Chromosomal anomalies in stage D1 prostate adenocarcinoma primary tumors and lymph node metastases detected by fluorescence in situ hybridization

We previously reported a HPLC assay method using fluorimetric detection for the simultaneous determination of urinary N2-(3-aminopropyl)biopterin (oncopterin, a natural pteridine newly found in urine from cancer patients), biopterin and neopterin. We now have observed that an unknown substance, which may be derived from methotrexate, in urine from a patient with stomach cancer interfered with the assay of oncopterin and demonstrated that oncopterin could be completely separated from the unidentified substance by HPLC using a Nucleosil 100-5SA strong cation-exchange column. Furthermore, oncopterin was not detectable by this HPLC-fluorimetric method in urine samples from patients with stomach cancer who were not treated with methotrexate. The content of urinary oncopterin from cancer patients is supposed to be very low, with less than 1 mumol/mol creatinine. The present results indicate that the peak found with elution from the C18 column was a methotrexate-derived compound and co-eluted with the analyte oncopterin.     

CT of blunt trauma to the bowel and mesentery

Injuries to the bowel and mesentery are found in approximately 5% of all patients undergoing laparotomy after blunt abdominal trauma. Bowel and mesenteric injuries are often subtle and difficult to diagnose, and a delay in the diagnosis is associated with increased mortality and morbidity. CT is the best imaging method for diagnosing injuries to the bowel and mesentery. With meticulous scanning techniques, most significant bowel and mesenteric injuries can be reliably identified with CT preoperatively, and associated injuries to other abdominal viscera can be confirmed.     

Pediatric emergency medicine fellow clinical work requirements

A wide range of clinical requirements exists among PEM fellowship programs. Programs are equally split concerning the question of whether fellows should work with supervision or independently in the first year; a significant number of fellowship programs require continued supervision of fellows in subsequent years. Orientation for first year fellows and requirements for completion of PALS, advanced pediatric life support (APLS), ACLS, or ATLS courses prior to their first independent shift varied greatly. In particular, a minority of programs required ATLS completion even though a majority of overall fellowship programs operate in a hospital designated as a Level 1 Trauma Center. Programs in which first-year fellows worked independently had fewer attendings and were less likely to provide 24-hour coverage. Fellows appear to work a similar or less demanding schedule than PEM attendings in most fellowship programs, and most fellowship directors feel that their fellows should continue with their current schedule.     

A review of Lewy body disease, an emerging concept of cortical dementia

Small-diameter vascular grafts rapidly fail after implantation, due to occlusion caused by thrombosis. This problem cannot be overcome using medication. A promising improvement of graft patency is the seeding of endothelial cells (EC) on the luminal surface of the vascular graft. Conjugates of albumin and heparin, which were developed to obtain nonthrombogenic coatings, could form an ideal coating for vascular grafts. Besides presenting anticoagulant function, heparin will bind proteins with cell adhesive properties, thus facilitating adherence of EC to the graft surface. EC were able to grow to confluency on CO(2) gas plasma-treated polystyrene (PS-CO(2)) coated with albumin-heparin conjugate. CO(2) gas plasma treatment resulted in the introduction of functional groups at the surface (e.g., hydroxyl, aldehyde, carboxylic acid, and epoxide groups). Addition of albumin-heparin conjugate to the functionalized surface in an aqueous solution with pH 8.2 yielded a stable monolayer of covalently bound conjugate. The number of cells adhering and proliferating on this surface was comparable to the number of cells on fibronectin-coated PS-CO(2). However, the structure and size of EC proliferating on surface-immobilized albumin-heparin was more irregular. Long-term adherence might be improved by adding fibronectin to the albumin-heparin surface, either as a mixture with albumin-heparin or in a separate incubation step.     

Analyzing the evidence on European health care reforms

Health system reform, in Europe as elsewhere, has often been influenced as much by theory and conjecture as by fact and experience. In a study published in September 1997, the Regional Office for Europe of the World Health Organization (WHO) drew together the available evidence about the health care systems in the fifty-one countries of the European region. This paper focuses on western European countries. It reviews a variety of policy strategies and then explores implications from this European experience for the formulation of U.S. health care policy.     

Quantifying characteristics of information-technology applications based on expert knowledge for detection of oestrus and mastitis in dairy cows

Expert opinions were elicited about the characteristics at the commercial-farm level of on-line information technology (IT) applications that are able to detect oestrus and mastitis in dairy cows. Since actual data of these characteristics are not available, judgmental data provided an alternative means to interpret the implications of research results for commercial farms. Applications included were activity measurement, milk-production measurement, electrical conductivity of quarter milk, automated concentrate feeders and milk-temperature measurement. Sensitivity and specificity of detection of oestrus (OD), clinical-mastitis (CMD) and subclinical-mastitis (SCMD) were ascertained. Conjoint-analysis was used to assess the effect of each application indirectly by decomposing the evaluated overall detection characteristics of a predefined number of IT combinations. The individual experts were consistent in evaluating the alternatives, but there was variation in estimates among experts. Estimations of the main effects of the applications and important first-order interactions were incorporated into the detection models. Implementation of all applications under study resulted in overall sensitivities and specificities of 82% and 90%, 73% and 87%, 58% and 82% for OD, CMD and SCMD, respectively. Further research is necessary that should take into account costs and benefits of the different detection systems based on the current status of farm performance (e.g. OD and mastitis incidence) and farm structure (e.g. farm size, years in operation of the milking parlour and parlour layout). Research to do this is currently in progress.     

The effect of FMRFamide analogs on [35S]GTP-gamma-S stimulation in squid optic lobes

Pharmacological study of Phe-Met-Leu-Phe-amide (FMRFa) receptors is hindered by the lack of selective ligands. The classification of these selective ligands is further hampered by the limited availability of functional assays. In this study, we evaluated several synthetic FMRFa analogs for agonist and antagonist activity by measuring their abilities to produce [35-S]-GTP-gamma-S stimulation or to inhibit FMRFa-induced [35S]-GTP-gamma-S binding in squid optic lobes. Analogs included acetyl-Phe-norLeu-Arg-Phe-amide (acFnLRFa), desamino-Tyr-Phe-Leu-Arg-amide (daYFLRa), desamino Tyr-Phe-norLeu-Arg-Phe-amide (daYFnLRFa), desamino Tyr-Phe-norLeu-Arg-[TIC]-amide (daYFnLR[TIC]a), desamino Tyr-Trp-norLeu-Arg-amide (daYWnLRa), (D)-Tyr-Phe-norLeu-Arg-Phe-amide (D)-YFnLRFa), Phe-Leu-Arg-Phe-amide (FLRFa), and the D-amino acid analogs of FMRFa (D-FMRFa, F-(D)-MRFa and FM-(D)-RFa). For agonist studies, full dose-response curves were generated and analyzed for potency and efficacy (maximal percent effect). FMRFamide as well as analogs ac-FnLRFa, daYFnLRFa, daYFnLR[TIC]a, D-YFnLRFa, FLRFa, and (D)-FMRFa stimulated [35S]-GTP-gamma-S binding. Analogs daYWnLRa, daYFLRa, F-(D)-MRFa, and FM-(D)-RFa failed to stimulate either [35S]-GTP-gamma-S binding or to inhibit FMRFa-induced [35S]-GTP-gamma-S binding. The rank order of potency was daYFnLRFa > or = daYFnLRF[TIC]a > acFnLRFa > (D)YFnLRFa > FLRFa > or = FMRFa > (D)-FMRFa. The order of efficacy was daYFnLRFa = acFnLRFa = (D)-YFnLRFa > FLRFa = FMRFa > or = (D)-FMRFa > or = daYFnLRF[TIC]a. Peptide analog daYFnLR[TIC]a was less efficacious (59% maximal stimulation) than analogs daYFnLRFa, acFnLRFa, and (D)-YFnLRFa (113-146% maximal stimulation). A maximal concentration of daYFnLR[TIC]a (10 microM) reduced daYFnLRFa, acFnLRFa, and (D)-YFnLRFa induced [35S]-GTP-gamma-S stimulation, indicating that daYFnLR[TIC]a is a partial agonist at the receptor stimulated by the FMRFamide analogs. Analysis of the structural requirements needed for promoting [35S]-GTP-gamma-S binding show that elongation (i.e., daYFnLRFa, D-YFnLRFa) or modification of Phe1 (ac-FnLRFa) leads to increased efficacy and potency. Moreover, elimination of the C-terminal Phe (daYWnLRa, daYFLRa,) leads to a loss of biological activity. However, substitution with L-1,2,3,4 tetrahydroisoquinoline-3-carboxylic acid, a rigid analog of the C-terminal Phe (daYFnLR[TIC]a), leads to decreased efficacy but not loss of potency. The data suggest that immobilization or modification of the C-terminal Phe may produce highly selective and potent FMRFamide antagonists. These results agree with published receptor radioligand studies and indicate that the [35S]GTP-gamma-S assay may be useful in classifying novel FMRFamide-selective ligands.