Localisation of a gene for non-specific X linked mental retardation (MRX46) to Xq25-q26

Feeding difficulty and malnutrition are common in disabled children. Intake may be reduced because of anorexia, chewing and swallowing difficulties, or vomiting. Feeding is often time consuming, unpleasant, and may result in aspiration. Malnutrition may result in impaired growth and neurodevelopment, and impaired cardiorespiratory, gastrointestinal, and immune functions. Multidisciplinary assessment is recommended and should include a feeding history, oral-motor examination, and nutritional assessment. The energy requirements of most disabled children are less than those for a normal child of the same age but may be increased by spasticity, athetosis, convulsions, and recurrent infections. Micronutrient deficiencies may occur even in children receiving nutritionally complete feeds if the volume is reduced because of low energy requirements. Oral intake may be improved by a change of posture, special seating, feeding equipment, oral desensitization, mashing or pureeing of lumpy food, thickening of liquids, use of calorie supplements, and treatment of reflux/esophagitis. Non-oral feeding should be considered when oral feeding is unsafe, not enjoyable, inadequate, or very time consuming. Long-term support requires a gastrostomy. This is less obtrusive than a nasogastric tube, less likely to become displaced, less traumatic, and is associated with improved quality of life, but is also associated with significant morbidity. If there is symptomatic reflux a fundoplication may be required, but this is associated with significant mortality and substantial morbidity.     

Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk

OBJECTIVE: To assess the factors that predict operative mortality after intestinal infarction, and show what effect referral patterns have on mortality. DESIGN: Retrospective study. SETTING: Two university departments of surgery, France. SUBJECTS: 144 patients with intestinal infarctions operated on between January 1980 and August 1995. INTERVENTIONS: Univariate and multivariate analyses. MAIN OUTCOME MEASURES: Operative mortality and the factors associated with it. RESULTS: Operative mortality was 67% (96/144) during the first 45 days postoperatively. The univariate analysis showed that age over 75 years (p=0.0002), female sex (p=0.007), the presence of shock (p < 0.0001), and referral from cardiovascular medical or surgical unit (p=0.01) were significantly associated with mortality. However, the multivariate analysis reduced these to extent of infarction (p=0.0001), the presence of shock (p=0.0002), age over 75 years (p=0.0001), and recent cardiac or vascular operation (p=0.03). CONCLUSIONS: The influence of referral pattern was related to previous cardiac or vascular operation, and the risk among women to the fact that their age was 10 years older than that of men. This study shows how the type of referral may explain the wide variations in reported mortality. To compare published series, care should be taken to avoid any selection bias.     

The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data

We describe a comprehensive retrospective analysis in which the abilities of several methods by which human pharmacokinetic parameters are predicted from preclinical pharmacokinetic data and/or in vitro metabolism data were assessed. The prediction methods examined included both methods from the scientific literature as well as some described in this report for the first time. Four methods were examined for their ability to predict human volume of distribution. Three were highly predictive, yielding, on average, predictions that were within 60% to 90% of actual values. Twelve methods were assessed for their utility in predicting clearance. The most successful allometric scaling method yielded clearance predictions that were, on average, within 80% of actual values. The best methods in which in vitro metabolism data from human liver microsomes were scaled to in vivo clearance values yielded predicted clearance values that were, on average, within 70% to 80% of actual values. Human t1/2 was predicted by combining predictions of human volume of distribution and clearance. The best t1/2 prediction methods successfully assigned compounds to appropriate dosing regimen categories (e.g., once daily, twice daily and so forth) 70% to 80% of the time. In addition, correlations between human t1/2 and t1/2 values from preclinical species were also generally successful (72-87%) when used to predict human dosing regimens. In summary, this retrospective analysis has identified several approaches by which human pharmacokinetic data can be predicted from preclinical data. Such approaches should find utility in the drug discovery and development processes in the identification and selection of compounds that will possess appropriate pharmacokinetic characteristics in humans for progression to clinical trials.     

Craig-Scott orthosis: a biochemical and functional evaluation

The Craig-Scott double upright knee ankle orthosis was subjected to a biomechanical evaluation which included analysis of the force interaction with the supported limb and a functional evaluation. The results were compared with data previously determined from biomechanical evaluations of other common orthoses. In the Craig-Scott design, the single application of the knee stabilizing force below the knee concentrates this force in a relatively small bony area, sometimes exceeding tolerance. This might be avoided by using a tibial closure with patellar tendon bearing features. The design was found to produce relatively low anatomic knee shear. In functional aspects such as donning, doffing, transfers and ambulation, the orthosis is essentially equivalent to other double upright designs. The rigidity of the orthosis with only a tibial band closure and a bail connecting the uprights was determined to be adequate. The limited number of bands and closures provides some advantages in reduced donning and doffing time; however, in the absence of posterior closures below the knee, the orthosis had a tendency to slide forward off the leg when transferring. This disadvantage was eliminated by adding a soft posterior closure below the knee, which produced a minimal increase in donning and doffing times.     

Effect of excess thymidine on the growth of human melanoma cells transplanted in thymus deficient nude mice

The effect of thymidine (TdR) on the growth of a human melanoma transplanted in nude mice has been studied. It was found that the injection of 1 g/kg/h of TdR for at least 72 h is sufficient to suppress the growth of the melanoma cells. This inhibition lasts for the duration of the treatment, and causes no apparent toxicity to the host. Nude mice treated for 6--9 days with TdR survived 158 days after melanoma transplant versus 126 days for the controls.