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The TREAT trial compared the effects of ciclosporin (CyA) and methotrexate (MTX) on severe atopic dermatitis in children, finding that CyA initially showed greater improvement but MTX was more effective in the long term. Both drugs can affect kidney function, but monitoring with standard tests may not be sensitive enough. The study recommended less frequent monitoring to reduce costs and make treatment more acceptable to children. The trial was funded by the UK Medical Research Council/NIHR EME Programme and approved by the Cambridge Research Ethics Committee. [Extracted from the article]

Background: Dried blood spot monitoring of nitisinone and succinylacetone in hereditary tyrosinaemia type 1 patients is not widely available in the United Kingdom. Currently, biochemical monitoring utilizes urinary succinylacetone, blood spot tyrosine and phenylalanine monitoring, which can lack in convenience and accuracy, respectively. Methods: We report the development of a dried blood spot assay for nitisinone and succinylacetone and analysed retrospective clinical and biochemical data for hereditary tyrosinaemia type 1 patients from a single UK centre. Results: A total of 13 hereditary tyrosinaemia type 1 patients were evaluated. Eleven presented with liver dysfunction (two with associated renal tubulopathy) and two were detected by early sibling screening. All patients (age 0.03–22 months) were commenced on a tyrosine-/phenylalanine-restricted diet and nitisinone at diagnosis. Ten patients were on twice daily dosing and three were on single daily dosing at the start of monitoring. One patient from each dosing group swapped between dosing regimens at 20 years of age and 8 months of age, respectively. A total of 684 dried blood spot samples were analysed; 80% of nitisinone concentrations were between 9.2 and 27 µ mol/L when succinylacetone was <0.3 µ mol/L. Patients on twice daily dosing regimens had significantly higher nitisinone concentration compared with those on once daily dosing (P < 0.0001). The median dose required in the twice daily doing group was significantly lower when compared with once daily dosing. Conclusions: Dried blood spot monitoring for nitisinone and succinylacetone concentrations in hereditary tyrosinaemia type 1 patients is a rapid and convenient method which allows physicians to individualize treatment plans and observe adherence to treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE The origins of cardiovascular and renal disease in type 1 diabetes begin during childhood. We aimed to evaluate carotid (cIMT) and aortic intima-media thickness (aIMT) and their relationship with cardiovascular risk factors and urinary albumin excretion in adolescents with type 1 diabetes in the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT). RESEARCH DESIGN AND METHODS A total of 406 adolescents with type 1 diabetes, who were 14.1 ± 1.9 years old with type 1 diabetes duration of 6.7 ± 3.7 years, and 57 age-matched control subjects provided clinical and biochemical data and ultrasound measurements of vascular structure (cIMT and aIMT). Vascular endothelial and smooth muscle function was also measured in 123 of 406 with type 1 diabetes and all control subjects. RESULTS In type 1 diabetic subjects, mean/maximal aIMT (P < 0.006; <0.008), but not mean/maximal cIMT, was greater than in control subjects. Mean/maximal aIMT related to urinary albumin-to-creatinine ratio (multiple regression coefficient [SE], 0.013 [0.006], P = 0.03; 0.023 [0.007], P = 0.002), LDL cholesterol (0.019 [0.008], P = 0.02; 0.025 [0.011], P = 0.02), and age (0.010 [0.004], P = 0.004; 0.012 [0.005], P = 0.01), independent of other variables. Mean/maximal cIMT was greater in males (0.023 [0.006], P = 0.02; 0.029 [0.007], P < 0.0001), and mean cIMT related independently to systolic blood pressure (0.001 [0.001], P = 0.04). Vascular smooth muscle function related to aIMT and cIMT but not to urinary albumin excretion. CONCLUSIONS aIMT may be a more sensitive marker of atherosclerosis than cIMT in type 1 diabetes during mid-adolescence. Higher urinary albumin excretion, even within the normal range, is associated with early atherosclerosis and should direct clinical attention to modifiable cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine if holding onto the handrails during treadmill exercise influenced VO2 and, if so, would the adjustment be central (Q) or peripheral (a-vO2 diff)? Twelve male and female subjects ranging in age from 20-30 yrs volunteered to take part in this study. Protocol A consisted of 10 min of walking at 3.5 mi·hr-1 without handrail support followed by 10 min of jogging at 5.5 mi·hr-1 with handrail support. Protocol B consisted of 10 min of walking at 3.5 mi·hr-1 with handrail support followed by 10 min of jogging at 5.5 mi·hr-1 without handrail support. During both protocols, the 10-min walking stage was followed by a small break to collect data and allow the subjects' HR return to a normal resting value. The results of this study indicate that in normal healthy college-aged adults, VO2 was not significantly altered when handrails were used during walking and jogging on the treadmill for 10 min. When the data was analyzed in regard to jogging at 5.5 mi·hr-1 on the treadmill, the same exact conclusions are warranted. The only exceptions to the findings just described are VCO2 and TV. Both were significantly increased when holding onto the handrails while jogging. There appears to be no scientific reason for not holding onto the handrails if the exerciser feels more confident in controlling his or her exercise session. [ABSTRACT FROM AUTHOR]

Hyaluronidase has been purified from the venom of the honey bee, Apis mellifera. The purification proved remarkably difficult, requiring a large number of chromatographic steps culminating in the removal of traces of phospholipase A2 with an affinity purified rabbit anti-phospholipase A2 immunosorbent column. The purified enzyme showed a 1143-fold increase in specific activity and was homogeneous. Electrophoresis in polyacrylamide gels (12%) containing sodium dodecyl sulphate (pH 8.9) or urea (pH 2.8) and electrofocusing in polyacrylamide (5%) gave a single band. The final product contained < 0.1%, phospholipase A2 and < 1.5% acid phosphatase and gave a single line of precipitation against rabbit anti-hyaluronidase but was not precipitated by rabbit anti-phospholipase A2. Previous reports of instability were not confirmed, and we found the enzyme to be highly stable over a wide range of temperature and pH, and to denaturing agents. Purified hyaluronidase was found to be ‘sticky’ when highly pure and at low concentration, and adhered strongly to Sephadex G-75. The relative molecular mass was estimated at 35000–37000 by gel filtration, and at 41000 by sodium dodecyl sulphate/polyacrylamide gel electrophoresis. A value of 50000 was obtained by ultracentrifugation assuming a partial specific volume of 0.73 cm3/g. Hyaluronidase was found to be a minor allergen in bee venom allergic patients. [ABSTRACT FROM AUTHOR]