Detection of the organophosphorus nerve agent soman by an ELISA using monoclonal antibodies

The development of a specific and sensitive immunologic ELISA detection system for methylphosphonoflouridic acid. 1,2,2-trimethylpropylester (soman) by the use of monoclonal antibodies (MAbs) is described. The monoclonal antibodies F71D7, F71H10, F71B12 and F71H9 originally produced against the soman derivative methyl phosphonic acid,p-aminophenyl 1,2,2-trimethylpropyldiester (MATP) also reacted with soman in a previously developed, direct competitive ELISA. After optimizing the ELISA system by varying the reaction mixture and the solvents for the organophosphate, 5.0×10^–7 mol/l soman (80% purity), e.g. 2.5 ng or 2 ng pure soman per 25 l test buffer, could be detected after a total test duration of 40 min. A shortening of the incubation time to 10 min resulted in a drop of sensitivity to 1.8×10^–6 mol/l soman. Various alcohols which may be used as extraction media for soman from various materials (isopropanol, ethanol and methanol) were shown to inhibit peroxidase activity and thereby reduce the sensitivity of the test. However, the influence of alcohols decreased with the shortening of incubation time. All monoclonal antibodies showed little cross reactivity to sarin and no cross reactivity to tabun and VX. Judging on the reactivity of the MAbs with MATP and soman oxidazed by 1,2-dihydrobenzol, some reactivity with some other (non-toxic) soman analogues containing the same pinacolyl group can be expected. There was no evidence for stereoselectivity of the MAbs tested. Finally, soman could be detected in different biological samples like human serum, goat serum, rabbit serum, chicken serum, milk, and tap water in concentrations between 1.3×10^–6 and 2.0×10^–6 mol/l.     

Influence of inflammatory reaction in primary fallopian-tube carcinoma (stage-I and stage-ii)

A retrospective evaluation of 68 Fallopian tube carcinomas (FTC) of a period of ten years (1980-1990) in stage I and II was performed. The aim of this study was to evaluate the prognostic impact of various factors. 68 cases were investigated for the prognostic influence of mitotic activity, degree of nuclear anaplasia and inflammatory reaction. Histological grading (p=0.08), and inflammatory reaction (p=0.003) showed to have a prognostic impact for survival in univariate analysis. Whereas, mitotic activity did not show any statistically significant influence. 47 (69%) tissue samples showed a positive inflammatory reaction which correlated with a significantly better outcome compared with tumors without this feature. However, this influence was proved in multivariate analysis for inflammatory reaction only (p=0.01). Although no data on the influence of the inflammatory reaction on prognosis in FTC has been published up to now, we can state that the determination of this factor can be useful for prognosis in this rare but highly aggressive tumor.     

Immunohistochemical localization of NMDA- and AMPA-type glutamate receptor subunits in the basal ganglia of red-eared turtles

Corticostriatal and thalamostriatal projection systems have been shown to utilize glutamate as a neurotransmitter in mammals and birds. Although corticostriatal and thalamostriatal projection systems have been demonstrated in turtles, it is uncertain whether they too use glutamate as their neurotransmitter. Immunohistochemical localization of glutamate and of NMDA- and AMPA-type ionotropic glutamate receptor subunits (NMDAR2A/B, GluR1, GluR2/3, and GluR4) were used to address this issue. Numerous medium-sized neurons that were rich in NMDAR2A/B and GluR2/3 were observed in the striatal part of the basal ganglia of red-eared turtles. Smaller numbers of medium-sized neurons and some large neurons rich in the GluR1 and GluR4 subunits were also observed in the striatum. The striatal neuropil was notably rich in GluR1, GluR2/3 and NMDAR2A/B subunits. The pallidal region was specifically rich in large neurons possessing GluR4 subunits. Consistent with the glutamate receptors on striatal and pallidal neurons, sources of input to the striatum and pallidum in turtle such as the dorsomedial and dorsolateral thalamic nuclei (which appear to correspond to intralaminar thalamic nuclei), telencephalic pallial cell groups, and the apparent subthalamic nucleus homologue were rich in glutamatergic neurons. The results show that the thalamostriatal, corticostriatal and subthalamo-pallidal projection systems of turtles are glutamatergic and that similar basal ganglia cell types in turtles and mammals have largely similar glutamate receptor characteristics. Copyright (R) 2000 S.Karger AG, Basel     

Changes in serum lipid and lipoprotein levels in postmenopausal patients with node-positive breast cancer treated with tamoxifen

Tamoxifen has been used for a long time as an adjuvant hormonal treatment in breast cancer patients. We studied 62 newly diagnosed postmenopausal women, aged 50-79 years, with node-positive breast cancer and receiving adjuvant tamoxifen (20 mg per day). Total serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, apo AI, apo AII, apo B and Lp(a) were determined before the surgery and 3, 6, 9, 12 and 24 months after starting tamoxifen treatment. Tamoxifen significantly reduced total serum cholesterol (6.13+/-1.20 mmol/L vs 5.21+/-1.05 mmol/L) (P <0.01), LDL-cholesterol (3.72+/-0.70 mmol/L vs 2.93+/-0.51) (P <0.01) and Lp(a) (0.11+/-0.07 g/L vs 0.02+/-0.01 g/L) (P < 0.01). There were no changes in triglycerides or HDL-cholesterol serum levels during tamoxifen treatment. The results indicate that an additional beneficial effect of adjuvant tamoxifen therapy may be that it decreases cardiovascular risk in such patients.     

Evaluation of the image quality of bi- and multifocal intraocular lenses with a new optical system]

By means of a new optical device developed by Reiner, an "optical implantation" of 6 different bi- and multifocal intraocular lenses (MIOLs) was performed in 20 young healthy subjects, and results were compared with those of a monofocal reference IOL. The following parameters were investigated: distance and near visual acuity, depth of focus and contrast sensitivity. The median of distance visual acuity was 1.0 in all IOLs with the exception of a 7-zone refractive MIOL (0.75). Near acuity without near addition was 1.0 in all MIOL models; through focus curves of all MIOLs showed an increase in depth of focus with a typical two peak course. Contrast sensitivity at high contrasts was reduced for the 7-zone-model, but contrast sensitivity at low contrasts was significantly reduced for all MIOLs, except the 2- and 3-zone refractive models.     

Intestinal non-Hodgkin's lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin's Lymphoma.

PURPOSE: Intestinal non-Hodgkin's lymphomas are not well characterized. We therefore studied prospectively their clinical features and response to standardized therapy. PATIENTS AND METHODS: Fifty-six patients with primary intestinal lymphoma were included in a prospective, nonrandomized multicenter study. Lymphoma resection was recommended and staging was performed according to the Ann Arbor classification. Patients were scheduled to receive six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy, and at stages EIII to EIV, they received additional involved-field radiotherapy. Corticosteroids were used in patients who could not receive chemotherapy. RESULTS: Thirty-five patients had intestinal T-cell lymphoma (ITCL), 21 patients had intestinal B-cell lymphoma (IBCL; 18 diffuse large-cell lymphomas, two marginal-cell lymphomas, and one follicle-center lymphoma). Thirty-four patients at stages EI to EII (14 ITCL and 20 IBCL) and nine patients at stages EIII to EIV (all ITCL) received chemotherapy. No patient in stages EIII to EIV received radiotherapy, because death occurred in 12 of 14 patients. Two-year cumulative survival in patients with IBCL was 94% (95% CI, 82% to 100%) and higher than in patients with ITCL (28% [95% CI, 13% to 43%]; P <.0001), even when only stages EI to EII were considered (ITCL, 37.5% [95% CI, 16.5% to 58.5%]; P <.0001). IBCL patients compared with ITCL patients were at lower lymphoma stages (P <.01), had higher Karnofsky status (P <.005), had intestinal perforation less often (P <.05), required emergency operation less often (P <.05), received CHOP (P <.05) more often, and reached complete remission (P <.0005) more frequently. CONCLUSION: IBCL patients at stages EI and EII respond well to chemotherapy, but the prognosis and treatment of ITCL patients is unsatisfactory.     

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.     

Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets

Endometrial carcinoma (EnCa) is the most common invasive gynaecologic carcinoma. Over 85% of EnCa are classified as endometrioid, expressing steroid hormone receptors and mostly involving pathological prestages. Human endogenous retroviruses (ERV) are chromosomally integrated genes, account for about 8% of the human genome and are implicated in the etiology of carcinomas. The majority of ERV envelope (env) coding genes are either not present or not consistently represented between common gene expression microarrays. The aim of this study was to analyse the absolute gene expression of all known 21 ERV env genes including 19 codogenic and two env genes with premature stop codons in EnCa, endometrium as well as in hyperplasia and polyps. For EnCa seven env genes had high expression with >200 mol/ng cDNA (e.g. envH1-3, Syncytin-1, envT), two middle >50 mol/ng cDNA (envFc2, erv-3) and 12 low <50 mol/ng cDNA (e.g. Syncytin-2, envV2). Regarding tumor parameters, Syncytin-1 and Syncytin-2 were significantly over-expressed in advanced stage pT2 compared to pT1b. In less differentiated EnCa Syncytin-1, erv-3, envT and envFc2 were significantly over-expressed. Syncytin-1, Syncytin-2 and erv-3 were specific to glandular epithelial cells of polyps, hyperplasia and EnCa using immunohistochemistry. An analysis of 10 patient-matched EnCa with endometrium revealed that the ERV-W 5'' long terminal repeat regulating Syncytin-1 was hypomethylated, including the ERE and CRE overlapping MeCP2 sites. Functional analyses showed that 10 env genes were regulated by methylation in EnCa using the RL95-2 cell line. In conclusion, over-expressed env genes could serve as indicators for pathological pre-stages and EnCa.     

Redefining the Practice of Peer Review Through Intelligent Automation Part 1: Creation of a Standardized Methodology and Referenceable Database

Conventional peer review practice is compromised by a number of well-documented biases, which in turn limit standard of care analysis, which is fundamental to determination of medical malpractice. In addition to these intrinsic biases, other existing deficiencies exist in current peer review including the lack of standardization, objectivity, retrospective practice, and automation. An alternative model to address these deficiencies would be one which is completely blinded to the peer reviewer, requires independent reporting from both parties, utilizes automated data mining techniques for neutral and objective report analysis, and provides data reconciliation for resolution of finding-specific report differences. If properly implemented, this peer review model could result in creation of a standardized referenceable peer review database which could further assist in customizable education, technology refinement, and implementation of real-time context and user-specific decision support.