Predictors of mortality in the prospective Dubbo study of Australian elderly

Background: A prospective study in non-institutionalised Australian elderly 60 years and over commenced in Dubbo, NSW in 1988. Aim: To examine clinical and socio-demographic predictors of all-causes mortality Methods: The data were derived from a community-based sample comprising 1236 men and 1569 women followed for a median period of 62 months. Results: Two hundred and thirty five men (19%) and 184 women (12%) died, 46% of male and 53% of female deaths respectively related to cardiovascular disease. In a proportional hazards model, the significant predictors of mortality were: older age, being married (relative risk [RR]=0.71 for men, 0.74 for women), current smoking for men (RR=3.11), taking more than three alcoholic drinks per day for men (RR=0.37), prior coronary heart disease for men (RR=1.36), severe hypertension for women (RR=1.99), use of anti-hypertensive medication for men (RR=1.74), diabetes for men (RR=1.62), poor-fair self-rated health for women (RR=1.74) and physical disability for men (RR=1.72). Serum cholesterol was associated with mortality in a ‘J-shaped’ relationship in men and in a reciprocal relationship in women. Blood pressure predicted mortality in an incremental fashion below 75 years, but in older subjects lower pressure was associated with excess mortality. Conclusion: Some predictors of mortality in the well elderly have been identified and a more extended period of follow-up will possibly resolve contradictory findings in some areas.     

Review article: cyclic vomiting syndrome in adults--rediscovering and redefining an old entity

Aliment Pharmacol Ther 2011; 34: 263–273

Summary

Background Cyclic vomiting syndrome is a disorder characterised by recurrent episodes of severe nausea and vomiting separated by symptom‐free periods. Aims To review the history, epidemiology, clinical aspects, pathophysiology, diagnosis and treatments of adult cyclic vomiting syndrome as well as to identify areas for further clinical research and the unanswered questions in this field. Methods We conducted a PubMed search using such keywords as cyclic vomiting syndrome; nausea; vomiting; pathophysiology; diagnosis; treatment; trigger factors; gastric emptying test; autonomic nerve function test; gastrointestinal hormones; outcome and natural history and combined this information with the knowledge and extensive clinical research and publications from the authors. Results Available data show that in adult cyclic vomiting syndrome, severe epigastric and sometimes diffuse abdominal pain accompanies most cycles of nausea and vomiting interspersed with periods of symptomatic remission. Psychological disorders, specifically anxiety and depression are common, and gastric emptying is actually rapid in approximately 60% of patients and normal in the remainder. There is an impressive and sustained response to high‐dose tricyclic antidepressants. In up to 15% who are regarded as poor responders to tricyclic antidepressants, a predictable profile can be identified related to co‐existing psychological disorders, marijuana use, poorly controlled migraine headache or chronic narcotic use. Conclusions Cyclic vomiting syndrome in adults is an entity that is being increasingly recognised, but the need to educate Internists, Gastroenterologists and Emergency Department staff remains an ongoing challenge.     

Penetrating Missile Injuries During the Iraqi Insurgency

INTRODUCTION

Since the invasion of Iraq in 2003, the conflict has evolved from asymmetric warfare to a counter-insurgency operation. This study investigates the pattern of wounding and types of injuries seen in casualties of hostile action presenting to a British military field hospital during the present conflict.

PATIENTS AND METHODS

Data were prospectively collected on 100 consecutive patients either injured or killed from hostile action from January 2006 who presented to the sole coalition field hospital in southern Iraq.

RESULTS

Eighty-two casualties presented with penetrating missile injuries from hostile action. Three subsequently died of wounds (3.7%). Forty-six (56.1%) casualties had their initial surgery performed by British military surgeons. Twenty casualties (24.4%) sustained gunshot wounds, 62 (75.6%) suffered injuries from fragmentation weapons. These 82 casualties were injured in 55 incidents (mean, 1.49 casualties; range 1–6 casualties) and sustained a total 236 wounds (mean, 2.88 wounds) affecting a mean 2.4 body regions per patient. Improvised explosive devices were responsible for a mean 2.31 casualties (range, 1–4 casualties) per incident.

CONCLUSIONS

The current insurgency in Iraq illustrates the likely evolution of modern, low-intensity, urban conflict. Improvised explosive devices employed against both military and civilian targets have become a major cause of injury. With the current global threat from terrorist bombings, both military and civilian surgeons should be aware of the spectrum and emergent management of the injuries caused by these weapons.     

Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Phase 1 Schizophrenia trial compared the effectiveness of one typical and four atypical antipsychotic medications. Although trials such as CATIE present important opportunities for pharmacogenetics research, the very richness of the clinical data presents challenges for statistical interpretation, and in particular the risk that data mining will lead to false-positive discoveries. For this reason, it is both misleading and unhelpful to perpetuate the current practice of reporting association results for these trials one gene at a time, ignoring the fact that multiple gene-by-phenotype tests are being carried out on the same data set. On the other hand, suggestive associations in such trials may lead to new hypotheses that can be tested through both replication efforts and biological experimentation. The appropriate handling of these forms of data therefore requires dissemination of association statistics without undue emphasis on select findings. Here we attempt to illustrate this approach by presenting association statistics for 2769 polymorphisms in 118 candidate genes evaluated for 21 pharmacogenetic phenotypes. On current evidence it is impossible to know which of these associations may be real, although in total they form a valuable resource that is immediately available to the scientific community.     

Molecular and morphological analysis of adenoid cystic carcinoma of the breast with synchronous tubular adenosis

Adenoid cystic carcinoma (ACC) of the breast is a rare tumour. Its recognition as a special type of breast carcinoma is very important because its prognosis is better than the not-otherwise-specified invasive ductal carcinoma and its treatment may not include axillary dissection. Tubular adenosis (TA) is a very rare condition of the breast that is histologically benign; however, it has been described in association with invasive ductal carcinoma. There are scant data regarding the molecular genomic alterations in ACC of the breast and no data has been presented on TA. Herein, we provide a morphological characterisation of TA arising synchronically with ACC in the breast. To characterise these lesions, we performed ultrastructural analysis, three-dimensional reconstruction and molecular analysis using immunohistochemistry and comparative genomic hybridisation. The copy number alterations found in ACC were restricted to small deletions on 16p and 17q only, whereas the TA harboured gains on 1q, 5p, 8q, 10q, 11p and 11q and losses on 1p, 10q, 11q, 12q, 14q, 15q and 16q. These molecular data highlight the genomic instability of TA, a benign florid proliferation intermingled with ACC, and do not provide evidence of molecular evolution from TA to ACC.     

Irbesartan-mediated reduction of renal and cardiac damage in insulin resistant JCR : LA-cp rats

Background and purpose:

Angiotensin II receptor antagonists (ARBs), originally developed for antihypertensive properties, have pleiotropic effects including direct vascular actions. We tested the hypothesis that the ARB irbesartan would be effective against micro- and macrovascular complications of the prediabetic metabolic syndrome using the obese, insulin-resistant JCR : LA-cp rat that exhibits micro- and macrovascular disease with ischaemic myocardial lesions and renal disease.

Experimental approach:

Obese male rats were treated with irbesartan (30 mg·kg⁻¹·day⁻¹, incorporated into chow) from 12 to 25 weeks of age.

Key results:

Irbesartan treatment caused no change in food intake or body weight. Fasting glycaemic control of the JCR : LA-cp rats was marginally improved, at the expense of increased plasma insulin levels (∼50%). Fasting plasma triglycerides were marginally reduced (∼25%), while cholesterol concentrations were unchanged. Elevated concentrations of adiponectin, monocyte chemotactic protein-1 and plasminogen activator inhibitor-1 were reduced along with severity of glomerular sclerosis. Macrovascular dysfunction (aortic hypercontractile response to noradrenergic stimulus and reduced endothelium-dependent relaxation) was improved and frequency of ischaemic myocardial lesions reduced (62%).

Conclusions and implications:

Irbesartan reduces markers of inflammation and prothombotic status, improves macrovascular function and reduces glomerular sclerosis and myocardial lesions in a model of the metabolic syndrome. Unlike pharmaceutical agents targeted on metabolic dysfunction, irbesartan reduced end-stage disease without major reduction of plasma lipids or insulin. The protective effects appear to be secondary to unknown intracellular mechanisms, probably involving signal transduction pathways. Understanding these would offer novel pharmaceutical approaches to protection against cardiovascular disease.     

Guidelines on nicotine dose selection for in vivo research

Rationale This review provides insight for the judicious selection of nicotine dose ranges and routes of administration for in vivo studies. The literature is replete with reports in which a dosaging regimen chosen for a specific nicotine-mediated response was suboptimal for the species used. In many cases, such discrepancies could be attributed to the complex variables comprising species-specific in vivo responses to acute or chronic nicotine exposure. Objectives This review capitalizes on the authors’ collective decades of in vivo nicotine experimentation to clarify the issues and to identify the variables to be considered in choosing a dosaging regimen. Nicotine dose ranges tolerated by humans and their animal models provide guidelines for experiments intended to extrapolate to human tobacco exposure through cigarette smoking or nicotine replacement therapies. Just as important are the nicotine dosaging regimens used to provide a mechanistic framework for acquisition of drug-taking behavior, dependence, tolerance, or withdrawal in animal models. Results Seven species are addressed: humans, nonhuman primates, rats, mice, Drosophila, Caenorhabditis elegans, and zebrafish. After an overview on nicotine metabolism, each section focuses on an individual species, addressing issues related to genetic background, age, acute vs chronic exposure, route of administration, and behavioral responses. Conclusions The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose–response relationships based on the precise parameters and conditions inherent to a specific hypothesis. This review provides a new, experimentally based compilation of species-specific dose selection for studies on the in vivo effects of nicotine.