Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.     

Efficacy of a patient-training videotape on motor fluctuations for on-off diaries in parkinson's disease

Patient on-off diaries are used in clinical trials, but a method to assure agreement between patient and examiner has never been developed. We tested whether a patient-teaching tape increased the rate of agreement between patient diary ratings and simultaneous neurologic assessment by a trained professional. A total of 32 consecutive patients who had Parkinson's disease with motor fluctuations independently completed a 4-h on-off diary (nine ratings) at the same time as an examiner. Those with <80% agreement with the examiner (n = 20) were randomized to view either a training tape that showed motor fluctuations (experimental group) or another videotape of general patient educational material (control group). All patients then underwent the same 4-h assessment of motor fluctuations. To test for long-term retention, they returned 1 month later and, without reviewing the videotape, underwent a final 4-h correlation assessment. After the training tape, the experimental group showed significant improvement, whereas the control group showed no improvement. Furthermore, another month later, the improvement in the experimental group was retained. Based on these findings, we suggest that future clinical trials assessing motor fluctuations incorporate this tape into their basic methodology.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.      

Tobacco or health in the Third World: a political economy perspective with emphasis on Mexico

In response to declining cigarette sales in the United States and Europe, transnational tobacco conglomerates have turned to the underdeveloped world to promote their unhealthy products for consumers who are at best only vaguely aware of the health risks associated with cigarette smoking. While cigarette sales in the Third World are growing "healthily," the consumers of these cigarettes generally are not. Along with the already difficult problems of malnutrition and communicable diseases, underdeveloped countries are facing the probability of a smoking epidemic, which is directly related to the penetration of capitalist tobacco interests into new markets. While the tobacco companies are quick to suggest that these people who can least afford cigarettes (both financially and in terms of health risks) are exercising their "free choice" as consumers in an "open marketplace," the author suggests that political and economic factors are central. Aided by two months of fieldwork in Mexico in 1986, the author examines smoking behavior and perceptions of associated health consequences. In addition, the influence of the tobacco companies and the Mexican government on tobacco production and consumption is analyzed.     

Switching dopamine agonists in advanced Parkinson's disease: is rapid titration preferable to slow?

BACKGROUND: New dopamine agonists are available, but no study has examined safe and effective ways to switch from one agonist to another. OBJECTIVE: To compare rapid- versus slow-titration schedules for starting a new dopamine agonist in patients already on chronic agonist therapy for Parkinson's disease. METHODS: Sixteen patients on stable carbidopa/levodopa and a dopamine agonist (bromocriptine or pergolide) switched to pramipexole using a conversion calculation of 1:1 for pergolide dose and 10:1 for bromocriptine dose. Patients were randomized to two titration schedules-either slow titration, following the package insert and taking up to 8 weeks to reach their equivalent dosage (8 patients), or rapid titration, receiving the full converted dose the day after stopping the former agonist (8 patients) with subsequent weekly dose adjustments. Using a blinded observer, the primary outcome variable was the time required to a Unified Parkinson's Disease Rating Scale (UPDRS) motor score superior to baseline without increased adverse effects. RESULTS: Both groups showed equivalent and statistically significant improvement after switching to the new agonist. The mean time to reach a UPDRS score that was superior to baseline without increased adverse effects was significantly shorter in the rapid-titration group (mean 2.1 weeks versus 5.3 weeks). Furthermore, with slow titration two patients experienced enhanced parkinsonian serious adverse effects requiring hospitalization (two falls with fractures). CONCLUSION: The switchover from one agonist to another can be safely and successfully accomplished with a rapid titration based on an equivalency dose calculation.