Outcomes after injury: a comparison of workplace and nonworkplace injury

BACKGROUND: Factors affecting recovery from injury are investigated comparing male emergency department patients involved in work-related and non-work-related accidents. METHODS: This was a prospective cohort study of 154 injured employed male emergency department patients recording demographic and accident details, return to work information, and involvement in litigation. Standardized questionnaires measured psychological, physical, and social responses. Evaluations were at admission, and at 6 weeks, 6 months, and 18 months after injury. RESULTS: Work-related injuries were less severe than non-work-related injuries (p = 0.006), and more patients became involved in litigation (p = 0.02) and suffered symptoms of posttraumatic stress disorder (p = 0.04). Psychosocial symptoms increased with nonreturn to work (p < 0.05). Factors predicting return to work include injury severity, blaming others, involvement in litigation, and subsequent physical and social functioning. CONCLUSION: Patients injured at work are more likely to commence litigation and develop symptoms consistent with posttraumatic stress disorder. Nonreturn to work is associated with higher psychosocial morbidity. Return to work is predicted from event and recovery period variables.     

Interleukin-10 modulation of alloreactivity and graft-versus-host reactions

BACKGROUND: The biological properties of interleukin (IL)-10 in tolerance induction and inhibition of alloreactivity have suggested a therapeutic use of this cytokine as an additional or alternative prophylaxis for graft-versus-host disease (GvHD). However, the effects of exogenous IL-10 on GvHD are mainly studied in animal models, and the results remain conflicting. This study aims to demonstrate, for the first time, whether the addition of exogenous IL-10 can reduce the severity of graft-versus-host reactions (GvHR) in humans. METHODS: The regulatory role of exogenous IL-10 in GvHR was investigated using an in vitro human skin explant model. The effects of IL-10 on skin GvHR were tested in parallel with allo-antigen induced T-cell proliferation, cytolytic reactivity, and cytokine production. RESULTS: In the presence of IL-10, the mixed lymphocyte reaction (MLR) primed responder cells showed significantly lower proliferative and cytolytic responses compared with the responder cells from the control MLR carried out in the absence of IL-10. The responder cells from IL-10 containing MLR induced significantly less severe skin GvHR and displayed a significantly reduced T-cell activation and cytokine production. A significant correlation was observed between the levels of TNF-alpha production and the sensitivity to IL-10 modulation of GvHR. CONCLUSIONS: The addition of exogenous IL-10 strongly inhibited the broad alloreactivity initiated by primary MLR and significantly reduced the overall severity of skin GvHR induced by MLR primed responder cells. Responder cells producing high TNF-alpha following allogeneic stimulation appeared to be less sensitive to IL-10 modulation of GvHR.     

Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise

We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake, glycogen synthase (GS) activity, and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic (100 microU/ml) clamp. On two occasions, seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp. Caffeine (5 mg/kg) or placebo was administered in a randomized, double-blind fashion 1 h before the clamp. During the clamp, whole-body glucose disposal was reduced (P < 0.05) in caffeine (37.5 +/- 3.1 micromol x min(-1) x kg(-1)) vs. placebo (54.1 +/- 2.9 micromol x min(-1) x kg(-1)). In accordance, the total area under the curve over 100 min (AUC(0--100 min)) for insulin-stimulated glucose uptake in caffeine was reduced (P < 0.05) by approximately 50% in rested and exercised muscle. Caffeine also reduced (P < 0.05) GS activity before and during insulin infusion in both legs. Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo. Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs. Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs. Caffeine did not alter insulin signaling in either leg. Plasma epinephrine and muscle cAMP concentrations were increased in caffeine. We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.     

Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes

Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3' end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.     

Acne treatment with a 1,450 nm wavelength laser and cryogen spray cooling

BACKGROUND AND OBJECTIVES: A laser with a wavelength in the mid-IR range targeting the depth in skin where sebaceous glands are located in combination with cryogen spray cooling was evaluated for treatment of acne. In this non-ablative treatment, the laser energy heats the dermal volume encompassing sebaceous glands whereas the cold cryogen spray preserves the epidermis from thermal damage. STUDY DESIGN/MATERIALS AND METHODS: Monte Carlo simulations and heat transfer calculations were performed to optimize the heating and cooling parameters. A variety of heating and cooling parameters were tested in an in vivo rabbit ear study to evaluate the histological effect of the device on sebaceous glands and skin. Similar experiments were performed on ex vivo human skin. A clinical study for the treatment of acne on backs of human males was also conducted. RESULTS: Monte Carlo simulations and heat transfer calculations resulted in a thermal damage profile that showed epidermal preservation and peak damage in the upper dermis where sebaceous glands are located. Ex vivo human skin histology confirmed the damage profile qualitatively. In vivo rabbit ear histology studies indicated short-term thermal alteration of sebaceous glands with epidermal preservation. In the human clinical study on the back, a statistically significant reduction in lesion count on the treated side compared to the control side was seen (p < 0.001). Side effects were transient and few. CONCLUSIONS: The studies reported here demonstrate the feasibility of treating acne using a photothermal approach with a mid-IR laser and cryogen cooling.     

Energy intake and resting metabolic rate in preschool Jamaican children with homozygous sickle cell disease

BACKGROUND: A relative energy deficiency consequent to a high resting metabolic rate (RMR) may contribute to growth impairment in persons with homozygous (SS genotype) sickle cell disease (SCD). The growth deficit in SCD emerges at an early age, but few studies have addressed the adequacy of energy intake relative to RMR in young children. OBJECTIVE: Our objective was to test the hypothesis that energy intake relative to RMR is lower in children with SCD than in control subjects. DESIGN: The dietary intake of 41 children with SCD and 31 control subjects with a normal hemoglobin genotype (AA) aged 3-6 y was assessed by weighing all food consumed during 3 d. RMR was determined with the use of indirect calorimetry. RESULTS: The RMR in the children with SCD ( +/- SD: 5.47 +/- 0.93 MJ/d) was higher than that in the control subjects (5.19 +/- 1.3 MJ/d) after adjustment for sex and weight (P = 0.04). Energy intake did not differ significantly between the 2 genotype groups. The ratio of energy intake to RMR was lower in the children with SCD ( +/- SD: 1.13 +/- 0.33) than in the control subjects (1.35 +/- 0.38) after adjustment for sex and weight (P = 0.005). CONCLUSIONS: Prepubertal children with SCD fail to compensate for their higher RMR by increasing their energy intake. This observation is consistent with a hypothesis of a relative energy deficiency in SCD.     

Effect of reduced dietary protein intake on hepatic and plasma essential fatty acid concentrations in the adult female rat: effect of pregnancy and consequences for accumulation of arachidonic and docosahexaenoic acids in fetal liver and brain

During pregnancy, the accumulation of long-chain polyunsaturated fatty acids (LCPUFA) in fetal tissues places a substantial demand upon maternal lipid metabolism. As lipid metabolism is intimately linked to aspects of protein metabolism, a reduced protein intake in pregnancy may impair activities of enzymes and transport proteins responsible for supplying LCPUFA to the fetus, thereby compromising fetal development. We have investigated the effect of reduced protein intake on LCPUFA status in the non-pregnant rat and in the pregnant rat, and in fetus at day 20 of gestation. Female rats (n 5 per group) were either mated and fed the control diet (180 g protein/kg) or low-protein diet (90 g protein/kg, LPD) diet throughout pregnancy, or fed the control diet or LPD for 20 d (non-pregnant animals). The fatty acid compositions of maternal liver and plasma, and fetal liver and brain were determined by GC. Feeding the LPD did not lead to any gross changes either in adult or fetal growth, or in total lipid concentrations in adult rat liver. However, the LPD was associated specifically with lower liver (42.6 %) and plasma (19.4 %) phosphatidylcholine (PC), and plasma triacylglycerol (28.6 %) docosahexaenoic acid (DHA) concentrations in pregnant rats and reduced fetal brain PC- (26.1 %) and phosphatidylethanolamine- (25.6 %) DHA concentrations. Together, these results show that variations in maternal dietary protein consumption alter DHA status in pregnancy and modify DHA accumulation into the fetal brain. The present results suggest that lower maternal protein intakes reduce delivery of DHA from the mother to the fetus, which may impair development and function of the fetal brain.     

Effect of temperature and pirimiphos methyl on biochemical biomarkers in Chironomus riparius Meigen

Fourth-instar Chironomus riparius Meigen larvae were exposed to the organophosphate (OP) insecticide pirimiphos methyl (0, 0.1, 1.0, and 10 microg/L) for 48, 72, or 96 h at three temperatures (3, 12, or 22 degrees C). Two biochemical biomarkers, acetylcholinesterase (AChE) and glutathione S-transferase (GST), were measured in individual larvae from each treatment. AChE activity was inhibited by the OP in a dose-responsive fashion. This response remained similar at all three temperatures, demonstrating that AChE is a robust and specific biomarker. Exposure duration had little effect on AChE activity. In contrast, GST activity was induced at the highest OP insecticide concentration, but induction was also evident at 3 degrees C. There was a significant effect of exposure duration, with an overall decline in GST activity over time. This result agrees with previous work suggesting that GSTs are not particularly suitable for use as a biomarker of pesticide exposure or effect in Chironomus.