Efficacy of piribedil as early combination to levodopa in patients with stable Parkinson's disease: a 6-month, randomized, placebo-controlled study.

Piribedil is a non-ergot D2/D3 agonist with a significant antagonist action on alpha2A and alpha2C adrenergic receptor subtypes. This double-blind placebo-controlled study was undertaken to confirm the efficacy of 150 mg/day piribedil po in improving motor symptoms of idiopathic Parkinson's disease (PD) in nonfluctuating patients insufficiently controlled by a stable daily dose of levodopa (L-dopa). Efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score as primary criterion over 4 months. A second comparison was planned at 6 months, after possible adjustment of L-dopa. At 4 months, the rate of response, defined as a 30% decrease from baseline on UPDRS III score, was significantly greater with piribedil compared with placebo (56.4% vs. 37.7%; P = 0.040). At 6 months, the better efficacy of piribedil was maintained (61.8% of responders vs. 39.6% on placebo; P = 0.020). The difference between groups on UPDRS III change from baseline reached statistical significance only at 6 months: -10.0 points in the piribedil group vs. -6.7 points in the placebo group (P = 0.037). Secondary end-points were not significantly different. The most frequently reported adverse events were gastrointestinal symptoms (27 of 61 patients in the piribedil group vs. 13 of 54 patients in the placebo group). In conclusion, a 6-month oral administration of 150 mg/day piribedil in combination with L-dopa is well tolerated, except for minor gastrointestinal symptoms at the beginning of the treatment and significantly improves motor symptoms compared with placebo in PD nonfluctuating patients.     

Measuring clinical outcome

At the present time, there are many fundamental issues coming from the Department of Health or from other national organizations, which will have an effect on the future development of the dietetic profession. The British Diatetic Association (BDA) Professional Development Committee will consider these issues, as and when appropriate, and will publish the information in the form of Briefing Papers.
The first Briefing Paper on 'Quality Assurance' was published by the BDA in November 1989. The second on 'Measuring clinical outcome' is published below. In each case the opinion of BDA members and specialist groups has been sought and the Professional Development Committee wishes to thank individuals and the specialist groups for their comments.
The Briefing Papers are intended to provide information and promote discussion among the membership. I would welcome further comments from readers, which may be directed to the British Dietetic Association Office.     

Practice guidelines: the radiology perspective

Clinical practice guidelines have emerged as a reality for medical practitioners over the past 20 years. Although virtually all groups interested in the development of practice guidelines hope for improvements in patient care, secondary expectations vary widely among those using them. Their use in daily practice by physicians has met with resistance from barriers including concerns of “cookbook” medicine, a loss of autonomy, and increased professional liability. The recent experience of the ACR in addressing these challenges illustrates that physicians are receptive to steps perceived to mitigate the risks accompanying the use of guidelines as well as to efforts to increase their understanding of implementing guidelines in clinical practice. The experiences of other medical societies and an inventory of future trends reveal additional challenges associated with the use of practice guidelines, as third parties look to guidelines as points of reference for gauging the performance of health care providers.     

Buchbesprechungen

Ohne Zusammenfassung     

Requirement for sulfur-containing amino acids in infancy

A series of studies designed to define the requirement of normal infants for sulfur-containing amino acids (methionine, cystine) was conducted with formulas providing 3.0, 2.8, 2.6, 2.2 or 1.8 g of isolated soy protein per 100 kcal. The formulas were fed with or without a methionine supplement. Adequacy of the diet was determined by measurement of growth, serum chemical indices and nitrogen balance. Nitrogen balance demonstrated a beneficial effect of methionine supplementation only at the lowest protein concentration (1.8 g/100 kcal). However, measurement of weight gain and/or serum concentrations of urea nitrogen and albumin clearly showed a beneficial effect of methionine supplementation at protein concentrations of 2.2 and 2.6 g/100 kcal. Intakes of sulfur-containing amino acids of 435 and 495 mumol/100 kcal therefore appear inadequate. At higher intakes of protein (2.8 and 3.0 g/100 kcal) there was no beneficial effect of methionine supplementation. Possible exceptions were male infants provided with 3.0 g protein per 100 kcal, in whom weight gain between 8 and 56 d of age was significantly (P less than 0.05) greater with than without a methionine supplement. Based on intakes of sulfur-containing amino acids from the formula providing 2.8 g of isolated soy protein per 100 kcal without methionine supplementation, we conclude that for male infants older than 56 d the requirement for sulfur-containing amino acids is no more than 588 mumol/100 kcal when intake of methionine is 264 mumol/100 kcal. However, it seems possible that such intake fails to meet the requirement in male infants less than 56 d of age. For female infants, regardless of age, 533 mumol/100 of sulfur-containing amino acids per 100 kcal meet the requirement when intake of methionine is 239 mumol/100 kcal.     

Characterization of normal and infarcted rat myocardium using a combination of small-animal PET and clinical MRI.

The combination of small-animal PET and MRI data provides quantitative in vivo insights into cardiac pathophysiology, integrating information on biology and morphology. We sought to determine the feasibility of PET and MRI for the quantification of ischemic injury in the rat model. METHODS: Fourteen healthy male Wistar rats were studied with 18F-FDG PET and cine MRI. Myocardial viability was determined in a transmural myocardial infarction model in 12 additional rats, using 18F-FDG PET and delayed-enhancement MRI with gadolinium-diethylenetriaminepentaacetic acid. All PET was acquired with a dedicated small-animal PET system. MRI was performed on a 1.5-T clinical tomograph with a dedicated small-animal electrocardiographic triggering device and a small surface coil. RESULTS: In normal rats, 18F-FDG uptake was homogeneous throughout the left ventricle. The lowest mean uptake of the 18F-FDG was found in the apical regions (79% +/- 6.0% of maximum) and the highest uptake was in the anterior wall (93% +/- 4.3 % of maximum). Myocardial infarct size as determined by histology correlated well with defects of glucose metabolism obtained with 18F-FDG PET (r = 0.89) and also with delayed-enhancement MRI (r = 0.91). Left ventricular ejection fraction in normal rats measured by cine MRI was 57% +/- 5.4% and decreased to 38% +/- 12.9% (P < 0.001) in the myocardial infarction model. CONCLUSION: Integrating information from small-animal PET and clinical MRI instrumentation allows for the quantitative assessment of cardiac function and infarct size in the rat model. The MRI measurements of scar can be complemented by metabolic imaging, addressing the extent and severity of ischemic injury and providing endpoints for therapeutic interventions.     

Challenges in accessing multidisciplinary pain treatment facilities in Canada

PURPOSE: The objective of this survey was to examine the services offered by multidisciplinary pain treatment facilities (MPTFs) across Canada and to compare access to care at these MPTFs. METHODS: A MPTF was defined as a clinic that advertised specialized multidisciplinary services for the diagnosis and management of patients with chronic pain, having a minimum of three different health care disciplines (including at least one medical speciality) available and integrated within the facility. The search method included approaching all hospital and rehabilitation centre administrators in Canada, the Insurance Bureau of Canada, the Workplace Safety and Insurance Board or similar body in each province. Designated investigators were responsible for confirming and supplementing MPTFs from the preliminary list for each province. Administrative leads at each eligible MPTF were asked to complete a detailed questionnaire regarding their MPTF infrastructure, clinical, research, teaching and administrative activities. RESULTS: Completed survey forms were received from 102 MPTFs (response rate 85%) with 80% concentrated in major cities, and none in Prince Edward Island and the Territories. The MPTFs offer a wide variety of treatments including non-pharmacological modalities such as interventional, physical and psychological therapy. The median wait time for a first appointment in public MPTFs is six months, which is approximately 12 times longer than non-public MPTFs. Eighteen pain fellowship programs exist in Canadian MPTFs and 64% engage in some form of research activities CONCLUSION: Canadian MPTFs are unable to meet clinical demands of patients suffering from chronic pain, both in terms of regional accessibility and reasonable wait time for patients' first appointment.     

Glucose tolerance behaviour before the onset of type I (insulin-dependent) diabetes in young people as a predictor of the further course of the disease: a retrospective analysis of 33 cases

A study was made of glucose tolerance and insulin secretion in 33 persons who later developed insulin-dependent diabetes (aged 4-24 years) and observation continued further in the first years after manifestation. Patients who developed the typical labile type of diabetes were of normal weight and had either normal glucose tolerance tests before diagnosis or had impaired glucose tolerance (IGT) for a short interval of 2-16 months. Subjects with IGT over a significantly (p less than 0.01) longer period of 32.30 +/- 6.25 (normal body weight) or 94.71 +/- 20.62 (obese) months developed a milder form of diabetes with retarded insulin dependency in obese subjects. The severe and mild form of IDDM are distinct with respect to insulin requirement (0.75 +/- 0.03 or 0.28 +/- 0.04 U/kg b.w., P less than 0.01) and glucagon stimulated C-peptide (0.18 +/- 0.05 or 1.41 +/- 0.27, P less than 0.01) in the first 2.5-3.5 years after onset. The two forms were not different regarding HLA-DR antigens. Islet cell surface antibodies investigated in 15 probands at 27 occasions before diabetes onset had no prognostic value. The development of a mild form of IDDM may be expected in cases with pre-existing IGT for more than one year. The insulin secretion is of low predictive value under these conditions. The observation is of practical use and theoretical interest.