Towards the development of a conceptual distance metric for the UMLS

The objective of this work is to investigate the feasibility of conceptual similarity metrics in the framework of the Unified Medical Language System (UMLS). We have investigated an approach based on the minimum number of parent links between concepts, and evaluated its performance relative to human expert estimates on three sets of concepts for three terminologies within the UMLS (i.e., MeSH, ICD9CM, and SNOMED). The resulting quantitative metric enables computer-based applications that use decision thresholds and approximate matching criteria. The proposed conceptual matching supports problem solving and inferencing (using high-level, generic concepts) based on readily available data (typically represented as low-level, specific concepts). Through the identification of semantically similar concepts, conceptual matching also enables reasoning in the absence of exact, or even approximate, lexical matching. Finally, conceptual matching is relevant for terminology development and maintenance, machine learning research, decision support system development, and data mining research in biomedical informatics and other fields.     

Isolation of putative dengue virus receptor molecules by affinity chromatography using a recombinant E protein ligand

Nucleotide sequences coding for the full-length envelope (E) glycoprotein gene of dengue virus type 4 was amplified using an RT-PCR method from infected C6/36 cells and cloned into pPROEx-Hta expression vector. The expression of the recombinant E protein in Escherichia coli was confirmed by Western blot using a polyclonal anti-dengue polyclonal antibody. The His-tagged fusion protein was obtained from the bacterial cellular extracts in almost pure form by immobilized metal affinity chromatography and the recombinant protein retained its ability to bind to 40 and 45 kDa proteins, previously described as putative receptors for dengue virus in C6/36 cells. To purify the 40 and 45 kDa molecules, a total protein extract from C6/36 cells was passed through an affinity chromatography column using immobilized recombinant E protein. After washing with isotonic buffer, elution was accomplished using a high salt buffer. The two proteins obtained, with molecular weights of 40 and 45 kDa, were recognized by dengue 4 virus, in virus overlay protein binding assay. This procedure allows further characterization of molecules that could be involved in dengue binding and entry.     

Modulatory effects of phosphatidylserine on the binding of muscarinic cholinergic receptor ligands

The modulation of the binding of muscarinic cholinergic receptor ligands by phosphatidylserine purified from bovine cerebral cortex (BC-PS) was examined in vitro and in vivo. The enrichment of bovine cerebral cortical synaptosomal membranes with BC-PS, using a fusion technique, produced a concentration-dependent decrease in the affinity (increase in K _d ) of [³H]quinuclidinyl benzylate (³H-QNB) specific binding to muscarinic acetylcholine receptors (mAChR), without changes in their maximal number (Bmax). Similar results were observed when [³H]oxotremorine (³H-OXO) was used to label a high affinity subpopulation of mAChR. On the other hand, preincubation of BC-PS liposomes with synaptosomal membranes in a nonoptimum fusion condition (at pH 7.4) did not alter the binding properties of both radioligands. Fusion experiments using a pure phosphatidylserine preparation from spinal cord revealed a similar decrement in the affinity of³H-QNB specific binding. Five day’s intraperitoneal (i.p.) administration of 15 mg/kg of BC-PS liposomes in rats increased the maximal number of cerebral cortical binding sites for³H-OXO. Scatchard analysis revealed no changes in the apparent dissociation constant. This modification is selective in relation to the neural structure studied. Thus, BC-PS treatment did not modify³H-OXO binding in the hippocampal formation and cerebellum. In contrast, parallel experiments using the muscarinic antagonist³H-QNB showed no alteration in the binding properties of mAChR. Five day’s i.p. administration of 15 mg/kg/d of phosphatidylcholine from bovine cerebral cortex (BC-PC) liposomes produced quite similar results to those obtained with BC-PS. These results indicate that mAChR are under the modulatory action of phosphatidylserine (PS) and phosphatidylcholine (PC), and suggest that this endogenous phospholipids may play a regulatory role on the mAChR. The possible implications of these findings on the effects of PC or PS treatment in neurological disorders involving a decrease in central cholinergic functions are discussed.     

Effects of acetylcholine, carbachol, and mannitol on rabbit corneal endothelial function as assessed by corneal deturgescence

Background: Anterior chamber miotic solutions are widely used in ophthalmic surgery to induce pupillary contraction. We investigated whether the acetylcholine, carbachol, or mannitol present in perfusing solutions can affect corneal endothelial function. Methods: Freshly dissected deepithelized rabbit corneas were mounted in a Dikstein-Maurice chamber at 36 °C. The endothelial sides were perfused with six solutions: (A) 55 mM (1%) acetylcholine Cl plus modified balanced salts; (B) control for A, with acetylcholine Cl replaced by sucrose; (C) 0.55 mM (0.01%) carbachol Cl plus balanced salts; (D) balanced salts solution (BS; control for C); (E) 3% mannitol plus modified balanced salts; and (F) modified balanced salts (control for E, with mannitol replaced by sucrose). Corneal thickness was followed for 3 h in each experiment. The effect of solution E did not differ from that of solution F. Results: The carbachol-containing solution produced a small increase in corneal thickness compared to the control solution, while the acetylcholine-containing solution resulted in corneal thickness lower than that in control preparations. Conclusion: From these data, acetylcholine is harmless to the endothelium, and may actually stimulate its fluid pump mechanism. Carbachol, on the other hand, appears to have a detrimental effect.     

Health care delivery system. Effects on surgical education: The Mexican panorama

Health care delivery in Mexico is divided in three groups: a social sector that covers approximately 53% of the population and is financed by the labor force, the state and the employer; a public, or open, sector that covers 33% of the population and is financed by federal and state funds; and a private sector that covers about 5% of the population and has two categories, the not-for-profit hospitals and the profit-oriented institutions. Most medical practitioners can work in any of the three groups or in several. Nine percent of Mexico's population, because of extreme ignorance, poverty, or isolation, have no or limited access to medical care. Mexico has 58 medical schools, which graduate about 7800 new physicians annually, awarding them the title Medico cirujano (Physician Surgeon). There are more than 160,000 physicians in Mexico, 20,000 of whom are unemployed. Each year, approximately 12,000 physicians compete for the 4306 places in the official residency training programs for all specialties. Of those taking the examination, 2000 try to get one of the 625 slots available for training in general surgery. Most of the surgical training programs in Mexico have a 3-year duration. The Mexican Academy of Surgery, the Mexican Society of General Surgery, and the Mexican Board of Surgery, as well as private individuals and organizations, are working to improve the quality of medical education and trying to establish a 5-year training program in surgery. The rapid movement toward modernization that is sweeping the country must include the improvement of surgical education as well.

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Resumen La atención de la salud en México está dividida en tres grupos: el Sector Social que cubre approximadamente el 53% de la población y que está financiado por la fuerza laboral, el Estado y el empleador; un Sector Público o Abierto que cubre el 33% de la población y que es financiado con fondos federales y estatales; y un Sector Privado que cubre el 5% de la población y que posee dos categorías: la de los hospitales sin ánimo de lucro y la de las instituciones con ánimo de lucro. La mayoría de los médicos pueden trabajar en cualquiera de los 3 grupos, o en combinación. El 9% de la población mexicana, por extrema ignorancia, pobreza y aislamiento no posee acceso alguno, o sólo lo tiene mínimo, a la atención médica.México posee 58 facultades de medicina, las cuales gradúan alrededor de 7.800 nuevos médicos anualmente, a quienes se les expide el título de médico cirujano.Hay más de 160.000 médicos en México, 20.000 de los cuales se encuentran desempleados. Cada año aproximadamente 12.000 médicos compiten por las 4.306 plazas en los programas oficiales de adiestramiento en las diferentes especialidades. De aquellos que presentan examen, 2.000 tratan de obtener uno de los 625 lugares disponibles para adiestramiento en círugía general.La mayoría de los programas de adiestramiento quirúrgico en la nación son de tres años de duración. La Academia Mexicana de Cirugía, la Asociación Mexicana de Cirugía General y el Consejo Mexicano de Cirugía, así como individuos y organizaciones privadas, trabajan en pro del mejoramiento de la calidad de la educación médica y tratan de establecer un programa de adiestramiento en cirugía de cinco años de duración. Los rápidos cambios de modernización que ocurren en el país deben incluir también el mejoramiento de la educación quirúrgica.

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Résumé L'administration des soins au Mexique est repartie entre trois secteurs: 1) Le secteur social qui couvre environ 53% de la population et qui est financé par la caisse des ouvriers, celle de l'état et celle du patronat; 2) un secteur public ou ouvert, qui couvre environ 33% de la population et qui est financé par des fonds fédéraux et gouvernementaux et enfin 3) un secteur privé, qui ne couvre que 5% environ de la population et qui comprend deux catégories, les hôpitaux à but non-lucratif et les institutions à but lucratif. La plupart des médecins peuvent exercer dans un ou plusieurs de ces trois groupes. Neuf pourcent de la population, en raison d'une extrême pauvreté, de son ignorance ou de son éloignement, a peu ou pas d'accés à des soins structurés.Il y a 58 écoles de Médecine au Mexique, produisant environ 7800 nouveaux médecins par an. Ils reçoivent le titre de Medico Cirujano littéralement, Médecin chirurgical. Il existe plus de 160000 médecins au Mexique, dont 20000 sont sans travail. Chaque année, environ 12000 médecins sont en compétition pour obtenir un des 4306 postes officiels de résidents, toutes spialités confondues. Parmi ceux qui se présentent, 2000 sont candidats pour un poste en chirurgie. La plupart des programmes d'enseignement durent trois ans. L'Académie de Chirurgie Mexicaine, La Société Mexicaine de chirurgie Générale et le comité d'accréditation chirurgicale, tout en accord avec les institutions privées et leur dirigeants oeuvrent pour un programme de cinq ans. La vague de progrès, ressentie dans tous les domaines, qui traverse actuellement le pays doit aussi intéresser l'amélioration de l'enseignement en chirurgie.

     

Virtual Changes of the Shape of the Lips

Many of the unsatisfactory results in cosmetic surgery are due not to the technique employed itself but to the virtual changes that our work has imposed in other areas. These changes are especially evident in the face, due to the small dimensions of its organs. The surgeon should do a thorough evaluation of the area to be treated prior to the surgery and make her/him notice not only the usual existing asymmetries, but also the modifications which probably will be noticed in the neighboring parts after surgery, to avoid later problems. The surgeon will discover then the many irregularities a patient may have, which have not been noticed by the patient before. These, if not detected in time, are weapons that may act as a boomerang against the surgeon later.     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.