Background & Aims Mortality studies in patients with hemochromatosis give conflicting results especially with respect to extrahepatic causes of death. Our objective was to assess mortality and causes ...of death in a cohort of patients homozygous for the C282Y mutation in the HFE gene, diagnosed since the availability of HFE testing. Methods We studied 1085 C282Y homozygotes, consecutively diagnosed from 1996 to 2009, and treated according to current recommendations. Mortality and causes of death were obtained from death certificates and compared to those of the general population. Standardized mortality ratios (SMRs) were used to assess specific causes of death and the Cox model was used to identify prognostic factors for death. Results Patients were followed for 8.3 ± 3.9 years. Overall the SMR was the same as in the general population (0.94 CI: 0.71–1.22). Patients with serum ferritin ⩾2000 μg/L had increased liver-related deaths (SMR: 23.9 CI: 13.9–38.2), especially due to hepatic cancer (SMR: 49.1 CI: 24.5–87.9). Patients with serum ferritin between normal and 1000 μg/L had a lower mortality than the general population (SMR: 0.27 CI: 0.1–0.5), due to a decreased mortality, related to reduced cardiovascular events and extrahepatic cancers in the absence of increased liver-related mortality. Age, diabetes, alcohol consumption, and hepatic fibrosis were independent prognostic factors of death. Conclusions In treated HFE hemochromatosis, only patients with serum ferritin higher than 2000 μg/L have an increased mortality, mainly related to liver diseases. Those with mild iron burden have a decreased overall mortality in relation to reduced cardiovascular and extrahepatic cancer-related events. These results support a beneficial effect of early and sustained management of patients with iron excess, even when mild.
The aim of the present study was to assess long-term survival of cadaveric second kidney allografts performed in our center and to determine risk factors predictive of long-term graft outcome.
Of ...1704 kidney transplantations performed between January 1985 and March 1998, 233 were second grafts. The majority of the recipients were sensitized. All patients were treated with the same quadruple immunosuppressive regimen.
Kaplan-Meier analysis documented graft survival of 89% at 1 year, 76% at 5 years, and 53% at 10 years. Graft survival was similar for second and primary kidney transplants performed during the same period of time. When long-term second graft survival was examined, only two risk factors were found to be significant: (1) the degree of human leukocyte antigen (HLA) DR mismatch (MM) and (2) the number of acute rejection episodes. Multivariate analysis of several pre- and posttransplant variables also confirmed the importance of HLA MM (DR> A), but also, identified serum creatinine at 12 months as the most significant predictor of graft survival. In addition, the Cox proportional hazards model revealed that only the year of transplantation had an independent significant effect on acute rejection occurrence (RR = 0.591, 95%CI 0.437 to 0.801, P < 0.0007). Indeed, the incidence of acute rejection was found to decrease over time (44% of patients experienced at least one episode of acute rejection before 1990 vs. 17% after 1990).
Finally, second graft long-term outcome shows an improved evolution according to the time period resulting from a strong decrease in acute rejection incidence and the impact of creatinine at 12 months.
In a large general French population of 100,000 subjects, the relationship of resting heart rate with age, gender, demographic parameters, physical activity and classical risk factors was evaluated.
...A population composed of all the subjects who had a free health check-up at the IPC Centre between 1992 and 1995 (62,353 men and 35,371 women) was analysed. Heart rate was considered either as a continuous parameter or as a qualitative parameter. The study population was divided into four heart rate classes: < 65, 65-74, 75-84 and > or = 85 beats/min.
Women had significantly higher heart rate values than men, and this gender difference was constant in the different age groups. In both genders, heart rate was positively associated with blood pressure, triglycerides, glycaemia and physical inactivity, and negatively with body height Heart rate was also correlated with total cholesterol but only in men. The only factor having opposite effects on heart rate in men and women was tobacco smoking (positive in men and negative in women). Among untreated hypertensive men, 21.3% had a heart rate > or = 85 beats/min compared with only 4.0% among normotensive men. In women, these percentages were 23.6 and 7.6%, respectively. Subjects with untreated mild hypertension or uncontrolled treated hypertension also showed increased rates of tachycardia compared to normotensives.
The present analysis, performed in a large French population, shows that high heart rate is associated with several other risk factors, especially hypertension, suggesting that tachycardic subjects have a high risk profile.
The T‐cell receptor (TCR) α locus is thought to undergo multiple cycles of secondary rearrangements that maximize the generation of αβ T cells. Taking advantage of the nucleotide sequence of the ...human Vα and Jα segments, we undertook a locus‐wide analysis of TCRα gene rearrangements in human αβ T‐cell clones. In most clones, VαJα rearrangements occurred on both homologous chromosomes and, remarkably, resulted in the use of two neighboring Jα segments. No such interallelic coincidence was found for the position of the two rearranged Vα segments, and there was only a loose correlation between the 5′ or 3′ chromosomal position of the Vα and Jα segments used in a given rearrangement. These observations question the occurrence of extensive rounds of secondary Vα→Jα rearrangements and of a coordinated and polarized usage of the Vα and Jα libraries. Fluorescence in situ hybridization analysis of developing T cells in which TCRα rearrangements are taking place showed that the interallelic positional coincidence in Jα usage cannot be explained by the stable juxtaposition of homologous Jα clusters.
A small fraction of T cells expresses killer-cell Ig-like receptors (KIR), a family of MHC class I-specific receptors that can modulate TCR-dependent activation of effector functions. Although KIR(+) ...cells are enriched within Ag-experienced T cell subsets, the precise relationships between KIR(+) and KIR(-) T cells and the stage of KIR induction on these lymphocytes remain unclear. In this study, we compared KIR(-) and KIR(+) alphabeta T cell clones, sorted by means of the CD158b (KIR2DL2/KIR2DL3/KIR2DS2) specific mAb GL183. We isolated several pairs of CD158b(+) and CD158b(-) alphabeta T cell clones sharing identical productive and nonproductive TCR transcripts. We showed that expression of functional KIR on T cells is regulated after termination of TCR rearrangements. Transcriptional regulation of KIR genes was documented in multiple T cell clones generated from the same donor, and the presence of KIR transcripts was also detected in KIR(-) T cells. These results document a complex regulation of KIR expression in T cells at both pre and posttranscriptional levels, under the control of yet undefined signals provided in vivo.
A case-control study of cancer of the nose and paranasal sinuses was conducted in France to determine whether occupational exposure to formaldehyde was associated with an increased risk of sinonasal ...cancer. Exposures to 14 other substances or groups of substances were also studied (wood dust, leather dust, textile dust, flour dust, sugar dust, coal/coke dust, nickel compounds, chromium compounds, chromium VI, welding fumes, soldering fumes, cutting oils, paints and lacquers, glues and adhesives). Cases (n = 207) and controls (n = 409) were interviewed to obtain detailed information on job history and other potential risk factors for sinonasal cancer. In addition, a questionnaire specially designed for this study was used to help assess exposures to formaldehyde and other substances of interest. The questionnaires were translated into history of occupational exposure by an expert in industrial hygiene, without knowledge of case-control status. Several exposure variables (lifetime average level, duration, cumulative level) were used to describe the risk related to exposure to formaldehyde. Potential confounding factors (occupational and non-occupational) were examined and adjusted for when necessary. No significant association was found between exposure to formaldehyde and squamous-cell carcinomas of the sinonasal cavities. Because of the strong association between exposure to wood dust and nasal adenocarcinoma, it was not possible to assess an independent effect of formaldehyde on this type of cancer. However, among males exposed to medium or high levels of wood dust, the risk of adenocarcinoma associated with formaldehyde was significantly elevated for the highest exposure categories for average level (OR = 5.3, 95% confidence interval = 1.3-22.2), cumulative level (OR = 6.9, 95% CI = 1.7-28.2) and duration of exposure (OR = 6.9, 95% CI = 1.7-27.8). Although a residual confounding effect of wood dust could not be excluded, this study suggests that exposure to both formaldehyde and wood dust may increase the risk of nasal adenocarcinoma, by comparison with the risk due to wood dust alone. This study also indicated an increased risk among males who had been exposed to glues and adhesives, for all histologic types, which was not explained by a confounding effect of paints and lacquers, wood dust or formaldehyde. No other significant association was observed.
In order to examine the relationship between wood dust and sino-nasal cancer, data from 12 case-control studies conducted in seven countries were pooled and reanalyzed. The relative risks associated ...with wood-related jobs and with exposure to wood dust, measured using a job exposure matrix based on occupation and industry titles, were examined using logistic regression. The combined data set consisted of 680 male cases, 2,349 male controls, 250 female cases, and 787 female controls. A high risk of adenocarcinoma among men was associated with employment in wood-related occupations (odds ratio OR = 13.5, 95% confidence interval CI = 9.0-20.0) and the risk was greatest among men who had been employed in jobs with the highest wood dust exposure (OR = 45.5, 95% CI = 28.3-72.9) and increased with duration of exposure. The risk of adenocarcinoma also appeared elevated among women employed in wood-related jobs (OR = 2.5, 95% CI = 0.5-12.3), but the small number of exposed cases precluded detailed analysis. Women in wood dust-exposed jobs appeared to have an excess of squamous cell carcinoma (OR = 2.1, 95% CI = 0.8-5.5) which increased with duration of exposure. An increased risk of squamous cell carcinoma in men was seen only among those employed for 30 or more years in jobs with exposure to fresh wood (OR = 2.4, 95% CI = 1.1-5.0). The results of this analysis provide strong support to the association between exposure to wood dust in a variety of occupations and the risk of sino-nasal adenocarcinoma and are consistent with the results of individual participating studies, although the magnitude of the excess risk varied. The evidence in regard to squamous cell carcinomas was ambiguous and there was a great deal of heterogeneity observed in individual study results. This may be due to differences in risk associated with exposure to hardwoods and softwoods or with other, as yet to be identified, aspects of exposure.
The role of occupational environment in the occurrence of low-back pain was analyzed for 1719 commercial travelers (1376 men and 343 women). At the beginning of the study (To) the group was ...interviewed to determine current lifestyle and occupational factors associated with low-back pain during the previous 12 months. Twelve months later (at T₁), a subsample of 1118 persons (893 men, 225 women) was reinterviewed to study the association between the incidence of low-back pain during the year of follow-up and the risk factors at T₀ . At T₀ low-back pain was significantly related with time spent driving a car at work, comfort of the car seat, carrying loads during work, standing for long periods at work, smoking, and psychosomatic factors. At T₁ driving 10 h/week or more, seat comfort, and psychosomatic factors were associated with first occurrence of low-back pain.
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