Dietary supplement use and medical conditions: the VITAL study

BACKGROUND: Over half of U.S. adults use vitamin or mineral supplements, and some are likely using supplements to treat chronic diseases or risk factors for disease. Information on the relationship between supplement use and medical conditions is useful to health professionals to understand the self-medication behavior of their patients, and important for researchers because medical conditions may be potential confounding factors in observational studies of supplement use and disease risk. METHODS: The cross-sectional data in this report are from 45,748 participants, aged 50 to 75 years, who completed a self-administered, mailed questionnaire on current dietary supplement use (multivitamins plus 16 individual vitamins or minerals), medical history (cancer, cardiovascular-related diseases, and other self-reported medical conditions), and demographic characteristics. RESULTS: Supplement use (mean number used at least once a week) was higher among respondents who were older, female, highly educated, Caucasian, and of normal body mass index (all p<0.001). After controlling for these covariates, supplement use was higher among those with the condition for 13 of the 21 conditions examined (p<0.01); only having diabetes or high stress was associated with using fewer supplements. For specific supplements, the strongest associations were for cardiovascular disease and its risk factors with vitamin E, niacin, and folate, and for calcium with indigestion and acid reflux disease. For several conditions, the relative odds of using specific supplements were consistently higher for men than for women. CONCLUSIONS: Supplement use was associated with many medical conditions in this cohort. However, these cross-sectional data do not permit inferences about the temporal sequence. Some associations appeared to be based on evidence for efficacy (e.g., folate with coronary artery disease), and others could be based on misinformation (e.g., selenium with benign prostatic hyperplasia).     

Chfr inactivation is not associated to chromosomal instability in colon cancers

Numerous observations suggest that chromosome instability is caused by mitotic abnormalities such as errors in the partitioning of chromosomes. Chfr was recently defined as a central component of a new mitotic checkpoint that delays chromosome condensation in response to mitotic stress. Chfr was shown to be frequently inactivated in several human neoplasms, including colon, lung and esophageal cancers. To test whether Chfr inactivation may lead or participate to chromosomal instability (CIN), we analysed the genetic and epigenetic status of the gene in a large panel of primary colon and breast cancers, as well as in colon and breast cancer cell lines displaying either a microsatellite instability or a CIN. Our results confirm that Chfr is frequently inactivated in colon cancers, through a mechanism of hypermethylation of the promoter sequences. In contrast, the loss of Chfr expression appears to be a rare event in breast cancers. Furthermore, our data demonstrate that Chfr inactivation is not associated with CIN in these frequent types of human cancers.     

Synergy Between 3′Azido-3′deoxythymidine and Paclitaxel in Human Pharynx FaDu Cells

Purpose. We recently demonstrated simultaneous targeting of telomere and telomerase as a novel cancer therapeutic approach, and that telomerase inhibitors such as 3azido-3deoxythymidine (AZT) significantly enhanced the antitumor activity of paclitaxel, which causes telomere erosion, in telomerase-positive human pharynx FaDu tumors in vitro and in vivo (1). The present study evaluated the synergy between AZT and paclitaxel to identify optimal combinations for future clinical evaluation. Methods. FaDu cells were incubated with or without AZT for 24 h and then treated with AZT with or without paclitaxel for an additional 48 h. Under these conditions, single agent paclitaxel produced a 60% maximum reduction of cell number (IC₅₀ was 7.3 nM), and single agent AZT produced a 97% reduction (IC₅₀ was 5.6 M). Synergy was evaluated using fixed-concentration and fixed-ratio methods, and data were analyzed by the combination index method. Results. The results indicate a concentration-dependent synergy between the two drugs; the synergy was higher for combinations containing greater paclitaxel-to-AZT concentration ratios and increased with the level of drug effect. For example, in combinations containing 1 M AZT, synergy was 1.3-fold at the 20% effect level and 3.1-fold at the 60% effect level. Because the major antitumor activity, determined by comparing the posttreatment cell number to the pretreatment cell number, was antiproliferation at the 20% effect level and cell kill at the 60% effect level, our results suggest that AZT mainly enhances the cell kill effect of paclitaxel. Conclusion. In summary, the present study demonstrates a synergistic interaction between paclitaxel and AZT and supports a combination using a low and nontoxic AZT dose in combination with a therapeutically active dose of paclitaxel.     

Biomechanical differences among pes cavus, neutrally aligned, and pes planus feet in subjects with diabetes

The purpose of this study was to quantify differences in joint range of motion, foot deformity, and foot morphology among pes cavus, neutrally aligned, pes planus rigid, and pes planus flexible feet. A cohort of 1047 veterans with diabetes (contributing 2047 feet) was enrolled in a prospective study of diabetic ulcer risk factors (the Seattle Diabetic Foot Study). Significant differences between foot types were found. Pes cavus feet had an increased percentage of prominent metatarsal heads, bony prominences, and hammer/claw toes (p < .0001), as well as significantly increased amounts of hallux dorsiflexion and decreased amounts of hallux plantarflexion (p < .0001) with a total range of motion equal to the other foot types (p = .3). Neutrally aligned feet had a lower percentage of intrinsic muscle atrophy, bony prominences, and hammer/claw toes (p < .0001). Pes planus feet had an increased lateral talometatarsal angle (p < .0001) and an increased second metatarsal length. These data demonstrate structural differences between foot types in a population with diabetes.     

Risk of Mortality during Four Years after Substance Detoxification in Urban Adults

The objective of this analysis was to assess the mortality rate and risk factors in adults, with substance dependence, who are not receiving primary medical care (PC). Date and cause of death were identified using the National Death Index data and death certificates for 470 adults without PC over a period of almost 4 years after detailed clinical assessment after detoxification. Factors associated with risk of mortality were determined using stepwise Cox proportional hazards models. Subjects were 76% male, 47% homeless, and 47% with chronic medical illness; 40% reported alcohol, 27% heroin, and 33% cocaine as substance of choice. Median age was 35. During a period of up to 4 years, 27 (6%) subjects died. Median age at death was 39. Causes included: poisoning by any substance (40.9% of deaths), trauma (13%), cardiovascular disease (13.6%), and exposure to cold (9.1%). The age adjusted mortality rate was 4.4 times that of the general population in the same city. Among these individuals without PC in a detoxification unit, risk factors associated with death were the following: drug of choice [heroin: hazard ratio (HR) 6.9 (95% confidence interval (CI) 1.6–31.1]; alcohol: HR 3.7 (95% CI 0.79–16.9) compared to cocaine); past suicide attempt (HR 2.1, 95% CI 0.96–4.5); persistent homelessness (HR 2.4, 95% CI 1.1–5.3); and history of any chronic medical illness (HR 2.1, 95% CI 0.93–4.7). Receipt of primary care was not significantly associated with death (HR 0.85, 95% CI 0.34–2.1). Risk of mortality is high in patients with addictions and risk factors identifiable when these patients seek help from the health care system (i.e., for detoxification) may help identify those at highest risk for whom interventions could be targeted. Saitz, Cheng, Richardson, and Samet are with the Clinical Addiction Research and Education Unit, Department of Medicine, Boston Medical Center, Boston, MA, USA; Saitz, Gaeta, Cheng, Richardson, and Samet are with the Section of General Internal Medicine, Department of Medicine, Boston Medical Center, Boston, MA, USA; Saitz and Richardson are with the Youth Alcohol Prevention Center, Boston University School of Public Health, Boston, MA, USA; Gaeta is with the Boston Health Care for the Homeless Program, Boston, MA, USA; Cheng is with the Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; Larson is with the New England Research Institutes, Watertown, MA, USA; Samet is with the Department of Social & Behavioral Sciences, Boston University School of Public Health, Boston, MA, USA.     

Toxocara seroprevalence and childhood asthma among Malaysian children

BACKGROUND: The larva of Toxocara spp., a common animal roundworm, may infect non-compatible hosts, causing a profound immunological reaction with marked eosinophil and IgE responses, not unlike in atopy. In this study, we determined the seroprevalence of Toxocara exposure in 66 asthmatic and 58 non-asthmatic children. METHODS: Exposure to Toxocara was determined by examining the serum samples of the children for specific IgG antibodies to L2 Toxocara larvae, using a commercially available diagnostic kit. RESULTS: There was no significant difference in the mean age, sex, social class, residence type and presence of domestic pets at home between the two children groups. Children with bronchial asthma were observed to have higher Toxocara seropositivity than that of the non-asthmatic controls (21.2 vs 8.6%, P=0.047). CONCLUSION: The observed relationship between exposure to Toxocara infection and bronchial asthma in Malaysian children warrants further evaluation. An understanding of any possible contribution to the pathogenesis of childhood asthma provides a potential avenue for prevention.     

Von Willebrand factor antigen levels in Kaposi''s sarcoma

Consistent elevations of plasma von Willebrand factor antigen were observed in otherwise healthy elderly patients with Kaposi's sarcoma. The elevations were predominantly of the endothelial cell--derived antigen, as opposed to the factor VIII procoagulant, with resultant elevations in the antigen/procoagulant ratios. Lesser elevations were seen in a group of age-matched control subjects who did not have Kaposi's sarcoma or intercurrent illness. The greater elevations in plasma von Willebrand factor antigen therefore appear to be the direct consequence of the presence of Kaposi's sarcoma cells. Our findings also suggest that there is a direct relationship between tumor load and degree of von Willebrand factor antigen elevation.     

Mixed land use and walkability: Variations in land use measures and relationships with BMI, overweight, and obesity

Few studies compare alternative measures of land use diversity or mix in relationship to body mass index. We compare four types of diversity measures: entropy scores (measures of equal distributions of walkable land use categories), distances to walkable destinations (parks and transit stops), proxy measures of mixed use (walk to work measures and neighborhood housing ages), and land use categories used in entropy scores. Generalized estimating equations, conducted on 5000 randomly chosen licensed drivers aged 25–64 in Salt Lake County, Utah, relate lower BMIs to older neighborhoods, components of a 6-category land use entropy score, and nearby light rail stops. Thus the presence of walkable land uses, rather than their equal mixture, relates to healthy weight.