CT and MRI features of ileostomies

OBJECTIVE: The purpose of this article is to describe CT and MRI features of normal anatomy, variants, and pathologic conditions of different ileostomies. CONCLUSION: Multiplanar imaging techniques are useful to identify the complications related to stoma construction and preexisting disease. Understanding the indications for ileostomy construction, surgical techniques, and postoperative anatomy is important for differentiating normal and abnormal imaging features.     

Increasing cancer mortality among opioid-dependent persons in Australia: a new public health challenge for a disadvantaged population

Objective: To examine cancer mortality in a population‐based cohort of opioid‐dependent persons. Methods: New South Wales opioid substitution therapy (OST) program registrants from 1985 to 2005 (n=43,789) were probabilistically linked to the National Death Index. Crude and standardised mortality rates and standardised mortality ratios (SMRs) were calculated. Results: The crude cancer mortality rate increased from 4 to 65 deaths per 100,000 person‐years (p trend <0.001). Overall, OST registrants were 1.7 times more likely to die of cancer than the general population (SMR 95% CI 1.4–1.9). Site‐specific SMRs were significantly elevated for lung cancer (3.6, 95% CI 2.8–4.6), liver cancer (6.9, 95% CI 4.3–10.5), and anogenital cancers (2.8, 95% CI 1.3–5.3), and significantly reduced for breast cancer (0.4, 95% CI 0.1–0.9). Conclusions: Cancer is an increasingly important cause of death among OST registrants as they live longer with their dependency. The site‐specific excess deaths suggest the role of tobacco, alcohol, and infection with hepatitis C and human papillomavirus. Implications: The OST setting may be a useful setting for the delivery of programs aimed at detection of precursor lesions, reducing exposure to established carcinogens, and treatment for those with HCV infection. Such targeted steps are likely to reduce the future cancer burden in this population.     

Mortality among cocaine users: A systematic review of cohort studies

AimsTo conduct a systematic review of mortality among cohort studies of cocaine users.MethodsThree electronic databases were searched (EMBASE, Medline and PsychINFO); other online databases were searched using online libraries and repositories of reports and literature in the drug and alcohol field, with requested contributions from trained librarians and experts. Searches and extraction were undertaken using protocols and cross-checking of decisions by two authors. Additional data were requested from study investigators where studies did not report relevant data.Results1911 articles and 2 reports were identified from searches, with data from another four studies located from review articles. Seven cohorts of “problem” or dependent cocaine users reported data that permitted mortality rates to be estimated. Crude mortality rates ranged from 0.53 (95% CI: 0.10–1.58) to 6.16 (95% CI: 5.21–7.11) per 100PY. Standardised mortality ratios (SMRs) reported in four studies suggested that mortality was four to eight times higher among cocaine users than age and sex peers in the general population.ConclusionsThere are limited data on the extent of elevated mortality among problematic or dependent cocaine users and it is unclear how generalisable the results of these studies may be to other populations of problematic cocaine users. Greater attention to both the method of recruitment, and the characteristics of cocaine users, would enhance our understanding of the mortality risks of problematic cocaine use.     

The labdane diterpene sclareol (labd-14-ene-8, 13-diol) induces apoptosis in human tumor cell lines and suppression of tumor growth in vivo via a p53-independent mechanism of action

The labdane diterpene sclareol has demonstrated significant cytotoxicity against human tumor cell lines and human colon cancer xenografts. Therefore, there is need to elucidate the mode of action of this compound as very little information is known for the anticancer activity of sclareol and other labdane diterpenes, in general. COMPARE analysis of GI(50) values for a number of human cancer cell lines was initially implicated in an effort to assign a putative mechanism of action to the compound. Sclareol-induced cell cycle arrest and apoptosis were assessed by flow cytometry and Western blot analyses. Finally, the anticancer ability of sclareol in vivo was assessed by using human colon cancer xenograft/mouse models. Sclareol arrested in vitro the growth of p53-deficient (HCT116(p53-/-)) human colon cancer cells and subsequently induced apoptosis by activating both caspases-8 and -9. Intraperitoneal administration of liposome-encapsulated sclareol at the maximum tolerated dose induced a marked growth suppression of HCT116(p53-/-) tumors established as xenografts in immunodeficient NOD/SCID mice. In conclusion, we demonstrate herein that sclareol kills human tumor cells by inducing arrest at the G(1)-phase of the cell cycle followed by apoptosis that involves activation of caspases-8, -9 and -3 via a p53-independent mechanism. These findings suggest that liposome-encapsulated sclareol possesses chemotherapeutic potential for the treatment of colorectal and other types of human cancer regardless of the p53-status.     

Relationship between African-American or Caucasian origin and outcomes in the olanzapine treatment of acute mania: a pooled analysis of three adult studies conducted in the United States of America

The aim of this study was to explore the role of ethnic origin in the treatment of acute bipolar mania. Treatment outcomes were studied in a post-hoc analysis of African-American (AA, n=41) and Caucasian (CA, n=190) adults treated with olanzapine in three studies conducted in the United States of America. Baseline demographics were similar except that the AA cohort had fewer women compared with the CA cohort (37 vs. 58%; P=0.01). Daily mean modal olanzapine dose and study discontinuation rate for AA and CA were: 16.2 mg vs. 16.6 mg and 41.5 vs. 25.3% (P=0.03), respectively. There were four (23.5% of discontinuers) and 19 (39.6% of discontinuers, P=0.14) discontinuations because of a poor response in the AA and CA groups, respectively. Drug exposure for the AA cohort was 18.7 days and that of the CA cohort was 19.3 days. Both cohorts showed similar symptom improvements, and safety outcomes were not statistically significantly different except for the following treatment-emergent adverse event frequencies for AA and CA cohorts, respectively: agitation (24.4 vs. 10.5%, P=0.04); dysmenorrhoea (20.0 vs. 3.6%, P=0.04); and dizziness postural (7.3 vs. 1.1%, P=0.04). Although study findings [limited by a smaller (18% of total population) AA cohort] need replication, they suggest that while many outcomes were similar in both cohorts, clinicians could benefit from the awareness of factors in the AA population that possibly influence study discontinuation rates, treatment-emergent adverse event reporting, and participation by sex.     

Early weight gain as a predictor of substantial weight gain with olanzapine/fluoxetine combination: an analysis of 2 adult studies in treatment-resistant depression

Weight gain during olanzapine/fluoxetine combination (OFC) therapy is very common. We examined early (at 2 weeks) weight gain as a predictor of later (at 26 weeks) substantial weight gain in patients with treatment-resistant depression during OFC pharmacotherapy. Data were analyzed from 2 studies (Study 1 and Study 2)-each with an acute, double-blind phase and an open-label phase-in patients who completed 26 weeks of open-label treatment (N = 306). Mean patient age was 46 years; the majority was female and white. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were examined using early weight gain of 2 kg or more as a predictor of 10 kg or more substantial weight gain. Sensitivity (true positive rate) and specificity for Study 1 (n = 73) were 33% and 71%, respectively; PPV and NPV were 23% and 80%, respectively. Sensitivity and specificity for Study 2 (n = 233) were 52% and 70%, respectively; PPV and NPV were 31% and 85%, respectively. Overall, in the 2 trials analyzed, for patients who did not gain 2 kg or more (2.54 lb) in the first 2 weeks of OFC treatment, the observed frequency was 16.3% for gaining 10 kg or more at 26 weeks. Compared to those with early weight gain, patients without early weight gain were less likely to have substantial weight gain after OFC treatment. Additional research is needed to further explore the predictive power of early weight gain for subsequent substantial weight gain in patients with treatment-resistant depression treated with OFC.     

Deletion of apoptosis signal-regulating kinase-1 prevents ventilator-induced lung injury in mice

Both hyperoxia and mechanical ventilation can independently cause lung injury. In combination, these insults produce accelerated and severe lung injury. We recently reported that pre-exposure to hyperoxia for 12 hours, followed by ventilation with large tidal volumes, induced significant lung injury and epithelial cell apoptosis compared with either stimulus alone. We also reported that such injury and apoptosis are inhibited by antioxidant treatment. In this study, we hypothesized that apoptosis signal-regulating kinase-1 (ASK-1), a redox-sensitive, mitogen-activated protein kinase kinase kinase, plays a role in lung injury and apoptosis in this model. To determine the role of ASK-1 in lung injury, the release of inflammatory mediators and apoptosis, attributable to 12 hours of hyperoxia, were followed by large tidal volume mechanical ventilation with hyperoxia. Wild-type and ASK-1 knockout mice were subjected to hyperoxia (Fi(O(2)) = 0.9) for 12 hours before 4 hours of large tidal mechanical ventilation (tidal volume = 25 μl/g) with hyperoxia, and were compared with nonventilated control mice. Lung injury, apoptosis, and cytokine release were measured. The deletion of ASK-1 significantly inhibited lung injury and apoptosis, but did not affect the release of inflammatory mediators, compared with the wild-type mice. ASK-1 is an important regulator of lung injury and apoptosis in this model. Further study is needed to determine the mechanism of lung injury and apoptosis by ASK-1 and its downstream mediators in the lung.     

Association between schizophrenia and common variation in neurocan (NCAN), a genetic risk factor for bipolar disorder

A recent study found genome-wide significant association between common variation in the gene neurocan (NCAN, rs1064395) and bipolar disorder (BD). In view of accumulating evidence that BD and schizophrenia partly share genetic risk factors, we tested this single-nucleotide polymorphism for association with schizophrenia in three independent patient-control samples of European ancestry, totaling 5061 patients and 9655 controls. The rs1064395 A-allele, which confers risk for BD, was significantly over-represented in schizophrenia patients compared to controls (p=2.28×10(-3); odds ratio=1.11). Follow-up in non-overlapping samples from the Schizophrenia Psychiatric GWAS Consortium (5537 patients, 8043 controls) provided further support for our finding (p=0.0239, odds ratio=1.07). Our data suggest that genetic variation in NCAN is a common risk factor for BD and schizophrenia.     

Association between copy number variants in 16p11.2 and major depressive disorder in a German case-control sample

The majority of genetic risk factors for major depressive disorder (MDD) still await identification. Since copy number variants (CNVs) have been implicated in various neuropsychiatric disorders, the question arises as to whether CNVs also play a role in MDD. We performed a genome-wide CNV study using Illumina's SNP array data from 604 MDD patients and 1,643 controls. Putative CNVs were detected with the CNV algorithms QuantiSNP and PennCNV. CNVs with ≥30 consecutive SNPs and a log Bayes Factor/confidence value of ≥30 were statistically analyzed using PLINK. Further analyses and technical verification were only performed in the case of regions for which CNV calls from both programs showed nominal significance. Set-based tests were used to test whether common variants in the CNV regions showed association in two GWAS datasets of MDD. CNVs from four chromosomal regions were associated with MDD. The following were more frequent in patients than controls: microdeletions in 7p21.3 (P?=?0.033) and 18p11.32 (P?=?0.030); microduplications in 15q26.3 (P?=?0.033); and the combination of microdeletion/duplications in 16p11.2 (P?≤?0.018). SNPs in CNV region 16p11.2 showed significant association in a set-based test (P?=?0.026). Microdeletions/duplications in 16p11.2 are the most promising CNVs, since these affect genes and CNVs in this region have been implicated in other neuropsychiatric disorders. The association finding for common SNPs provides further support for the hypothesis that this region is involved in the development of MDD. ? 2012 Wiley Periodicals, Inc.