Effects of clonidine in schizophrenic patients with primary polydipsia: three single case studies

A pilot study was conducted in schizophrenic patients with primary polydipsia to determine the tolerability of adding clonidine to an existing antipsychotic drug regimen and to seek evidence of an antidipsic effect. Three patients with chronic schizophrenia and primary polydipsia underwent open controlled prospective trials of treatment with clonidine in doses of up to 800 microg/day. The trials lasted from 2 to 5 months each, and analysis of variance was used to test for changes in dependent variables on a case-by-case basis. Blood pressure and pulse declined significantly in a dose-dependent manner, but fluid intake, as assessed by measurements of weight and 24-h urine volume, was not affected. Hypotension and bradycardia limited the extent to which the dose of clonidine could be increased. The lack of evident effect of clonidine on polydipsia in this small sample and the inconsistent results of two other recent studies of clonidine in patients with schizophrenia and primary polydipsia provide little overall support for the effectiveness of clonidine treatment in primary polydipsia associated with schizophrenia.     

Effects of oral racemic citalopram on neuroendocrine responses

Citalopram, a selective serotonin reuptake inhibitor (SSRI), has been used as a neuroendocrine probe to assess serotonin (5-HT) function in human subjects. In an effort to characterize the oral citalopram challenge, we hypothesized that oral racemic citalopram would increase plasma cortisol, prolactin and adrenocorticotropic hormone (ACTH) concentrations; ACTH had not been measured in previous studies on the neuroendocrine effects of citalopram. Nine healthy male subjects initially received 20 mg of citalopram in an open-label study, and subsequently received placebo and 40 mg of citalopram in a single-blind, randomized, cross-over study. The administration of citalopram 20 mg failed to produce a significant neuroendocrine response but 40 mg resulted in reliably increased plasma cortisol concentrations. The 40 mg dose, however, did not reliably influence the levels of plasma prolactin or plasma ACTH. The results of this study indicate that caution should be used in accepting oral racemic citalopram as a potential presynaptic serotonergic challenge agent. Further studies are needed to fully determine the validity of racemic citalopram and the active enantiomer, escitalopram, as 5-HT probes.     

Clinical outcome and memory function with maintenance electroconvulsive therapy: a retrospective study

Although maintenance electroconvulsive therapy (ECT) appears to be the logical choice for the prevention of relapses and recurrences in patients with refractory depression who have responded to a course of ECT, the perception of ECT's negative effect on memory continues to limit its wider use. This retrospective study of depressed patients maintained on ECT after an initial course revealed that maintenance ECT was effective in sustaining clinical improvement, particularly in patients who showed a satisfactory clinical response to the initial course of ECT, and that memory difficulties were limited and tolerable.     

Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis: results of a randomized controlled trial

BACKGROUND: Few randomized trials have compared the survival benefit of interferon-alfa over controls in metastatic renal cell carcinoma, and none has been performed using interleukin-2. The Programme Etude Rein Cytokines (PERCY) Quattro trial was designed to evaluate both cytokines for their survival benefit to intermediate prognosis patients, who represent the majority of candidates for these treatments. METHODS: Patients were randomized in a 2-by-2 factorial design to medroxyprogesterone acetate 200 mg daily, interferon-alfa 9 million IU 3 times a week, subcutaneous interleukin-2 9 million IU daily, or a combination of both cytokines. Tumor response was evaluated at Week 12 and Month 6; progression-free patients received further identical treatment for a maximum of 3 additional months. Primary endpoint was overall survival; secondary endpoints were disease-free survival, response rate, toxicity, and quality of life. Survival was analyzed on an intent-to-treat basis. RESULTS: From January 2000 to July 2004, 492 patients were enrolled. Analysis was performed after a 29.2-month median follow-up (range, 0 months to 54.6 months). There were no significant survival differences between the 244 interferon-alfa-treated patients and 248 noninterferon-alfa patients (hazard ratio, 1.00; 95% CI, 0.81-1.24) or between the 247 interleukin-2 and 245 noninterleukin-2-treated patients (hazard ratio, 1.07; 95% CI, 0.87-1.33; log rank, 0.99 and 0.52, respectively). Grade 3-4 toxicities were significantly more frequent in cytokine-treated patients than in medroxyprogesterone-treated patients. CONCLUSIONS: Subcutaneous interleukin-2 and/or interferon-alfa provide no survival benefit in metastatic renal cancers of intermediate prognosis, and they induce a significant risk of toxicity. Newly available angiogenesis inhibitors should be preferred for these patients.     

Rituximab in the treatment of relapsed thrombotic thrombocytopenic purpura

Several reports have defined nonfamilial thrombotic thrombocytopenic purpura (TTP) as an autoimmune disorder caused by antibodies to von Willebrands factor-cleaving protease (vWF-CP). This raises the possibility that rituximab, a monoclonal antibody against CD20 present in B-lymphoid cells, may have utility in the treatment of TTP. We report five consecutively treated patients with relapsed TTP who responded rapidly to immune suppression by rituximab at our institution. These two male and three female patients had a median age of 37 years (27–70). The median time from diagnosis to therapy was 24 months (8–60). Prior therapies included plasma exchange and corticosteroids in all cases, splenectomy (4), vincristine and aspirin (3), and azathioprine (2). The median number of plasma exchanges received prior to therapy was 59 (21–158). The cohort had a median platelet count of 48×10⁹/l (23–110), median hemoglobin of 9 g/dl (8–11), and median lactate dehydrogenase of 632 IU/l (311–945) prior to administration of rituximab. Analysis of vWF-CP activity demonstrated absent or decreased activity with detectable inhibitors in four patients. All patients attained a complete response. The median time to response after the first dose of rituximab was 5 weeks. Responses are maintained in all patients from 10 to 21 months after treatment. This report adds to the evidence that rituximab has efficacy in nonfamilial TTP and warrants further study.     

Delayed versus immediate exercises following surgery for breast cancer: a systematic review

SummaryBackground Seroma formation, wound healing and fluid drainage are a concern for both surgeons and patients. Excessive fluid production can result in seroma formation, and inadequate drainage of seromas is known to cause infection, pain, discomfort and longer periods of hospitalisation. Postoperative exercises given to maintain movement of the arm are believed to increase the amount of fluid production following surgery. This review aimed to determine whether a program of delayed exercises reduces the risk of seroma formation, fluid loss and hospital stay, without loss of arm movement.Method A systematic review. RCTs of early versus delayed shoulder mobilisation after surgery in females with breast cancer were included in the review. Outcomes. One or more measurements of shoulder range of motion, wound complications, fluid drainage volumes and incidence of seroma formation. Design. Randomised controlled trials, control group of delayed exercise/mobilisation. Validity assessment was carried out using a data extraction form based on the CONSORT statement. Study characteristics recorded include sample size, intervention, control, period of exercise delay, surgical procedure and conclusions drawn. Data synthesis was carried out using random effects and weighted mean differences to test for heterogeneity and combined effects.Results 12 RCTs were included in the review of which 6 were included for meta-analysis. Delaying exercises significantly decreases seroma formation (OR=0.4; 95%CI 0.2–0.5; p=0.00001). No significant differences were found for drainage volume or hospital stay.Conclusion Current evidence from RCTs supports the use of a delayed program of arm exercises to reduce seroma formation. Clinical and statistical inconsistencies between studies did not allow any conclusions to be drawn regarding the effects of delayed exercises on fluid drainage, hospital stay and immediate or long term ability to move the arm.     

Development of the approaches to work and workplace climate questionnaires for physicians

Two questionnaires were developed to investigate the workplace learning of physicians. The Approaches to Work Questionnaire for Physicians and the Workplace Climate Questionnaire for Physicians were adapted from general measures developed by Kirby, Knapper, Evans, Carty, and Gadula. These questionnaires were administered to a random sample of Ontario physicians. Consistent with the results of Kirby et al., three dimensions of approaches to work were observed: Deep. Surface-Rational, and Surface-Disorganized. Three dimensions of workplace climate were also found, Supportive-Receptive, Choice-Independence, and Workload. Results indicate that physicians adopt primarily a Deep approach to work, but that there is a smaller tendency toward Surface-Disorganized learning, one that is strongly correlated with perceptions of heavy workload. The Deep approach was associated with work environments perceived to be Supportive-Receptive and offer Choice-Independence. The use of these questionnaires in research and practice is discussed.     

Does PBL Matter? Relations Between Instructional Context,Learning Strategies,and Learning Outcomes

Purpose:To compare learning strategies used in Problem based learning (PBL) and lectures, and the relations between learning strategies and learning outcomes to determine how different learning strategies associated with PBL and lectures contribute to aspects of clinical competence. Design:The 52-item learning strategies questionnaire was given to preclinical medical students during lecture and PBL sessions in first and third year from 1994 to1998. Response patterns were compared across the two contexts and factor structures investigated. Regression analyses examined relations between learning strategies and outcomes.Main Outcome Measures/Results:Comparison of responses on the 326 complete pairs of lecture and PBL questionnaires indicated differences at the 0.05 level on 44 of the 52 items. The mean differences were greater than 0.5 (on a 5 point scale)at the 0.001 level for 20 items. Of these, five strategies were used more often in PBL and 15 in lectures. Comparisons of learning strategy use across years showed significant changes with time in both instructional contexts. Principal component analysis revealed a stable factor structure with 4 factors distinctly associated with PBL and 4 factors with the lecture learning context. The remaining 6 factors were mixed and independent of context. Exploratory regression analysis revealed that learning outcomes in examinations were influenced by learning strategies. Multiple choice performance was positively predicted by learning associated with lecture class notes and negatively by group work, whereas the OSCE (objective structured clinical exam) performance was positively predicted by class participation in PBL, self-directed note making and lecture class notes.Conclusion:We have developed a learning strategies questionnaire that shows that students' learning strategies are influenced by instructional context, and patterns of learning strategy use change over time. There is tentative evidence that the students' learning strategies influence learning outcomes. This revised version was published online in June 2006 with corrections to the Cover Date.     

Post-esophagectomy gastric outlet obstruction: role of pyloromyotomy and management with endoscopic pyloric dilatation.

OBJECTIVE: Gastric outlet obstruction is common after esophagectomy. Our goal was to determine the incidence of gastric outlet obstruction after esophagectomy with or without pyloromyotomy and analyze its management by endoscopic pyloric dilatation. METHODS: Two hundred forty-two patients underwent esophagectomy with gastric conduit from January 2002 to June 2006. Subjects were divided into two groups: Group A had no pyloromyotomy (n=83) and Group B had a pyloromyotomy (n=159). Gastric outlet obstruction was strictly defined to include patients with clinical delayed gastric emptying supported by symptoms, barium swallow studies, persistent air-fluid level and dilated conduit on radiography, or endoscopic or surgical intervention to improve gastric drainage. RESULTS: The groups were similar except for a higher percentage of cervical anastomosis and older age (64- vs 61-year-old) in Group A. The overall incidence of gastric outlet obstruction was 15.3% (37/242). Pyloromyotomy did not reduce the incidence of gastric outlet obstruction (Group A 9.6% vs Group B 18.2%, p=0.078). One patient required a late pyloroplasty. Successful management of gastric outlet obstruction with pyloric dilatation (96.7%, 28/29) was unaffected by pyloromyotomy. There was no difference in length of stay, pneumonia (Group A 27.7% vs Group B 19.5%, p=0.15), respiratory failure or anastomotic stricture. There was no difference in anastomotic leaks when controlling for the anatomic location of the anastomosis (p=0.36). Mortality was equivalent between groups (2.4 vs 2.5%, p=0.96). CONCLUSION: Pyloromyotomy does not reduce the incidence of symptomatic delayed gastric emptying after esophagectomy. Post-operative gastric outlet obstruction can be effectively managed with endoscopic pyloric dilatation. Routine pyloromyotomy for the prevention of post-esophagectomy gastric outlet obstruction may be unwarranted.