Cerebrospinal fluid inflammatory cytokine profiles of patients with neurotropic parasitic infections.

The pathogenesis of chronic parasitic central nervous system (CNS) infections, including granulomatous amoebic meningoencephalitis (GAE), cerebral toxoplasmosis (CT), and neurocysticercosis (NCC), is primarily due to an inflammatory host reaction to the parasite. Inflammatory cytokines produced by invading T cells, monocytes, and CNS resident cells lead to neuroinflammation which underlie the immunopathology of these infections. Immune molecules, especially cytokines, can therefore emerge as potential biomarker(s) of CNS parasitic infections. In this study, cerebral spinal fluid (CSF) samples from suspected patients with parasitic infections were screened for pathogenic free-living amoebae by culture (n=2506) and PCR (n=275). Six proinflammatory cytokines in smear and culture-negative CSF samples from patients with GAE (n = 2), NCC (n = 7), and CT (n = 23) as well as control (n = 7) patients were measured using the Multiplex Suspension assay. None of the CSF samples tested was positive for neurotropic free-living amoebae by culture and only two samples showed Acanthamoeba 18S rRNA by PCR. Of the six cytokines measured, only IL-6 and IL-8 were significantly increased in all three infection groups compared to the control group. In addition, TNFa levels were higher in the GAE and NCC groups and IL-17 in the GAE group compared to controls. The levels of IL-1b and IFNg were very low in all the infection groups and the control group. There was a correlation between CSF cellularity and increased levels of IL-6, IL-8, and TNFa in 11 patients. Thus, quantifying inflammatory cytokine levels in CSF might help with understanding the level of neuroinflammation in patients with neurotropic parasitic diseases. Further studies with clinico-microbiological correlation in the form of reduction of cytokine levels with treatment and the correlation with neurological deficits are needed.

Characterization of cast-to implant components from five manufacturers.

STATEMENT OF PROBLEM: Cast-to components are commonly used in screw-retained implant-supported restorations to produce precise fit. There is little information in the literature about the compositions and microstructures of commercially available products. PURPOSE: The purpose of this study was to characterize as-received cast-to components from 5 manufacturers (Dentsply Friadent CeraMed, Lifecore Biomedical, Inc, Nobel Biocare AB, Institut Straumann AG, and Zimmer Dental). MATERIAL AND METHODS: Two components from each manufacturer were mounted in metallographic resin, sectioned into quarters, remounted, wet polished with alumina abrasives, cleaned by ultrasonic agitation in distilled water, etched with aqua regia solutions, and carbon coated for scanning electron microscope (SEM) observation. Secondary (SE) and backscattered electron (BSE) images were collected to investigate the variations in surface topography and composition, respectively. Elemental analyses (EDS) were performed using an energy-dispersive x-ray spectrometer coupled to the SEM. Overall Vickers hardness (500-g load) and Vickers hardness of the 2 primary microstructural constituents (10-g load) were measured. Mean values and standard deviations were determined for the composition and Vickers hardness data. RESULTS: All implant components were composed of 2 distinctive parallel-band constituents containing gold, palladium, and platinum. Trace concentrations of iridium were also found. Elemental compositions of the darker bands observed by BSE differed by up to 20% for Au and Pt in the 5 products, whereas there was a minimal difference in Pd content. The lighter bands observed by BSE had nearly the same compositions in all 5 products, and contained much more Au and much less Pt than the darker bands. The gold-rich bands in each product were found to have much lower Vickers hardness. At high magnifications, each of the 2 bands appeared to contain 2 phases. CONCLUSIONS: The elemental compositions, microstructures, and Vickers hardness of the 5 as-received cast-to implant components were similar. Because both microstructural bands principally contain gold, palladium, and platinum, these noble cast-to implant components should be metallurgically compatible with noble metal casting alloys.

Trace Level Determination of Mesityl Oxide and Diacetone Alcohol in Atazanavir Sulfate Drug Substance by a Gas Chromatography Method.

A capillary gas chromatography method with a short run time, using a flame ionization detector, has been developed for the quantitative determination of trace level analysis of mesityl oxide and diacetone alcohol in the atazanavir sulfate drug substance. The chromatographic method was achieved on a fused silica capillary column coated with 5% diphenyl and 95% dimethyl polysiloxane stationary phase (Rtx-5, 30 m x 0.53 mm x 5.0 µm). The run time was 20 min employing programmed temperature with a split mode (1:5) and was validated for specificity, sensitivity, precision, linearity, and accuracy. The detection and quantitation limits obtained for mesityl oxide and diacetone alcohol were 5 µg/g and 10 µg/g, respectively, for both of the analytes. The method was found to be linear in the range between 10 µg/g and 150 µg/g with a correlation coefficient greater than 0.999, and the average recoveries obtained in atazanavir sulfate were between 102.0% and 103.7%, respectively, for mesityl oxide and diacetone alcohol. The developed method was found to be robust and rugged. The detailed experimental results are discussed in this research paper.

Secondary hormonal therapy for advanced prostate cancer.

PURPOSE: Androgen ablation remains the cornerstone of management for advanced prostate cancer. Therapeutic options in patients with progressive disease following androgen deprivation include antiandrogen withdrawal, secondary hormonal agents and chemotherapy. Multiple secondary hormonal agents have clinical activity and the sequential use of these agents may lead to prolonged periods of clinical response. We provide a state-of-the-art review of the various agents currently used for secondary hormonal manipulation and discusses their role in the systemic treatment of patients with prostate cancer. MATERIALS AND METHODS: A comprehensive review of the peer reviewed literature was performed on the topic of secondary hormonal therapies, including oral antiandrogens, adrenal androgen inhibitors, corticosteroids, estrogenic compounds, gonadotropin-releasing hormone antagonists and alternative hormonal therapies for advanced prostate cancer. RESULTS: Secondary hormonal therapies can provide a safe and effective treatment option in patients with AIPC. The use of steroids and adrenolytics, such as ketoconazole and aminoglutethimide, has resulted in symptomatic improvement and a greater than 50% prostate specific antigen decrease in a substantial percent of patients with AIPC. A similar clinical benefit has been demonstrated with estrogen based therapies. Furthermore, these therapies have demonstrated a decrease in metastatic disease burden. Other novel hormonal therapies are currently under investigation and they may also show promise as secondary hormonal therapies. Finally, guidelines from the United States Food and Drug Administration Prostate Cancer Endpoints Workshop were reviewed in the context of developing new agents. CONCLUSIONS: Secondary hormonal therapy serves as an excellent therapeutic option in patients with AIPC in whom primary hormonal therapy has failed. Practicing urologists should familiarize themselves with these oral medications, their indications and their potential side effects.

Snodgrass hypospadias repair with vascularized dartos flap: the perfect repair for virgin cases of hypospadias?

PURPOSE: Since its introduction, the Snodgrass hypospadias repair has been applied to virtually all forms of hypospadias repair. However, fistula rates have still been reported to be as high as 5% from large center, multiple surgeon studies and 16% from smaller center studies. We report on the use of the Snodgrass repair in conjunction with routine use of a vascularized dartos flap and 2-layer closure of the neourethra from multiple institutions. MATERIALS AND METHODS: Records of patients who underwent a primary 1-stage hypospadias repair with the Snodgrass technique in conjunction with vascularized dartos flap coverage were reviewed. Nearly identical surgical technique was used by all 6 surgeons in each case, which included a 2-layer closure of the neourethra, preservation of the well vascularized periurethral tissue and routine use of vascularized dartos flap coverage. A total of 514 cases were identified, including 414 with distal and 100 with midshaft or proximal hypospadias. Stents were used in 292 of the 514 repairs. RESULTS: Of the 414 distal cases there were no fistulas and 1 case of meatal stenosis. Of the 100 proximal cases there were 3 fistulas and 1 case of meatal stenosis. The overall complication rate was less than 1% for all cases combined. CONCLUSIONS: This series represents the largest reported multi-institutional experience with the Snodgrass technique. When used in conjunction with vascularized dartos flap coverage, 2-layer closure of the neourethra and special attention to preservation of the periurethral vascular supply, this repair can be performed with a near 0 complication rate. We believe that this is the optimal repair for routine cases of hypospadias.