Clustering of autoimmune disease in parents of siblings from the Type 1 diabetes Warren repository.

AIMS: Autoimmune disorders co-exist in the same individuals and in families, implying a shared aetiology. The aim of this study was to compare the prevalence of the common autoimmune diseases in the parents of siblings from the Type 1 diabetes Warren repository with the general population. METHODS: Between 1989 and 1996, 505 British families with at least two siblings affected by Type 1 diabetes were recruited. Clinical information was collected regarding the presence of autoimmune disease in the parents and the prevalence of disease in the parents was compared with that expected in the general population. RESULTS: The prevalence of autoimmune disease in the parents was significantly higher in the repository compared with that expected in the general population [P-value = 1.98 x 10(-5) (female), P-value = 1.1 x 10(-8) (male)]. Type 1 diabetes was recorded in 63/1010 (6.2%) parents with a marked paternal preponderance (9.5 vs. 3%P = 0.002). Other autoimmune diseases affected 27% of parents with diabetes and 13.2% of parents without diabetes (P < 0.01). CONCLUSION: These data confirm the importance of family history as a significant risk factor for the development of Type 1 diabetes and support the hypothesis that the common autoimmune diseases share at least some aetiological mechanisms.     

Alteration of cytosine-guanine interactions due to N7 metal cation binding: a structure-activity relationship for cisplatin analogues

Metal cation binding to N7 of guanine (G) and the resulting altered interaction with cytosine (C) were investigated by ab initio quantum chemical calculations for the ions Li+, Na+, B+, Be2+, and Mg2+. It was found that the CG H-bonding interaction becomes more stable and the stacking interaction less stable as the charge density for the ion (ion charge/ionic radius) increases. From this observation a hypothesis is presented for a structure-activity relationship, which is supported by in vivo animal data, that may permit the design of less toxic analogues of the antitumor agent cisplatin.     

Preventing the airborne spread of Staphylococcus aureus by persons with the common cold: effect of surgical scrubs, gowns, and masks.

OBJECTIVE: Transmission of Staphylococcus aureus via air may play an important role in healthcare settings. This study investigates the impact of barrier precautions on the spread of airborne S. aureus by volunteers with experimentally induced rhinovirus infection (ie, the common cold). DESIGN: Prospective nonrandomized study. SETTING: Wake Forest University School of Medicine (Winston-Salem, NC).Participants. A convenience sample of 10 individuals with nasal S. aureus carriage selected from 593 students screened for carriage. INTERVENTION: Airborne S. aureus dispersal was studied in the 10 participants under the following clothing conditions: street clothes, surgical scrubs, surgical scrubs and a gown, and the latter plus a face mask. After a 4-day baseline period, volunteers were exposed to a rhinovirus, and their clinical course was followed for 12 days. Daily swabs of nasal specimens, pharynx specimens, and skin specimens were obtained for quantitative culture, and cold symptoms were documented. Data were analyzed by random-effects negative binomial models. RESULTS: All participants developed a common cold. Incidence rate ratios (IRRs) indicated that, compared with airborne levels of S. aureus during sessions in which street clothes were worn, airborne levels decreased by 75% when surgical scrubs were worn (P<.001), by 80% when scrubs and a surgical gown were worn (P<.001), and by 82% when scrubs, a gown, and a face mask were worn (P<.001). The addition of a mask to the surgical scrubs and gown did not reduce the airborne dispersal significantly (IRR, 0.92; P>.05). Male volunteers shed twice as much S. aureus as females (incidence rate ratio, 2.04; P=.013). The cold did not alter the efficacy of the barrier precautions. CONCLUSIONS: Scrubs reduced the spread of airborne S. aureus, independent of the presence of a rhinovirus-induced cold. Airborne dispersal of S. aureus during sessions in which participants wore surgical scrubs was not significantly different from that during sessions in which gowns and gowns plus masks were also worn.     

Long-term precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism.

(18)F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed K(i), reflects regional bone metabolism. The aim of this study was to compare the long-term precision of (18)F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo. METHODS: Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent (18)F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the (18)F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (K(i-4k)), a 3k 3-compartmental model using nonlinear regression analysis (K(i-3k)), Patlak analysis (K(i-PAT)), and standardized uptake values. RESULTS: With the exception of a small but significant decrease in K(i-3k) at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%-19%), 13.8% (10%-22%), 14.4% (11%-22%), and 26.6% (19%-40%) for K(i-3k), K(i-PAT), mean standardized uptake value, and K(i-4k), respectively. For comparison, the precision of the biochemical markers was 10% (7%-15%), 18% (13%-27%), and 14% (10%-21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for K(i-4k) to 0.85 for K(i-3k). No significant correlation was found between the repeated mean standardized uptake value measurements. CONCLUSION: The precision and intraclass correlation observed for K(i-3k) and K(i-PAT) was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of (18)F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.     

Physical activity consultation for people with Type 2 diabetes: evidence and guidelines.

Physical activity is an important, but often underused, therapeutic strategy within diabetes care. To date, little is known about the best way to promote physical activity in diabetes care. Physical activity consultation is an intervention designed to promote physical activity behaviour change. This article provides guidelines on how to conduct a physical activity consultation with people who have Type 2 diabetes, and reviews the evidence surrounding the effectiveness of this intervention in this population. The trans-theoretical model is the underlying theory of behaviour change for the physical activity consultation intervention. The review identifies research which supports the use of this model for understanding physical activity behaviour in people with Type 2 diabetes. The review outlines a number of modifiable variables associated with physical activity behaviour change in this population. How each of these variables is addressed within the guidelines for conducting a physical activity consultation is identified. Finally, limited but consistent research highlights the effectiveness of physical activity consultation for promoting physical activity in people with Type 2 diabetes.     

Geometric indices of bone strength are associated with physical activity and dietary calcium intake in healthy older women.

A population-based study on 1008 postmenopausal women identified that the 24% of women achieving high levels of PA and CI had 3.4-4.4% higher femoral bone strength in axial compression and 1.7-5.2% in bending than those achieving low levels, indicating that lifestyle factors influence bone strength in the proximal femur. INTRODUCTION: Extensive research has shown that increased physical activity (PA) and calcium intake (CI) decrease the rate of bone loss; however, there is little research on how these lifestyle variables affect bone geometry. This study was designed to investigate the effects of modifiable lifestyle variables, habitual PA and dietary CI, on femoral geometry in older women. MATERIALS AND METHODS: Femoral geometry, habitual PA, and dietary CI were measured in a population-based sample of 1008 women (median age+/-interquartile range, 75+/-4years) enrolled in a randomized controlled trial (RCT) of calcium supplementation. Baseline PA and CI were assessed by validated questionnaires, and 1-year DXA scans (Hologic 4500A) were analyzed using the hip structural analysis technique. Section modulus (Z), an index of bending strength, cross-sectional area (CSA), an index of axial compression strength, subperiosteal width (SPW), and centroid position, the position of the center of mass, were measured at the femoral neck (NN), intertrochanter (IT), and femoral shaft (FS) sites. These data were divided into tertiles of PA and CI, and the results were compared using analysis of covariance (ANCOVA), with corrections for age, height, weight, and treatment (calcium/placebo). RESULTS AND CONCLUSIONS: PA showed a significant dose-response effect on CSA all hip sites (p<0.03) and Z at the narrow neck and intertrochanter sites (p<0.02). For CI, there was a dose-response effect for centroid position at the intertrochanter (p=0.03). These effects were additive, such that the women (n=240) with PA in excess of 65.5 kcal/day and CI in excess of 1039 mg/day had significantly greater CSA (NN, 4.4%; IT, 4.3%; FS, 3.4%) and Z (NN, 3.9%; IT, 5.2%). These data show a favorable association between PA and aspects of bone structural geometry consistent with better bone strength. Association between CI and bone structure was only evident in 1 of 15 variables tested. However, there was evidence that there may be additive effects, whereby women with high levels of PA and CI in excess of 1039 mg/day had significantly greater CSA (NN, 0.4%; FS, 2.1%) and Z (IT, 3.0%) than women with high PA but low CI. These data show that current public health guidelines for PA and dietary CI are not inappropriate where bone structure is the health component of interest.     

Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair.

We hypothesized that ZA treatment would bolster fracture repair. In a rat model for closed fracture healing, a single dose of ZA at 0, 1, or 2 wk after fracture significantly increased BMC and strength of the healed fracture. Delaying the dose (1 or 2 wk after fracture) displayed superior results compared with dosing at the time of fracture. INTRODUCTION: Bisphosphonates are known to increase bone strength and thus the resistance to fracture by decreasing osteoclastic bone resorption. These properties may enable bisphosphonates to also increase the strength of fracture repair. Zoledronic acid (ZA) is a potent bisphosphonate with a high affinity for bone mineral, allowing bolus intravenous dosing in a range of indications. In this study, we examined the application of bolus dose ZA in endochondral fracture repair. MATERIALS AND METHODS: Carbon-14 labeled ZA was used in a closed rat fracture model. Rats were divided into five treatment groups (n = 25 per group): saline control, local ZA (0.01 mg/kg), and three systemic bolus ZA groups (0.1 mg/kg) with different administration times: at fracture, 1 wk after fracture, and 2 wk after fracture. Rats were killed 6 wk postoperatively. Postmortem analyses included radiography, QCT, microCT, biomechanical testing, scintillation counting, autoradiography, and histology. RESULTS: Single-dose systemic ZA administration significantly increased callus volume, callus BMC, and mechanical strength. Perioperative treatment increased mechanical strength by 30% compared with controls (p < 0.05). Administering the systemic dose at 1 or 2 wk after fracture further increased mechanical strength compared with controls by 44% and 50%, respectively (p < 0.05). No significant differences in mechanical parameters were seen with local injection at the dose studied. Autoradiographic analysis indicated that ZA binds significantly to bone that is present at the time of administration. ZA quantification indicated that delayed administration significantly increased the uptake efficiency in the callus. Histological and microCT analysis showed that ZA treated calluses had a distinctive internal structure consisting of an intricate network of retained trabecular bone. CONCLUSIONS: The timing of a single systemic dose of ZA plays an important role in the modulation of callus properties in this rat fracture model; delaying the single dose produces a larger and stronger callus.     

Features of the metabolic syndrome of "hypertriglyceridemic waist" and transplant coronary artery disease.

BACKGROUND: This study evaluated the prevalence of the atherogenic metabolic triad and the hypothesis that waist circumference and fasting triglyceride concentrations could be used as screening tools for identification of the atherogenic metabolic triad in a population of heart transplant men. It also evaluated the relationship between the atherogenic metabolic triad and coronary artery disease (CAD). METHODS: In the study group of 83 consecutive male heart transplant patients having their routine annual coronarography, 23 patients (28%) were characterized by the atherogenic metabolic triad defined by the presence of elevated fasting insulin and apolipoprotein B concentrations and by small low-density lipoprotein (LDL) particles. RESULTS: Seventy-seven per cent of patients with waist circumference values >/= 90 cm and with elevated triglyceride levels (>/=2.0 mmol/liter) were characterized by this atherogenic metabolic triad. Patients with the atherogenic metabolic triad were at markedly increased risk of CAD (odds ratio of 25.3, 95% CI: 1.11-577.3, p < 0.04) compared to heart transplant patients without the atherogenic metabolic triad. CONCLUSIONS: About 30% of heart transplant patients showed the features of the atherogenic metabolic triad. Measurement and interpretation of waist circumference and fasting triglycerides could be used among heart transplant patients to early identify men characterized by the presence of elevated fasting insulin and apolipoprotein B concentrations and small LDL particles. The presence of the atherogenic metabolic triad identified patients at high risk of CAD even in the heart transplant population.