The effect of pramipexole on mood and motivational symptoms in Parkinson's disease: a meta-analysis of placebo-controlled studies.

BACKGROUND: Mood and motivational symptoms have been reported in up to 35% and 51%, respectively, of patients with Parkinson's disease (PD). Preliminary evidence indicates that pramipexole may have a positive effect on these symptoms. OBJECTIVE: This analysis was conducted to evaluate the effects of pramipexole on mood and motivational symptoms in patients with PD. METHODS: Data for the meta-analysis were extracted from all randomized, double-blind, placebo-controlled trials of pramipexole in the manufacturer's database that included part I of the Unified Parkinson's Disease Rating Scale (UPDRS) as an outcome measure. Only patients with baseline scores >0 (range, 0-4) on item 3 (mood) and item 4 (motivation) were included. Separate analyses were performed for mood and motivational symptoms. The outcome of interest was improvement in scores, with no improvement including both unchanged and increased scores. Odds ratios (ORs), 95% CIs, and Cochran-Mantel-Haenszel tests were calculated to compare rates of improvement and no improvement, stratified by trial. RESULTS: Fourteen randomized, double-blind, placebo-controlled trials of pramipexole were identified, all employing the severity of motor symptoms of PD as a primary outcome. Seven of these trials (N = 1296) employed part I of the UPDRS as a secondary outcome measure and were included in the meta-analysis; no other measure of mood or motivational symptoms was used in any of the 14 studies. Six of the 7 studies included patients with motor fluctuations due to levodo-pa treatment, and the remaining study included patients who did not yet require levodopa. Six studies were published in peer-reviewed journals, and all 7 were included in the New Drug Application for pramipexole. The published study reports were usually limited to motor symptoms; only 1 reported on mood and motivation. However, for the purpose of this meta-analysis, the authors had access to data that were not reported in the original publications. In the pooled data set, 480 patients (59.8% male; mean age, 63.3 years) had a baseline score >0 on item 3 (mood). These mood symptoms improved in 64.7% of patients treated with pramipexole and 43.4% of those receiving placebo (OR weighted by trial = 2.41; P < 0.001). Five hundred seventy patients (64.9% male; mean age, 64.1 years) had a baseline score >0 on item 4 (motivation). These motivational symptoms improved in 63.2% of patients treated with pramipexole and 45.0% of those receiving placebo (OR weighted by trial = 2.06; P < 0.001). CONCLUSIONS: This meta-analysis of 7 randomized controlled trials suggests that pramipexole had a beneficial effect on mood and motivational symptoms in PD patients who did not have major depressive disorder. The clinical value of pramipexole in the treatment of depressive and apathetic syndromes requires further investigation.

Robotic partial nephrectomy: a multi-institutional analysis.

Laparoscopic partial nephrectomy for kidney tumors has demonstrated durable oncologic and functional outcomes. The feasibility of robotic partial nephrectomy (RPN) has been demonstrated in several small, single-institution studies. We performed a large, multi-institutional analysis to determine early oncologic results and perioperative outcomes after RPN. Between October, 2002 and September, 2007, 148 patients underwent RPN at six different centers by nine different primary surgeons for localized renal tumors. Medical and operative records were reviewed for clinical characteristics, pathologic findings, and follow-up information. A total of 148 patients underwent RPN. Mean tumor size was 2.8 cm. Renal hilar clamping was utilized in 120 patients, with a mean warm ischemia time of 27.8 min. Positive surgical margins were identified in six patients (4%), of which two had cautery artifact obscuring the margin after off-clamp cautery excision and one underwent completion radical nephrectomy with no evidence of cancer. There is no evidence of tumor recurrence at mean follow-up of 7.2 months (range 2-54 months) overall, and mean follow-up of 18 months (range 12-23 months) for patients with positive surgical margin. Complications occurred in nine patients (6.1%), including hematoma requiring drainage (n = 1), prolonged ileus (n = 3), pulmonary embolus (n = 2), prolonged urine leak (n = 2), and rhabdomyolysis (n = 1). Two patients underwent open conversion for failure to progress, one patient with morbid obesity and one patient with adhesions from prior ureterolithotomy. Mean hospital stay was 1.9 days. In this multi-institutional series of surgeons beginning their initial experience in RPN, the procedure is a feasible option for minimally invasive, nephron-sparing surgery, with immediate oncologic results and perioperative outcomes comparable with more mature laparoscopic series.

The obstetric trials and tribulations of Dr. John Mackieson, Charlottetown, Prince Edward Island, 1827-1857.

For 30 years, from 1827 to 1857, Dr. John Mackieson, a medical practitioner in Charlottetown, Prince Edward Island, Canada, kept a detailed account of complicated obstetric cases. An analysis of this casebook provides a unique profile of obstetric complications and their management in eastern Canada 150 years ago. The main causes of maternal death were puerperal sepsis and hemorrhage. The reported perinatal deaths most often were associated with traumatic vaginal delivery.

The casebook, the daybook, and the diary as sources in medical historiography.

Casebooks, daybooks and diaries were among a number of literary forms commonly used by physicians in the nineteenth century to record the details of their medical cases. Because they constitute primary sources on medical practice in that era they have value to the medical historian. To illustrate this, the writings of three Canadian physicians' -John Mackieson, Jonathan Woolverton, and James Langstaff- are discussed, together with a consideration of some of the principles relating to the study of their manuscripts, particularly in relation to the study of the history of practice in rural areas.

Cerebral bioenergetics in stable chronic obstructive pulmonary disease.

Cerebral intracellular energy production (cerebral bioenergetics) via oxidative phosphorylation and the production of adenosine triphosphate (ATP) is critical to cerebral function. To test the hypothesis that patients with chronic stable hypoxia also generate neuronal ATP via an anaerobic metabolism, we studied the changes in cerebral (31)P magnetic resonance spectra ((31)P MRS) in patients with stable chronic obstructive pulmonary disease (COPD), and compared the results with MR spectra from similar areas of the brain in control subjects. Ten patients with stable COPD (age: 65 +/- 9 yr [mean +/- SD]; Pa(O(2)): 8.8 +/- 1.2 kPa; Pa(CO(2)): 6.1 +/- 0.8 kPa; pH 7.42 +/- 0.03, and FEV(1): 41 +/- 20% predicted) and five healthy volunteers underwent cerebral (31)P MRS (TR-5,000 ms) at 1.5 T. When COPD patients were compared with controls, the percentage MR signal with respect to total MR-detectable phosphorus-containing metabolites was increased from inorganic phosphate (Pi) (7.1 +/- 1. 3% versus 3.9 +/- 0.7%, p = 0.0001) and phosphomonoesters (PMEs) (9. 4 +/- 1.2% versus 6.9 +/- 0.3%, p = 0.0001), whereas the signal from phosphodiesters was reduced (34.8 +/- 3.2 versus 40.4 +/- 3.3%, p = 0.015). The ratios of Pi to betaATP (0.8 +/- 0.2 versus 0.4 +/- 0.1, p = 0.001) and of PME to betaATP (1.0 +/- 0.2 versus 0.7 +/- 0.1, p = 0.015) were increased, but the phosphocreatine-to-Pi ratio (2.1 +/- 0.6 versus 3.2 +/- 0.6, p = 0.01) was reduced in patients as compared with controls. This alteration in phosphorus-containing metabolites within cerebral cells provides evidence of extensive use of anaerobic metabolism in hypoxic COPD patients.

A light on medical practice in 19th-century Canada: the medical manuscripts of Dr. John Mackieson of Charlottetown.

During his long career as a physician in Charlottetown, Dr. John Mackieson (1795-1885) compiled 4 medical manuscripts: 2 sets of case records, a synopsis of the medical conditions that were common in his day and a formulary. As primary sources, these documents provide information about medicine in 19th-century Canada and augment our knowledge of the problems of medical practice in that era. They illustrate aspects of the work of Dr. Mackieson, a generalist with interests in surgery and obstetrics, and they facilitate an understanding of the rationale underlying the treatments that he and his contemporaries used. Although 150 years old, the case records can be appreciated for their relevance to the art of medicine. Two excerpts from the case records, presented in this article, provide a sense of Dr. Mackieson's writings and introduce a discussion on the significance of these manuscripts in relation to the ideas on disease and treatment that governed medical practice, both in Prince Edward Island and elsewhere in Canada, in the 19th century.

Cytomegalovirus involving gastrointestinal tract in renal transplant recipients.

Infection due to cytomegalovirus (CMV) is a substantial cause of mortality and morbidity among renal transplant recipients but the prognosis of the disease has changed dramatically since the introduction of ganciclovir (GAN). During a period of 5 years we treated 54 patients who developed CMV disease. From this group of patients we identified 7 patients with primary gastrointestinal tract (GIT) CMV disease who received treatment with GAN. Tissue diagnosis was made by endoscopy of the upper GIT (6 patients) or sigmoidoscopy (one patient) and histological examination. All patients improved after treatment with GAN; three patients required additional treatment for recurrent CMV disease and recovered, and 1 patient relapsed without GIT involvement (P = 0.014). Recurrent CMV disease was more severe (mean score of 15 in relapse compared to 7 in the first episode). We believe relapse to be more common and the disease to be more severe in the presence of GIT involvement suggesting that a longer duration of treatment with GAN may be required in this clinical manifestation of CMV disease.