Morphine Preconditions Purkinje Cells against Cell Death under In Vitro Simulated Ischemia-Reperfusion Conditions

Background: Morphine pretreatment via activation of [delta]1-opioid receptors induces cardioprotection. In this study, the authors determined whether morphine preconditioning induces ischemic tolerance in neurons.

Methods: Cerebellar brain slices from adult Sprague-Dawley rats were incubated with morphine at 0.1-10 [mu]m in the presence or absence of various antagonists for 30 min. They were then kept in morphine- and antagonist-free buffer for 30 min before they were subjected to simulated ischemia (oxygen-glucose deprivation) for 20 min. After being recovered in oxygenated artificial cerebrospinal fluid for 5 h, they were fixed for morphologic examination to determine the percentage of undamaged Purkinje cells.

Results: The survival rate of Purkinje cells was significantly higher in slices preconditioned with morphine (>= 0.3 [mu]m) before the oxygen-glucose deprivation (57 +/- 4% at 0.3 [mu]m morphine) than that of the oxygen-glucose deprivation alone (39 +/- 3%, P < 0.05). This morphine preconditioning-induced neuroprotection was abolished by naloxone, a non-type-selective opioid receptor antagonist, by naltrindole, a selective [delta]-opioid receptor antagonist, or by 7-benzylidenenaltrexone, a selective [delta]1-opioid receptor antagonist. However, the effects were not blocked by the [mu]-, [kappa]-, or [delta]2-opioid receptor antagonists, [beta]-funaltrexamine, nor-binaltorphimine, or naltriben, respectively. Morphine preconditioning-induced neuroprotection was partially blocked by the selective mitochondrial adenosine triphosphate-sensitive potassium channel antagonist, 5-hydroxydecanoate, or the mitochondrial electron transport inhibitor, myxothiazol. None of the inhibitors used in this study alone affected the simulated ischemia-induced neuronal death.     

Ano-cutaneous flap repair for complex and recurrent supra-sphincteric anal fistula.

BACKGROUND: Suprasphincteric fistulae remain the most difficult to cure. OBJECTIVES: The purpose of this study was to evaluate the healing rate of suprasphincteric anal fistula treated by ano-cutaneous advancement flap repair, and the impact of this procedure on continence and quality of life. METHOD: Sixteen patients with complex, recurrent or chronic suprasphincteric fistulae associated with significant tissue damage (necrotizing fasciitis, keyhole deformity and anal stenosis) or who had failed previous surgical procedures were treated by ano-cutaneous flap closure. They were assessed pre and postoperatively by the treating surgeon for wound healing and fistula recurrence and later followed up by phone interview using the St Mark's Hospital incontinence score and the Perianal Disease Activity Index (PDAI) as indicators of treatment outcome. RESULTS: Fifteen patients had successful healing of their fistula with the cutaneous flap, with recurrence in only one. The most common short-term complications were minor graft site wound separation, which healed in all cases without intervention, and wound pain, which settled over time and was not associated with recurrence. Continence improved for almost 70% of the patients, with a significant reduction in St Mark's incontinence scores (t = 2.62, 15 d.f., P = 0.02). PDAI also decreased significantly (t = 7.55, 15 d.f., P < 0.001), demonstrating improvement in quality of life for most patients. CONCLUSION: Ano-cutaneous flap can achieve healing of complex and recurrent suprasphincteric anal fistula in patients who had previously failed at other forms of treatment thus improving their quality of life and continence.     

Use of health care services for psychological distress by immigrants in an urban multicultural milieu.

OBJECTIVE: Research in the United States tends to attribute low rates of use of mental health services by immigrants to economic barriers. The purpose of our study was to examine this issue in the context of Canada's universal health care system. METHODS: A survey of the catchment area of a comprehensive clinic in Montreal interviewed random samples of 924 Canadian-born individuals and 776 immigrants born in the Caribbean (n = 264), Vietnam (n = 234), or the Philippines (n = 278) to assess their health care use for somatic symptoms, psychological distress, and recent life events. RESULTS: Overall rates of use of medical services in the past year were similar in immigrant (78.5%) and nonimmigrant (76.5%) groups. Rates of use of health care services for psychological distress were significantly lower among immigrants (5.5% compared with 14.7%, P < 0.001). This difference was attributable both to a lower rate of use of specialty mental health services by immigrants (2.5% compared with 11.7%, P < 0.001) and to differential use of medical services for psychological distress (3.5% compared with 5.8%, P = 0.02). When level of psychological distress was controlled, Vietnamese and Filipino immigrants were one-third as likely as Canadian-born residents to make use of mental health services. The lower rate of use by immigrants could not be explained by differences in sociodemographics, somatic or psychological symptoms, length of stay in Canada, or use of alternative sources of help. CONCLUSION: Immigrant status is associated with lower rates of use of mental health services, even with universal health insurance. This lower rate of use likely reflects cultural and linguistic barriers to care.     

Immunosuppression: evolution in practice and trends, 1993–2003

Immunosuppression trends for solid organ transplantation have undergone a perceptible shift over the past decade. This period is of interest because it was during this time that the Food and Drug Administration (FDA) expanded the variety of medications to allow for alternatives in immunosuppressive management. An organ-by-organ review of SRTR data identifies several important trends. Antibody induction continues to be used for the majority of kidney (70%) , simultaneous pancreas-kidney (SPK, 79%) pancreas after kidney (PAK, 74%), and intestine recipients (74%). It is used for under half of thoracic organ recipients and remains uncommon for liver transplant recipients (20%). The type of antibody preparation utilized has shifted from muromonab-CD3 and horse ATG to rabbit ATG and monoclonal anti-IL-2 receptor antagonists. Calcineurin inhibitors continue to be used for maintenance immunosuppression for most recipients, although there has been a shift from cyclosporine to tacrolimus. A clear transition is apparent in the choice of antimetabolite from azathioprine to mycophenolate mofetil. Although corticosteroids continue to be used as maintenance immunosuppression for most recipients prior to discharge, there is evidence that efforts of steroid avoidance protocols are having an impact across all organs, as slight decreases in their use have been observed.     

Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.     

Treatment of congenital cystic adenomatoid malformation-does resection in the early postnatal period increase surgical risk?

OBJECTIVE: The recent development of fetal ultrasonography has allowed for an increasing number of prenatal diagnoses for congenital cystic adenomatoid malformation (CCAM). However, the appropriate surgical timing of these patients has not been studied as of yet. The aim of this study is to suggest a safe strategy for the treatment of CCAM by identifying the relationship between the timing of surgery and postoperative outcome. METHODS: Between 1987 and 2003, 40 patients (28 males, 12 females) underwent surgical resection for CCAM. The mean age was 38.6+/-9.1 (2 days-13 years) months. CCAM was diagnosed by prenatal ultrasonography in eight patients. Early operations were performed in four out of the eight. Operation was deferred until 2-12 months of age for the remaining four patients. RESULTS: Type I CCAM was found in 20 patients, type II in 20 and no patient exhibited type III. Five patients had associated pectus excavatum anomaly. There were no cases of operative mortality. Seventeen minor postoperative complications developed in 16 patients (40.0%): prolonged chest tube drain in 10, wound infection in 4, and 1 case of pneumonia, empyema and pleural space, respectively. The average hospital stay was 11.8 (6-29) days. During the mean follow-up period of 67.5 months, one patient died of accidental aspiration 7 months after operation during the postoperative recovery course of Ravich operation for pectus excavatum. The remaining patients reported doing well with normal physical activity. All five patients who underwent surgery at the age of under 1 month did not exhibit increased postoperative morbidity. CONCLUSIONS: We concluded that surgery for CCAM could be safely performed in all age groups with satisfactory long-term outcomes. It is suggested that early elective surgical correction can be recommended for a patient whose diagnosis was made in utero.     

A randomized, double-blind, crossover comparison of risperidone and haloperidol in Korean dementia patients with behavioral disturbances.

OBJECTIVE: Behavioral disturbances in dementia are extremely prominent and distressful, and often result in serious physical, social, and economic consequences. The authors compared the efficacy and tolerability of risperidone and haloperidol in the treatment of behavioral and psychological symptoms of dementia (BPSD) in institutionalized elderly Korean patients with Alzheimer disease, vascular dementia, or mixed dementia. METHODS: This was an 18-week double-blind, crossover study involving 120 patients who were randomly assigned to receive flexible doses (0.5-1.5 mg/day) of risperidone or haloperidol. BPSD were assessed using the Korean version of the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD-K), the Korean version of the Cohen-Mansfield Agitation Inventory (CMAI-K), and the Clinical Global Impression of Change scale (CGI-C). Safety and tolerability assessments included the Extrapyramidal Symptom Rating Scale and the incidence of adverse events. RESULTS: Both risperidone and haloperidol were efficacious in alleviating BPSD. However, when receiving risperidone, patients showed significantly greater improvement than when receiving haloperidol in the total and subscale scores of the BEHAVE-AD-K, the total and subscale scores of the CMAI-K, and the scores on the CGI-C scale. Also, risperidone had an additional benefit on aggressiveness and anxieties/phobias. The risk of antipsychotic-induced parkinsonism throughout this study was significantly lower with risperidone than with haloperidol. CONCLUSION: Risperidone had a favorable efficacy and tolerability profile compared with haloperidol in the treatment of BPSD in this patient population.     

Predictors of successful labor induction with oral or vaginal misoprostol.

OBJECTIVE: To identify independent predictors of successful labor induction with oral or vaginal misoprostol. METHODS: Women enrolled in four previous randomized trials involving oral or vaginal misoprostol for cervical ripening and labor induction were included in the present cohort study, with dosing of 25-50 microg every 4 to 6 h vaginally (n = 574) or 50 microg every 4 h orally (n = 207). Multiple logistic regression was performed to identify factors independently associated with successful labor induction -- defined as vaginal delivery within 12 h, vaginal delivery within 24 h and spontaneous vaginal delivery. Predictors of Cesarean birth and the need for only one dose of misoprostol were also identified. Variables included in the models were maternal age, weight, height, parity, gravidity, membrane status, route of misoprostol, gestational age, birth weight, and Bishop score and its individual components. RESULTS: Maternal age, height, weight, parity, birth weight, dilatation, effacement and cervical station were associated with vaginal delivery within 24 h of induction. Maternal age, height, weight, nulliparity, birth weight and route of misoprostol were associated with Cesarean birth, with oral misoprostol being associated with a lower rate of Cesarean birth. The need for only one dose of misoprostol was predicted by maternal height, weight, parity, gestational age, Bishop score and route of misoprostol. CONCLUSION: Characteristics of the woman (height, weight, parity), the fetus (birth weight) and some of the individual components of the Bishop score, were associated with successful labor induction, with oral misoprostol being associated with a lower rate of Cesarean birth.