Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term,placebo-controlled trials

Aripiprazole is a novel antipsychotic with a unique mechanism of action. Presented here is a pooled analysis of safety and tolerability data from all completed short-term, placebo-controlled trials in schizophrenia from the aripiprazole clinical development program. Data were analyzed from five 4- to 6-week double-blind multicenter studies of patients hospitalized with acute relapse of schizophrenia or schizoaffective disorder randomized to aripiprazole (n=932), placebo (n=416), or haloperidol (n=201). Daily aripiprazole doses ranged from 2 to 30 mg. Safety assessments included adverse event (AE) reports, EPS scales, ECGs, weight, and prolactin, glucose and cholesterol levels. Aripiprazole was well tolerated, with similar AE incidence rates to placebo, and lower rates than haloperidol for akathisia, extrapyramidal syndrome and somnolence. Objective EPS assessments demonstrated no significant differences between aripiprazole and placebo on Simpson-Angus Scale (SAS) scores, no dose-dependent effects on Barnes Akathisia scores, and significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores from baseline vs. placebo (p相似文献   

Estrogen regulates Ah responsiveness in MCF-7 breast cancer cells

Cytochrome P450 (CYP)1A1 and CYP1B1, which are under the regulatory control of the aryl hydrocarbon (Ah) receptor (AhR), catalyze the metabolic activation of numerous procarcinogens and the hydroxylation of 17beta-estradiol (E2) at the C-2 and C-4 positions, respectively. There is evidence of cross-talk between estrogen receptor alpha (ERalpha)- and AhR-mediated signaling in breast and endometrial cells. To further examine these interactions, we investigated the short- and long-term effects of E2 exposure on Ah responsiveness in MCF-7 human breast cancer cells. Short-term exposure to 1 nM E2 elevated the ratio of the 4- to 2-hydroxylation pathways of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced E2 metabolism and the ratio of the induced CYP1B1 to CYP1A1 mRNA levels, as determined by real-time PCR. Cells maintained long-term (9-12 months) in low-E2 medium progressively lost Ah responsiveness, as indicated by diminished rates of TCDD-induced E2 metabolism and ethoxyresorufin O-deethylase activity, and the reduced expression of the CYP1A1 and CYP1B1 mRNAs and proteins levels. These E2-deprived cells showed elevated levels of ERalpha mRNA, depressed levels of AhR mRNA, and unchanged levels of the AhR nuclear translocator mRNA. Transient transfection studies using a CYP1B1-promoter-luciferase reporter construct showed that reduced CYP1B1 promoter activity in E2-deprived cells could be restored by co-transfection with an AhR expression construct, indicating that AhR expression was limiting in these cells. The reduced Ah responsiveness of E2-deprived cells was reversed by culture for four passages in medium supplemented with 1 nM E2; ERalpha and AhR mRNAs returned to near-normal levels and the inducibility of the CYP1A1 and CYP1B1 mRNAs, proteins, and E2 metabolic activities by TCDD was restored. These studies indicate that the continued presence of estrogen is required to maintain high levels of AhR expression and inducibility of the procarcinogen-bioactivating enzymes, CYP1A1 and CYP1B1, in MCF-7 cells.     

Orthotopic liver transplantation for epithelioid haemangioendothelioma.

AIMS: To report seven cases of epithelioid haemangioendothelioma (EHE) of the liver, a rare, low-grade malignant neoplasm of vascular origin that have been treated in our institution. MATERIALS AND METHODS: Patients with ages ranging from 25 to 60 years presenting mainly with non-specific symptoms, such as right upper quadrant abdominal pain or weight loss. The tumours presented as multiple, nodular lesions involving both lobes of the liver. This type of tumour is often difficult to diagnose, with the final diagnosis being established only by histological examination. The key to diagnosis was the demonstration of cells containing factor VIII-related antigen. RESULTS: Five patients underwent orthotopic liver transplantation (OLT), four of whom are alive at a median follow up 38 months (11-88 months). One patient died of recurrent of disease at 88 months. Two patients did not receive an OLT since they presented with extrahepatic metastatic disease; they died at 21 and 25 months from diagnosis. CONCLUSION: Orthotopic liver transplantation may be considered as a potentially curative treatment for this rare form of tumour when the disease is confined to the liver.     

Impact of multicentricity on clinical outcome in patients with T1-2, N0-1, M0 breast cancer

Background: The objective was to determine the impact of multicentric breast cancer on recurrence and survival and to evaluate the current tumor, node, metastasis staging system recommendations for multicentricity in the breast. Methods: This study included 284 nonpregnant patients with T1-2, N0-1, M0 breast cancer, without previous cancer, who were treated by modified radical mastectomy followed by doxorubicin-based adjuvant chemotherapy. Clinical and pathological data were collected retrospectively and survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. Results: The median follow-up time was 8 years (range, 0.3–24.0), and the median age was 47 years (range, 23–76). The median clinical size of the index tumor was 2.5 cm. In 17% of patients, the clinical nodal status was N1. In 84% of patients, pathology of the index lesion was invasive ductal ± in situ. Multicentric breast cancer was detected in 60 patients (21%): 30 patients with two lesions, 13 patients with three lesions, and 17 patients with four or more lesions. Locoregional recurrence, contralateral breast cancer, distant metastasis, and survival (disease-specific and disease-free) were similar in both groups of multicentric versus unicentric breast tumors. There was a significant difference between groups in estrogen receptor and axillary lymph node positivity, but these did not contribute significantly to outcome on multivariate analysis. Conclusions: Multicentricity does not increase the risk of poor outcomes in patients with early-stage breast cancer. This supports the current recommendations of the tumor, node, metastasis staging system that tumor size should be based on the diameter of the largest lesion in patients with multicentric breast cancer.     

The Use of Reproductive Health Services by Young Women in Australia

Summary: Retrospective analysis of clinical data from 8 State/Territory Family Planning Organizations (FPO) was conducted to determine the reproductive health services used by young women. Between July, 1996 and June, 1997, a total of 185, 879 client visits were recorded at FPO clinics, of which 72,303 (39%) were by young clients. The results showed that young women tended to use a combined oral pill, postcoital pill and spermicides more than those older than 25 years (p < 0.05). Young women were also more likely to use services for management of sexually transmitted disease (STD), counselling for HIV, STD and sexual assault (p < 0.05). However, there were considerable differences among the 3 groups of women: Aboriginal clients, those who did not speak English at home, and those who were born outside Australia. This study confirms that young women are using FPO services especially for emergency/postcoital contraception, STD screening and counselling. FPOs need to continue their existing role of providing reproductive and sexual health services catering to the need of this special segment of the population.     

Unsafe injections and the transmission of hepatitis B and C in a periurban community in Pakistan

Following reports of frequent deaths associated with jaundice and chronic liver disease among adults in a periurban community of Karachi, Pakistan, an investigation was conducted to evaluate the relationship between injections and viral hepatitis infections, to identify the reasons why patients received frequent injections, and to observe the injection practices employed in clinics. Two hundred and three adult patients were interviewed as they left each of the 18 area clinics. Practitioners were interviewed and three consecutive injections were observed at each clinic. Eighty-one per cent of patients received an injection on the day of the interview. Of the 135 patients who provided a serum sample, 59 (44%) had antibodies against hepatitis C virus and 26 (19%) had antibodies against hepatitis B virus. Patients who received more injections were more likely to be infected with hepatitis C. If oral and injected medications were equally effective, 44% of patients preferred injected medication. None of the practitioners knew that hepatitis C could be transmitted by injections. Non-sterile syringes and needles that had been used earlier in the day on other patients were used for 94% of the observed injections. Interventions to limit injections to those which are safe and clinically indicated are needed to prevent injection-associated infections in Pakistan and other low-income countries.     

Immune response of buffaloes to vaccination with Brucella abortus strain 19

The immune response of buffalo calves and heifers to a full or half dose of Brucella abortus strain 19 vaccine was studied. Buffalo calves developed high serum agglutination test (SAT) titres following full dose vaccination. These titres declined more rapidly in calves of six months of age than in calves of eleven to twelve months of age. Specific immunoglobulin G titres, as measured by 2-mercaptoethanol-treated serum agglutination, declined much earlier than SAT titres. Buffalo heifers vaccinated with a full or half dose developed high SAT titres. The rate of decline of SAT titres in heifers was much slower than in calves. Vaccination with a half dose did not appear to offer any advantage in terms of disappearance of SAT titres.     

Comparison of the effects of 0.5% timolol maleate, 2% carteolol hydrochloride, and 0.3% metipranolol on intraocular pressure and perimetry findings and evaluation of their ocular and systemic effects

PURPOSE: To compare the effects of 0.5% timolol maleate, 2% carteolol, and 0.3% metipranolol on intraocular pressure (IOP) in 45 patients with primary open-angle glaucoma (POAG) and ocular hypertension. A secondary goal of this study was to evaluate the ocular and systemic side effects of these medications. METHODS: Measurements of IOP were taken at baseline (pretreatment) and 2, 6, and 12 hours after instillation on treatment days 15, 30, 60, and 90. Mean sensitivity (MS) and mean defect (MD) values of perimetry before and after treatment and the effects of the three beta blockers on serum lipid profiles were determined. Ocular and systemic side effects were recorded. RESULTS: The most prominent IOP lowering effect was noted with metipranolol at 2 and 6 hours on day 15, and with timolol maleate at 12 hours on day 15 and at all hours of the subsequent days on which measurements were taken. Timolol maleate produced a significant decrease in IOP at 12 hours on day 15 compared with carteolol. There was not a statistically significant difference between the MS and MD values on perimetry before and after treatment for any treatment. There was a statistically significant decrease in levels of total cholesterol and high-density lipoprotein (HDL) cholesterol and a significant increase in triglyceride levels; these changes were observed for all treatments. CONCLUSION: The effects of the three medications were not statistically different from each other in terms of IOP reduction and visual field changes. Careful monitoring of blood lipid levels is necessary with long-term treatment with beta blockers, because these agents reduced serum levels of HDL and total cholesterol while increasing triglycerides. Such changes in lipid levels could lead to increased incidence of complications, particularly in patients with atherosclerosis or coronary heart disease.     

The usefulness of the brainstem auditory evoked potential in the early diagnosis of cranial nerve neuropathy associated with diabetes mellitus

BACKGROUND: An evaluation of the extent and mechanism of damage of the central nervous system in diabetes mellitus is of high value in current neurological research. Electrophysiological abnormalities are frequently present is completely asymatomatic diabetes mellitus (DM) patients. Limited data is available in the use of brainstem auditory evoked potential (BAEP) in DM. AIM: Is to evaluate the efficacy of BAEP as a method useful in the diagnosis of subclinical damage of the central nervous system in DM. MATERIAL AND METHOD: 67 diabetes and 32 healthy controls - age and sex matched - were chosen. The diabetes were of type I and II and more than or less than 10 years duration. The BAEP was elicited by using auditory stimulus by using Dantec Evomatic 4000 evoked potential machine. The latency of component response recored as waves I, III and V, interpeak latency (IPLs) I - III, I - V, III - V and amplitude of waves V. RESULTS: The difference was highly significant in the increased latency of waves I, III and V, interpeak latency (IPLs) I - III, I - V, III - V and amplitude of waves V of each type of diabetes as compared to control. Comparison of the type and duration of diabetes between each other showed no significant difference. CONCLUSION: BAEP recording can represent an objective, clinically useful and non invasive procedure to stress the early impairment both of the auditory nerve and of brainstem function.