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PubMed2000

Evaluation of in vitro bone resorption: high-performance liquid chromatography measurement of the pyridinolines released in osteoclast cultures.

None of the currently used methods to evaluate bone resorption by osteoclasts cultured on bone substrate measures directly the amounts of degraded bone collagen, which is a direct reflection of the osteoclast "work done." We therefore propose a reliable biochemical method to evaluate the in vitro collagenolysis process. Bone-resorbing activity was evaluated, after HPLC separation, by fluorimetric measurement of hydroxylysylpyridinoline (HP), a collagen cross-link molecule, released in culture supernatants. We first confirm previous data reporting that HP is released in the culture medium in a peptide-conjugated form. After acid hydrolysis, we show that HP is highly correlated with the lacunae area (r = 0.68, P<0.0001) and with the amounts of antigenic collagen fragments (Cross-laps for culture) released in culture medium (r = 0.77, P<0.0002). Using a cysteine protease inhibitor, we observed that lacunae areas are dramatically less inhibited (35% inhibition) than the release of bone-degraded products, including HP and antigenic collagen fragments (96 and 92% inhibition, respectively). Coupled to the resorbed area measurement, biochemical evaluations offer both quantitative and qualitative complementary measurements of the osteoclastic bone-resorbing process.

Animals↗
PubMed2000

The accuracy of citation and quotation in otolaryngology/head and neck surgery journals.

A high rate of errors of citation and quotation has been reported in the publications of many medical specialties. The aim of this study was to determine the prevalence of citation and quotation errors in otolaryngology/head and neck surgery journals. A retrospective analysis was performed based on the first issue for 1997 of each of four journals: Laryngoscope; Annals of Otology, Rhinology and Laryngology; Clinical Otolaryngyology; and Journal of Laryngology and Otology. A sample of 50 references from each journal was randomly selected and each was checked for accuracy against the original referenced paper. Citation errors were categorized as major, intermediate or minor and quotation errors as major or minor. Citation errors occurred in 37.5% of the references, 11.9% of which were considered major errors. Quotation errors occurred in 17%, with 11.1% major errors. This prevalence is similar to the established error rate in medical literature.

Bibliometrics↗
PubMed2006

Modelling SF-6D health state preference data using a nonparametric Bayesian method.

This paper reports on the findings from applying a new approach to modelling health state valuation data. The approach applies a nonparametric model to estimate SF-6D health state utility values using Bayesian methods. The data set is the UK SF-6D valuation study where a sample of 249 states defined by the SF-6D (a derivative of the SF-36) was valued by a representative sample of the UK general population using standard gamble. The paper presents the results from applying the nonparametric model and comparing it to the original model estimated using a conventional parametric random effects model. The two models are compared theoretically and in terms of empirical performance. The paper discusses the implications of these results for future applications of the SF-6D and further work in this field.

Bayes Theorem↗
PubMed2003

A European survey of diagnostic methods and testing protocols for Clostridium difficile.

OBJECTIVE: To conduct a survey of the methods used in clinical microbiology laboratories in Europe to diagnose infection with Clostridium difficile. METHODS: A questionnaire was devised and sent to a co-ordinating member of the Study Group in each of eight European countries. This co-ordinator was in charge of forwarding the questionnaire to hospital laboratories arbitrarily selected. The number of laboratories in each country was determined on the basis of one laboratory for 10,000 beds of hospitalization. This questionnaire covered different aspects pertaining to Clostridium difficile associated to diarrhea (CDAD) diagnosis such as circumstances of request, criteria used for undertaking C. difficile investigations, methods used for the diagnosis, etc. RESULTS: A total of 212 questionnaires were completed and submitted for analysis: 87.7% of laboratories reported routinely performing C. difficile diagnostic tests. Methods used included toxin detection (93%), culture (55%), and glutamate dehydrogenase (GDH) detection (5.9%). Among the laboratories detecting toxins, different enzyme immunoassays (EIA) and cytotoxicity assays were used in 79% and 17.3% of cases, respectively. Among the different strategies reported, 4.8% were considered suboptimal for the diagnosis of C. difficile infections, but marked discrepancies could be observed between countries. The overall incidence (median) of CDAD was estimated at 1.1 for 1,000 patient admissions. CONCLUSION: The results of this study suggest marked discrepancies between laboratories and also between countries regarding the criteria by which C. difficile is investigated for, and the methods and the strategies that are used for the diagnosis of C. difficile. These discrepancies could be explained by the lack of clear guidelines for C. difficile diagnosis in each country, and by the importance that physicians attach to C. difficile. Precise guidelines for C. difficile diagnosis would be the first step to make possible accurate comparison of the incidence and the epidemiology of CDAD from one hospital to another or from one country to another.

Bacterial Proteins↗
PubMed1997

Evaluation of anti-AIDS drugs in conventional mice implanted with a permeable membrane device containing human T cells infected with HIV.

We now report the confirmation of the work of Hollingshead et al. (1995) on development of a cell based hollow fiber (HF) system for evaluating potential anti-AIDS drugs in vivo using conventional mice rather than SCID mice. CD4 +, CEM-SS cells infected with HIV/1, strain RF, at a multiplicity of infection of 0.1 were placed into HFs. The fibers were implanted into the peritoneal cavity of outbred Swiss mice. Using this model, the antiviral activity of azidothymidine (AZT) at doses of approximately 150, 75 and 37.5 mg/kg/day was evaluated by administering AZT to the mice in drinking water. Upon fiber removal on day 6, AZT treatment was shown to significantly increase CEM cell viability over the untreated, virus control group and significantly reduced the levels of HIV p24 and HIV RT activity.

Acrylic Resins↗
PubMed2006

Comparative phylogenomics of Clostridium difficile reveals clade specificity and microevolution of hypervirulent strains.

Clostridium difficile is the most frequent cause of nosocomial diarrhea worldwide, and recent reports suggested the emergence of a hypervirulent strain in North America and Europe. In this study, we applied comparative phylogenomics (whole-genome comparisons using DNA microarrays combined with Bayesian phylogenies) to model the phylogeny of C. difficile, including 75 diverse isolates comprising hypervirulent, toxin-variable, and animal strains. The analysis identified four distinct statistically supported clusters comprising a hypervirulent clade, a toxin A(-) B(+) clade, and two clades with human and animal isolates. Genetic differences among clades revealed several genetic islands relating to virulence and niche adaptation, including antibiotic resistance, motility, adhesion, and enteric metabolism. Only 19.7% of genes were shared by all strains, confirming that this enteric species readily undergoes genetic exchange. This study has provided insight into the possible origins of C. difficile and its evolution that may have implications in disease control strategies.

Animals↗
PubMed2005

Clinical and laboratory safety of one year's use of a combination calcium + vitamin D tablet in ambulatory elderly women with vitamin D insufficiency: results of a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: This article presents the results of an evaluation of the clinical and laboratory safety of a 1-year course of treatment with a combination calcium and vitamin D tablet in ambulatory women aged >65 years with vitamin D insufficiency. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study conducted in France, women with a 25-hydroxyvitamin D level < or =12 ng/mL were randomized to receive either a combination tablet containing calcium carbonate 500 mg and vitamin D3 400 IU taken twice daily or a matching placebo tablet for 1 year. A complete clinical examination was performed at baseline and at 3, 6, 9, and 12 months of treatment; blood and urine samples were collected for laboratory analyses at the same time points. Safety was monitored based on adverse events recorded during the treatment period and on the results of laboratory tests, including measurement of creatinine and uric acid levels. RESULTS: The study included 192 women (mean [SD] age, 74.6 [6.9] years; mean weight, 64.0 [12.5] kg), 95 in the calcium + vitamin D group and 97 in the placebo group. Fifty women (21/95 [22.1%] calcium + vitamin D, 29/96 [30.2%] placebo) were prematurely withdrawn from the study for various reasons, with no difference in withdrawals between groups. Treatment-related adverse events were reported in 21 (22.1%) and 23 (24.0%) women in the respective treatment groups. These events consisted mainly of metabolic disorders (9 [9.5%] and 10 [10.4%], respectively), particularly hypercalcemia (6 [6.3%] and 8 [8.3%]) and gastrointestinal disorders (9 [9.5%] and 8 [8.3%]). No major complications directly related to calcium and vitamin D supplementation occurred during the course of treatment. Although renal function was not altered, the group who received calcium + vitamin D had significantly elevated concentrations of serum uric acid compared with those who received placebo (52.3% vs 37.2%; P = 0.046) but not urinary uric acid. CONCLUSIONS: In these ambulatory elderly women with vitamin D deficiency, supplementation with calcium + vitamin D appeared to be well tolerated over 1 year of treatment. No significant effects on creatinine clearance were observed. However, the proportion of women with elevated serum uric acid concentrations was significantly greater in those who received calcium + vitamin D compared with those who received placebo.

Aged↗
PubMed2005

Health state values for the HUI 2 descriptive system: results from a UK survey.

This paper reports the results of a study to estimate a statistical health state valuation model for a revised version of the Health Utilities Index Mark 2, using Standard Gamble health state preference data. A sample of 51 health states were valued by a sample of the 198 members of the UK general population. Models are estimated for predicting health state valuations for all 8000 states defined by the revised HUI2. The recommended model produces logical and significant coefficients for all levels of all dimensions in the HUI2. These coefficients appear to be robust across model specifications. This model performs well in predicting the observed health state values within the valuation sample and for a separate validation sample of health states. However, there are concerns over large prediction errors for two health states in the valuation sample. These problems must be balanced against concerns over the validity of using the VAS based health state valuation data of the original HUI2 valuation model.

Data Collection↗
PubMed2006

Modelling covariates for the SF-6D standard gamble health state preference data using a nonparametric Bayesian method.

It has long been recognised that respondent characteristics can impact on the values they give to health states. This paper reports on the findings from applying a non-parametric approach to estimate the covariates in a model of SF-6D health state values using Bayesian methods. The data set is the UK SF-6D valuation study, where a sample of 249 states defined by the SF-6D (a derivate of the SF-36) was valued by a sample of the UK general population using standard gamble. Advantages of the nonparametric model are that it can be used to predict scores in populations with different distributions of characteristics and that it allows for an impact to vary by health state (whilst ensuring that full health passes through unity). The results suggest an important age effect, with sex, class, education, employment and physical functioning probably having some effect, but the remaining covariates having no discernable effect. Adjusting for covariates in the UK sample made little difference to mean health state values. The paper discusses the implications of these results for policy.

Adult↗
PubMed1999

[Inhibition of gastric secretion by omeprazole and efficacy of calcium carbonate in the control of hyperphosphatemia in patients on maintenance hemodialysis].

UNLABELLED: Apparent contradictions exist in the literature regarding the effect of gastric secretion inhibition on phosphatemia. In healthy adults, omeprazole has been reported to prevent the increase of plasma phosphate or of phosphaturia observed after an acute phosphate load suggesting an inhibition of phosphate absorption. In patients on chronic hemodialysis their hyperphosphatemia is associated to gastric hypersecretion but the inhibition of this latter by ranitidine in patients taking CaCO3 has been reported to increase their plasma phosphate. Because of this contradiction, we have made an open cross-over study in 16 stable and compliant patients in chronic hemodialysis taking a mean daily dose of 9.4 +/- 4 g of CaCO3 and compared their predialysis plasma concentration of phosphate, calcium, protides, bicarbonates, intact PTH, urea and creatine for two successive periods of two months without or with 20 mg of omeprazole. Plasma phosphate did not increased significantly with omeprazole (from 1.80 +/- 0.38 to 1.89 +/- 0.42 mmol/l) whereas plasma corrected calcium significantly decreased from 2.41 +/- 0.18 to 2.36 +/- 0.16 mmol/l (p = 0.04) and plasma bicarbonate decreased significantly from 26.7 +/- 3.5 to 25.7 +/- 3.1 mmol/l (p < 0.05). No significant change was observed in plasma creatine and urea suggesting stability of dialysis efficiency and of protein and therefore phosphate intake. CONCLUSION: These data do not support that CaCO3 efficiency as phosphate binder is decreased with inhibition of the gastric secretion by omeprazole.

Adult↗
PubMed2002

The estimation of a preference-based measure of health from the SF-36.

This paper reports on the findings of a study to derive a preference-based measure of health from the SF-36 for use in economic evaluation. The SF-36 was revised into a six-dimensional health state classification called the SF-6D. A sample of 249 states defined by the SF-6D have been valued by a representative sample of 611 members of the UK general population, using standard gamble. Models are estimated for predicting health state valuations for all 18,000 states defined by the SF-6D. The econometric modelling had to cope with the hierarchical nature of the data and its skewed distribution. The recommended models have produced significant coefficients for levels of the SF-6D, which are robust across model specification. However, there are concerns with some inconsistent estimates and over prediction of the value of the poorest health states. These problems must be weighed against the rich descriptive ability of the SF-6D, and the potential application of these models to existing and future SF-36 data set.

Activities of Daily Living↗
PubMed2005

The impact of age-related macular degeneration on health status utility values.

PURPOSE: To estimate health status utility values in patients with age-related macular degeneration (ARMD) associated with visual impairments, by using preference-based measures of health. METHOD: This was a cross-sectional study involving patients with unilateral or bilateral ARMD who attended a large teaching hospital. Patients underwent visual tests (near and distant visual acuity [VA] and contrast sensitivity [CS]) and completed health status questionnaires including the Index of Visual Function (VF)-14 and three preference-based measures (the Health Utilities Index Mark III [HUI-3], the EuroQoL Health Questionnaire [EQ-5D], and the Short Form 6D Health Status Questionnaire [SF-6D]) and the time tradeoff (TTO). The mean health status is presented for five groups, defined according to the VA in the better-seeing eye and for four CS groups. RESULTS: Two hundred nine patients were recruited with substantial loss of visual function as obtained by visual tests (mean decimal VA in the better-seeing eye: 0.2) and self-report (mean VF-14 score: 41.5). The mean (+/-SD) utilities were 0.34 +/- 0.28 for HUI-3, 0.66 +/- 0.14 for SF-6D, 0.72 +/- 0.22 for EQ-5D, and 0.64 +/- 0.31 for TTO. The HUI-3 had the highest correlation with VA and CS (0.40 and -0.34), followed by TTO (0.25 and -0.21). Across the VA and CS groups, only HUI3 and TTO had a significant linear trend (P < 0.05). In a regression model with CS and VA as explanatory variables, only the coefficient on CS was statistically significant. CONCLUSIONS: ARMD is associated with a substantial impact on patients' health status, but this was not reflected in two of the generic preference-based measures used. The HUI-3 seems to be the instrument of choice for use in economic evaluations in which community data are needed. It may be more appropriate to base economic models on CS or some combination of CS and VA rather than on VA alone.

Aged↗
PubMed2003

What is the relationship between the minimally important difference and health state utility values? The case of the SF-6D.

BACKGROUND: The SF-6D is a new single summary preference-based measure of health derived from the SF-36. Empirical work is required to determine what is the smallest change in SF-6D scores that can be regarded as important and meaningful for health professionals, patients and other stakeholders. OBJECTIVES: To use anchor-based methods to determine the minimally important difference (MID) for the SF-6D for various datasets. METHODS: All responders to the original SF-36 questionnaire can be assigned an SF-6D score provided the 11 items used in the SF-6D have been completed. The SF-6D can be regarded as a continuous outcome scored on a 0.29 to 1.00 scale, with 1.00 indicating "full health". Anchor-based methods examine the relationship between an health-related quality of life (HRQoL) measure and an independent measure (or anchor) to elucidate the meaning of a particular degree of change. One anchor-based approach uses an estimate of the MID, the difference in the QoL scale corresponding to a self-reported small but important change on a global scale. Patients were followed for a period of time, then asked, using question 2 of the SF-36 as our global rating scale, (which is not part of the SF-6D), if there general health is much better (5), somewhat better (4), stayed the same (3), somewhat worse (2) or much worse (1) compared to the last time they were assessed. We considered patients whose global rating score was 4 or 2 as having experienced some change equivalent to the MID. In patients who reported a worsening of health (global change of 1 or 2) the sign of the change in the SF-6D score was reversed (i.e. multiplied by minus one). The MID was then taken as the mean change on the SF-6D scale of the patients who scored (2 or 4). RESULTS: This paper describes the MID for the SF-6D from seven longitudinal studies that had previously used the SF-36. CONCLUSIONS: From the seven reviewed studies (with nine patient groups) the MID for the SF-6D ranged from 0.010 to 0.048, with a weighted mean estimate of 0.033 (95% CI: 0.029 to 0.037). The corresponding Standardised Response Means (SRMs) ranged from 0.11 to 0.48, with a mean of 0.30 and were mainly in the "small to moderate" range using Cohen's criteria, supporting the MID results. Using the half-standard deviation (of change) approach the mean effect size was 0.051 (range 0.033 to 0.066). Further empirical work is required to see whether or not this holds true for other patient groups and populations.

Aged↗
PubMed2003

International typing study of toxin A-negative, toxin B-positive Clostridium difficile variants.

Clinically important strains of Clostridium difficile that do not produce toxin A but produce toxin B and are cytotoxic (A(-)/B(+)) have been reported from multiple countries. In order to compare the relatedness of these strains, we typed 23 A(-)/B(+) C. difficile isolates from the United Kingdom (6 isolates), Belgium (11 isolates), and the United States (6 isolates) by three well-described typing methods. Restriction endonuclease analysis (REA), PCR ribotyping, and serogrouping differentiated 11, 4, and 3 different strain types, respectively. Twenty-one of the 23 A(-)/B(+) variants had a 1.8-kb truncation of the toxin A gene characteristic of toxinotype VIII strains; 20 of the 21 toxinotype VIII-like strains were PCR type 17. PCR type 17 isolates could be differentiated into two separate strain groups by serogrouping and by REA. REA further discriminated these isolates into eight subgroups (REA types). PCR type 17-serogroup F-REA group CF isolates were recovered from all three countries, and one specific REA type, CF4, was recovered from patients with C. difficile disease in the United Kingdom and the United States. C. difficile A(-)/B(+) variants of apparent clonal origin are widely distributed in Europe and North America.

Adult↗
PubMed1992

Cost effectiveness of minor surgery in general practice: a prospective comparison with hospital practice.

The cost effectiveness of general practitioners undertaking minor surgery in their practices was determined in a prospective comparison of patients having minor surgery undertaken in five general practices over a 12 week period in 1989, and in the departments of dermatology and general surgery in Rotherham District General Hospital over a contemporaneous eight week period. There were no differences between the settings in the reported rates of wound infection or other complications and only one general practice patient was subsequently referred to hospital for specialist treatment. General practitioners sent a smaller proportion of specimens to a histopathology laboratory than hospital doctors (61% versus 90%, P less than 0.001); incorrectly diagnosed a larger proportion of malignant conditions as benign (10% versus 1%, P less than 0.05) and inadequately excised 5% of lesions where this never happened in hospital (difference not significant). General practice patients had shorter waiting times between referral and treatment, spent less time and money attending for treatment and more of them were satisfied with their treatment. The cost of a procedure undertaken in general practice was less than in hospital--pounds 33.53 versus pounds 45.54 for the excision of a lesion and pounds 3.00 versus pounds 3.22 for cryotherapy of a wart (1989-90 prices). Performing minor surgery in general practice would seem cost effective compared with a hospital setting. However, the risk of general practitioners inadequately excising a malignancy and not sending it to a histopathology laboratory must be addressed and the conclusion regarding cost effectiveness only applies where general practice is a substitute for the hospital setting and not an additional activity.

Case-Control Studies↗
PubMed2004

Pharmacokinetics of omeprazole in healthy adults and in children with gastroesophageal reflux disease.

Studies of the pharmacokinetics of omeprazole in children with gastroesophageal reflux disease (GERD) remain scarce despite the vast number of reports on its efficacy. The objectives of this study were to assess the pharmacokinetics of omeprazole in healthy adults and in children with GERD. Omeprazole (Losec, delayed-release capsules) was administered orally to 18 healthy adults (mean age 36.8 years) and 12 children with GERD (mean age 6.1 years). Blood samples were collected over 5 hours, and plasma concentrations were assessed using liquid chromatography. Population pharmacokinetic parameters were calculated using NONMEM. A 1-compartment model with zero-order absorption and a lag time was used. The population approach was well suited to the limited number of samples available, and residual variability was low. Oral clearance (CL/F) and apparent volume of distribution (V(ss)/F) in healthy adults (Mean +/- SD: 0.62 +/- 0.27 L/h/kg and 0.76 +/- 0.26 L/kg, respectively) were not significantly different than those in children with GERD (0.51 +/- 0.34 L/h/kg and 0.66 +/- 0.25 L/kg, respectively). Healthy adults displayed a statistically significantly longer delay in drug absorption (Lag time: 0.62 +/- 0.15 hours) as compared with that observed in children with GERD (0.12 +/- 0.03 hours, P < 0.05). On the basis of these findings, omeprazole dosings on a milligram-per-kilogram basis are recommended with no further adjustments for the treatment of GERD in children.

Adult↗
PubMed2006

Imatinib mesylate (Gleevec) enhances mature osteoclast apoptosis and suppresses osteoclast bone resorbing activity.

Recent studies have reported that imatinib mesylate, a kinase inhibitor that targets the intracellular tyrosine kinase BCR-ABL and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, c-FMS. Given that M-CSF signalling through c-FMS plays an important role in osteoclast biology, we speculated that blocking such a pathway with imatinib may modulate osteoclast activity. Using a cell model of mature rabbit osteoclasts, we thus investigated the effect of imatinib on in vitro osteoclast apoptosis and bone resorbing activity. Our findings demonstrate that imatinib dose-dependently stimulates osteoclast apoptosis, a phenomenon which is blocked by the caspase I inhibitor Z-VAD-fmk. The ability of imatinib to enhance osteoclast cell death was accompanied by a dose-dependent inhibition of osteoclast bone resorbing activity. Imatinib was also found to inhibit M-CSF-induced osteoclast survival as well as M-CSF-induced osteoclast bone resorbing activity, but was without effect on interleukin 1alpha (IL-1alpha) and receptor activator of nuclear factor kappa B ligand (RANKL)-induced inhibition of osteoclasts apoptosis, further supporting the hypothesis that imatinib may affect mature osteoclasts through the inhibition of c-FMS. Taken together, these results suggest that imatinib could be of clinical value in treating diseases where bone destruction can occur due to excessive M-CSF production such as osteoporosis, inflammatory-and tumor-induced osteolysis.

Amino Acid Chloromethyl Ketones↗
PubMed2004

Characterization of toxin A-negative, toxin B-positive Clostridium difficile isolates from outbreaks in different countries by amplified fragment length polymorphism and PCR ribotyping.

Clinical Clostridium difficile isolates of patients with diarrhea or pseudomembranous colitis usually produce both toxin A and toxin B, but an increasing number of reports mention infections due to toxin A-negative, toxin B-positive (A(-)/B(+)) strains. Thirty-nine clinical toxin A(-)/B(+) isolates, and 12 other unrelated isolates were obtained from Canada, the United States, Poland, the United Kingdom, France, Japan, and The Netherlands. The isolates were investigated by high-resolution genetic fingerprinting by use of amplified fragment length polymorphism (AFLP) and two well-described PCR ribotyping methods. Furthermore, the toxin profile and clindamycin resistance were determined. Reference strains of C. difficile representing 30 known serogroups were also included in the analysis. AFLP discriminated 29 types among the reference strains, whereas the two PCR ribotyping methods distinguished 25 and 26 types. The discriminatory power of AFLP and PCR ribotyping among 12 different unrelated isolates was similar. Typing of 39 toxin A(-)/B(+) isolates revealed 2 AFLP types and 2 and 3 PCR ribotypes. Of 39 toxin A(-)/B(+) isolates, 37 had PCR ribotype 017/20 and AFLP type 20 (95%). A deletion of 1.8 kb was seen in 38 isolates, and 1 isolate had a deletion of approximately 1.7 kb in the tcdA gene, which encodes toxin A. Clindamycin resistance encoded by the erm(B) gene was found in 33 of 39 toxin A(-)/B(+) isolates, and in 2 of the 12 unrelated isolates (P < 0.001, chi-square test). We conclude that clindamycin-resistant C. difficile toxin A(-)/B(+) strain (PCR ribotype 017/20, AFLP type 20, serogroup F) has a clonal worldwide spread.

Bacterial Proteins↗