Treatment of essential tremor with the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid).

The effect of the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid; DMMDPB) on essential tremor, given in twice daily doses of 400 and 300 mg, was assessed in two brief, randomized, placebo-controlled, parallel-group, double-blinded, single-center trials in 12 and 22 patients, respectively. These trials represent the first clinical use of T2000 for a specific indication. The primary endpoint was the change in the mean scores of the treated and control groups based on the Fahn-Tolosa-Marin tremor scale. In the first study of 12 patients treated with 400 mg or placebo twice daily for 14 days, the mean change from baseline at day 14 was 19.3 (P < 0.0001) in the treated group and 9.0 (P = 0.0121) in the control group. Using a two-factor mixed ANOVA model to evaluate within group and between group changes, the effect of T2000 was significantly different from that of the placebo group (P = 0.03). In the second study of 22 patients treated with 300 mg of T2000 or placebo twice daily for 20 days, statistically significant changes were seen in treated patients compared to baseline, but the ANOVA model did not demonstrate a significant treatment effect of T2000 compared to placebo. When the treated groups from each study are compared, the 800-mg daily group is significantly different from the 600-mg daily group (P = 0.02). Some treated patients in each study, but no placebo patients, experienced marked improvement. These results support further evaluation of T2000 in the treatment of essential tremor.     

Renal angiomyolipoma: 6 case reports and literature review

We report 6 cases of renal angiomyolipomas and review the pertinent literature concerning this disease. One case involved the rare association of tuberous sclerosis and pregnancy. Another patient without tuberous sclerosis had renal cell carcinoma and later suffered a contralateral angiomyolipoma. The pathological conditions of renal angiomyolipomas with and without tuberous sclerosis are discussed. Since angiomyolipomas present with multiple clinical similarities to renal cell carcinoma, the primary task for the clinician is to differentiate this hamartoma from carcinoma. The distinguishing characteristics and the clinical management of renal angiomyolipomas are discussed.     

Transmyocardial revascularization ameliorates ischemia by attenuating paradoxical catecholamine-induced vasoconstriction

Background  The mechanism by which transmyocardial revascularization (TMR) offers clinical benefit is controversial. We hypothesized that TMR ameliorates ischemia by reversing paradoxical catecholamine-induced vasoconstriction. Methods and Results  Chronic ischemic cardiomyopathy was created in 11 dogs by placing ameroid constrictors on the proximal coronary arteries and their major branches. Six weeks later, 35 channels were created percutaneously in the left circumflex artery region, with the left anterior descending artery region serving as control. At rest, wall thickening and myocardial blood flow did not change in the treated region, whereas they deteriorated in the control bed. Contractile and myocardial blood flow reserve increased in the treated region but deteriorated in the control region. There was diminished iodine 123 metaiodobenzylguanidine uptake and a significant reduction in noradrenergic nerves in the treated region compared with the control region, with a corresponding reduction in tissue tyrosine hydroxylase activity. Conclusions  We conclude that the absence of a catecholamine-induced reduction in MBF reserve and contractile reserve in the TMR-treated region with associated evidence of neuronal injury indicates that the relief of exercise-induced ischemia after TMR most likely results from reversal of paradoxical catecholamine-induced vasoconstriction. These findings may have implications in selecting patients who would benefit from TMR. Supported in part by grants from the National Institutes of Health (R01-HL66034 and K-08-HL074290-01). Bethesda. Md. The radio-labeled microspheres were provided by DuPont Pharmaceuticals, North Billerica. Mass, and the ultrasound equipment was supplied by Philips. Andover, Mass. Dr Leong-Poi was the recipient of a Fellowship Training Grant from the Canadian Institute of Health Research and the Heart and Stroke Foundation of Canada.     

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.     

Predictors of non-spine fracture in elderly men: the MrOS study.

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age > or =80 years, and depressed mood. INTRODUCTION: There are few prospective studies of fracture determinants in men. We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD. MATERIALS AND METHODS: A total of 5995 men > or =65 years of age were recruited from six communities in the Unites States and followed prospectively for an average of 4.1 years. Baseline assessments of demographic, lifestyle, medical history, functional status, anthropometry, and cognitive, visual, and neuromuscular function were assessed by questionnaire or examination. Triannual mailed questionnaires ascertained incident fracture; reported fractures were adjudicated by physicians using medical records and X-ray reports. Proportional hazards models were used to develop multivariable models, selecting variables and controlling for BMD. RESULTS: Of 5876 men, 4.7% (N = 275) reported an incident nonspine fracture during follow-up (11.46/1000 person-years). Tricyclic antidepressant use (hazard ratio [HR], 2.36; 95% CI, 1.25-4.46), history of fracture at or after age 50 (HR, 2.07; 95% CI, 1.62-2.65), inability to complete a narrow walk trial (HR, 1.70; 95% CI, 1.23-2.34), falls in previous year (HR, 1.59; 95% CI, 1.23-2.05), age > or =80 years (HR, 1.33; 95% CI, 1.01-1.76), depressed mood (HR, 1.72; 95% CI, 1.00-2.95), and decreased total hip BMD (HR, 1.53; 95% CI, 1.34-1.74) were independently related to increased risk. Compared with having none (48.0% of men), having three or more of the clinical risk factors (4.9% of men) increased fracture risk 5-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile. CONCLUSIONS: Several clinical risk factors were independently associated with nonspine fractures in elderly men. The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk.