Effects of group B streptococci on cord and adult mononuclear cell interleukin-12 and interferon-gamma mRNA accumulation and protein secretion.

Group B streptococci (GBS) are a major cause of early-onset infection in neonates. Neonates, who have defects in neutrophil function that likely contribute to susceptibility to GBS infection, are deficient in the production of the phagocyte activator interferon (IFN)-gamma. GBS-stimulated mRNA accumulation and protein secretion of IFN-gamma and interleukin (IL)-12, a major enhancer of IFN-gamma production, by mixed mononuclear cells (MMCs) from umbilical cord and adult peripheral blood was examined. GBS-exposed cord blood MMCs secreted lower concentrations of both IL-12 and IFN-gamma proteins than did MMCs from adults. IL-12 and IFN-gamma mRNA accumulation was examined by use of comparative reverse transcriptase-polymerase chain reaction. Cord blood MMCs accumulated less mRNA for both IL-12 and IFN-gamma than did adult blood MMC. The deficiency in cord blood cell production of IL-12 may have a role in inadequate IFN-gamma production, which contributes to the unique susceptibility of neonates to GBS infections.

Comparative prevalence of infection with Trichomonas vaginalis among men attending a sexually transmitted diseases clinic.

OBJECTIVE: Although established in women as a common cause of vaginal discharge, the prevalence of Trichomonas vaginalis (TV) in men compared with other classic urethral pathogens has not been well characterized. To assess this issue, the authors compared the prevalence of Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), and TV in consecutive men attending a sexually transmitted diseases (STD) clinic. METHODS: From June 1, 1998 to July 27, 1998, 454 consecutive men presenting to the Denver Metro Health Clinic with a new problem were tested for GC by urethral swab culture, for CT by polymerase chain reaction of urine, and for TV by urine sediment culture. RESULTS: GC, CT, and TV were detected in 23 (5.1%), 34 (7.5%), and 13 (2.8%) of men, respectively. There were significant differences by age for both CT (11.3% in men younger than 30 years versus 3.3% in men 30 years and older, P < 0.05) and TV (0.8% in men younger than 30 years versus 5.1% in men 30 years and older, P < 0.05). In 50 men 30 years or older with symptoms of urethral discharge, TV prevalence (12.0%) rivalled that of GC (12.0%) and CT (14.0%). In 45 men 30 years and older with nongonococcal urethritis, the prevalence of TV and CT were each 13.3%. Multivariate logistical regression analysis showed the presence of discharge and nongonococcal urethritis in men 30 years and older to be an independent predictor of TV. CONCLUSIONS: TV is common in men attending sexually transmitted disease clinics, especially in those 30 years or older, in whom it may account for as much urethritis as GC or CT. These findings suggest that in older men with nongonococcal urethritis, diagnostic evaluation, empiric treatment, and partner management should include the possibility of TV infection.

Intracellular and extracellular cytokine production by human mixed mononuclear cells in response to group B streptococci.

Group B streptococci (GBS) are a major cause of severe infection in newborns, pregnant females, and other immunocompromised hosts. Infection often includes septicemia, shock, pneumonia, and respiratory failure. In previous studies, we have reported that GBS induce marked production of tumor necrosis factor alpha (TNF-alpha) by human mononuclear cells. The present study was designed to measure the production of TNF-alpha as well as additional cytokines, including interleukin 1beta (IL-1beta), IL-6, IL-8, IL-12, and gamma interferon (IFN-gamma) but also to determine from what cells and at what time point during incubation with GBS that these cytokines are produced. Mixed mononuclear cells were incubated with heat-killed GBS, media alone, or 1 microg of Escherichia coli lipopolysaccharide (LPS). Brefeldin A was added to each sample prior to staining, which prevented the export of cytokines by the Golgi apparatus. The cells were then stained with the appropriate conjugated antibodies and analyzed by using a flow cytometer. Results indicate that intracellular cytokines appear, in almost all cases, simultaneous to or before secreted proteins are detected. In contrast to the response to LPS, where TNF-alpha, IL-1beta, IL-6, and IL-8 appear almost simultaneously, the human monocyte response to GBS results in the production of TNF-alpha but delayed appearance of IL-1beta, IL-6, and IL-8. The lymphocyte response to GBS was also strikingly different from that to LPS in that both secreted IFN-gamma and IL-12 was detected, while LPS failed to induce production of these critical cytokines. This suggests an important role for TNF-alpha, IFN-gamma, and IL-12 in GBS pathogenesis and/or immunity.

Pro-convulsant actions of theophylline and caffeine in the hippocampus: implications for the management of temporal lobe epilepsy.

The pro-convulsant actions of theophylline and caffeine have been investigated using the hippocampal slice preparation and rats administered kainic acid or Metrazol. Both theophylline and caffeine induced the generation of epileptiform activity in the CA3 region of the hippocampal slice with convulsive dose50 (CD50) values of 3 microM respectively. Kainic acid-induced bursting in hippocampal slices was enhanced by theophylline (0.3-30 microM) and caffeine (1-100 microM). Theophylline induced burst firing in response to electrical stimulation in hippocampal area CA3 but not area CA1. Theophylline (50 mg/kg) strongly potentiated the effect of the limbic convulsant kainic acid in vivo whilst a dose of 200 mg/kg was necessary to significantly lower the threshold dose of Metrazol required to induce generalized convulsions. We conclude that alkylxanthines, probably by antagonizing the effect of endogenous adenosine, exert a pro-convulsant action in the hippocampus which preferentially promotes limbic seizures.

Evaluation of a medication-monitoring service for geriatric patients in a congregate housing facility.

The effects of a medication-monitoring service provided by a pharmacist in a congregate housing facility for geriatric patients were evaluated. A medication-monitoring service was provided by a clinical pharmacist to geriatric patients in two congregate housing facilities during an 18-month period. Patients were offered the service if they had histories of noncompliance and were referred for this reason to the study by physicians, staff, or family. The clinical pharmacist made weekly visits to each patient for assessment and provision of instructions and reinforcement regarding medication compliance. Medications were provided in special reminder packages prepared by a technician, and cost data for both materials and time were recorded. A total of 14 patients were referred to the study and received services for at least three months. Eight of these patients received services for one year. The costs of providing the service were $33/patient/month for personnel and $2/patient/month for materials. An 82-100% compliance rate was recorded; the mean compliance rate was 96%. Patients or their legal representatives paid the pharmacist directly for costs incurred. A medication-monitoring service is useful for geriatric patients whose primary limitation is inability to administer their own medications.