Subclinical course of adult visceral Niemann–Pick type C1 disease. A rare or underdiagnosed disorder?

Summary  We present the third case of Niemann–Pick disease type C without neurological symptoms. The patient was a 53-year-old woman without significant prior health problems who died of acute pulmonary embolism. Autopsy findings of hepatosplenomegaly, lymphadenopathy and ceroid-rich foam cells raised the suspicion of the visceral form of acid sphingomyelinase deficiency (Niemann–Pick disease type B; NPB) or a much rarer disorder, variant adult visceral form of Niemann–Pick disease type C (NPC). To verify the histopathological findings, SMPD1, NPC1 and NPC2 genes were analysed. Two novel sequence variants, c.1997G>A (S666N) and c.2882A>G (N961S) were detected in the NPC1 gene. No pathogenic sequence variants were found either in the SMPD1 gene mutated in NPB or in NPC2 gene. The pathogenicity of both NPC1 variants was supported by their location in regions important for the protein function. Both variations were not found in more than 300 control alleles. Identified sequence variations confirm the diagnosis of the extremely rare adult visceral form of Niemann–Pick disease type C, which is otherwise dominated by neurovisceral symptoms. Although only three patients have been reported, this (most probably underdiagnosed) form of NPC should be considered in differential diagnosis of isolated hepatosplenomegaly with foam cells in adulthood. Electronic supplementary material  Supplementary material is available for this article at     

Lipid peroxidation, occupational stress and aging in workers of a prehospital emergency service.

BACKGROUND: Stressful conditions lead to formation of excessive free radicals, and lipid peroxidation is one of the major outcomes of free radical-mediated injury that directly damages membranes and generates a number of secondary products. OBJECTIVES: To determine the levels of malondialdehyde, an end product of lipid peroxidation, according to demographic and occupational variables in workers of a prehospital emergency service and to analyse the relationship between malondialdehyde levels and burnout. MATERIAL AND METHODS: One hundred and eleven healthy workers of a prehospital emergency service and eighty aged-matched healthy individuals of both sexes as a control group were surveyed. Malondialdehyde levels were measured by the Bull and Marnett method. To measure burnout, the Maslach Burnout Inventory was used. RESULTS: Professional category is associated with lipid peroxidation and burnout levels (Malondialdehyde levels were: physicians 338.10+/-14.47, nurses 329.17+/-12.62 and technicians 296.74+/-14.28; burnout levels were: physicians 41.29+/-3.59, nurses 37.38+/-6.05 and technicians 35.33+/-5.87). Working at night and in the evening increased malondialdehyde and burnout levels. Malondialdehyde levels increase with age. No significant variations with respect to sex were detected. Significant variations in malondialdehyde levels were detected between singles (303.13+/-12.74) and married people (344.43+/-13.43) but not with respect to divorcees (326.44+/-11.74). Significant differences were detected in erythrocyte malondialdehyde levels between smokers (341.37+/-17.09) and nonsmokers (302.21+/-12.38), but not for alcohol consumption. CONCLUSIONS: These findings suggest a positive correlation between malondialdehyde, a biomarker of lipid peroxidation and occupational stress, as estimated by elements of the Maslach Burnout Inventory, and oxidative stress.     

Increased incidence of Lyme borreliosis in southern Sweden following mild winters and during warm, humid summers

The aim of the present study was to investigate the long-term incidence rate of Lyme borreliosis and, additionally, to determine whether a correlation exists between climatic factors and summer-season variations in the incidence of Lyme borreliosis. Climatic variability acts directly on tick population dynamics and indirectly on human exposure to Lyme borreliosis spirochetes. In this study, conducted in primary healthcare clinics in southeastern Sweden, electronic patient records from 1997–2003 were searched for those that fulfilled the criteria for erythema migrans. Using a multilevel Poisson regression model, the influence of various climatic factors on the summer-season variations in the incidence of erythema migrans were studied. The mean annual incidence rate was 464 cases of erythema migrans per 100,000 inhabitants. The incidence was significantly higher in women than in men, 505 and 423 cases per 100,000 inhabitants, respectively (p<0.001). The summer-season variations in the erythema migrans incidence rate correlated with the monthly mean summer temperatures (incidence rate ratio 1.12; p<0.001), the number of winter days with temperatures below 0°C (incidence rate ratio 0.97; p<0.001), the monthly mean summer precipitation (incidence rate ratio 0.92; p<0.05), and the number of summer days with relative humidity above 86% (incidence rate ratio 1.04; p<0.05). In conclusion, Lyme borreliosis is highly endemic in southeastern Sweden. The climate in this area, which is favourable not only for human tick exposure but also for the abundance of host-seeking ticks, influences the summer-season variations in the incidence of Lyme borreliosis.     

p53 expression and disease outcome of breast cancer patients undergoing primary chemotherapy with anthracycline-containing regimens

Primary chemotherapy administered to breast cancer patientsis the best model to identify baseline features able to predictwhich patients may be most likely to benefit or not from a cytotoxicregimen. In the March issue of Annals of Oncology two papersevaluated the predictive role of immunohistochemical p53 expressionon