Premature introduction of progestin-only contraceptive methods during lactation

INTRODUCTIONS: Cochlear implants are used for the rehabilitation of bilaterally deaf patients. Due to the improvements in speech processing they might be also useful for patients with residual hearing and some speech understanding. METHODS: Pre- and postoperative speech understanding scores in 26 patients receiving implants were evaluated in a retrospective study. RESULTS: The preoperative pure-tone threshold in the implanted ear was between 80 and 115 dB in the frequency range of 500 to 2000 Hz. On the contralateral side the mean threshold was 10 dB better. The mean score for the number test was 11.3%, for the monosyllables below 5%. Postoperatively speech understanding improved significantly up to 97% for numbers and 48% for monosyllables (tested with the Freiburger Speech Test). Cochlear implantation also benefits patients with residual hearing and some speech understanding with hearing aids under optimum conditions. The speech understanding scores must be below certain limits. General selection criteria cannot yet be specified. The individual decision must be based upon several criteria, especially the speech understanding scores in quiet and noise under optimum conditions. A prospective study is needed to develop generally applicable criteria.     

Diazepam alters caffeine-induced effects on beta-endorphin levels in specific rat brain regions

The present study was conducted to evaluate the effects of caffeine and the benzodiazepine agonist diazepam, and a combination of both on beta-endorphin (beta-EN) levels in specific rat brain regions. Male Sprague-Dawley rats (150-200 g) adapted to a 12-hour light: 12-hour dark illumination cycle were used in this study. Caffeine (10 mg/kg), diazepam (2 mg/kg) or a combination of caffeine (10 mg/kg) and diazepam (2 mg/kg) were administered intraperitoneally to rats at 11:00 hr. Control animals were injected with saline. Animals were sacrificed by decapitation 1 h after injection, the brains were immediately removed; the cortex, hippocampus, hypothalamus and midbrain were dissected and their B-EN levels measured by radioimmunoassay. Caffeine administration significantly increased B-EN levels in the cortex. Similarly, administration of diazepam alone resulted in a significant increase of B-EN levels in cortex. However, concurrent administration of diazepam and caffeine resulted in higher increase of B-EN levels in cortex. No significant changes in B-EN levels were detected in hippocampus and midbrain after administration of either caffeine or diazepam alone. On the other hand, when diazepam and caffeine were concurrently administered a significant increase of B-EN levels were observed in the midbrain. Moreover, administration of diazepam alone resulted in a significant increase of B-EN levels in hypothalamus. This increase was still observed following concurrent administration of diazepam and caffeine. These results clearly indicate that diazepam alters caffeine-induced effects on B-EN in specific rat brain regions.     

Arterial reactivity is enhanced in genetic males taking high dose estrogens

OBJECTIVES: We sought to assess whether high dose estrogen treatment is associated with enhanced arterial reactivity in genetic males. BACKGROUND: Although estrogens have been shown to enhance arterial reactivity in women, and are thereby thought to confer cardiovascular benefit, the vascular effects of long-term estrogen therapy in genetic males is unknown. METHODS: We studied the arterial physiology of 30 genetic males--15 male to female transsexuals receiving long-term high dose estrogen therapy and 15 healthy male control subjects matched for age, smoking history and vessel size. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation [EDD]) and after nitroglycerin (GTN), an endothelium-independent dilator. Blood pressure, cholesterol and testosterone levels were also measured in each subject. RESULTS: Total testosterone and free testosterone index levels were lower in the transsexuals compared with the control subjects (p < 0.001). In contrast, EDD was significantly higher in the transsexuals than in the control males (mean [+/-SD] 7.1 +/- 3.1% vs. 3.2 +/- 2.8%, p = 0.001), as was the GTN response (21.2 +/- 6.7% vs. 14.6 +/- 3.3%, p = 0.002). Total and high density lipoprotein cholesterol, blood pressure levels and baseline vessel size were similar in the two groups. On multivariate analysis, enhanced EDD was associated independently with estrogen therapy (p = 0.02) and with low total cholesterol (p = 0.04). An enhanced GTN response was also significantly associated with estrogen therapy (p = 0.03). CONCLUSIONS: Long-term treatment with high dose estrogens is associated with enhanced arterial reactivity in genetic males, which may be due to the effects of estrogen excess or androgen deprivation, or both.     

Epitope cleavage by Leishmania endopeptidase(s) limits the efficiency of the exogenous pathway of major histocompatibility complex class I-associated antigen presentation

The activation of CD8+ T cell responses is commonplace during infection with a number of nonviral pathogens. Consequently, there has been much interest in the pathways of presentation of such exogenous antigens for major histocompatibility complex class I-restricted recognition. We had previously shown that Leishmania promastigotes transfected with the ovalbumin (OVA) gene could efficiently target OVA to the parasitophorous vacuole (PV), with subsequent recognition by class II-restricted T cells. We now report the results of studies aimed at evaluating the PV as a route of entry into the exogenous class I pathway. Bone marrow-derived macrophages can present soluble OVA (albeit at high concentrations) to the OVA(257-264)-specific T cell hybridoma 13.13. In contrast, infection with OVA-transfected Leishmania promastigotes failed to result in the stimulation of this hybridoma. This appeared unrelated to variables such as antigen concentration, parasite survival, and macrophage activation status. These results prompted an analysis of the effects of promastigotes on class I peptide binding using RMA-S cells and OVA(257-264). Our data indicate that the major surface protease of Leishmania, gp63, inhibits this interaction by virtue of its endopeptidase activity against the OVA(257-264) peptide. The data suggest that this activity, if maintained within the PV, would result in loss of the OVA(257-264) epitope. Although we can therefore draw no conclusions from these studies regarding the efficiency of the PV as a site of entry of antigen into the exogenous class I pathway, we have identified a further means by which parasites may manipulate the immune repertoire of their host.     

Ultrastructural analysis of primary human urethral epithelial cell cultures infected with Neisseria gonorrhoeae

In men with gonococcal urethritis, the urethral epithelial cell is a site of infection. To study the pathogenesis of gonorrhea in this cell type, we have developed a method to culture primary human urethral epithelial cells obtained at the time of urologic surgery. Fluorescent analysis demonstrated that 100% of the cells stained for keratin. Microscopic analyses indicated that these epithelial cells arrayed in a pattern similar to that seen in urethral epithelium. Using immunoelectron and confocal microscopy, we compared the infection process seen in primary cells with events occurring during natural infection of the same cell type in men with gonococcal urethritis. Immunoelectron microscopy studies of cells infected with Neisseria gonorrhoeae 1291 Opa+ P+ showed adherence of organisms to the epithelial cell membrane, pedestal formation with evidence of intimate association between the gonococcal and the epithelial cell membranes, and intracellular gonococci present in vacuoles. Confocal studies of primary urethral epithelial cells showed actin polymerization upon infection. Polyclonal antibodies to the asialoglycoprotein receptor (ASGP-R) demonstrated the presence of this receptor on infected cells in the primary urethral cell culture. In situ hybridization using a fluorescent-labeled probe specific to the ASGP-R mRNA demonstrated this message in uninfected and infected cells. These features were identical to those seen in urethral epithelial cells in exudates from males with gonorrhea. Infection of primary urethral cells in culture mimics events seen in natural infection and will allow detailed molecular analysis of gonococcal pathogenesis in a human epithelial cell which is commonly infected.     

The arterioportal fistula syndrome: clinicopathologic features, diagnosis, and therapy

BACKGROUND & AIMS: Arterioportal fistulas (APFs) are rare vascular disorders of the mesenteric circulation. The aim of this study was to determine the etiology, anatomical location, and main symptom at presentation of APFs, and analyze the various modes of treatment. METHODS: The etiology, clinical presentation, radiographs, and treatment of 12 patients with APFs are reported in detail, and another 76 cases published since 1980 are reviewed. RESULTS: APFs result from trauma (n = 25, 28%), iatrogenic procedures (n = 14, 16%), congenital vascular malformations (n = 13, 15%), tumor (n = 13, 15%), aneurysm (n = 12, 14%), and other causes (n = 11, 12%). The origin of APFs is the hepatic artery in the majority of patients (n = 56, 65%). The main symptoms at presentation are lower or upper gastrointestinal bleeding (n = 29, 33%), ascites (n = 23, 26%), heart failure (n = 4.5%), or diarrhea (n = 4.5%). Radiological intervention provides definitive treatment in 42% (n = 33) of patients, whereas the remainder are treated by surgery alone (n = 27, 31%) or a combination of radiological intervention and surgery (n = 8, 9%). CONCLUSIONS: APFs result in a protean syndrome variously combining portal hypertension and other hemodynamic imbalances (heart failure, intestinal ischemia). Single or multiple interventional radiological procedures using arterial and/or venous approaches allow definitive treatment of most APFs. With increasing technological advances, it is anticipated that surgery will only be indicated in rare instances after failure of radiological intervention(s).     

Random sequence multisets for synchronous code-divisionmultiple-access channels

The effect of using randomly selected sequence multisets for the uplink of a synchronous code-division multiple-access channel is considered. A tight lower bound on the expected value of the sum capacity over the ensemble of randomly selected sequence multisets is given. For large systems, the sum rate penalty for using randomly selected multisets is shown to be at most 1 nat and to vanish as the number of users becomes large, compared to the sequence length