Gender moderates the health-effects of job strain in managers.

PURPOSE: To investigate cross-sectional associations between main, interactive and gender-dependent effects of the demand-control-support (DCS) model and subjective health in managers. METHODS: Data of 424 German, Austrian and Swiss managers were collected at leadership seminars and through presentation of the study at meetings of staff managers and senior executives. Hierarchical regression models controlling for age, hierarchy and non-linear relationships were computed to assess associations between main, interactive and gender-dependent effects of the DCS dimensions (measures of job demands, job control, social support) and subjective health (measures of self rated health and psychosomatic complaints). RESULTS: Social support was associated with both indicators of subjective health. Inconsistent results were obtained for the main effects of job demands and job control. Concerning the interaction effects of the model, a significant three-way interaction was observed: high job control and high social support seem to buffer the adverse health effects of high job demands. This interaction was moderated by gender. Female managers experience more psychosomatic complaints working in high demand, low control, low support settings than their male colleagues. While women seem to experience a higher buffering effect from social support than from job control, male managers may benefit equally from social support and job control. CONCLUSIONS: In managers, gender moderates the health-related effects of the psychosocial work environment. The gender-dependent effects of the DCS model may play a crucial role in the understanding of female managers' adverse health perceptions. Increasing social support for female managers may help to overcome gender inequalities in management positions.

SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory neuropathies.

BACKGROUND: The variable clinical features of hereditary sensory and autonomic neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory neuropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be recognised as familial. OBJECTIVE: To screen persons with dominantly inherited HSAN I and others with idiopathic sensory neuropathies for known mutations of SPTLC1 and RAB7. PATIENTS: DNA was examined from well characterised individuals of 25 kindreds with adult onset HSAN I for mutations of SPTLC1 and RAB7; 92 patients with idiopathic sensory neuropathy were also screened for known mutations of these genes. RESULTS: Of the 25 kindreds, only one had a mutation (SPTLC1 399T-->G). This kindred, and 10 without identified mutations, had prominent mutilating foot injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity with injuries but no weakness, one had restless legs and burning feet, and one had dementia with hearing loss. No mutation of RAB7 was found in any of these. No known mutations of SPTLC1 or RAB7 were found in cases of idiopathic sensory neuropathy. CONCLUSIONS: Adult onset HSAN I is clinically and genetically heterogeneous and further work is required to identify additional genetic causes. Known SPTLC1or RAB7 mutations were not found in idiopathic sensory neuropathy.

Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta149 Leu)].

Splenomegaly with sea-blue histiocytes is not associated with dyslipidemia, except in severe cases of hypertriglyceridemia, Tangier disease, or lecithin cholesterol acyltransferase deficiency. We describe two kindreds in which the sea-blue histiocyte syndrome was associated with an apoE variant in the absence of severe dyslipidemia. Both patients presented with mild hypertriglyceridemia and splenomegaly. After splenectomy both patients developed severe hypertriglyceridemia. Pathological evaluation of the spleen revealed the presence of sea-blue histiocytes. A mutation of apoE was demonstrated, with a 3-bp deletion resulting in the loss of a leucine at position 149 in the receptor-binding region of the apoE molecule [apoE (delta149 Leu)]. Although both probands were unrelated, they were of French Canadian ancestry, suggesting the possibility of a founder effect. In summary, we describe two unrelated probands with primary sea-blue histiocytosis who had normal or mildly elevated serum triglyceride concentrations that markedly increased after splenectomy. In addition, we provide evidence linking the syndrome to an inherited dominant mutation in the apoE gene, a 3-bp deletion on the background of an apoE 3 allele that causes a derangement in lipid metabolism and leads to splenomegaly in the absence of severe hypertriglyceridemia.

Prevalence and clinical significance of HFE gene mutations in patients with iron overload.

OBJECTIVE: The HFE gene contains two mutant alleles; C282Y and H63D. The C282Y mutation occurs in 55-100% of patients with hereditary hemochromatosis. The aim of our study was to re-examine the frequencies of the C282Y and H63D mutations in patients with mild and marked iron overload and in normal subjects. METHODS: A total of 82 patients with iron overload were included in this study and had hepatic iron index determination and/or quantitation of iron stores by phlebotomy. The control group consisted of 81 healthy blood donors. HFE mutation analysis was performed on leukocyte DNA using PCR-amplified genomic DNA. RESULTS: Of patients with iron overload, 70/82 (85%) were homozygous for C282Y versus 2/81 (2.5%) in the control population. Four patients had no HFE mutations despite significant iron overload, including a sister and brother (brother not included in the study group) with hepatic iron concentrations >500 micromoles/g dry weight. CONCLUSIONS: In all, 85% of our patients with iron overload were C282Y homozygotes, although a few had no HFE gene mutations. Pooled data and analysis of chromosomes considered to be at risk for H63D indicate that H63D is associated with iron overload.

Iron overload in cirrhosis-HFE genotypes and outcome after liver transplantation.

Previously, we found appreciable hepatic iron deposition in one third of our patients undergoing liver transplantation (LTx) with approximately 10% of cases having quantifiable iron in the range of that seen in hereditary hemochromatosis (HHC). The aim of this study was to compare clinical outcome in liver transplant patients with and without iron overload. We also sought to determine the prevalence of HFE mutations in liver transplant patients with iron overload. Of 456 consecutive liver transplants, 41 explants had an hepatic iron index (HII) greater than 1.9, and these cases were compared to 41 matched liver transplant recipients without increased hepatic iron. Posttransplantation complications, along with patient and graft survival were monitored. HFE gene testing was performed using DNA-based techniques. Kaplan-Meier 5-year patient survival after LTx was significantly lower in cases with hepatic iron overload compared to matched controls without iron excess (48% vs. 77%; P =.045). Fatal infections (especially fungal) were more common in patients with iron overload (24% vs. 7%; P =.03). Of the 41 patients with a liver explant HII greater than 1.9, only 4 were C282Y homozygotes. Patients with severe hepatic explant iron overload undergoing LTx have a reduced survival compared to liver transplant recipients without explant iron excess. The reduced survival was attributable mainly to fatal bacterial and fungal infections. Despite the iron overload, HFE gene mutations were uncommon in patients with hepatic explant hemosiderosis.

Sequence analysis of the fragile X trinucleotide repeat: implications for the origin of the fragile X mutation.

This study addresses mechanism of instability of the FMR-1 (CGG)n-repeat, and investigates features which may distinguish between normal stable and fragile X unstable repeats. To achieve this, we have sequenced 178 alleles to analyze patterns of AGG interruptions within the CGG repeat, and have typed the (CA)n-repeat at DXS548 for 204 chromosomes. Overall, our data is consistent with the idea that the length of uninterrupted CGG repeats determines instability. We predict that certain sequence configurations [no AGG, and (CGG)9-11AGG(CGG) > or = 20] present in the general population, are predisposed towards replication slippage. Association between these proposed predisposing repeats and DXS548 alleles may explain the previously reported frequencies of fragile X mutations and large-size normal repeats on specific haplotype backgrounds. We propose that predisposing alleles arise in the general population by as yet undefined mechanism(s) which introduce a relatively long stretch of pure CGG repeat at the 3'-end (relative to the direction of transcription) of the FMR-1 repeat region. The 3' pure repeat may then be susceptible to further expansion by replication slippage. Slippage on these predisposing chromosomes could accumulate over many generations until a threshold size is reached, at which point the repeat is susceptible to greater instability (i.e. premutation stage). Thus, results suggest that evolution of fragile X full mutations could involve 4 definable stages: 1) ancestral events leading to the formation of predisposing alleles which have large total repeat length (e.g. between 35 to 50) but no AGG or 1 AGG; 2) gradual slippage of these predisposing alleles to small premutations (S alleles); 3) conversion from S alleles to larger premutations (Z); 4) massive expansion from a Z allele to a full mutation (L).

A conceptual model for determining the least restrictive treatment-training modality.

Much attention has been paid in recent years to the concept of the least restrictive treatment or training for developmentally disabled individuals. However, few well-defined procedures exist for determining the restrictiveness of modalities commonly used with these individuals. The authors identified ten frequently used modalities and six criteria for determining their relative restrictiveness. A total of 97 mental health professionals rated each modality according to the criteria, and a generalized rank order of the ten was obtained. Criteria were then established for applying the more restrictive modalities to individual residents' cases. The authors propose a four-part review process to ensure that the individual needs and rights of residents are respected.