IL-7R is probably not due to endogenous IL-7, since it was not detectable in the culture supernatants of the patients studied. HIV-1 proteins may cause down-modulation of IL-7R expression, either by producing an insufficient number of molecules or by rapid decay of IL-7R on T cells. These changes may alter the cells' capability to respond to the IL-7 growth signal, resulting in CTL failure and subsequent mishandling of the virus.

Adult↗
PubMed1994

The effects of disease progression and zidovudine therapy on semen quality in human immunodeficiency virus type 1 seropositive men.

OBJECTIVE: To investigate the effects of disease progression and zidovudine antiretroviral therapy on semen parameters in human immunodeficiency virus type 1 (HIV-1) seropositive men. DESIGN: Cross-sectional analysis of semen parameters of 166 HIV-1 seropositive men in various stages of disease progression as defined by peripheral CD4+ cell count. Clinical symptoms and zidovudine therapy status were obtained from medical records and clinical interviews. PATIENTS: Human immunodeficiency virus type 1 seropositive men participating in clinical studies at the Fenway Community Health Center (Boston, MA), the University of San Francisco (San Francisco, CA), and Brown University (Providence, RI). MAIN OUTCOME MEASURES: Ejaculate volume; sperm concentration, motility, forward progression, morphology, total sperm count; seminal immature germ cell; and white blood cell (WBC) concentrations. RESULTS: Human immunodeficiency virus type 1 seropositive men that were not on zidovudine therapy and were in early disease stage (> 200 CD4+ cells/mm3) had normal semen parameters as defined by World Health Organization criteria. In contrast untreated men in advanced disease stage (< or = 200 CD4+ cells/mm3) had significant reductions in sperm concentration and total sperm count and an increased percentage of abnormal sperm forms. Men receiving zidovudine antiretroviral therapy, regardless of disease stage, had normal semen parameters similar to those of untreated early disease stage patients. Seminal WBC concentrations were not affected significantly by disease progression but were reduced in patients receiving zidovudine. CONCLUSION: Most HIV-1-infected men in this study had semen parameters consistent with fertility. Disease progression was associated with reduced semen quality, but this effect appeared to be abrogated by zidovudine therapy. Zidovudine was also associated with a significant reduction of WBC numbers in semen. As seminal WBC are principal HIV-1 host cells in ejaculates of HIV-1-infected men, this effect could explain recent laboratory and epidemiological evidence that zidovudine therapy is associated with a reduced prevalence of HIV-1 in semen and a lower rate of sexual transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Videoendoscopic removal of a mediastinal cyst.

A 41-year-old woman was admitted to the hospital for obstetric surgery. A preoperative chest x-ray film showed a mediastinal mass. After examinations with echocardiography, computed tomography, and magnetic resonance imaging, we removed a cyst that was 2.7 x 3.5 cm in size by thoracoscopic means. The patient left the hospital 3 days after the operation.

Adult↗
PubMed1994

VATS (video-assisted thoracic surgery) of undefined pulmonary nodules. Preoperative evaluation of videoendoscopic resectability.

Peripheral undefined pulmonary nodules have become a favorable indication for the videoendoscopic approach in thoracic surgery. In our latest experience, we also successfully applied this technique in centrally located lesions of the lung. In reviewing our first 29 cases, we looked for preoperative features of videoendoscopic resectability. From March 1992 to September 1993, 29 patients underwent videothoracoscopy for undefined pulmonary nodules at our hospital. This group consisted of 17 men and 12 women (aged 25 to 77 years). Pulmonary nodules of this group of patients were defined as centrally located when close attachment to the segmental or subsegmental bronchopulmonary unit was observed and/or the distance to the visceral pleura exceeded 10 mm. Nodules that did not meet any of these criteria were hence interpreted as peripheral lesions. In the course of 21 excisions of peripheral lesions, we had to convert to open thoracotomy only once for anatomic reasons. When using the video-assisted thoracic surgery (VATS) approach for centrally located lesions, we succeeded in removing four of six. We failed only if the lesions were located in the upper lobe but could easily apply the technique for centrally located lesions in the lower lobes. In conclusion, undefined peripheral pulmonary nodules are a favorite indication for VATS. Centrally located pulmonary nodules of the lower lobes can often be managed easily by VATS, especially if the interlobar fissure extends to the stem of the pulmonary artery. Centrally located pulmonary nodules in the upper lobes may not be suitable for the VATS approach due to the special anatomic arrangement of the upper lobe segmental arteries and bronchioles.

Adult↗
PubMed1994

A phase I/II trial of intravenous L-2-oxothiazolidine-4-carboxylic acid (procysteine) in asymptomatic HIV-infected subjects.

Twenty-four asymptomatic, HIV-1-seropositive subjects with CD4 cell counts of > or = 400/microliters participated in a Phase I/II, dose escalation trial of intravenous L-2-oxothiazolidine-4-carboxylic acid (OTC: Procysteine). Four groups of six subjects each were consecutively assigned to receive OTC at an initial dose of 3, 10, 30, or 100 mg/kg, followed by the same dose given twice weekly for 6 weeks. Increases in whole-blood glutathione were observed in the highest dosage group after 6 weeks of therapy. No effects on changes in CD4 cell counts, viral load, or proviral DNA frequency were observed among the four dosage groups, although a decline in beta 2-microglobulin levels was apparent in the highest dosage group. One subject withdrew due to headaches; other probable adverse events including rash, flushing, pruritus, lightheadedness, and diminished concentration were self-limited.

Adult↗
PubMed1993

Risk of human immunodeficiency virus infection from unprotected receptive anal intercourse increases with decline in immunologic status of infected partners.

To determine whether human immunodeficiency virus (HIV) type 1 infection among unprotected receptive anal partners of HIV type 1-infected men varies by the immunologic status of the HIV type 1-infected index case, 187 sexual partners of 164 HIV type 1-infected index subjects were enrolled at a community health center in Boston, Massachusetts, from 1985-1990. All subjects were interviewed regarding their sexual practices and tested for HIV type 1. Fifty-seven of the 187 sexual partners were infected with HIV type 1. The strongest risk factor for HIV type 1 infection among these partners was unprotected receptive anal intercourse with a known HIV type 1-infected index subject (odds ratio (OR) = 7.2, 95% confidence interval (CI) 3.1-16.3). The risk of unprotected receptive anal intercourse was highest among partners of HIV-infected index subjects who had a T lymphocyte subset ratio of 0.50 or less (OR = 11.4, 95% CI 3.0-43.5) compared with partners of HIV type 1-infected index subjects with a T cell ratio of greater than 0.50 (OR = 5.3, 95% CI 1.9-15.2). After adjustment for confounding, the risk of HIV type 1 infection remained substantially higher among sexual partners who had had unprotected receptive anal intercourse with infected index subjects with a T lymphocyte subset ratio of less than or equal to 0.50 (OR = 7.0, 95% CI 1.8-28.0) compared with partners who had had unprotected receptive anal intercourse with infected index subjects with a T cell ratio of greater than 0.50 (OR = 3.3, 95% CI 1.1-10.0). It would appear that the risk of HIV type 1 infection from unprotected receptive anal intercourse increases as the immunologic status of the HIV type 1-infected insertive anal partner decreases.

Adult↗
PubMed1993

2',3'-didehydro-3'-deoxythymidine (d4T) in patients with AIDS or AIDS-related complex: a phase I trial.

2',3'-didehydro-3'-deoxythymidine (d4T) is a pyrimidine analogue and inhibitor of reverse transcriptase with potent in vitro activity against human immunodeficiency virus (HIV). A phase I trial of d4T was conducted in 41 HIV-infected patients, 12 with AIDS and 29 with AIDS-related complex (ARC). Thirty-six patients were evaluatable. The maximum tolerated dose was 2 mg/kg/day. The dose-limiting toxicity was sensory peripheral neuropathy, which occurred in 20 patients (55%). Four patients (11%) developed hepatotoxicity. Five (14%) developed anemia requiring a transfusion but not discontinuation of drug. The mean +/- SE plasma elimination half-life at all dose levels was 1.2 +/- 0.09 h. Increased or stable absolute CD4 counts were seen in most patients. The majority of patients with detectable serum p24 antigen levels had a persistent decrease by 6 months. d4T is a promising drug for patients with AIDS or ARC. This clinical trial is continuing to determine the minimal effective dose.

AIDS-Related Complex↗
PubMed1993

[Community-acquired pneumonia].

Pneumonias are inflammatory diseases of the lung parenchyma, infection is one of possible causes. With regard to the causes of community acquired pneumonias it is possible to distinguish those typical ones (caused by pneumococcus, legionella and other bacteria) and atypical ones (caused by mycoplasma, chlamydiae and others). Contrary to the atypical ones, typical pneumonias are characterized by sudden onset, high fever, chills, sometimes bloody expectoration and pains, as well as segmental or lobar changes and high leukocyte counts. Patients with tachycardia, diastolic blood pressure below 60 mm Hg and a blood urea nitrogen (BUN) of more than 7 mmol/l, as well as those with chronic basic diseases and a severe course should be hospitalized, further also those, who do not improve after 2 or 3 days therapy, in all cases of suspected pneumonia, with smokers and with patients aged over 40 years, a thorax X-ray should be executed. Typical pneumonias should be treated with penicillin or macrolide antibiotics, atypical ones with macrolide antibiotics, pneumonias with severe course additionally with a second generation cephalosporin. Where these simple rules are observed, a reduction of the still high mortality due to externally acquired pneumonias might be expected.

Adult↗
PubMed1992

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↗
PubMed1992

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↗