Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping

BACKGROUND: Infarct border zone (IBZ) geometry likely affects inducibility and characteristics of postinfarction reentrant ventricular tachycardia, but the connection has not been established. OBJECTIVE: The purpose of this study was to determine characteristics of postinfarction ventricular tachycardia in the IBZ. METHODS: A geometric model describing the relationship between IBZ geometry and wavefront propagation in reentrant circuits was developed. Based on the formulation, slow conduction and block were expected to coincide with areas where IBZ thickness (T) is minimal and the local spatial gradient in thickness (DeltaT) is maximal, so that the degree of wavefront curvature rho proportional, variant DeltaT/T is maximal. Regions of fastest conduction velocity were predicted to coincide with areas of minimum DeltaT. In seven arrhythmogenic postinfarction canine heart experiments, tachycardia was induced by programmed stimulation, and activation maps were constructed from multichannel recordings. IBZ thickness was measured in excised hearts from histologic analysis or magnetic resonance imaging. Reentrant circuit properties were predicted from IBZ geometry and compared with ventricular activation maps after tachycardia induction. RESULTS: Mean IBZ thickness was 231 +/- 140 microm at the reentry isthmus and 1440 +/- 770 microm in the outer pathway (P <0.001). Mean curvature rho was 1.63 +/- 0.45 mm(-1) at functional block line locations, 0.71 +/- 0.18 mm(-1) at isthmus entrance-exit points, and 0.33 +/- 0.13 mm(-1) in the outer reentrant circuit pathway. The mean conduction velocity about the circuit during reentrant tachycardia was 0.32 +/- 0.04 mm/ms at entrance-exit points, 0.42 +/- 0.13 mm/ms for the entire outer pathway, and 0.64 +/- 0.16 mm/ms at outer pathway regions with minimum DeltaT. Model sensitivity and specificity to detect isthmus location was 75.0% and 97.2%. CONCLUSIONS: Reentrant circuit features as determined by activation mapping can be predicted on the basis of IBZ geometrical relationships.     

Microsatellite analysis in Turner syndrome: parental origin of X chromosomes and possible mechanism of formation of abnormal chromosomes.

Turner syndrome is a chromosomal disorder in which all or part of one X chromosome is missing. The meiotic or mitotic origin of most cases remains unknown due to the difficulty in detecting hidden mosaicism and to the lack of meiotic segregation studies. We analyzed 15 Turner patients, 10 with a 45,X whereas the rest had a second cell line with abnormal X-chromosomes: a pseudodicentric, an isochromosome, one large and one small ring, and the last with a long arm deletion. Our aims were: to detect X cryptic mosaicism in patients with a 45,X constitution; to determine the parental origin of the abnormality; to infer the zygotic origin of the karyotype and to suggest the timing and mechanism of the error(s) leading to the formation of abnormal X chromosomes from maternal origin. Molecular investigation did not revealed heterozygosity for any microsatellite, excluding X mosaicism in the 45,X cases. Parental origin of the single X chromosome was maternal in 90% of these patients. Three of the structurally abnormal Xs were maternally derived whereas the other two were paternal. These results allowed us to corroborate breakpoints in these abnormal X chromosomes and suggest that the pseudodicentric chromosome originated from post-zygotic sister chromatid exchange, whereas the Xq deleted chromosome probably arose after a recombination event during maternal meiosis.     

HLA-DRB1*1602 allele is positively associated with HPV cervical infection in Bolivian Andean women

Incidence of cervical cancer is high among Bolivian Andean women. Human papillomavirus (HPV) infection is known as the major risk factor of cervical cancer. The host immune system plays an important role in the outcome of HPV infection and associated malignancies. In order to study the immunogenetic background of Bolivian Andean women with regard to HPV infection status, we compared HLA class I and class II allele frequencies between 37 HPV positive and 68 HPV negative Bolivian women. Demographic variables, including distribution of Andean ethnicities, were similar in both groups. Comparison of HLA class I allele frequencies between both groups indicated no significant difference. In contrast, HLA class II DRB1*1602 allele, an Amerindian allele, was significantly higher in the HPV positive women compared with HPV negative controls (chi(2) = 5.2, p < 0.05, odds ratio = 3.17; 95% confidence interval = 1.4-8.8). HPV types present in the HPV positive group were HPV-18, -16, -31, -33, and -58. These results suggest that HLA class II DRB1*1602 may confer susceptibility to infection with genetically related HPV types. This is the first report of an HLA class II association with HPV infection in an Andean population.     

Molecular characterization of invasive and noninvasive Campylobacter jejuni and Campylobacter coli isolates

Campylobacter jejuni is one of the most common causes of bacterial diarrhea worldwide and is the primary bacterial cause of food-borne illness. Adherence to and invasion of epithelial cells are the most important pathogenic mechanisms of Campylobacter diarrhea. Molecular characterization of invasive and noninvasive Campylobacter isolates from children with diarrhea and symptom-free children was performed by random amplified polymorphic DNA techniques (RAPD). A distinct RAPD profile with a DNA band of 1.6 kb was observed significantly more frequently among invasive (63%) than among noninvasive (16%) Campylobacter isolates (P = 0.000005). The 1.6-kb band was named the invasion-associated marker (IAM). Using specifically designed primers, a fragment of 518 bp of the iam locus was amplified in 85% of invasive and 20% of noninvasive strains (P = 0.0000000). Molecular typing with a PCR-restriction fragment length polymorphism assay which amplified the entire iam locus showed a HindIII restriction fragment polymorphism pattern associated mainly with invasive strains. Although cluster analysis of the RAPD fingerprinting showed genetic diversity among strains, two main clusters were identified. Cluster I comprised significantly more pathogenic and invasive isolates, while cluster II grouped the majority of nonpathogenic, noninvasive isolates. These data indicate that most of the invasive Campylobacter strains could be differentiated from noninvasive isolates by RAPD analysis and PCR using specific primers that amplify a fragment of the iam locus.     

Trisomy 3q25.1-qter and monosomy 8p23.1-pter in a patient: cytogenetic and molecular analysis with delineation of the phenotype

We describe a 4-year-old boy with partial 3q trisomy and distal 8p monosomy. The patient presented with mental retardation, dysmorphic face, congenital heart defect, brain and genital anomalies, and behavioral problems. The conventional cytogenetic analysis showed a 46,XY,add(8p) karyotype. Reverse painting and microsatellite analysis demonstrated a partial monosomy of 8p23.1 --> pter and a partial trisomy of 3q25.1 --> qter. The data suggest that the chromosomal rearrangement originated from a de novo translocation in a paternal germinal cell. The phenotype observed in our patient resulted from the combination of those defects described in the isolated dup(3q) and distal del(8p) syndromes.     

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.

     

P53 alterations show significant correlation with gene amplification and s-phase index in breast-cancer

Correlation of p53 gene/protein alterations with incidence of oncogene amplification, a potential marker of prognosis, was evaluated in 26 fresh breast cancer samples. p53 gene was analyzed by SSCP and DNA sequencing while p53 protein status was investigated by immunohistochemistry (IH). Amplification of c-erbB2/neu, c-myc, N-ras, int-2, hst, PRAD-1 and EGFR genes was studied by slot blot and in situ hybridizations. p53 alterations were found in 31% cases by SSCP and 42% by IH; gene amplification was detected in 27% cases. p53 gene alterations correlated significantly with gene amplification (p=0.006) and also with higher S-phase index (p=0.026), aneuploidy (p=0.026) and negative progesterone receptor status (p=0.043).