High-Density SNP genotyping defines 17 distinct haplotypes of the TNF block in the Caucasian population: implications for haplotype tagging

The region spanning the tumor necrosis factor (TNF) cluster in the human major histocompatibility complex (MHC) has been implicated in susceptibility to numerous immunopathological diseases, including type 1 diabetes mellitus and rheumatoid arthritis. However, strong linkage disequilibrium across the MHC has hampered the identification of the precise genes involved. In addition, the observation of "blocks" of DNA in the MHC within which recombination is very rare, limits the resolution that may be obtained by genotyping individual SNPs. Hence a greater understanding of the haplotypes of the block spanning the TNF cluster is necessary. To this end, we genotyped 32 human leukocyte antigen (HLA)-homozygous workshop cell lines and 300 healthy control samples for 19 coding and promoter region SNPs spanning 45 kb in the central MHC near the TNF genes. The workshop cell lines defined 11 SNP haplotypes that account for approximately 80% of the haplotypes observed in the 300 control individuals. Using the control individuals, we defined a further six haplotypes that account for an additional 10% of donors. We show that the 17 haplotypes of the "TNF block" can be identified using 15 SNPs.     

IS1245 Restriction Fragment Length Polymorphism Typing of Mycobacterium avium Isolates: Proposal for Standardization

Mycobacterium avium has become a major human pathogen, primarily due to the emergence of the AIDS epidemic. Restriction fragment length polymorphism (RFLP) typing, using insertion sequence IS1245 as a probe, provides a powerful tool in the molecular epidemiology of M. avium-related infections and will facilitate well-founded studies into the sources of M. avium infections in animal and environmental reservoirs. The standardization of this technique allows computerization of IS1245 RFLP patterns for comparison on a local level and the establishment of M. avium DNA fingerprint databases for interlaboratory comparison. Moreover, by combining international DNA typing results of M. avium complex isolates from a broad spectrum of sources, long-lasting questions on the epidemiology of this major agent of mycobacterial infections will be answered.     

Adequacy and support of physiological functions in the acutely ill cirrhotic patient

The cirrhotic condition is characterized by a series of changes in physiological functions and of subclinical alterations that imply an abnormal and fragile adaptive pattern with reduced resistance to superimposed distress. In the care of the critically ill cirrhotic patient, the supportive measures aimed at maintaining physiological stability through the control of such debilitating factors have a key role and are not secondary in importance to the more obvious measures needed to treat clinically evident and specific alterations or complications. The relationship between hepatic malfunction and the development of these physiological abnormalities is not fully understood. Our knowledge of the problem, however, has been recently improved and the need for supportive measures motivated by a series of notions on cardiorespiratory and metabolic abnormalities and interactions in hepatic decompensation.

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Resumen La condición cirrótica se caracteriza por una serie de cambios en las funciones fisiológicas y por alteraciones subclinicas que implican un patrón de adaptación anormal y fragil de resistencia reducida al estrés. Estas incluyen disfunción respiratoria con tendencia a la hipoxemia arterial en presencia de elevados indices cardiacos, una situatión crónica de hiperdinamismo cardiovascular pero con precaria eficacia miocárdica y latente riesgo de falla de alto débito, y cambios metabólicos que se traducen en un estado de fallas multisistémicas interrelacionadas características del cirrótico. En el cuidado del paciente cirrótico en estado crítico, las medidas de soporte orientadas al mantenimiento de la estabilidad fisiológica mediante el control de tales factores debilitantes tienen una importancia capital y no son secundarias frente a aquellas muy obvias que se requieren para tratar alteraciones o complicaciones específicas y clínicamente evidentes. La relación entre la disfunción hepática y el desarrollo de las mencionadas anormalidades fisiológicas no está totalmente aclarada, sin embargo, el estado de nuestro conocimiento sobre el problema ha sido enriquecido recientemente y se ha fortalecido la necesidad de establecer medidas de soporte por una serie de nociones relativas a las anormalidades e interacciones cardiorrespiratorias y metabólicas de la descompensación hepática.

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Résumé La cirrhose est caractérisée par des séries de variations des fonctions physiologiques et de modifications cliniques qui impliquent des modalités d'adaptation anormale et fragile se traduisant par une résistance réduite à l'état de détresse ou peut se trouver le cirrhotique. Des mesures appropriées pour maintenir la stabilité physiologique ont un rôle principal en présence de ces facteurs défavorables. Elles ne doivent pas être considérées comme moins importantes que les mesures essentielles qui sont nécessaires pour traiter les complications et les modifications cliniques spécifiques. La relation entre l'altération des fonctions du foie et le développement des anomalies physiologiques précitées n'est pas parfaitement élucidée, cependant, nos connaissances de ce problème ont été récemment améliorées et le besoin de mesures adéquates de soutien est devenu manifeste en raison de séries acquises de notions concernant les anomalies cardio-respiratoires et métaboliques ainsi que les interactions de la décompensation hépatique.

     

Structure-intestinal transport and structure-metabolism correlations of some potential cancerostatic pyrimidine nucleosides in isolated rat jejunum

Summary Both transport and biotransformation processes for a series of pyrimidine nucleobases, ribonucleosides, 2-deoxyribonucleosides, and acetyl and 5-substituted derivatives of the cancerostatic agent araC were studied in the isolated everted rat jejunum with a continuous perfusion technique. Metabolic alterations during penetration were assessed by HPLC. 5-Halogeno and 5-deoxy derivatives of cytosine nucleosides exhibited higher transport rates and higher stability towards the deamination reaction than did unsubstituted derivatives. Octanol-buffer partition coefficients were estimated for the study compounds, and fragmental constants for the sugar moieties of nucleosides were assessed. With the present study compounds there was no correlation between lipophilicity and transport rate, as previously reported, but there was a correlation between lipophilicity and metabolic alteration of araC derivatives (r=0.99, n=5).     

Validation of low-cost models for minimal invasive surgery training of congenital diaphragmatic hernia and esophageal atresia

BackgroundMinimal invasive surgery (MIS) is increasingly used for the correction of congenital diaphragmatic hernia (CDH) and esophageal atresia (EA). It is important to master these complex procedures, preferably preclinically, to avoid complications. The aim of this study was to validate recently developed models to train these MIS procedures preclinically.MethodsTwo low cost, reproducible models (one for CDH and one for EA) were validated during several pediatric surgical conferences and training sessions (January 2017–December 2018), used in either the LaparoscopyBoxx or EoSim simulator. Participants used one or both models and completed a questionnaire regarding their opinion on realism (face validity) and didactic value (content validity), rated on a five-point-Likert scale.ResultsOf all 60 participants enrolled, 44 evaluated the EA model. All items were evaluated as significantly better than neutral, with means ranging from 3.7 to 4.1 (p < 0.001). The CDH model was evaluated by 48 participants. All items scored significantly better than neutral (means 3.5–3.9, p < 0.001), with exception of the haptics of the simulated diaphragm (mean 3.3, p = 0.054). Both models were considered a potent training tool (means 3.9).ConclusionThese readily available and low budget models are considered a valid and potent training tool by both experts and target group participants.Type of studyProspective study.Level of evidenceLevel II.     

Scarf osteotomy for hallux valgus deformity: Radiological outcome,metatarsal length and early complications in 118 feet

BackgroundScarf osteotomy has been widely used to restore axial orientation of the first ray in the treatment of hallux valgus deformity. The aim of the study was to present our radiological outcomes of bunion reconstruction, identify surgical complications in early follow-up, and assess to what extent a shortening of the first metatarsal is present after surgery as a possible cause of postoperative metatarsalgia.MethodsWe enrolled 106 patients (118 feet) and assessed patients’ pre- and postoperative measurements of hallux valgus and intermetatarsal angles on weightbearing X-ray images. Three different methods of measuring metatarsal length were compared and early postoperative complications noted.ResultsHallux valgus angle decreased significantly by an average of 18.7 degrees and the intermetatarsal angle by 7.8 degrees. Using three methods of measuring metatarsal length, all showed significant shortening of the first metatarsal. Mean relative lengthening of the second metatarsal averaged 0.45 mm. The Coughlin method showed the highest interrater reliability (ICC = 0.96).ConclusionsSignificant reduction of the hallux valgus angle and intermetatarsal angle was demonstrated with a low complication rate. There was significant shortening of the first metatarsal. The Coughlin method clearly demonstrated an excellent interrater reliability.Level of evidenceLevel IV.     

Endoscopic therapy of weight regain after bariatric surgery

Weight regain following primary bariatric surgery occurs in a significant proportion of patients and is attributed to epidemiological, anatomical and metabolic factors. Surgical revision of these patients has significant risks and limited benefits. Endoscopic revisions that reduce gastric pouch size and diameter of the gastrojejunal anastomosis may offer an effective, safe, less invasive and even reproducible treatment. We herein discuss the indication, selection and feasibility of different endoscopic techniques that could be used in the management of weight regain following primary bariatric surgery. Future research could optimize a personalized approach not only in the endoscopic management but also in combination with other therapeutic modalities for weight regain after bariatric surgery.     

Reported disease and psychological well-being in Swiss adults

Summary In Switzerland, and in many other countries as well, the distribution of morbidity and perceived health in the general population and their determining factors have not been systematically studied so far. This article reports an exploratory study of prevalence of two complex health indicators, longstanding disease (Disease) and psychological well-being (Well-being) and of their environmental, person-specific and behavioural determinants. Data from a health survey conducted in five cantons and three language regions as part of the Swiss Intercantonal Health Indicators Project were used. Whereas distributions of prevalence of Disease according to gender, age, level of education and place of living confirm results of other studies, unexpected prevalence patterns were found for Well-being, especially with regard to gender differences. Multivariate analyses by general linear models (independent sub-samples of the study population were used to develop and validate models) showed different sets of environmental, person-specific and behavioural factors to explain inter-individual differences of Disease and Well-being, both in the total validation sample and in sub-samples of women and men. The results are discussed with regard to implications for socioepidemiological health research.

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Zusammenfassung Wie in zahlreichen anderen Ländern so sind bisher in der Schweiz die Verteilung und die Determinanten von Morbidität und wahrgenommener Gesundheit in der Gesamtbevölkerung nicht systematisch untersucht worden. Die vorliegende Arbeit berichtet über eine explorative Studie über die Prävalenz zweier komplexer Gesundheitsindikatoren, länger andauernde Krankheit (Disease) und psychisches Wohlbefinden (Well-being), und über deren jeweilige umweltbedingte, personale und verhaltensbezogene Einflußfaktoren. Grundlage dafür waren Daten, die in einer Bevölkerungsbefragung in 5 Kantonen und 3 Sprachregionen im Rahmen des Interkantonalen Gesundheitsindikatorenprojekts (IGIPPROMES) erhoben wurden. Während die Verteilung der Prävalenz von Krankheit nach Geschlecht, Alter, Bildungsstatus und Wohnortgrösse den Ergebnissen anderer Studien entspricht, ergaben sich bei der Prävalenz von Wohlbefinden unerwartete Verteilungsmuster, insbesondere Unterschiede zwischen Frauen und Männern. Eine Analyse interindividueller Unterschiede von Krankheit und Wohlbefinden mit Hilfe eines allgemeinen linearen Modells (Modellentwicklung und Validierung an unabhängigen Teilstichproben) zeigte, dass diese durch jeweils spezifische Konstellationen von Umwelt-, Personen- und Verhaltensfaktoren erklärt werden können, sowohl in der gesamten Validierungsstichprobe als auch in den Teilstichproben für Frauen und Männer. Die Ergebnisse der Studie werden in Hinblick auf die Weiterentwicklung der sozialepidemiologischen Gesundheitsforschung diskutiert.

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Résumé En Suisse, comme dans beaucoup d'autres pays, la morbidité et le bien-être psychologique de la population générale n'ont presque pas été étudiés jusqu'à présent. Dans ce rapport, les résultats d'une étude exploratoire sur deux indicateurs complexes de santé, maladie chronique (Disease) et bien-être psychologique (Well-being) et sur les facteurs de l'environnement, de la personnalité et du comportement qui influencent ces deux indicateurs sont présentés. Cette étude faisait part du projet intercantonal sur les indicateurs de santé (IGIP-PROMES) et se base sur les données tirées d'une enquête auprès des populations de cinq cantons et trois régions linguistique de la Suisse. Tandis que la prévalence de l'indicateur «maladie» par sexe, age, degré de formation et dimension du lieu de résidence était conforme aux résultats d'autres études, des distributions inattendues de la prévalence de «bien-être psychologique», notamment des différences entre hommes et femmes ont été trouvées. Une analyse des différences entre individue de «maladie» et «bien-être» au moyen d'un modèle linéaire généralisi — le développement et l'évaluation duquel ont été faits à l'aide de deux échantillons d'occasion indépendents — a montré que des constellations spécifiques constituées de facteurs de l'environnement, de la personnalité et du comportement, peuvent expliquer ces différences, soit dans l'échantillon d'évaluation totale, soit dans les échantillons partiels de femmes et d'hommes. Ces résultats sont discutés par rapport à l'évolution de la recherche socio-épidémiologique.

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Paper presented at a symposium on The Public Health Perspective of Social and Preventive Medicine, in celebration of the 20th anniversary of the Department of Social and Preventive Medicine, University of Berne, 25 June 1992 in Berne.