Binding characteristics of the 5-HT2A receptor antagonists altanserin and MDL 100907

To study the 5-HT(2A) receptors in the living human brain, using positron emission tomography (PET), two selective radiotracers are currently in use: [(18)F]altanserin and [(11)C]MDL 100907. It is, however, currently unknown to what extent data obtained with either tracer are directly comparable. The aim of this study was to compare binding characteristics of these two radiotracers in rat brain with respect to affinity (K(d)), receptor binding density (B(max)), binding potential (BP), and nonspecific binding. Further, binding kinetics, sensitivity towards competition with the endogenous transmitter serotonin, and the competitive/noncompetitive interaction between the two radioligands were evaluated. In addition, the selectivity of [(18)F]altanserin for the 5-HT(2A) receptor was assessed.The K(d) value of [(18)F]altanserin and [(3)H]MDL 100907 was in the order of 0.3 nM. B(max) in frontal cortex was 523 and 527 fmol/mg protein, respectively. The binding of [(18)F]altanserin was not influenced by blocking either the 5-HT(2B/2C) or the alpha(1)-adrenergic receptors. At 37 degrees C the association t(1/2) was 2.8 and 2.7 min and the dissociation t(1/2) was 11 and 13.5 min for [(18)F]altanserin and [(3)H]MDL 100907, respectively.Both radioligands were displaced by 5-HT, only at high concentrations; the K(i) value of 5-HT ranging between 650 and 3,300 nM. This indicates that binding of both radioligands in PET studies is not directly influenced by changes in endogenous 5-HT.Overall, the binding of [(18)F]altanserin and [(3)H]MDL 100907 to the 5-HT(2A) receptor was very comparable, showing selective high affinity binding in the subnanomolar range.     

Randomized clinical trial comparing an oral carbohydrate beverage with placebo before laparoscopic cholecystectomy

BACKGROUND: Preoperative oral carbohydrate can attenuate postoperative insulin resistance and catabolism, and may have the potential to improve postoperative recovery. There are no data from randomized studies on postoperative clinical outcome after specific surgical procedures. This study evaluated the clinical effects of a preoperative carbohydrate beverage in patients undergoing laparoscopic cholecystectomy. METHODS: Ninety-four patients undergoing laparoscopic cholecystectomy were included in a randomized clinical trial. Patients were randomized to receive 800 ml of an iso-osmolar 12.5 per cent carbohydrate-rich beverage the evening before operation (100 g carbohydrate) and another 400 ml (50 g carbohydrate) 2 h before initiation of anaesthesia, or the same volume of a placebo beverage. The primary endpoint was general well-being the day after operation. Patients were evaluated from 5 days before to 5 days after operation. Daily scores of general well-being, fatigue, appetite and pain, computerized measurements of physical activity and sleep (actigraphy), and subjective sleep quality were recorded. Nausea and vomiting were assessed twice within the first 24 h after surgery. RESULTS: Data from 86 patients were available for statistical analysis, 43 in each treatment group. No significant intergroup differences in general well-being or any other outcome variable were found. CONCLUSION: A preoperative carbohydrate beverage did not improve clinical outcome after laparoscopic cholecystectomy.     

ITIH5, a novel member of the inter-alpha-trypsin inhibitor heavy chain family is downregulated in breast cancer

The inter-alpha-trypsin inhibitor (ITI) family constitutes a group of proteins built up from one light chain and a variable set of heavy chains. Originally identified as plasma protease inhibitors, recent data indicate that ITI plays a role in extracellular matrix (ECM) stabilization and in prevention of tumor metastasis. Here we describe cloning as well as phylogenetic and expression analysis of a novel member of the heavy chain gene family, ITIH5. ITIH5 contains the two domains conserved in all known ITIHs, the vault protein inter-alpha-trypsin (VIT) domain and a von Willebrand type A (vWA) domain. However, ITIH5 diverged early from a common ancestor of the other subfamilies. We found strong downregulation of ITIH5 expression in breast tumors by real-time PCR and RNA in situ hybridization. While normal breast epithelial cells clearly express ITIH5, expression is consistantly lost or strongly downregulated in invasive ductal carcinoma. ITIH5 mRNA was neither detectable in cancerous nor benign breast cell lines. We propose that loss of ITIH5 expression may be involved in breast cancer development.     

Cerebral venous thrombosis and Escherichia coli infection in neonates

AIM: To present a possible association between cerebral venous thrombosis (CVT) and infection with Escherichia coli. METHODS: Four neonates with deep CVT occurring during an E. coli infection are presented. RESULTS: In these patients the thrombotic disease was found by Doppler ultrasonography. The thrombosis involved at least the sagittal sinus and the transverse sinus according to subsequent MRI scans. The E. coli strains did not produce verotoxin or haemolysin. Disseminated intravascular coagulation was not demonstrated. Three patients presented with seizures. At discharge, all of the patients had signs of neurological damage, but two of them have improved significantly since then. None of the patients has had recurrent (venous) thrombosis. CONCLUSION: E. coli infections in neonates may predispose to CVT, a finding that has clinical implications.     

A fusidic acid-resistant clone of Staphylococcus aureus associated with impetigo bullosa is spreading in Norway

OBJECTIVE: To investigate the possibility that the increased prevalence of fusidic acid-resistant Staphylococcus aureus in Norway is caused by clonal spread. METHODS: Fusidic acid-resistant and -susceptible clinical isolates of S. aureus from patients with skin infections in the Norwegian county of Telemark and fusidic acid-resistant isolates from other parts of Scandinavia were compared. MICs of fusidic acid for bacterial isolates and pulsed-field gel electrophoresis (PFGE) patterns were investigated. Prevalence data for fusidic acid-resistant S. aureus for the period 1992-2001 were obtained. RESULTS: The prevalence of fusidic acid resistance in S. aureus increased from 1992 to 2001. Eighty per cent of the resistant isolates investigated shared an identical PFGE pattern. The same pattern was found in fusidic acid-resistant isolates from other parts of Scandinavia. Fusidic acid-resistant S. aureus was typically found in impetigo bullosa-like skin disease in children mostly in the summer months. CONCLUSIONS: Fusidic acid resistance among S. aureus is increasing in Norway and is predominantly caused by one clone of S. aureus. The clone may spread further to other countries, and dissemination may be facilitated by extensive use of topical fusidic acid.     

Comparison of procedures for evaluating laboratory performance in external quality assessment schemes for lead in blood and aluminum in serum demonstrates the need for common quality specifications

BACKGROUND: The different scoring methods used by eight European External Quality Assessment Schemes (EQASs) for occupational and environmental laboratory medicine were compared to develop suitable quality specifications as a step toward harmonization. METHODS: Real results for blood lead and serum aluminum assays, reported by participants in Italian and United Kingdom EQASs, were evaluated according to individual scheme scoring criteria. The same results were then used to produce z scores using scheme-based between-laboratory SDs as the estimate of variability to determine whether simple performance-derived quality specifications produced better agreement among schemes. RESULTS: The schemes gave conflicting assessments of participants' performance, and participants judged to be successful by one scheme could be defined as performing inadequately by another. An approach proposed by Kenny et al. (Scand J Clin Lab Invest 1999;59:585), which uses clinical inputs to set targets for analytical imprecision, bias, and total error allowable, was then used to elaborate quality specifications. CONCLUSIONS: We suggest that the CLIA '88 recommendations for blood lead (+/- 40 micro g/L or +/- 10% of the target concentration, whichever is the greater) could be used as a quality specification, although a revision to +/- 30 micro g/L or +/- 10% is recommended. For serum aluminum, a suitable quality specification of +/- 5 micro g/L or +/- 20% of the target concentration, whichever is the greater, is suggested. These specifications may be used to compare laboratory performance across schemes.     

Brachytherapy for prostate cancer: a systematic review of clinical and cost effectiveness

OBJECTIVES: Brachytherapy is emerging as a new treatment option for prostate cancer, and is increasingly being used in Europe and North America. METHODS: A systematic review of studies that compared clinical or cost effectiveness of prostate brachytherapy with radical prostatectomy or external beam radiation for patients with localised prostate cancer. RESULTS: No randomised controlled trials were identified, but five observational studies with comparable patient groups were included in the review. There were no valid data on overall or disease-free survival. There was no difference in disease-free survival based on PSA as a surrogate measure, or in rates of complications. No cost effectiveness studies were found. Based on Norwegian data, the one-year cost of the three treatment options seem fairly similar, while long term cost data are lacking due to lack of data on long term clinical outcome. CONCLUSION: The evidence on the clinical effectiveness of therapies for localised prostate cancer is scarce, but the outcome appears to be comparable for radical prostatectomy, external beam radiotherapy and brachytherapy.     

Are expert panel judgments of medical benefits reliable? An evaluation of emergency medical service programs

OBJECTIVE: We have used multidisciplinary expert panels to assess the health benefits from two different emergency medical service programs in Norway. This gave the opportunity to study the reliability of the expert panel method. METHODS: Two panels assessed case reports for 18 children, and two other panels assessed case reports for 64 adult patients. The assessments of each case report were compared. These assessments were also compared with assessments of the same case reports, done by the same panels 1 and 9 years earlier. RESULTS: Two different panels agreed on the benefit/no benefit conclusion in at least 75% of the patients, both for children and adult patients (kappa 0.88-0.50). For groups of patients assessed to have some health benefit, the magnitude of the benefit estimates differed by 25% between the panels. When the same panels assessed the same patient groups twice, 1 and 9 years apart, their estimates of total benefit differed up to 30%. However, estimates for single patients, as well as estimates from single panel members, varied considerably more. CONCLUSIONS: Use of multidisciplinary expert panels is a useful method for estimating health benefits on program level or for groups of patients. But assessments from single panelists, and for single patients may be seriously biased.     

Impact of payment method on behaviour of primary care physicians: a systematic review

OBJECTIVE: To review the impact of payment systems on the behaviour of primary care physicians. METHODS: All randomised trials, controlled before and after studies, and interrupted time series studies that compared capitation, salary, fee-for-service or target payments (mixed or separately) that were identified by computerised searches of the literature. Methodological quality assessment and data extraction were undertaken independently by two reviewers using a data checklist. Study results were qualitatively analysed. RESULTS: Six studies met the inclusion criteria. There was considerable variation in the quality of reporting, study setting and the range of outcomes measured. Fee-for-service resulted in a higher quantity of primary care services provided compared with capitation but the evidence of the impact on the quantity of secondary care services was mixed. Fee-for-service resulted in more patient visits, greater continuity of care, higher compliance with a recommended number of visits, but lower patient satisfaction with access to a physician compared with salary payment. The evidence of the impact of target payment on immunisation rates was inconclusive. CONCLUSIONS: There is some evidence to suggest that how a primary care physician is paid does affect his/her behaviour but the generalisability of these studies is unknown. Most policy changes in the area of payment systems are inadequately informed by research. Future changes to doctor payment systems need to be rigorously evaluated.