Saturation analysis of specific 11C Ro 15-1788 binding to the human neocortex using positron emission tomography

The ¹¹C-labelled benzodiazepine antagonist Ro 15–1788 (flumazenil) and positron emission tomography (PET) were used to determine quantitative characteristics of benzodiazepine receptor binding in the neocortex of healthy young men. Saturating doses of unlabelled flumazenil administered i.v., before or together with the ligand-reduced ¹¹C-flumazenil accumulation in the neocortex by about 90 per cent. Saturating doses of unlabelled flumazenil had little effect on the accumulation of radioactivity in the benzodiazepine receptor-poor regions such as pons or white matter. By giving graded doses of unlabelled flumazenil together with the tracer, saturation isotherms were obtained allowing the calculation of receptor density (B_max) and equilibrium dissociation constant (K_d) values on the basis of certain assumptions B_max values were in the order of 90 pmol/g and K_d values in the order of 10 nM in the neocortex. Scatchard and Hill plots of the radioactivity data indicated that ¹¹C-flumazenil binds to saturable sites of a homogeneous population. The data indicate that intravenous doses of 1 or 2 mg flumazenil result in a benzodiazepine receptor occupancy of about 50 per cent. The method described should be useful for studying regional differences in benzodiazepine receptor characteristics in the living human brain in healthy subjects and neuropsychiatric disorders, and also in relation to treatment with drugs interacting with benzodiazepine receptors.     

Issues in selecting outcome measures to assess functional recovery after stroke

Most patients who survive a stroke experience some degree of physical recovery. Selecting the appropriate outcome measure to assess physical recovery is a difficult task, given the heterogeneity of stroke etiology, symptoms, severity, and even recovery itself. Despite these complexities, a number of strategies can facilitate the selection of functional outcome measures in stroke clinical trial research and practice. Clinical relevance in stroke outcome measures can be optimized by incorporating a framework of health and disability, such as the International Classification of Functioning, Disability, and Health (ICF). The ICF provides the conceptual basis for measurement and policy formulations for disability and health assessment. All outcome measures selected should also have sound psychometric properties. The essential psychometric properties are reliability, validity, responsiveness, sensibility, and established minimal clinically important difference. It is also important to establish the purpose of the measurement (discriminative, predictive, or evaluative) and to determine whether the purpose of the study is to evaluate the efficacy or effectiveness of an intervention. In addition, when selecting outcome measures and time of assessment, the natural history of stroke and stroke severity must be regarded. Finally, methods for acquiring data must also be considered. We present a comprehensive overview of the issues in selecting stroke outcome measures and characterize existing measures relative to these issues.     

Natural history of vascular calcification in dialysis and transplant patients

Nephrol Dial Transplant 2004; 19:     

Lisch nodules after trabeculectomy.

The development of Lisch nodules in an eye that had undergone trabeculectomy with mitomycin C is described. Complete ophthalmologic examinations and genetic testing of a 12-year-old boy were performed. Lisch nodules can develop after trabeculectomy without the systemic manifestations of neurofibromatosis type 1.     

Pelvic floor muscle training with biofeedback and bladder training in elderly women: a feasibility study.

OBJECTIVE: It is generally assumed that interventions used to treat urinary incontinence (UI) in young women could simply be applied to older competent and motivated women, but these assumptions have not been formally tested. The purpose of this study was to determine the feasibility of using physical therapies to treat UI in older women. DESIGN: Twelve-week time series. SETTINGS AND SUBJECTS: We recruited women older than 75 years with UI from an outpatient urology clinic and a waiting list for incontinence surgery. METHODS: After a baseline evaluation, the women collected data on their incontinence symptoms and bladder habits for 3 weeks using the 72-hour voiding diary and the 24-hour pad test. They then received 6 physical therapy treatments consisting of a combination of bladder training and pelvic floor muscle training assisted with biofeedback for 6 weeks. This was followed by another 3-week period of data collection and a final evaluation. RESULTS: Ten women participated in the study; 7 completed it. They were all comfortable with the treatment. They complied with the study demands in terms of attendance at treatment session (100%), data collection (96%), and completion of exercises at home (82%). The authors observed a decrease in the number of incontinent and urgency episodes. CONCLUSION: This preliminary study demonstrates that some women older than 75 years are good candidates to undertake physical therapies for UI and follow study demands. Random controlled studies that include this population will provide evidence regarding the effectiveness of these therapies.     

Cognitive symptoms and correlates of physical disability in individuals with multiple sclerosis.

There are inconsistencies in the literature regarding the prevalence of cognitive impairment among individuals with multiple sclerosis (MS). The purpose of this study was to examine perceived cognitive impairment in secondary progressive and relapsing-remitting multiple sclerosis (MS) and to examine the relationship between level of disability, age, and number of years with MS and self-reported cognitive symptoms. The sample consisted of 447 individuals (96 participants with secondary progressive MS and 351 participants with MS) who responded to mailed data collection instruments. The Performance Scales, a self-report measure of disability in eight domains of function, and a sociodemographic data sheet were analyzedfor this study. Of individuals with secondary progressive MS, 83% reported cognitive symptoms, while 82% of individuals with relapsing-remitting MS reported cognitive symptoms. Individuals with secondary progressive MS were reportedly experiencing a significantly greater level of total disability. A statistically significant, strong, positive relationship was found between cognitive symptoms and fatigue for those with secondary progressive MS and those with relapsing-remitting MS. Statistically significant, moderate, positive relationships were also found between cognitive symptoms in those with secondary progressive MS and those with relapsing-remitting MS, and sensory symptoms, vision, hand function, bladder/bowel symptoms, and spasticity. A statistically significant, weak, positive relationship was found between cognitive symptoms and mobility in individuals with relapsing-remitting MS. There was no relationship between cognitive symptoms and mobility in those with secondary progressive MS. Cognitive symptoms were not significantly related to age in those with secondary progressive MS or those with relapsing-remitting MS. In addition, cognitive symptoms were not significantly related to the number of years with MS in individuals with secondary progressive MS or those with relapsing-remitting MS. The perception of cognitive deficits in individuals with MS was found in this study to be even more prevalent than previously reported. Because cognitive deficits occur at all stages of MS, early identification and treatment is essential. Healthcare providers must aggressively screen for cognitive impairment and rehabilitate individuals with MS who exhibit symptoms.