A prosthetic vas deferens

Six dogs were implanted with the synthetic vas deferens device as part of our continuing research into the development of a reversible occlusive device for implant in the transected vas deferens. The experimental objectives were to assess the effects of sperm path length and duration of aspermia on total sperm count and motility by implanting three different lengths of the device in animals with different degrees of aspermic duration induced by bilateral vasectomy. Device lengths varied from 1.55 cm to 4.3 cm including the pilot tubes. The prosthesis is fabricated entirely of silicone rubber with Dacron velour tissue ingrowth material bonded to the outside surface of the ring to which vas ends are sutured. The pilot tubes extend 4 mm beyond the suture rings and are 0.6 mm OD with a 0.3 mm ID that extends through the entire length of the device. The flexible pilot tubes are an important feature of this design and insert into the vas lumen ensuring alignment between the device and the vas deferens while maintaining the necessary resiliency to adapt to the inherent movements of the vas without perforation. All animals included in these experiments were carefully selected and conditioned before implant. The evaluation of performance was based on semen samples collected at one week intervals. Sperm subsequently appeared in the ejaculate of all 6 dogs, demonstrating that the restoration of sperm transport can be restored after bilateral vasectomy through the implantation of a prosthetic vas deferens. The potential application of this device to the human male for the restoration of fertility appears excellent.     

Infection with Salmonella typhimurium modulates the immune response to Schistosoma mansoni glutathione-S-transferase

Immune response polarization is controlled by several factors, including cytokines, antigen-presenting cells, antigen dose, and others. We have previously shown that adjuvants and live vectors play a critical role in polarization. Thus, immunization with the Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28-GST) in aluminum hydroxide induced a type 2 cytokine profile and the production of immunoglobulin G1 (IgG1)- and IgE-specific antibodies. In contrast, mice infected with recombinant Salmonella typhimurium expressing Sm28-GST developed a type 1 cytokine profile and produced IgG2a-specific antibodies against Sm28-GST and Salmonella antigens. In this study, to determine if S. typhimurium not expressing Sm28-GST would still influence the type of the response against this antigen, we compared the profiles of the immune responses generated against Sm28-GST administered in alum in mice infected and not infected with S. typhimurium. Infected mice generated both IgG1 and IgG2a antibodies against Sm28-GST, while noninfected mice produced only IgG1 anti-Sm28-GST antibodies. Moreover, interleukin-4 (IL-4) mRNA expression in infected mice was near background levels, while gamma interferon (IFN-gamma) mRNA expression in coinfected mice was significantly higher than in mice immunized with Sm28-GST in alum only. However, after antigen-specific stimulation in vitro with Sm28-GST, levels of IL-4 and IFN-gamma cytokine production were similar in the two groups of mice. These results suggest that (i) the immune milieu produced during an infection may modify the response against an irrelevant antigen and (ii) isotype switching may be influenced by the cytokine environment of a bystander immune response, even though the specific antigen-driven cytokine production is not modified. Thus, the isotypic profile is not always an absolute reflection of the cytokines produced by antigen-specific Th cells.     

Receiver operator characteristic analysis of endoscopy as a test for gastritis

Endoscopic evaluation of the presence or absence of gastritis is often performed in lieu of biopsy and histologic diagnosis. The purpose of our study was to assess the value of endoscopic examination as a diagnostic test for gastritis. Two endoscopists prospectively assessed the antrum of 73 patients undergoing upper gastrointestinal endoscopy and graded, on a scale of 0-4 (0 = completely absent, 4 = definitely present), the likelihood of gastritis. The following features were also assessed at the time of endoscopy: erythema, nodularity, erosion, edema, and friability. Two concomitant antral biopsies (3 cm from the pylorus on the greater curvature of the stomach) were performed regardless of the endoscopic impression. The histologic findings were graded independently on a scale of 0-3 by two pathologists who were not aware of the endoscopic findings. The following histologic features were graded: acute inflammation, chronic inflammation, lymphoid aggregates, intestinal metaplasia, and quantity of Helicobacter pylori organisms. Receiver operator characteristic analysis, a method derived from signal detection theory, assesses the trade-off of sensitivity and specificity over all cutoff points of a test and is considered the best method by which to compare tests and determine the diagnostic utility of a given test. Receiver operator characteristic analysis gave an area of 0.65 +/- 0.01 SE for endoscopy as a test for gastritis (0.5 = chance, 1 = perfect) as defined by the histologic presence of inflammation. Additionally, endoscopy as a test for the presence of histologically proven Helicobacter pylori gave an area of 0.55 +/- 0.01 SE. All endoscopically graded features treated as separate tests for gastritis and/or H. pylori gave areas of approximately 0.44-0.61, indicative of a poor test. While H. pylori was always associated with at least some degree of inflammation, linear regression analysis revealed no correlation among any of the histologic features or of any histologic feature with any endoscopic feature. We conclude that a tissue diagnosis is essential for the proper diagnosis of gastritis.     

Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas

OBJECTIVE: This study used quantitative radiological imaging to determine the effect of surgical resection on postoperative survival of patients with malignant astrocytomas. Previous studies relied on the surgeons' impressions of the amount of tumor removed, which is a less reliable measure of the extent of resection. METHODS: Information concerning possible prognostic factors was collected for 75 patients undergoing magnetic resonance imaging or computed tomography preoperatively and within 10 days postoperatively. Image analysis of the neuroradiological studies was conducted to quantify pre- and postoperative total tumor volumes and enhancing volumes. Univariate and multivariate proportional hazards models were used to analyze the regression of survival regarding 22 covariates that might affect survival. The covariates that were entered included age, gender, tumor grade, cumulative radiation dose, chemotherapy, seizures as a first symptom, Karnofsky performance status at presentation, pre- and postoperative total and enhancing tumor volumes, ratio of pre- to postoperative total and enhancing tumor volumes, tumor location, surgeon's impression of the degree of resection, and subsequent surgery. RESULTS: There were 23 patients with anaplastic astrocytomas and 52 with glioblastomas multiforme. The estimated mean survival time was 27 months for patients undergoing gross total resection, 33 months for subtotal resection, and 13 months for open or stereotactic biopsy. Five factors that were significant predictors of survival in multivariate analysis were tumor grade, age, Karnofsky performance status, radiation dose, and postoperative complications (P < 0.05). In univariate analysis, tumor grade, radiation dose, age, Karnofsky status, complications, presence of enhancing tumor in postoperative imaging, and postoperative volume of enhancing tumor were significantly associated with survival (P < 0.05). CONCLUSION: We conclude that the most important prognostic factors affecting survival of patients with anaplastic astrocytomas and glioblastomas multiforme are tumor grade, age, preoperative performance status, and radiation therapy. Postoperative complications adversely affect survival. Aggressive surgical resection did not impart a significant increase in survival time. Surgical resection may improve survival, but its importance is less than that of other factors and may be demonstrable only by larger studies.     

Expression of the L8 lipopolysaccharide determinant increases the sensitivity of Neisseria meningitidis to serum bactericidal activity

The influence of lipopolysaccharide (LPS) expression on the sensitivity of Neisseria meningitidis to serum bactericidal activity was investigated by using a series of variants that expressed different LPS determinants. For each of two different strains, a series of three LPS variants that expressed L3,7, L8, or both were analyzed. LPS variants were identified and monitored by colony blotting with murine monoclonal antibodies specific for the L8 or the L3,7,9 immunotype determinants. Differences in LPS expression were verified by analysis of proteinase K lysates of whole cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then by silver staining or immunoblotting. The variants were used as test strains in bactericidal assays with human sera and with murine sera and monoclonal antibodies. Expression of the L8 LPS epitope was correlated with increased sensitivity to serum bactericidal activity. The geometric mean bactericidal titers of 12 to 16 sets of pre- and postvaccination sera were determined for each variant. Mean serum titers increased progressively with increased expression of L8 on the target strain. The bactericidal titers of anti-outer membrane protein monoclonal antibodies also increased with increased L8 expression.