INTELLECTUAL FUNCTIONS OF PATIENTS WITH CHILDHOOD-ONSET EPILEPSY

The intellectual functions of 64 epileptic patients who had had an initial evaluation between five and 16 years of age, including the WISC, were re-evaluated after a period of at least five years. In general the seizure states had improved, and 50 per cent were in remission for between two and eight years. All but four were still taking at least one anticonvulsant drug. WISC IQ estimates showed a slight decrease. Verbal and performance areas could be differentially affected, and a gain in one could be offset by a loss in the other, so the Full-scale IQ might not be a reliable measure of day-to-day performance. Those whose seizures remained uncontrolled had a statistically significant decrease in performance IQ, whereas in general it was stable or increased for patients in remission. There was evidence that decreased IQ indicated slower mental growth rather than loss of previously acquired function. Phenobarbital but not phenytoin levels were inversely correlated with IQ, suggesting that the upper limit of the 'therapeutic range' of phenobarbital may already be toxic with regard to learning abilities. To optimize an epileptic child's functioning in school and to prevent long-term intellectual problems, it is advisable that IQ testing should be part of the routine initial evaluation, and that drug levels should be checked at regular intervals.     

Curcumin Reduces Burn Progression in Rats

Objectives Cutaneous burns are dynamic injuries with a central zone of necrosis surrounded by a zone of ischemia. Conversion of this ischemic zone to full necrosis over the days following injury is due in part to highly reactive oxygen radicals. Curcumin is a component of the Oriental spice turmeric that has been shown to have antioxidant and antiapoptotic properties. The authors hypothesized that treatment of burns with curcumin would reduce the conversion of the ischemic zone to full necrosis. Methods This was a randomized controlled experiment. Twenty Sprague‐Dawley rats were used. Two burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 × 20–mm full‐thickness burns separated by three 5 × 20–mm unburned interspaces (zone of ischemia). Animals were randomized to curcumin or vehicle by oral gavage 30 minutes before injury and at 24, 48, and 72 hours after injury. Wounds were observed at one, two, and three days after injury for visual evidence of necrosis in the unburned interspaces. Full‐thickness biopsy specimens from the interspaces were evaluated with hematoxylin and eosin staining seven days after injury for evidence of necrosis. The percentage of interspaces that progressed to necrosis was compared with chi‐square tests. Results Forty comb burns with 120 unburned interspaces were created, evenly distributed between curcumin and vehicle alone. The percentage of interspaces that progressed to full‐thickness necrosis at one, two, three, and seven days after injury in the curcumin and vehicle groups were 30% versus 63% (p = 0.003), 30% versus 70% (p < 0.001), 63% versus 95% (p = 0.02), and 63% versus 95% (p = 0.02), respectively. Conclusions Pretreatment of rats with oral curcumin followed by once‐daily oral treatment for three days reduced the percentage of unburned skin interspaces that progressed to full necrosis.     

Simulation model of renal replacement therapy: predicting future demand in England.

BACKGROUND: The demand for renal replacement therapy (RRT) in England has risen steadily, although from a lower base than many other developed countries. Predicting the future demand for RRT and the impact of factors such as the acceptance rate, transplant supply and patient survival, is required in order to inform the planning of such services. METHODS: A discrete event simulation model estimates the future demand for RRT in England in 2010 for a range of scenarios. The model uses current prevalence and current and projected future acceptance rates, survival rates and the transitions between modalities to predict future patient numbers. National population and mortality data, published literature and data from the UK Renal Registry and UK Transplant, are used to estimate unmet need for RRT, the impact of changing demography and incidence of Type 2 diabetes, patient haemodialysis (HD) survival and transplant supply. RESULTS: By 2010 the predicted prevalence will have increased from about 30,000 in 2000 to between 42 and 51,000 (900-1000 p.m.p.), an average annual growth of 4.5-6%. Changing transplant supply has a small effect on overall numbers but changes the proportion of patients with functioning graft by up to 8%. Even with an optimistic increase in transplant supply (11% p.a. for 5 years), numbers on HD will continue to rise substantially, especially in the elderly. The factors most influencing future patient numbers are the acceptance rate and dialysis survival. CONCLUSION: This model predicts a substantial growth in the RRT population to 2010 to a rate approaching 1000 p.m.p., particularly in the elderly and those on HD, with a steady state not being reached for at least 25 years.     

The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?

The substitution of leucine for valine at amino acid position 34 of the factor XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous leucine/leucine genotype has been reported to confer protection against venous thromboembolism, but previous studies have not evaluated a population limited to those with idiopathic venous thromboembolism. The primary objective of the study was to determine whether the FXIII Val34Leu polymorphism is independently associated with the occurrence of idiopathic venous thromboembolism. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic venous thromboembolism. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. All participants were tested for the FXIII Val34Leu polymorphism in addition to several well-known thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the dominant model. Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population.     

Studies of the human oropharyngeal airspaces using magnetic resonance imaging IV--the oropharyngeal retention effect for four inhalation delivery systems.

Magnetic resonance imaging (MRI) of the oropharyngeal region from 20 adult volunteers using four model inhalation devices (varying mouthpiece diameters, airflow resistances) and tidal breathing was carried out. Statistical analysis (convex hull method) selected 12 scans from 80 data sets representing the extremes of all dimensions in the population. Twelve physical mouth-throat models were made by stereolithography using the exact scan data. The aim was to produce models with varying dimensions to span the adult population, and to investigate if oropharyngeal dimensions affected throat retention for different delivery systems. In an in vitro analysis, the models were used to determine the retention effect of the oropharyngeal airspaces when drug aerosols were administered from four inhalation delivery systems: a pressurised metered dose inhaler (pMDI), two different dry powder inhalers (DPIs A and B), and a nebulizer. The aims of this work were to determine the key parameters governing mouth-throat retention and whether retention was dependent on the delivery system used. Characterizing the throat models by measuring 51 different dimensional variables enabled determination of the most influential variables for dose retention for each inhalation delivery system. Throat model retention was found to be dependent on the delivery system (pMDI approximately DPI(A) > DPI(B) > Neb.). The most influential variable was the total throat model volume. Throat models representing high, median, and low oropharyngeal filtration in healthy adults have been identified.     

Announcement of a special issue of the Journal of Primary Prevention

Announcement of a special issue of the Journal of Primary Prevention     

Safety of, and biological and functional response to, a novel metallic implant for the management of focal full-thickness cartilage defects: Preliminary assessment in an animal model out to 1 year.

Focal full-thickness cartilage lesions of the human medial femoral condyle (MFC) can cause pain and functional impairment. Affected middle-aged patients respond unpredictably to existing treatments and knee arthroplasty may be required, prompting risk of revision. This study assesses the safety of, and biological and functional response to, a metallic resurfacing implant which may delay or obviate the need for traditional arthroplasty. The anatomic contour of the surgically exposed MFC of six adult goats was digitally mapped and an 11 mm diameter full-thickness osteochondral defect was created. An anchor-based Co-Cr resurfacing implant, matching the mapped articular contour, was implanted. Each goat's contralateral unoperated femorotibial joint was used as a control. Postoperative outcome was assessed by lameness examination, radiography, arthroscopy, synoviocentesis, necropsy, and histology up to 26 (n = 3) or 52 (n = 3) weeks. By postoperative week (POW) 4, goats demonstrated normal range of motion, no joint effusion, and only mild lameness in the operated limb. By POW 26 the animals were sound with only occasional very mild lameness. Arthroscopy at POW 14 revealed moderate synovial inflammation and a chondral membrane extending centrally across the implant surface. Radiographs at POWs 14 to 52 implied implant stability in the operated joints, as well as subchondral bone remodeling and mild exostosis formation in the operated and contralateral unoperated joints of some goats. By POW 26, histology revealed new trabecular bone abutting the implant. At POWs 26 and 52 MFC cartilage was metachromatic and intact in the operated and unoperated femorotibial joints. Proximal tibiae of some operated and unoperated limbs demonstrated limited subchondral bone remodeling and foci of articular cartilage fibrillation and thinning. The chondral membrane crossing the prosthesis possessed a metachromatic matrix containing singular and clustered chondrocytes. Our data imply the safety, biocompatibility, and functionality of the implant. Focal articular damage was documented in the operated joints at POWs 26 and 52, but lesions were much reduced over those previously reported in untreated defects. Expanded animal or preclinical human studies are justified.     

Polymorphism in the promoter region of the apolipoprotein AI gene associated with differences in apolipoprotein AI levels: The European Atherosclerosis Research Study

The effect associated with the substitution of adenine (A) for guanidine (G) in the promoter region of the apolipoprotein AI gene (?75 bp) with plasma apo AI and high-density lipoprotein (HDL) levels was investigated in the European Atherosclerosis Research Study (EARS). This is a study of healthy offspring (cases) of fathers who had suffered premature myocardial infarction (MI) before age 55 years (n = 565) and age- and sex-matched controls (n = 1,078) from 12 European countries, divided into 5 regions based on geography and language. The frequency of the polymorphism was not significantly different among the regions and the relative frequency of the rare A allele was similar in cases and controls (0.159 vs. 0.142) combining data from all regions. Individuals with one or more A allele had significantly higher plasma apo AI levels (P < 0.05) than individuals homozygous for the G allele. This effect was consistent in all regions. The data were analyzed separately in males and females. In females, those with one or more A allele had significantly higher apo AI levels (P = 0.05) than individuals homozygous for the G allele, and this raising effect of the A allele was greater in cases than controls for both apo AI (5.23% vs. 1.56%) and HDL (4.48% vs. 1.89%). In males, the A allele was associated with higher levels of apo AI and HDL, but the effect was much smaller and the differences did not reach statistical significance. In the females, where the effect of the A allele was strongest, the effect on apo AI associated with genotype was evident in non-smokers, and individuals with one or two A alleles had 3.6% higher apo AI and 3.14% higher HDL levels than individuals homozygous for the G allele. However, in the female smokers the raising effect of the A allele was greatly reduced (0.56%). Thus genetic variation in the promoter region of the apo AI gene is associated with differences in apo AI and HDL levels in healthy individuals throughout Europe, but the effect is modulated by gender, environmental factors such as smoking, and a family history of MI.