Low vitamin D status in relation to cardiovascular disease and mortality in Swedish women - Effect of extended follow-up.

BACKGROUND AND AIMS: The impact of vitamin D concentrations on subsequent cardiovascular disease (CVD) and overall mortality has been generally examined for periods under two decades. The magnitude of the association may depend on follow-up length. We aimed to investigate the relationship between baseline vitamin D and risk of total CVD, stroke and all-cause mortality over three decades of follow-up. Secondly, we aimed to assess how follow-up affects the associations. METHODS AND RESULTS: Concentrations of 25-hydroxyvitamin D (25D) were measured in a population-based sample of 1227 middle-aged women using serum collected at baseline and categorized into low (lowest 25D quartile) vs high 25D status (upper three 25D quartiles). Hazard ratio (HR) of the endpoints was estimated for low 25D. The impact of follow-up was examined in intermediary analyses where follow-up was interrupted up to four times, each time decreasing it by five years. There were 596 cardiovascular events and 635 participants died. During the first 17 years, the low 25D group experienced a 29% higher CVD risk and 3.3-fold higher stroke risk after accounting for confounders. Longer follow-up diminished significantly these risks and 25D status had no contribution at 32 years. For mortality, the decline over time was less dramatic, with HR = 1.96 (1.25; 3.08) at 17 years and HR = 1.42 (1.17; 1.72) at 37 years. CONCLUSION: Low 25D status increased the risk for all endpoints, but a lengthy follow-up diminished these risks towards the null. The impact of follow-up depends on the outcome. Future studies of 25D and disease should use repeated 25D assessments.

Maternal fatty acid intake during pregnancy and the development of childhood overweight: a birth cohort study.

BACKGROUND: Maternal diet during pregnancy may contribute to the risk of offspring adiposity. OBJECTIVES: The objective of the study is to explore the associations between maternal antenatal dietary fatty acid intake and the risk of offspring overweight and obesity at the ages of 2 to 7 years. METHODS: In a prospective Finnish birth cohort with 3807 mother-child pairs, maternal diet in late pregnancy was assessed with a food frequency questionnaire. Intakes of total fatty acids and individual saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were calculated. Generalized estimating equation models were used to study the associations of maternal dietary variables with repeatedly measured offspring overweight and obesity. RESULTS: In girls, maternal intake ratio of n-6:n-3 PUFAs had a U-shaped association with obesity (adjusted OR for the lowest 2.0 [95% CI 1.27-3.20] and the highest 1.7 [1.03-2.73] vs. the two middle quartiles of n-6:n-3 PUFAs, p = 0.01). In boys, arachidonic acid (20:4n-6): docosahexaenoic acid + eicosapentaenoic acid ratio was associated with obesity (adjusted OR for the lowest 1.0 [0.60-1.57] and the highest 0.5 [0.26-0.88] vs. the two middle quartiles, p = 0.02). Saturated fatty acids and monounsaturated fatty acids were not associated with overweight or obesity in either sex. CONCLUSIONS: Maternal intakes of PUFAs in late pregnancy were associated with risk of later obesity differently in girls and boys.

Serum 25-hydroxy vitamin D levels in middle-aged women in relationship to adiposity and height trajectories over three decades.

BACKGROUND/OBJECTIVES: The long-term chronology of the association between low serum concentrations of 25-hydroxy vitamin D (25(OH)D) and weight status is unclear. We examined whether lower 25(OH)D in middle-aged women drives upwards the weight, body mass index (BMI) and waist-hip ratio (WHR) over the next 32 years, and whether higher 25(OH)D might predict less decline in the mid- to late-life height trajectory. SUBJECTS/METHODS: The Population Study of Women in Gothenburg started in 1968-1969 (the baseline) in 38-60-year-old women residing in Gothenburg, Sweden. Anthropometric measures were taken at baseline and 4 re-examinations until 2000-2003. Levels of 25(OH)D were analyzed in serum stored since baseline in 1227 (84%) women. Repeated measures analyses were used to model associations between 25(OH)D (dichotomized, cut point 51.45 nmol/l) at baseline and anthropometric trajectories, adjusting for fixed and time-dependent covariates. RESULTS: At baseline, mean BMI was 25.2 kg/m(2) in women with low 25(OH)D and 23.8 kg/m(2) in the remaining women (P<0.001), but this difference did not increase over 32 years and longitudinal differences were explained by the baseline BMI. Similar results were observed for weight and WHR. In contrast, no association was seen for height at baseline or longitudinally. CONCLUSIONS: No relationship was observed between 25(OH)D height trajectory, but lower 25(OH)D was associated with higher BMI, weight and WHR differences that were maintained over three decades. This provides no evidence for the direction of causality, but for a life-long difference in adiposity-related measures according to the 25D level in middle-aged women.

Inconsistent identification of pit bull-type dogs by shelter staff.

Shelter staff and veterinarians routinely make subjective dog breed identification based on appearance, but their accuracy regarding pit bull-type breeds is unknown. The purpose of this study was to measure agreement among shelter staff in assigning pit bull-type breed designations to shelter dogs and to compare breed assignments with DNA breed signatures. In this prospective cross-sectional study, four staff members at each of four different shelters recorded their suspected breed(s) for 30 dogs; there was a total of 16 breed assessors and 120 dogs. The terms American pit bull terrier, American Staffordshire terrier, Staffordshire bull terrier, pit bull, and their mixes were included in the study definition of 'pit bull-type breeds.' Using visual identification only, the median inter-observer agreements and kappa values in pair-wise comparisons of each of the staff breed assignments for pit bull-type breed vs. not pit bull-type breed ranged from 76% to 83% and from 0.44 to 0.52 (moderate agreement), respectively. Whole blood was submitted to a commercial DNA testing laboratory for breed identification. Whereas DNA breed signatures identified only 25 dogs (21%) as pit bull-type, shelter staff collectively identified 62 (52%) dogs as pit bull-type. Agreement between visual and DNA-based breed assignments varied among individuals, with sensitivity for pit bull-type identification ranging from 33% to 75% and specificity ranging from 52% to 100%. The median kappa value for inter-observer agreement with DNA results at each shelter ranged from 0.1 to 0.48 (poor to moderate). Lack of consistency among shelter staff indicated that visual identification of pit bull-type dogs was unreliable.

Disposition of oral clarithromycin in foals.

Clarithromycin offers numerous advantages over erythromycin and thus, is an attractive alternative for the treatment of Rhodococcus equi infections in foals. The disposition of clarithromycin was investigated in 6 foals after intragastric administration at a dose of 10 mg/kg body weight. Detectable serum concentrations of clarithromycin were found in 3 of 6 foals at 10 minutes and in all foals by 20 minutes post-administration. Time to peak serum concentration (Tmax) was 1.5 hours and peak serum concentration (Cmax) was 0.92+/-0.17 microg/ml. Mean serum concentrations decreased to 0.03 microg/ml at 24 h. No adverse reactions were noted during or after IG administration in any of the foals. Based on the pharmacokinetic parameters, the MIC90 of R. equi isolates, and predicted steady state concentrations, an oral dose of 7.5 mg/kg given every 12 hours would appear appropriate for the treatment of R. equi infections in foals.

Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals.

OBJECTIVE: To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals. ANIMALS: 6 healthy 6- to 10-week-old foals. PROCEDURE: Azithromycin (10 mg/kg of body weight) was administered to each foal via i.v. and intragastric (i.g.) routes in a crossover design. After the first i.g. dose, 4 additional i.g. doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. RESULTS: Azithromycin elimination half-life was 20.3 hours, body clearance was 10.4 ml/min x kg, and apparent volume of distribution at steady state was 18.6 L/kg. After i.g. administration, time to peak serum concentration was 1.8 hours and bioavailability was 56%. After repeated i.g. administration, peak serum concentration was 0.63 +/- 0.10 microg/ml. Peritoneal and synovial fluid concentrations were similar to serum concentrations. Bronchoalveolar cell and PELF concentrations were 15- to 170-fold and 1- to 16-fold higher than concurrent serum concentrations, respectively. No adverse reactions were detected after repeated i.g. administration. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of pharmacokinetic values, minimum inhibitory concentrations of Rhodococcus equi isolates, and drug concentrations in PELF and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R. equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate.

Effects of cyclopentyladenosine on isoproterenol response in adult and senescent cardiac tissue from Fischer 344 rats.

To characterize age-related changes in beta-adrenergic responsiveness and to test the hypothesis that an increase in the effects of adenosine contribute to impaired beta-adrenergic responsiveness, Fischer 344 rat right atria (RA), left atria (LA), and left ventricular trabeculae carnae were exposed to the beta-receptor agonist isoproterenol (ISO), followed by four doses of the selective adenosine A(1) receptor agonist cyclopentyladenosine (CPA). Spontaneous contractile rates of adult RA were inhibited more than senescent RA by CPA. Contractility (+dF/dt) of adult LA was reduced more than senescent LA by CPA. Left trabeculae carnae tissue responded weakly to CPA, but senescent tissue was less responsive than adult tissue. Senescent atrial A(1) receptor density was 56% greater than in adult tissue, whereas the density in senescent ventricles was 39% lower than in adult tissue. No significant difference in antagonist affinities (K(d)) of A(1) receptor was observed between adult and senescent atria. In addition, agonist competition curves indicated a significant increase in senescent atrial and a decrease in senescent ventricular tissue in the affinity of agonist for high-affinity A(1) receptors with no difference in dissociation constant (K(i)). No significant age-related differences in atrial or ventricular tissues occurred in either the antagonist affinity (K(d)) or density (B(max)) of the beta-adrenergic receptors. CPA was found to inhibit ISO-stimulated adenylate cyclase activity more in senescent than in adult atrial and ventricular membrane preparations. We conclude that age-related differences in functional response to ISO and CPA, A(1) receptor density, and ISO-stimulated adenylate cyclase activity differ in atrial and ventricular myocardium.

A retrospective analysis of lingual nerve sensory changes after mandibular bilateral sagittal split osteotomy.

PURPOSE: The purpose of this retrospective study was to determine the patient-reported incidence, duration, and perceived deficit in daily activities associated with lingual nerve (LN) sensory changes after bilateral sagittal split osteotomy (BSSO) of the mandible and to compare them with inferior alveolar nerve (IAN) sensory changes in the same study population. MATERIALS AND METHODS: Questionnaires were mailed to 316 patients who had undergone BSSO procedures between 1980 and 1993. The patients were queried for perceived sensory changes in the distribution of the IAN and LN; duration of these sensory changes; and alteration in daily activities caused by these sensory changes. The same questionnaire was mailed to 47 patients who had undergone isolated genioplasty (GP) to control for the normal variance of non-BSSO surgery on perceived LN sensory changes. RESULTS: Forty-three percent of the BSSO patients and 38% of the GP patients returned the questionnaires. Within the BSSO group, 19.4% reported LN sensory changes, of which 69.3% reported that these changes resolved within 1 year; 88% reported altered daily activities. By comparison, 95.5% reported a perceived IAN sensory change, of which 27.3% reported that these changes resolved within 1 year; 57% reported altered daily activities. Within the GP control group, 11% reported LN sensory changes; none of the reported sensory changes lasted longer than 1 month. CONCLUSIONS: A small percentage of patients report LN sensory changes after BSSO. When compared with IAN reported sensory changes, LN sensory changes resolve more frequently and sooner, but they are associated with greater perceived deficits in daily activity. The interpretation of the reported incidence of LN change must be critically reviewed because control subjects also responded positively.

Relapse prevention treatment for cocaine dependence: group vs. individual format.

To investigate the role of treatment modality in relapse prevention treatment, 32 cocaine-dependent subjects were randomly assigned by cohorts to group-based relapse prevention (G-RP) or individually based RP (I-RP). The two RP formats were identical in content, consisting of 12 outpatient treatment sessions over a 2-month period immediately following hospitalization. The proportion of subjects providing cocaine-free urines at the end of RP treatment did not differ between formats; however, G-RP subjects reported using cocaine on significantly fewer days during treatment, and experiencing fewer cocaine-related problems than did I-RP subjects. Follow-up data collected at 12 and 24 weeks' posttreatment revealed no significant differences between RP formats on any cocaine-use outcome measures. Regardless of therapy format. RP treatment was related to statistically significant and sustained improvements in other areas of psychosocial functioning, including addiction severity, coping, and craving for cocaine. The overall findings suggest that the efficacy of relapse prevention training is not limited by therapy format.

Fear of pain in recurrent headache sufferers.

We investigated the role of fear of pain in headache sufferers using the Fear of Pain Questionnaire (FPQ). Seventy-six headache sufferers and 58 controls completed the FPQ and measures of depression, anxiety, and anger. Headache sufferers also completed measures of stress-related physical symptoms and coping with pain. We found that the FPQ has excellent internal consistency as well as good concurrent and construct validity indicated by the high correlations between the FPQ subscales and both anxiety and depression but low correlations with anger. There were marked differences between headache sufferers and controls on the FPQ; headache sufferers showed much greater fear of severe and medical pain and lower fear of minor pain. Fear of pain was generally not related to headache characteristics such as frequency, severity, or duration. On the other hand, it was related to headache impact such as disruption of pleasurable activities. These results are consistent with models of chronic pain disorders which emphasize the role of fear of pain over the nociceptive intensity of the pain stimulus.