Familial clustering of insulin sensitivity.

This study's objective was to determine whether there is familial clustering of insulin sensitivity (SI) or insulin-independent glucose uptake (SG), which would be evidence that they are genetically determined traits. Outpatients had a 3-h intravenous glucose tolerance test. Nondiabetic individuals (n = 183), ranging in age from 16 to 60 yr, were from 105 families that had 2 parents with non-insulin-dependent diabetes mellitus. Of these families, 62 contributed 1 offspring, 21 contributed 2, 13 contributed 3, 6 contributed 4, and 2 and 1 contributed 5 and 6, respectively. The minimal model of glucose disposal and the glucose and insulin values from the intravenous glucose tolerance tests were used to estimate SI and SG. The intraclass correlation coefficient was used to compare the within-family variability of SI and SG with the respective between-family distributions. The intraclass correlation coefficients were 0.26 (P = 0.008) for SI and 0.081 (P = 0.45) for SG. SI and SG were uncorrelated (r = -0.059, P = 0.42). The intraclass correlation of SI could not be explained by familial clustering of fasting insulin or ideal body weight. Finally, the 10 families with the lowest values of SI had a significantly higher within-sibship variability of SI than the other 33 families (P less than 0.001, F test). SI but not SG showed familial clustering, which is consistent with a polygenic determinant of SI. In addition, a large within-family variability of SI in some families is compatible with a major gene effect with a dominant mode of inheritance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epithelial-mesenchymal interactions in experimental oral mucosal carcinogenesis: establishing a technique.

The carcinogen 4-nitroquinoline-1-oxide was applied to the palatal mucosa of rats for varying periods of time. This tissue was separated into epithelial and connective components and then recombined in various combinations and implanted into hypothymic mice. Seventy-two per cent of the implants were recovered and were suitable for detailed histological analysis. The technique provides a suitable model for the assessment of epithelial-connective tissue interactions in experimental oral mucosal carcinogenesis.     

A longitudinal study of mental health consumer/survivor initiatives: Part 3—A qualitative study of impacts of participation on new members

This article examines the outcomes of participation in mental health Consumer/Survivor Initiatives (CSIs) and identifies helpful qualities of CSIs through a longitudinal, qualitative study that involved in‐depth interviews of people who experienced severe mental health challenges in Ontario, Canada. We used a nonequivalent control group design in which we compared active participants in CSIs ( n = 15) with nonactive participants ( n = 12) at baseline and at 9‐ and 18‐month follow‐up intervals. Compared with non‐CSI participants, CSI participants reported more stable mental health, enhanced social support, sustained work, stable income, and participation in education and training at 9‐ and 18‐month interviews. The helpful qualities of CSIs that participants reported were (1) safe environments that provide a positive, welcoming place to go; (2) social arenas that provide opportunities to meet and talk with peers; (3) an alternative worldview that provides opportunities for members to participate and contribute; and (4) effective facilitators of community integration that provide opportunities to connect members to the community at large. The findings are discussed in terms of previous research in self‐help and consumer‐run organizations in mental health. © 2006 Wiley Periodicals, Inc.     

Isoflurane Pretreatment Has Immediate and Delayed Protective Effects against Cytokine-induced Injury in Endothelial and Vascular Smooth Muscle Cells

Background: Volatile anesthetics have protective effects against cytokine-induced injury in endothelial and vascular smooth muscle cells. The authors hypothesized that isoflurane pretreatment may trigger immediate and delayed protection that is modulated by adenosine triphosphate-sensitive potassium channels.

Methods: Human and bovine endothelial cells and rat vascular smooth muscle cells were pretreated with isoflurane (1.5% for 30 min) and then exposed to cytokines (tumor necrosis factor-[alpha], interferon-[gamma], and interleukin-[beta]) for 72 h. Cytokine exposure was initiated immediately after isoflurane pretreatment or after a delay of 1-48 h. Cell survival and viability were evaluated by trypan blue exclusion and lactate dehydrogenase release. The role of mitochondrial and cell membrane adenosine triphosphate-sensitive potassium channels, or both, were evaluated with the antagonists 5-hydroxydecanoate, HMR-1098, or glybenclamide.

Results: Immediate isoflurane pretreatment was approximately 70% effective in increasing cell survival and prevented lactate dehydrogenase release in all cell lines. However, cellular protection was completely lost if the time between isoflurane and cytokine exposure was extended to 2-12 h, depending on the cell type. Delayed protection was equal to immediate protection when the interval was extended to 12-24 h, with protection being sustained at 48 h in human endothelial and rat vascular smooth muscle cells. The immediate and delayed protection was inhibited by glybenclamide and 5-hydroxydecanoate but not by HMR-1098, whereas diazoxide, a mitochondrial adenosine triphosphate-sensitive potassium channels agonist, mimicked the time course of isoflurane-induced immediate and delayed protection in all cell lines.     

Ten-year trends in neonatal assisted ventilation of very low-birthweight infants.

OBJECTIVES: To examine ventilatory support for the VLBW infant over the past 10 years in a single academic NICU and determine factors that predicted length of ventilation, death, and CLD. STUDY DESIGN: A retrospective cohort review of neonatal blood gases, ventilatory support, and clinical outcomes. RESULTS: From 1992 through October 2002, 6254 infants were admitted, of whom 2388 required intubation for mechanical ventilation. Of these, 837 were <1500 g at birth (VLBW) infants and 453 were less than 1000 g (ELBW). Total duration of ventilation decreased in all weight groups. Noninvasive ventilatory support increased from 20 to 55% of total ventilation from 1997 to 2002. During this same period, CLD decreased from 20 to 11% in ventilated VLBW infants. Duration of total ventilation was best predicted by birth weight, with each 100 g increment decreasing the duration of ventilation by 71 hours. Lower birth weight, male sex, and a longer total duration of ventilatory support were significant factors in predicting the occurrence of CLD. Death alone was best predicted by lower birth weight and maximum oxygen index (OI). Transported infants had significantly increased maximal OIs, durations of ventilation, and incidence of death. A total of 48% of infants with a single OI >10 either died or survived with CLD. CONCLUSIONS: Birth weight is the best predictor of duration of ventilation, and CLD is best predicted by birth weight, duration of ventilation and male sex. The increasing use of noninvasive strategies has not been associated with an observable increase in respiratory morbidity. VLBW infants with a single OI>10 may benefit from inclusion in future interventional rescue studies.     

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