Adiposity and physical activity as predictors of cardiovascular mortality.

OBJECTIVE: To investigate whether cardiovascular mortality related to obesity could be modified by physical activity. DESIGN: Mortality follow-up. SETTING: Population study. PARTICIPANTS: Participants in a health survey: 34 868 women and 32 872 men free from known cardiovascular disease or diabetes at baseline. MAIN OUTCOME MEASURES: Total cardiovascular mortality. MAIN RESULTS: During 16 years of follow-up, 3026 women and 3526 men had died from cardiovascular causes. In middle age, obesity [body mass index (BMI) of 30 or higher] was associated with increased risk of cardiovascular death, but the association weakened with age. After 70, there was no association between BMI and cardiovascular death. At all ages, a lower level of physical activity was associated with a higher cardiovascular mortality. In women with high physical activity, indicated by at least 30 min of moderate to vigorous activity more than once a week, cardiovascular mortality was only slightly higher in the obese compared to lean women (adjusted relative risk, 1.27; 95% confidence interval, 0.80-2.00). In men with high physical activity, cardiovascular mortality was, however, significantly higher among the obese (relative risk, 1.62; 95% confidence interval, 1.09-2.40). In both genders cardiovascular mortality was substantially higher in obese people who reported no regular physical activity compared to obese people with a high level of physical activity. CONCLUSION: In obese women, being highly active may, to a large extent, compensate for the risk-increasing effect of being obese, whereas in obese men who engage in a high level of physical activity, the risk of cardiovascular death may be higher than in lean and equally active men.     

Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer

Carcinogenesis, 25, 229–235, 2004 We reported the association of     

Biomonitoring of genotoxic exposure of aluminium plant workers.

Humans are environmentally and occupationally exposed to polycyclic aromatic hydrocarbons (PAH). PAH's are a class of tumorigenic compounds which act through metabolic transformation to chemically reactive forms, epoxides, which covalently bind to DNA forming DNA adducts. To evaluate the genotoxic effects of PAH's, air and urine samples were analyzed for PAH. Blood samples were analyzed for benzo(a)pyrene-diol-epoxide-DNA (BPDE-DNA) adducts. New methods for analyzing DNA adducts in lymphocytes have been used to study the genotoxic effects of human exposure to carcinogens. BPDE-DNA adducts in lymphocytes have been used as internal dosimeters of exposure to PAH's and several studies have been conducted. We measured BPDE-DNA adducts in aluminium plant workers with immuno-assay and physico-chemical methods. PAH-DNA adducts were detectable to a lesser extent in subjects working in an aluminium plant compared to subjects working in a coke oven plant.     

The Frequency of Human Papillomavirus Detection in Postmenopausal Women on Hormone Replacement Therapy

Postmenopausal women enrolled in the Iowa portion of the postmenopausal estrogen/progestin interventions randomized clinical trial (n= 105) during 1989–1991 were studied for (i) the prevalence of human papillomavirus (HPV) in this older age population (ages 45–64), and (ii) the association between hormone replacement therapies (HRTs) and changes in detection of HPV over a 2-year time period. HPV is causative in most cervical and some other genital cancers and in the presence of steroid hormones has been shown to increase neoplastic transformation by HPVin vitro.Using PCR to detect HPV DNA, the overall frequency of the virus regardless of time period was 50.3% (n= 53) with a baseline (BL) frequency of 38.1% and the second year follow-up (FU) of 22.9%. The oncogenic types HPV-16 (75.5%) and HPV-31 (20.8%) were the most commonly reported. All those with persistently detected infection (10.5%), defined as HPV+ at both BL and FU, were identified with HPV-16 or -18. Between these two time periods there were no significant differences in HPV frequency between the placebo and combined HRT groups (BL−/FU+, 21% vs 18%; BL+/FU−, 71% vs 80%). While the study is based on a small sample, the findings suggest that short-term use of HRTs is not associated with an increased risk of HPV detection, but assessment of effects from long-term use is needed. The data also indicate that the frequency of HPV found in older women is higher than previously suspected but that short-term changes in HPV detected in this age group are unrelated to the development of precancerous cervical lesions.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Residual effects of prior exercise and recovery on subsequent exercise-induced metabolic responses

Abstract Data on the metabolic responses to repeated endurance exercise sessions are limited. Thus, the aims of this study were to examine (1) the impact of prior exercise on metabolic responses to a subsequent exercise session and (2) the effect of different recovery periods between two daily exercise sessions on metabolic responses to the second bout of exercise. Nine male elite athletes participated in four 25-h trials: one bout of exercise (ONE), two bouts of exercise separated by 3 h of rest and one meal (SHORT), two bouts of exercise separated by 6 h of rest and two meals (LONG), and a trial with no exercise (REST). All exercise bouts consisted of 10 min cycling at 50% followed by 65 min at 75% of maximal O₂ uptake. Compared to no prior exercise (ONE), a previous bout of exercise (SHORT) was followed by higher mean O₂ uptake, heart rate (HR), rectal temperature (T_R), excess post-exercise oxygen consumption and lower respiratory exchange ratio (R) during and after a similar exercise session 3 h later. A longer rest interval between the two exercise bouts (6 h versus 3 h) and an additional meal resulted in a decrease in O₂ uptake, HR, T_R and an increase in R during the second bout of exercise, but no effects on post-exercise metabolism were found. Thus, augmented metabolic stress was observed when strenuous exercise was repeated after only 3 h of recovery, but this was attenuated when a longer recovery period including an additional meal was provided between the exercise sessions.     

Prevalence of generalized anxiety at eight weeks postpartum

Summary Objective: This study investigated the prevalence and nature of generalized anxiety symptoms in women who were eight weeks postpartum. Method: A community-based sample of 68 postpartum women completed an interview assessing generalized anxiety disorder and depression and a self-report measure of worry associated with concerns relevant to postpartum women. Results: Three women (4.4%) met DSM-IV criteria for generalized anxiety disorder, and an additional 19 women (27.9%) endorsed subsyndromal difficulties with generalized anxiety. Approximately one third of these women endorsed symptoms of depression. In contrast, only two woman met criteria for major depressive disorder. Conclusion: Postpartum generalized anxiety has a higher prevalence than postpartum depression. Received February 26, 2002; accepted November 11, 2002 Published online January 31, 2003 Acknowledgement This work was supported by a New Faculty Scholar Award and a Graduate Research Fellowship from the University of North Dakota. The authors would like to express their appreciation to Jennifer Brendle, Peter Schmutzer, Talia Tweten, and Chad Lystad for their assistance with this research. Correspondence: Amy Wenzel, Ph.D., Department of Psychology, University of North Dakota, Grand Forks, ND 58202-8380, U.S.A.; e-mail: amy_wenzel@und.nodak.edu     

Extraskeletal myxoid chondrosarcoma: multimodal diagnosis and identification of a new cytogenetic subgroup characterized by t(9;17)(q22;q11)

Extraskeletal myxoid chondrosarcoma is a rare malignant soft tissue tumour that can be difficult to diagnose correctly, especially preoperatively. We describe four cases of extraskeletal myxoid chondrosarcoma of the extremities diagnosed by a multimodal approach. The cytological examination of fine-needle aspirates showed small and round, mildly pleomorphic cells lying in sheets and cords, but also dispersed within a myxoid and metachromatic intercellular substance. Histological, electron microscopic and immunocytochemical examination also yielded findings compatible with the diagnosis of extraskeletal myxoid chondrosarcoma. Cytogenetic analysis demonstrated a t(9;22)(q22;q12) in two tumours and a t(9;17)(q22;q11) in the third and fourth. The translocation t(9;22)(q22;q12) has been described repeatedly in extraskeletal myxoid chondrosarcoma but never in other tumours; hence, the detection of this pathognomonic chromosome abnormality in short-term cultured cells from fine-needle aspirates verified the diagnosis in two of the cases. The t(9;17)(q22;q11) found in the last two cases probably represents a new cytogenetic subgroup of extraskeletal myxoid chondrosarcoma as it, too, is unknown in other contexts. The multimodal approach taken in these four cases enabled a definite diagnosis of a rare malignant tumour whose cytological and histological features alone are usually not sufficiently distinct to rule out other differential diagnostic possibilities. Received: 16 March 1999 / Accepted: 1 June 1999     

A nasal whole-cell pertussis vaccine induces specific systemic and cross-reactive mucosal antibody responses in human volunteers

A whole-cell pertussis vaccine, each dose consisting of 250 microg of protein, was given intranasally four times at weekly intervals to six adult volunteers. All vaccinees responded with increases in nasal fluid IgA antibodies to Bordetella pertussis whole-cell antigen. Three vaccinees with high nasal antibody responses also developed increased serum IgA and IgG antibodies to this antigen. Salivary antibody responses to the whole-cell antigen, as well as antibodies in serum and secretions to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were negligible, except for a moderate increase in nasal fluid antibodies to FHA. Unexpectedly, the same vaccinees developed significant rises in nasal and salivary IgA antibodies to meningococcal outer-membrane antigens, whereas corresponding serum IgA and IgG antibodies were unchanged. Thus it appears that mucosal immunisation may induce secretory antibodies with broader specificities than can be found in serum.