Imatinib mesylate (STI-571 Glivec,Gleevec) is an active agent for gastrointestinal stromal tumours,but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study

The aim of this study was to assess the antitumour response and time to progression (TTP) of patients treated with imatinib mesylate (Glivec, Gleevec, formerly STI-571) who had advanced and/or metastatic gastrointestinal stroma tumours (GIST) or other soft tissue sarcomas (STS). Patients with measurable lesions and adequate organ function were entered. They were treated with imatinib mesylate at the dose of 400 mg twice daily (bid). All tumours were subject to a stringent pathological review by an expert panel. Immunohistochemical expression of KIT expression was evaluated. A total of 51 patients (27 GIST, 24 other STS), median age 53 years, median World Health Organization (WHO) performance score 1, were entered. 71% of the patients had received prior chemotherapy. The most frequent side-effects were anaemia (92%), periorbital oedema (84%), skin rash (69%), fatigue (76%), nausea (57%), granulocytopenia (47%) and diarrhoea (47%). Most of these side-effects were mild to moderate and no patient was taken off study due to side-effects. Skin rash and periorbital oedema frequently seem to be self limiting, despite continued treatment. In GIST patients, the current response rates (RRs) are 4% complete remission (CR), 67% partial remission (PR), 18% stable disease (SD) and 11% progression (PD). 73% of GIST patients are free from progression at 1 year. In the other STS group, there were no objective responses. The median time to progression in this subgroup was only 58 days. Imatinib mesylate is well tolerated at a dose of 400 mg bid. This dose is active in patients with KIT-positive GIST, but patients with other STS subtypes unselected for a molecular target are unlikely to benefit.     

Socioeconomic deprivation, coronary heart disease prevalence and quality of care: a practice-level analysis in Rotherham using data from the new UK general practitioner Quality and Outcomes Framework

BACKGROUND: The provision of coronary heart disease (CHD) health care has been shown to be inequitous, with those most in need having the least access to high-quality care. The new UK general practitioner (GP) Quality and Outcomes Framework (QOF) contract offers substantial financial rewards to general practices that combine maximal CHD case finding with high-quality CHD care. OBJECTIVE: To examine whether GP practice-level CHD prevalence and the measures of quality of care derived from the new QOF data are associated with area-level socioeconomic deprivation. METHODS: An ecological study of 38 GP practices contracting with Rotherham Primary Care Trust, United Kingdom, was carried out. We calculated Spearman rank correlation coefficients for practice-level age-sex-standardized QOF CHD prevalence against area deprivation score and for 11 QOF CHD indicator achievements against area deprivation score. RESULTS: Practice-level CHD prevalence showed a positive correlation with deprivation (r=0.64, p<0.001), as did one of the 11 quality-of-care indicators (recording of smoking status, r=0.34, p=0.04). The remaining 10 quality-of-care indicators showed no significant correlation with deprivation. CONCLUSION: Practice-level CHD prevalence is associated with deprivation, but we found no evidence of socioeconomic inequality in CHD care. This finding is in contrast to that from previous studies and the widely reported inverse care law.     

Fibromyalgia and myofascial pain syndromes and the workers' compensation environment: an update

Fibromyalgia and myofascial pain syndromes are terms used to describe a constellation of complaints ranging from generalized aches to specific tender trigger points often accompanied by fatigue, depression, and sleep disturbances. In the past 5 years, research has been directed primarily at determining the pathophysiology of fibromyalgia and myofascial pain syndromes and the treatment of patients' comorbidities to alleviate their symptomatology. Controversy exists as to whether fibromyalgia and myofascial pain syndromes represent a specific pathology or are merely terms to describe clinical conditions that provide patients with the reassurance that their symptoms are real and help clinicians with therapeutic direction. In the occupational health setting, this uncertainty can lead to significant difficulty in determining short- and long-term disability and assigning culpability to an individual's work environment.     

Multiple valvar replacements for hypereosinophilic syndrome

A boy with familial eosinophilia had the hypereosinophilic syndrome, with involvement of mitral and tricuspid valves. Between the ages of 11 and 20 years, he underwent eight surgical procedures on his atrioventricular valves. The pathology included recurrent thrombotic vegetative masses related to hypereosinophilia. Initial repair of the mitral valve was shortlived, but recurrent repairs of the tricuspid valve were helpful. Mechanical prostheses inserted in the mitral position thrombosed despite anticoagulant therapy, and bioprosthetic valves deteriorated with thrombus, fibrosis, or tearing. The hypereosinophilic syndrome is unusual in children, and produces additional problems with valvar surgery.     

Language -- the barrier and the bridge between science and public

What does modern science tell people? That life is ultimately DNA, and DNA is genes, and genes are just so many bits of Lego, little building blocks manipulated by Nature for 3.8 thousand billion years, rather economically, so that much the same genes pop up in a nematode worm, a fruit fly, a lettuce, and a thriller writer. And that genes can be transferred from one species, or genus, or phylum, or even one kingdom to another. That is why there is unease, and newspapers reflect that unease, they do not create it. By helping people confront that unease, they probably help people come to terms with it. In the course of history, people have felt pretty uneasy about blood transfusion, heart transplants, test tube babies, and AIDS, and over the years, have calmed down considerably about each, to the advantage of both society and science. It will be the same for the human genome project, in a while.     

Nonpeptide endothelin antagonists in clinical development

Endothelins (ET-1, ET-2 and ET-3) are 21-amino-acid peptides with two disulfide bonds that belong to the sarafotoxin family. ET-1, ET-2 and ET-3 are produced endogenously from preproendothelin to give big endothelins, which are cleaved by endothelin-converting enzyme (ECE) to yield the active protein. Endothelin has been shown to play important physiological and pathological roles by interacting with its G-protein-coupled receptors. There are two cloned ET receptors: the ET(A) receptor, which is selective for ET-1, and the ET(B) receptor, which binds ET-1, ET-2 and ET-3 with similar affinities. Since the discovery of endothelin, and especially since the availability of peptide ET antagonists such as BQ-123 and BQ-788, and nonpeptide compounds such as bosentan, considerable effort has been spent on better understanding the role of endothelin and its receptor antagonists. As a result, endothelin has been implicated in a variety of serious diseases, such as congestive heart failure, hypertension, pulmonary hypertension and prostate cancer. Research in pharmaceutical and biotechnology laboratories has generated many endothelin antagonists with either sulfonamide or triaryl carboxylic acid scaffolds, and a number of ET(A)-selective or nonselective ET(A)/ET(B) endothelin antagonists have entered clinical trials. This article will review the small-molecule ET(A)-selective and nonselective ET(A)/ET(B) antagonists that are under clinical evaluation, and highlight a member of this group of compounds, sitaxsentan. A summary of the medicinal chemistry that led to the identification of sitaxsentan will be presented, followed by selected animal and human clinical trial data. (c) 2001 Prous Science. All rights reserved.     

The risks of injury in public ice skating.

A prospective survey has been made of the injuries to members of the public attending a well established ice rink in a major city. Comparison is made with series in the literature reporting high levels of injuries, with corresponding demands on local hospital services, from newly established ice rinks. The main conclusion is that demands on hospital services have been markedly reduced for the well established rink, with corresponding savings in health service resources.