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OBJECTIVES: To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. METHODS: 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers' ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. RESULTS: Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. CONCLUSIONS: The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM.

Aims/hypothesis: The aim of this study was to evaluate the risk of adverse cardiovascular outcomes in patients with type 2 diabetes newly treated with sulfonylureas and metformin. Subjects and methods: The Diabetes Audit and Research in Tayside Scotland (DARTS) diabetes information system and the Medicines Monitoring Unit (MEMO) dispensed prescribing database for the population of Tayside, Scotland (400,000 people) were employed. Patients newly prescribed with oral hypoglycaemic agents between 1994 and 2001 were classified into five study cohorts according to the treatment received:metformin only, sulfonylureas only, sulfonylureas added to metformin, metformin added to sulfonylureas, and both drugs simultaneously. In Cox regression analyses, we estimated relative risks for all-cause mortality, cardiovascular mortality and cardiovascular hospital admission for patients in the five study cohorts, with metformin monotherapy as the reference group. Results: Of the 5,730 study patients, 1,000 died during a maximum of 8 years follow-up. Patients in the sulfonylureas only cohort had increased risks of mortality and cardiovascular mortality, with unadjusted relative risks of 3.12 (95% CI 2.54-3.84) and 3.71 (95% CI 2.64-5.22), respectively. After adjusting for differences between groups (age, sex, duration of diabetes, blood pressure, cholesterol, HbA1c, smoking, previous hospital admission, treatment with cardiovascular medication), these relative risks were 1.43 (95% CI 1.15-1.77) and 1.70 (95% CI 1.18-2.45), respectively. Patients in the combination cohorts had significantly increased risks of cardiovascular hospital admission, as well as increased risks of mortality and cardiovascular mortality. Conclusions/interpretation: In this cohort study of patients newly treated with oral hypoglycaemic agents, those treated with sulfonylureas only, or combinations of sulfonylureas and metformin, were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.

Aim: The DARTS diabetes register was used to determine incidence rates of diabetes and related complications in 1997. Methods: The diabetes register records detailed clinical information for all patients diagnosed with diabetes in Tayside, Scotland. The study population included patients who were alive and registered with a Tayside GP for the duration of 1997 or who died in Tayside during this time. Patients who had diabetes prior to 1997, those who developed diabetes in 1997, and those who developed diabetic complications in 1997, were identified. Results: In the Tayside population of 385 774 at the start of 1997, there were 942 and 6632 patients with Type 1 and Type 2 diabetes, with a further 29 and 744 patients diagnosed in 1997. The incidence rates (with 95% confidence intervals) of diabetic complications per 1000 patients with Type 1 and Type 2 diabetes, respectively, were: angina 8.8 (4.5-17.3) and 38.4 (33.4-44.2); myocardial infarction 8.6 (4.4-16.9) and 21.9 (18.4-25.9); cerebrovascular accident 1.1 (0.3-6.0) and 14.2 (11.6-17.5); lower extremity amputation 3.2 (1.2-9.4) and 3.1 (2.1-4.8); peripheral vascular disease 5.5 (2.4-12.8) and 13.6 (11.0-16.8); registered blindness 1.1 (0.3-5.9) and 1.6 (0.9-2.9); end-stage renal failure 6.4 (3.0-13.8) and 5.0 (3.6-7.0). Mortality was 14.6 per 1000 (9.6-25.7) in Type 1 diabetes and 50.0 per 1000 (45.1-55.3) in Type 2 diabetes. Conclusion: This study provides baseline figures for rates of diabetic complications for Type 1 and Type 2 diabetes, and confirms the increased burden of macrovascular disease in Type 2 diabetes.

In 6 adults with dermatomyositis, minimally weak or nonweak muscles that showed inconclusive light-microscopic alterations were examined by electron microscopy. In all 6 specimens, this revealed pathologic changes in endomysial capillaries. The endothelial cells harbored microtubular inclusions and microvacuoles in all cases; pale swollen endothelial cells were observed in 3 specimens. There were no significant ultrastructural changes in the muscle fibers. In all cases, a small proportion of muscle capillaries were immunoreactive for complement membrane attack complex neoantigens. The findings imply that in adult dermatomyositis capillary injury precedes muscle fiber damage and infiltration by inflammatory cells, and that the microvasculature is an early and specific target of the disease process in muscle