Naltrexone is neuroprotective against traumatic brain injury in mu opioid receptor knockout mice

AimsNaltrexone is a mu opioid receptor (MOR) antagonist used to treat drug dependence in patients. Previous reports indicated that MOR antagonists reduced neurodegeneration and inflammation after brain injury. The purpose of this study was to evaluate the neuroprotective effect of naltrexone in cell culture and a mouse model of traumatic brain injury (TBI).MethodsThe neuroprotective effect of naltrexone was examined in primary cortical neurons co‐cultured with BV2 microglia. Controlled cortical impact (CCI) was delivered to the left cerebral cortex of adult male MOR wild‐type (WT) and knockout (KO) mice. Naltrexone was given daily for 4 days, starting from day 2 after lesioning. Locomotor activity was evaluated on day 5 after the CCI. Brain tissues were collected for immunostaining, Western, and qPCR analysis.ResultsGlutamate reduced MAP2 immunoreactivity (‐ir), while increased IBA1‐ir in neuron/BV2 co‐culture; both responses were antagonized by naltrexone. TBI significantly reduced locomotor activity and increased the expression of IBA1, iNOS, and CD4 in the lesioned cortex. Naltrexone significantly and equally antagonized the motor deficits and expression of IBA1 and iNOS in WT and KO mice. TBI‐mediated CD4 protein production was attenuated by naltrexone in WT mice, but not in KO mice.ConclusionNaltrexone reduced TBI‐mediated neurodegeneration and inflammation in MOR WT and KO mice. The protective effect of naltrexone involves non‐MOR and MOR mechanisms.     

Effect of media reporting of the suicide of a singer in Taiwan: the case of Ivy Li

Background  

Suicide attempters are known to be vulnerable to the influence of media reporting of suicide events. This study investigates possible influences of media reporting of a celebrity suicide on subsequent suicide attempts and associated risk factors among suicide attempters.     

Phyllodes tumors of the breast: the role of pathologic parameters

We aimed to establish whether morphologic parameters were prognostically important in a large series of breast phyllodes tumors in Asian women. Of 335 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital, Singapore, between January 1992 and December 2002, 250 (74.6%) were benign, 54 (16.1%) borderline, and 31 (9.3%) malignant, based on histologic review of archival slides. Of the women, 43 (12.8%) experienced recurrences during the follow-up period. Recurrent disease was correlated with grade or classification (P = .028), stromal atypia (P = .016), stromal hypercellularity (P = .046), and permeative microscopic borders (P = .021). Multivariate analysis revealed that independent predictors of recurrence were pseudoangiomatous stromal hyperplasia (PASH) and margin status, whereby the presence of PASH and complete or negative margins reduced recurrence hazards by 51.3% and 51.7% respectively. The 7 women who died of disease during follow-up had malignant phyllodes tumor at the outset and experienced recurrences, and death was preceded by distant metastases.     

Myocardial ischemia during endoscopic retrograde cholangiopancreatography: An overlooked issue with significant clinical impact

Background and Aim: The occurrence of peri‐procedural myocardial ischemia with endoscopic retrograde cholangiopancreatography (ERCP) has been documented, but its significance remains controversial. This study aimed to investigate the incidence and risk factors of myocardial ischemia during ERCP procedures and to analyze the potential association between myocardial ischemia and post‐ERCP complications. Methods: Ambulatory 24‐h ST‐segment monitoring from 30 min prior to 24 h after ERCP was obtained on 71 patients from September 2006 to August 2007. Changes in vital signs during ERCP, post‐ERCP complications, and their outcomes were recorded and analyzed. Results: Cardiac ischemia occurred in 13 patients (18.3%) during ERCP and one patient developed myocardial infarction. More patients in the ischemic group (38.5%) than in the non‐ischemic group (5.2%) had ST‐T changes in pre‐ERCP resting electrocardiography (P < 0.01). Hypotension during ERCP was found only in the ischemic group (15.4% vs 0%; P = 0.03). Patients with cardiac ischemia during ERCP had a significantly higher rate of elevated serum amylase and lipase levels (53.8% vs 15.5%; P < 0.01) and post‐ERCP pancreatitis (30.8% vs 6.9%; P = 0.03). Multivariable logistic regression analysis revealed that cardiac ischemia during ERCP (OR: 5.21, P = 0.050) and pancreatic duct cannulation (OR: 5.7, P = 0.036) were independent predictors for post‐ERCP pancreatitis. Conclusions: ST‐T changes on resting electrocardiography and intra‐procedural hypotension are risk factors of myocardial ischemia during ERCP. Post‐ERCP hyperamylasemia, hyperlipasemia, and pancreatitis were associated with myocardial ischemia during ERCP.     

Treatment of refractoriness to platelet transfusion by protein A column therapy

Ten thrombocytopenic patients (platelets < 10–24 × 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy. Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response. All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500. Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens. Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient. Patients received from 1 to 14 treatments. A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500. Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/− 11 × 10(9) per L as compared with counts of 16 +/− 7 × 10(9) per L (p < 0.0005) before treatment. Posttransfusion CCI values determined in four of these patients averaged 2480 +/− 810 and 10,010 +/− 3540 (p < 0.005) before and after treatment, respectively. In contrast, among the four unresponsive patients, platelet counts averaged 10 +/− 9 and 13 +/− 10 × 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/− 1410 and 1520 +/− 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metformin use and incidence cancer risk: evidence for a selective protective effect against liver cancer

Purpose

Several observational studies suggest that metformin reduces incidence cancer risk; however, many of these studies suffer from time-related biases and several cancer outcomes have not been investigated due to small sample sizes.

Methods

We constructed a propensity score-matched retrospective cohort of 84,434 veterans newly prescribed metformin or a sulfonylurea as monotherapy. We used Cox proportional hazard regression to assess the association between metformin use compared to sulfonylurea use and incidence cancer risk for 10 solid tumors. We adjusted for clinical covariates including hemoglobin A1C, antihypertensive and lipid-lowering medications, and body mass index. Incidence cancers were defined by ICD-9-CM codes.

Results

Among 42,217 new metformin users and 42,217 matched-new sulfonylurea users, we identified 2,575 incidence cancers. Metformin was inversely associated with liver cancer (adjusted hazard ratio [aHR]?=?0.44, 95% CI 0.31, 0.64) compared to sulfonylurea. We found no association between metformin use and risk of incidence bladder, breast, colorectal, esophageal, gastric, lung, pancreatic, prostate, or renal cancer when compared to sulfonylurea use.

Conclusions

In this large cohort study that accounted for time-related biases, we observed no association between the use of metformin and most cancers; however, we found a strong inverse association between metformin and liver cancer. Randomized trials of metformin for prevention of liver cancer would be useful to verify these observations.