Risk factors for osteoporosis in Caucasian patients with moderate chronic obstructive pulmonary disease: a case control study

The prevalence of osteoporosis is high in chronic obstructive pulmonary disease (COPD) patients. The gold standard for the diagnosis of osteoporosis is bone mineral density (BMD) measurements as assessed by dual energy absorptiometry (DXA) scanning as well as vertebral fractures as assessed by instant vertebral assessment (IVA). The aim of this study was to compare COPD GOLD II patients (that is, patients with moderate COPD, stage II, according to the GOLD classification) with osteoporosis (cases) to COPD GOLD II patients without osteoporosis (controls) to identify risk factors for osteoporosis. The diagnosis of osteoporosis was based on BMD and vertebral fractures. Cases (n=49) were matched for gender, age and forced expiratory volume in the first second to controls (n=49). We assessed pulmonary function, body composition, vitamin D, emphysema score (by high-resolution computer tomography), medical history and medication use in all patients. Variables that were significantly different between the cases and controls were included in a logistic regression analysis. COPD patients with osteoporosis had a significantly lower body mass index (BMI) and higher residual volume as the percentage of total lung capacity (RV%TLC) compared to COPD patients without osteoporosis. Decreasing BMI and increasing RV%TLC increased the odds ratio for osteoporosis. Overweight and obese BMI values were protective for osteoporosis. Screening for osteoporosis should be performed even in moderate COPD patients, especially in those with a low BMI and/or a high RV%TLC.     

Developing a spatial-statistical model and map of historical malaria prevalence in Botswana using a staged variable selection procedure

Background  

Several malaria risk maps have been developed in recent years, many from the prevalence of infection data collated by the MARA (Mapping Malaria Risk in Africa) project, and using various environmental data sets as predictors. Variable selection is a major obstacle due to analytical problems caused by over-fitting, confounding and non-independence in the data. Testing and comparing every combination of explanatory variables in a Bayesian spatial framework remains unfeasible for most researchers. The aim of this study was to develop a malaria risk map using a systematic and practicable variable selection process for spatial analysis and mapping of historical malaria risk in Botswana.     

Variable heavy chain gene analysis of follicular lymphomas: correlation between heavy chain isotype expression and somatic mutation load

The expansion of follicular lymphomas (FLs) resembles, both morphologically and functionally, normal germinal center B-cell growth. The tumor cells proliferate in networks of follicular dendritic cells and are believed to be capable of somatic hypermutation and isotype switching. To investigate the relation between somatic mutation and heavy chain isotype expression, we analyzed the variable heavy (V(H)) chain genes of 30 FL samples of different isotypes. The V(H) genes of the FLs were heavily mutated (29.3 mutations on average). In addition, isotype-switched lymphomas contained more somatic mutations than immunoglobulin M-positive lymphomas (33.8 mutations per V(H) gene versus 23.0, respectively). In all but one of the FLs, the ratios of replacement versus silent mutations in the framework regions were low, independent of the absolute number of somatic mutations and the level of intraclonal variation. Analysis of relapse samples of 4 FLs showed no obvious increase in somatic mutation load in most FLs and a decrease in intraclonal variation in time. In 3 of 4 cases, we obtained evidence for selection of certain subclones, rather than clonal evolution. Our findings question if intraclonal variation is always a reflection of ongoing somatic hypermutation. This may have implications for the concept of antigen-driven lymphomagenesis. (Blood. 2000;95:2922-2929)     

A physiological threshold for protection against menadione toxicity by human NAD(P)H:quinone oxidoreductase (NQO1) in Chinese hamster ovary (CHO) cells

NAD(P)H:quinone oxidoreductase 1 (NQO1) has often been suggested to be involved in cancer prevention by means of detoxification of electrophilic quinones. In the present study, a series of Chinese hamster ovary (CHO) cell lines expressing various elevated levels of human NQO1 were generated by stable transfection. The level of NQO1 over-expression ranged from 14 to 29 times the NQO1 activity in the wild-type CHO cells. This panel of cell lines, allowed investigation of the protective role of NQO1 in quinone cytotoxicity. It could be demonstrated that menadione toxicity was significantly reduced in all NQO1-transfected CHO clones compared to the wild-type cells, but the clones did not show differences in their level of protection against menadione. This observation pointed at a critical threshold concentration of NQO1 above which a further increase does not provide further protection against quinone cytotoxicity. Additional studies in which the NQO1 activity was inhibited by dicoumarol showed that only dicoumarol concentrations of about five times the EC(50) for NQO1 inhibition were able to reduce NQO1 levels below the apparent threshold, making the cells more sensitive. The level of this threshold was estimated to be in the range of base line NQO1 activities observed in several tissues and species. Thus, the results of the present study indicate that beneficial effects of NQO1 induction by, for example, cruciferous vegetables might be absent or present depending on the NQO1 activity threshold for optimal protection and the basal level of NQO1 expression in the tissue and species of interest.     

Alcohol use,cigarette consumption and chronic post-traumatic stress disorder

AIMS: The relationship between alcohol consumption, cigarette smoking and post-traumatic stress disorder (PTSD) was studied in 147 male former members of the civilian resistance against the Nazi occupation of Holland during World War II. METHODS: The subjects were interviewed at home. Measures included rating of current PTSD and a self-report measure of smoking and alcohol use. RESULTS: The weekly alcohol consumption reported by veterans was substantially below that of the general population. Furthermore, there was no significant difference in self-reported alcohol consumption between veterans with and without current PTSD. Cigarette smoking, however, was more prevalent in those with current PTSD. CONCLUSIONS: The absence in these veterans of a correlation between PTSD and alcohol consumption is contrary to the results of most studies on this subject. It may be related to the exclusion from organized resistance activities of people prone to the over-consumption of alcohol. It is hypothesized that, in trauma survivors, current substance use is associated with peri-traumatic patterns of psychological tension-reduction modes.     

Contractile properties and fatigue of quadriceps muscles in multiple sclerosis

Functional characteristics of electrically stimulated quadriceps muscles of patients with multiple sclerosis (MS) were determined to investigate whether adaptations in muscle properties contribute to the higher fatigability of these patients. The estimated maximal isometric force generating capacity of MS patients was only 11.2% (P < 0.05) lower than control subjects. However, the patients were only able to voluntarily exert 75 +/- 22% (n = 12) of their maximal capacity, against 94 +/- 6% (n = 7) for the control subjects. There were no differences in muscle speed, suggesting that muscle fiber distribution was not different in the MS patients due to reduced muscle usage. During a series of repeated contractions, greater decrements occurred in isometric force and in maximal rate of force rise in the MS patients (by 31.3 +/- 10.3% and 50.1 +/- 10.0%, respectively; n = 13) than control subjects (23.8 +/- 6.6% and 39.0 +/- 8.1%, n = 15), suggesting a lower oxidative capacity. The results indicate that increasing the mass of their muscles by training may help to reduce the excessive muscle fatigue of MS patients.     

Biased Iglambda expression in hypermutated IgD multiple myelomas does not result from receptor revision.

Normal IgM(-)IgD(+) CD38(+) B cells and IgM(-)IgD(+) multiple myelomas (MM) are characterized by Cmu deletion, biased Iglambda expression and hypermutated IgV regions. The predominant Iglambda usage has been proposed as resulting from secondary Ig gene rearrangements during extensive clonal expansion in the germinal center environment. Here, four cases of IgDlambda MM were studied to address the question of light chain receptor revision in a 'single cell' model. Detailed analyses of both IGK and IGL alleles of each case were performed by Southern blotting, (RT-) PCR, and sequencing. The expressed IgV genes were extensively mutated and Cmu deletion was confirmed in two cases. In addition, in the four MM a total of six non-functional deletional IGK rearrangements were identified, which proved to be unmutated. We conclude that IgD myelomas indeed originate from (post) germinal center B cells in which, in spite of the fact that they are hypermutated, there is no evidence of receptor revision.     

False negative biliary scintigraphy in gangrenous cholecystitis

Gangrenous cholecystitis is a serious complication of acute cholecystitis and is associated with increased morbidity and mortality rates. We report a case in which the diagnosis was suggested by ultrasound, but cholecystectomy delayed due to atypical clinical presentation and a false negative radionuclide biliary scan.