Molecular basis of protein S deficiency in three families also showing independent inheritance of factor V leiden

The molecular basis of type I or III Protein S deficiency has been investigated in three kindred also showing independent inheritance of factor V (FV) Leiden. A T to C transition in codon 570 (Met-->Thr) was identified in the propositi and shown to segregate with protein S deficiency in all but one of the affected members of two kindred. This individual was heterozygous for a second transition (C to T) causing substitution of serine 624 by leucine. A second member of the same family, with markedly reduced free protein S levels when compared with affected relatives, was heterozygous for both mutations. Haplotype analysis of individuals with the mutated ATG570ACG allele in the two kindred suggested they may have been related by a common ancestor. A G to A transition resulting in substitution of cysteine 145 by tyrosine was detected in the third kindred. All mutations are believed to interfere with protein S binding to C4b-binding protein resulting in reduced free protein S levels. Of the five individuals studied who had experienced thrombotic events, three had combined protein S deficiency and FV Leiden reemphasising the importance of FV Leiden as an additional risk factor for thrombosis in protein S deficiency.     

Adrenal tissue characterization using MR imaging

Using a superconducting magnet operating at 0.35 T, the authors investigated the adrenal tissue characterization potential of magnetic resonance (MR) in 28 patients with 33 adrenal masses. There were 13 adrenal adenomas (12 non-hyperfunctioning, one aldosteronoma), nine adrenal metastases, four pheochromocytomas, two neuroblastomas, two adrenal lymphomas, two myelolipomas, and one adrenal cortical carcinoma. Spin-echo pulse sequences were obtained at TR 0.5, 2.0 sec and TE 28, 56 msec. Both qualitative (visual assessment) and quantitative (absolute signal intensity, intensity ratios, T1, T2) data were used for tissue characterization. The results suggest that non-hyperfunctioning adrenal adenomas can be distinguished from non-adenomas using both qualitative and quantitative data: 16/19 non-adenomas were visually hyperintense compared with liver at TR 2.0 sec, TE 56 msec, while none of the non-hyperfunctioning adenomas was relatively hyperintense at any pulse sequence used. Of the quantitative data, the intensity ratios of adrenal lesion/liver at TR 0.5 sec, TE 56 msec were most useful in diagnosis: all adenomas had ratios less than 0.83, while 19/20 non-adenomas had ratios exceeding this value. It is concluded that MR has considerable promise in adrenal tissue characterization.     

Genotoxic activity in human faecal water and the role of bile acids: a study using the alkaline comet assay

Human faecal waters from 35 healthy non-smoking volunteers (23 from England and 12 from Sweden) consuming their habitual diet were screened for genotoxicity by the single-cell gel electrophoresis (comet) assay using a human colon adenocarcinoma cell line (CACO-2) as the target. Hydrogen peroxide induced DNA damage was categorized as low, intermediate or high for tail moments greater than 5, 17 and 32, respectively: 11 samples were highly genotoxic, four were intermediate, one was low and 19 showed no activity. Endonuclease III treatment significantly increased DNA damage for all except the non-genotoxic faecal waters, suggesting that faecal water genotoxicity may be due, at least in part, to oxidative damage. Faecal water cytotoxicity has previously been attributed to the bile and fatty acid content. In the comet assay no DNA damage was induced by deoxycholate or lithocholate at normal physiological concentrations, suggesting that the genotoxicity of faecal water was due to other substances. Both bile acids induced DNA damage above 300 microM, levels often found in patients with colonic polyps and there was a significant increase in genotoxicity after endonuclease III treatment indicative of oxidative DNA damage.      

The energy requirement of the dental cutting process

The results are presented of research into the efficiency of various forms of dental burs. This research was carried out at the Delft University of Technology in collaboration with the Subfaculty of Dentistry of the Free University of Amsterdam. The process efficiency was measured during burring of both human teeth and amalgam plugs, with diamond burs and tungsten carbide burs at different speeds and diameters of the bur. Only the efficiency of the cutting process was evaluated, disregarding a number of other essential aspects of the burring process, such as the remaining surface quality after burring and the vibrations generated during burring.     

Outcome from a rapid-assessment chest pain clinic

Chest pain accounts for much of the rising numbers of emergency admissions, but in-patient assessment is not necessarily the best way of dealing with these patients. We ran a 'rapid-assessment chest pain clinic' to provide an alternative route of assessment, and audited its outcome. General practitioners referred patients with recent-onset chest pain, increasing chest pain, chest pain at rest, or other chest pain of concern, on the understanding that they would be seen within 24 h. During 8 1/2 months, 334 patients were referred and 317 patients were seen, most of whom had exercise electrocardiography. A median of 6 months later, 278 patients were personally contacted to determine outcome. Of these, 18% had been admitted immediately with acute coronary syndromes, and 49% had been diagnosed as non-coronary chest pain (none of whom subsequently infarcted or died). Continuing symptoms were infrequent, and satisfaction was high, although 13% of patients had been revascularized. A significant number of patients required immediate admission and/or ultimate revascularization, but many more did not. The majority of these patients had non-coronary chest pain, and this diagnosis was substantiated by their excellent outcome and (in some cases) by further investigation.      

The added value of ordinal analysis in clinical trials: an example in traumatic brain injury

Introduction  

In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial.     

Do knowledge infrastructure facilities support Evidence-Based Practice in occupational health? An exploratory study across countries among occupational physicians enrolled on Evidence-Based Medicine courses

Background  

Evidence-Based Medicine (EBM) is an important method used by occupational physicians (OPs) to deliver high quality health care. The presence and quality of a knowledge infrastructure is thought to influence the practice of EBM in occupational health care. This study explores the facilities in the knowledge infrastructure being used by OPs in different countries, and their perceived importance for EBM practice.