Continuous parathyroid hormone induces cortical porosity in the rat: effects on bone turnover and mechanical properties.

We examined the time course effects of continuous PTH on cortical bone and mechanical properties. PTH increased cortical bone turnover and induced intracortical porosity with no deleterious effect on bone strength. Withdrawal of PTH increased maximum torque to failure and stiffness with no change in energy absorbed. INTRODUCTION: The skeletal response of cortical bone to parathyroid hormone (PTH) is complex and species dependent. Intermittent administration of PTH to rats increases periosteal and endocortical bone formation but has no known effects on intracortical bone turnover. The effects of continuous PTH on cortical bone are not clearly established. MATERIALS AND METHODS: Eighty-four 6-month-old female Sprague-Dawley rats were divided into three control, six PTH, and two PTH withdrawal (WD) groups. They were subcutaneously implanted with osmotic pumps loaded with vehicle or 40 microg/kg BW/day human PTH(1-34) for 1, 3, 5, 7, 14, and 28 days. After 7 days, PTH was withdrawn from two groups of animals for 7 (7d-PTH/7d-WD) and 21 days (7d-PTH/21d-WD). Histomorphometry was performed on periosteal and endocortical surfaces of the tibial diaphysis in all groups. microCT of tibias and mechanical testing by torsion of femora were performed on 28d-PTH and 7d-PTH/21d-WD animals. RESULTS AND CONCLUSIONS: Continuous PTH increased periosteal and endocortical bone formation, endocortical osteoclast perimeter, and cortical porosity in a time-dependent manner, but did not change the mechanical properties of the femur, possibly because of addition of new bone onto periosteal and endocortical surfaces. Additionally, withdrawal of PTH restored normal cortical porosity and increased maximum torque to failure and stiffness. We conclude that continuous administration of PTH increased cortical porosity in rats without having a detrimental effect on bone mechanical properties.     

Evidence for a Type 1 diabetes‐specific mechanism for the insulin gene‐associated IDDM2 locus rather than a general influence on autoimmunity

Aims The Type 1 diabetes susceptibility locus, IDDM2, has been mapped to a variable number of tandem repeats (VNTR) region 5′ upstream of the insulin (INS) and insulin‐like growth factor (IGF2) genes on chromosome 11p15. The function of the VNTR is uncertain; however, it may influence the thymic expression of the insulin gene and affect the development of immune self‐tolerance. The aim of this study was to investigate whether the INS VNTR region is a Type 1 diabetes‐specific locus or acting as a general autoimmunity gene. Methods We genotyped the INS‐IGF2 VNTR [using the surrogate INS?23 HphI single nucleotide polymorphism (SNP)] in 823 Graves’ disease (GD)/multiple sclerosis (MS) families, 1433 GD/MS patients and 837 healthy control subjects. Results We found no evidence of excess transmission of the allele associated with Type 1 diabetes to individuals affected by GD or MS within the families. Analysis of the case–control dataset showed no genotypic or allelic difference between the two populations. Conclusions These data suggest that the INS‐IGF2 VNTR is acting as a Type 1 diabetes‐specific susceptibility gene rather than as an influence on general autoimmunity.     

Office versus Home-Based Family Therapy for Runaway, Alcohol Abusing Adolescents: Examination of Factors Associated with Treatment Attendance

There is a dearth of research examining treatment engagement and attendance among runaway youth and their families. Such research is needed in order to inform treatment providers on factors associated with engagement and maintenance of these difficult to engage families into counseling. This study examined differential treatment attendance for alcohol abusing runaway youth residing at a local shelter. A traditional office-based family systems approach, Functional Family Therapy (FFT), was compared to a non-traditional, home-based, multi-systemic family therapy approach, Ecologically Based Family Therapy (EBFT). As expected, treatment engagement and attendance was significantly higher for those assigned to EBFT (N = 37) compared to FFT (N = 40). Predictors of treatment attendance (income, family chaos, externalization problems and level of youth substance use) were examined within each treatment modality. Findings suggest that home-based (compared to office-based) treatment modalities may significantly increase treatment attendance and engagement of runaway youth and their families. Non-traditional forms of treatment may need to be considered in order to best meet the needs of highly chaotic and disorganized family systems.     

Quantitative analysis of 8-isoprostane and hydrogen peroxide in exhaled breath condensate.

Exhaled breath condensate (EBC) provides a noninvasive means of sampling the lower respiratory tract. Collection of EBC might be useful in the assessment of airway oxidative stress in smokers. The aim of this study was to determine 8-isoprostane and hydrogen peroxide levels in EBC, and, in addition, to investigate the reproducibility of these measurements. EBC samples were collected from 12 healthy male smokers at three time points within 1 week. 8-isoprostane and H2O2 were measured in nonconcentrated EBC using immunochemical and colorimetric assays, respectively. 8-isoprostane and H2O2 were detected in only 36 and 47% of all EBC samples, respectively. It was not possible to calculate the within-subject variation in a reliable manner since only three of the 12 smokers exhibited detectable 8-isoprostane concentrations on all three occasions (mean 4.6 pg x mL(-1); range 3.9-7.7 pg x mL(-1)), whereas H2O2 could not be detected on all three occasions in any of the smokers. Spiking experiments revealed a recovery of 83.5-109.5% for 8-isoprostane and 69.9-129.0%, for H2O2 in fresh EBC samples. It was concluded that levels of 8-isoprostane and hydrogen peroxide cannot be reproducibly assessed in exhaled breath condensate from healthy smokers because of their low concentration and/or the lack of sensitivity of the available assays.     

Tightly clustered outbreak of group A streptococcal disease at a long-term care facility.

OBJECTIVE: To describe investigation of a tightly clustered outbreak of invasive group A streptococcal (GAS) disease associated with a high mortality rate in a long-term care facility (LTCF). DESIGN: Cross-sectional carriage survey and epidemiologic investigation of LTCF resident and employee cohorts. SETTING: A 104-bed community LTCF between March 1 and April 7, 2004. PATIENTS: A cohort of LTCF residents with assigned beds at the time of the outbreak. INTERVENTIONS: Reinforcement of standard infection control measures and receipt of chemoprophylaxis by GAS carriers. RESULTS: Four confirmed and 2 probable GAS cases occurred between March 16 and April 1, 2004. Four case patients died. The final case occurred during the investigation, before the patient was determined to be a GAS carrier. No case occurred during the 6 months after the intervention. Disease was caused by type emm3 GAS; 16.5% of residents and 2.4% of employees carried the outbreak strain. Disease was clustered in 1 quadrant of the LTCF and associated with nonintact skin. GAS disease or carriage was associated with having frequent personal visitors. CONCLUSIONS: Widespread carriage of a virulent GAS strain likely resulted from inadequate infection control measures. Enhanced infection control and targeted prophylaxis for GAS carriers appeared to end the outbreak. In addition to employees, regular visitors to LTCFs should be trained in hand hygiene and infection control because of the potential for extended relationships over time, leading to interaction with multiple residents, and disease transmission in such residential settings. Specific attention to prevention of skin breaks and proper wound care may prevent disease. The occurrence of a sixth case during the investigation suggests urgency in addressing severe, large, or tightly clustered outbreaks of GAS infection in LTCFs.     

Country-specific cost-effectiveness of early intervention with budesonide in mild asthma.

Early intervention with budesonide is an effective strategy for mild persistent asthma, which has been shown to provide additional clinical benefits at a low incremental cost using USA cost data. The present authors analysed whether this strategy would be cost-effective using cost data for other countries. Based on the 3-yr prospective, randomised, double-blind inhaled Steroid Treatment As Regular Therapy (START) in early asthma study (comparing budesonide and placebo combined with usual asthma therapy), the cost-effectiveness was estimated separately for eight different countries, from both healthcare payer and societal perspectives, of adding budesonide to usual asthma therapy. Local unit costs were applied to data for the total trial population. Incremental cost-effectiveness ratios (ICER) were estimated as cost per symptom-free day (SFD) gained. Budesonide increased SFDs by an average of 14.1 days annually. From a healthcare payer perspective, budesonide would reduce the total cost of asthma care in Australia. In Sweden, Canada, France, Spain, UK, China and the USA, the ICER ranged from US$2.4-11.3 per SFD. From a societal perspective, budesonide would be cost-saving in Australia, Canada and Sweden. In conclusion, for countries where costs with budesonide are higher, the policy implication has to be determined by that health system's willingness to pay for an additional symptom-free day. However, where budesonide therapy increases symptom-free days and reduces total costs, the policy conclusion clearly favours early intervention.     

Paediatric lung transplantation.

Since 1990, lung transplantation has been performed in infants, children and adolescents in small numbers, and the numbers, in comparison with adult transplants, remain small today. The indications for lung transplantation are similar in childhood when compared with adults, but the disease entities are distinct. In children, severe pulmonary vascular disease is most commonly associated with developmental abnormalities or congenital heart disease, as opposed to idiopathic pulmonary hypertension. Cystic fibrosis is the dominant indication for lung transplantation in older childhood and adolescence. The operative approach to lung transplantation in early life differs from that in adults, in that cardiopulmonary bypass is more likely to be utilised and bilateral lung transplantation is strongly preferred to single lung transplantation. Living donor lung transplantation is proportionately more common in children and adolescents than in adults. Post-transplant complications related to viral infection and post-transplant lymphoproliferative disease are more common and more likely to be severe and life-threatening. Bronchiolitis obliterans is the most important complication after paediatric lung transplantation and limits both the quality of life and duration of survival, as in adults.     

Developing a Peer Review Process for Web-based Curricula

The World Wide Web creates new challenges and opportunities for medical educators. Prominent among these are the lack of consistent standards by which to evaluate web-based educational tools. We present the instrument that was used to review web-based innovations in medical education submissions to the 2003 Society of General Internal Medicine (SGIM) national meeting, and discuss the process used by the SGIM web-based clinical curriculum interest group to develop the instrument. The 5 highest-ranked submissions are summarized with commentary from the reviewers.