bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bactericidal activity of antimicrobial coated polyurethane sleeves for external fixation pins
Authors: Forster Hamish , Marotta James S. , Heseltine Kim , Milner Richard , Jani Shilesh 
Published: November 2003

AbstractThis study was conducted to assess the potential of gentamicin coated polyurethane sleeves to inhibit bacterial colonization on external fixation pins and wires. These antimicrobial sleeves have been designed to be fitted over the pins and wires, at the time of surgery, as a prophylactic approach to combat the major complication of external fixation treatment, pin tract infection. Elution testing was conducted to estimate the amount of gentamicin released into the pin tract. These gentamicin concentrations were compared to the gentamicin minimal inhibitory concentration (MIC) level for common pin tract pathogens. Elution testing revealed that the gentamicin coated polyurethane sleeves released significant quantities of the antibiotic for up to 26 weeks. The initial bolus release was characterized by predicted pin tract gentamicin concentrations of >80 μg/ml at the 2 h and 1 day elution time points. These amounts of gentamicin, delivered directly to the pin tract, are far beyond those that could be achieved via oral or intravenous administration. Furthermore, the expected concentration of gentamicin in the pin tract remained above the National Committee for Clinical Laboratory Standards (NCCLS) MIC breakpoint of 4 μg/ml, [Performance standards for antimicrobial susceptibility testing: twelfth informational supplement M100‐S12, NCCLS, Wayne, PA, 2002], for at least 20 weeks. Data from the SENTRY antimicrobial surveillance program (1997–2002) established a high level of bactericidal activity for gentamicin, with 83.1% of the common pin tract pathogen isolates found to be susceptible to the antibiotic. The initial burst and subsequent long‐term sustained local delivery of effective amounts of gentamicin from the antimicrobial sleeves would be expected to inhibit bacterial colonization on external fixation pins and wires. This inhibition of bacterial colonization should substantially reduce the incidence of pin tract infection, and improve the overall outcome and cost effectiveness of external fixation fracture management. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Testing for Offsetting Behavior and Adverse Recruitment Among Drivers of Airbag‐Equipped Vehicles
Authors: Harless David W. , Hoffer George E. 
Published: November 2003

AbstractEarlier studies reported that an insurance industry index of personal‐injury claims rose after automobiles adopted driver's side airbags and that drivers of airbag‐equipped vehicles were more likely to be at fault in fatal multivehicle accidents. These findings can be explained by the offsetting behavior hypothesis or by at‐risk drivers systematically selecting vehicles with airbags (i.e., adverse recruitment). We test for offsetting behavior and adverse recruitment after airbag adoption using a database containing information on fatal accidents including information on drivers' previous records and drivers' actions that contributed to the occurrence of the accident. Further, we reexamine the personal injury claims index data for newly airbag‐equipped vehicles and show that the rise in the index after airbag adoption may be attributable to moral hazard and a new vehicle ownership pattern. Rental car drivers are much more likely to commit grievous acts than other drivers, and the proportion of new automobiles in daily rental service more than doubled during the period of airbag adoption.
The Economic Effects of Road Safety Improvements: An Insurance Claims Analysis
Authors: Feber David J. , Feldmeier Judith M. , Crocker Keith J. 
Published: November 2003

AbstractThis article demonstrates the feasibility of exploiting insurance claims data to estimate the marginal benefits to society of highway infrastructure improvements. We construct a unique database linking claims expenditures for a major auto insurer in Michigan to infrastructure investments at 62 intersections in the City of Detroit, and conclude that the addition of a left‐turn lane, or left‐turn phase in the signal, decreases the insurer's average monthly claims costs at a representative intersection by $944 or $1,062, respectively. The evidence also indicates that these cost savings are a result of reductions in accident severity, rather than being a consequence of fewer accidents.
Do Property‐Casualty Insurance Underwriting Margins Have Unit Roots?
Authors: Harrington Scott E. , Yu Tong 
Published: November 2003

AbstractA growing literature analyzes determinants of insurance prices using time series data on insurer underwriting margins. If the variables analyzed are stationary, conventional regression models may be appropriately used to test hypotheses. Based on pretests for a unit root, several studies have instead used co‐integration analysis to analyze the long‐run relationship between purportedly nonstationary underwriting margins and macroeconomic variables. We apply a battery of unit root tests to investigate whether underwriting margins are stationary under different assumptions concerning deterministic components in the data generating process (DGP). When linear and/or quadratic trends are included in the assumed DGPs, the tests reject the null hypothesis of a unit root for loss ratios, expense ratios, combined ratios, and economic loss ratios from 1953 through 1998 for many of the individual lines examined and for all lines combined. Consistent with prior work on whether macroeconomic variables have unit roots, a simulation of test power for underwriting margins during the sample period demonstrates that nonrejections of the null hypothesis of a unit root could easily reflect low power. The overall findings suggest that conventional regression methods can be used appropriately to analyze underwriting margins after controlling for deterministic influences and transforming any nonstationary regressors.
Claiming Behavior in Workers' Compensation
Authors: Biddle Jeff , Roberts Karen 
Published: November 2003

AbstractUsing administrative data on workers' compensation claims in Michigan combined with data collected from a sample of workers identified by physicians as having work‐related pain in their backs, wrists, hands, or shoulders, this article provides evidence that a substantial number of potentially eligible workers do not file workers' compensation claims. Multivariate analysis identifies the effects of various factors on the probability of filing a workers' compensation claim, conditional on having a work‐related health problem. We find that the severity of the worker's condition and the worker's general health are the most important determinants of the decision to file, and that the generosity of wage loss benefits also affects the decision of an eligible worker to file. Finally, claims propensities vary considerably across workplaces, holding all other measured factors constant.
Effect of atrial natriuretic factor and fate of cyclic‐guanosine‐monophosphate in the rat kidney
Authors: SYRÉN M.‐L. 
Published: November 2003

The mechanisms whereby atrial natriuretic factor (ANF) induces natriuresis are not clarified. Here, the effects of ANF and the cGMP analogue, 8‐bromo‐cGMP, on Na+, K+‐ATPase activity in microdissected segments from rat medullary thick ascending limb of Henle (TAL) were evaluated. ANF‐induced cGMP accumulation and the cellular handling of intracellularly produced cGMP were also investigated, by measuring the accumulation of extracellular cGMP in suspensions of tubules from outer medulla, enriched in TAL, and of isolated glomeruli.ANF dose‐dependently inhibited Na+, K+‐ATPase activity in isolated TAL in a parallel fashion with increasing cGMP accumulation in OM tubules. For both parameters, pharmacological concentrations (≥ 10−6 m) of ANF were needed to induce a significant effect. 8‐Bromo‐cGMP mimicked the inhibitory effect of ANF. The increase in the intracellular cGMP level in response to ANF was dose‐dependently reflected in the extracellular level. This finding contrasted with that in the glomerular preparation, where cGMP in response to ANF accumulated entirely intracellularly. Also in glomeruli, high (≥ 10−6 m) concentrations of ANF were needed to induce a significant effect on cGMP accumulation.In conclusion, ANF inhibited Na+, K+‐ATPase activity in TAL and the effect was mimicked by 8‐bromo‐cGMP. cGMP, produced in response to ANF, was extruded from the tubular epithelial cells, but not from glomeruli.
The involvement of nurses in reporting suspected adverse drug reactions: experience with the meningococcal vaccination scheme
Authors: Ranganathan S. Sri , Houghton J. E. , Davies D. P. , Routledge P. A. 
Published: November 2003

Aims  In order to aid the monitoring of the new Meningococcal serogroup C Conjugate (Men C) vaccine, the Yellow Card Scheme was extended to allow nurses for the first time to report any suspected adverse reactions associated with these vaccines. We have analysed the Yellow Cards received by the Committee on Safety of Medicines (CSM) Wales from nurses reporting a suspected reaction in association with these vaccines during the first 16 months of the programme.Methods  CSM Wales receives Yellow Cards from healthcare professionals in Wales. Details of Yellow Cards reporting a suspected adverse reaction associated with Men C vaccines during the study period were extracted from the CSM Wales database and analysed according to health professional category [nurses, General Practitioners (GP), hospital doctors or pharmacists].Results  During the study period 534 117 doses of Men C vaccines were administered in Wales; in the same period CSM Wales received 1095 Yellow Cards containing 1952 suspected reactions. Nurses completed 529 [48.3%, 95% confidence interval (CI) 43.6, 53.1] Yellow Cards compared with 294 (26.8%, 95% CI 22.7, 30.8) from GPs, 262 (23.9%, 95% CI 20.1, 27.6) from hospital doctors and 10 (0.91%, 95% CI 0.43, 1.73) from others, which include hospital pharmacists, community pharmacists and health visitors. The proportion of Yellow Cards sent by nurses was significantly higher than those sent by GPs and hospital doctors. Ninety‐five percent CIs for differences in proportions (CI diff prop) were (0.175, 0.254) and (0.204, 0.282), respectively. The majority (90.9%, 95% CI 88.7, 93.5) of the Yellow Cards from nurses reported suspected reactions children in over the age of 5 (95% CI diff prop 0.861, 0.917). The spectrum of suspected adverse drug reactions (ADRs) involved the skin and subcutaneous tissue, central nervous system, general reactions, and the gastrointestinal tract. Of the suspected reactions reported by nurses, GPs and hospital doctors, 13.4% (95% CI 10.5, 15.8), 12.9% (95% CI 9.6, 16.8) and 9.1% (95% CI 6.5, 11.8), respectively, were of serious reactions. Nurses reported 52.5% (95% CI 45.4, 60.6) of all the suspected serious reactions, which was statistically more significant than hospital doctors [χ2 = 5.864, degree of freedom (DF) = 1, P < 0.05] but not GPs (χ2 = 0.066, DF = 1, P > 0.05).Conclusions  Nurses were the health professionals who provided the largest proportion of reports of suspected ADRs and almost half of all reports during the Men C vaccination campaign. Their reports contained an equal proportion of serious suspected ADRs and the reports were documented as completely as those from GPs and hospital doctors.
Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity
Authors: Härtter Sebastian , Nordmark Anna , Rose Dirk‐Matthias , Bertilsson Leif , Tybring Gunnel , Laine Kari 
Published: November 2003

Aims  The aim of this study was to assess the influence of concomitant caffeine intake on the pharmacokinetics of oral melatonin, a probe drug for CYP1A2 activity.Methods  Twelve healthy subjects, six smokers and six nonsmokers, were given melatonin (6 mg) either alone or in combination with caffeine (3 × 200 mg). Blood samples for the analysis of melatonin or caffeine and paraxanthine were taken from 1 h before until 6 h after intake of melatonin. Subjects were genotyped with respect to the CYP1A2*1F (C734A) polymorphism.Results  When caffeine was coadministered the Cmax and AUC of melatonin were increased on average by 142% (P = 0.001, confidence interval on the difference 44, 80%) and 120% (P < 0.001, confidence interval on the difference 63, 178%), respectively. The inhibitory effect of caffeine was more pronounced in nonsmokers and in individuals with the *1F/*1F genotype.Conclusion  The results of this study revealed a pronounced effect of caffeine on the bioavailability of orally given melatonin, most probably due to inhibition of CYP1A2 activity.
Effect of food on the pharmacokinetics of multiple‐dose oral voriconazole
Authors: Purkins Lynn , Wood Nolan , Kleinermans Diane , Greenhalgh Katie , Nichols Don 
Published: November 2003

Aims Voriconazole is a new triazole antifungal agent with activity against a range of clinically important and emerging pathogens. This study determined the effect of food on the pharmacokinetics of voriconazole in healthy volunteers.Methods This was an open, randomized, two‐way crossover, multiple‐dose study in male volunteers. Twelve subjects received voriconazole 200 mg twice daily for 6.5 days. Each dose was administered either with food or in the fasted state, i.e. not within 2 h of food. Treatment periods were separated by a minimum 7‐day washout period. Plasma samples were taken for the estimation of voriconazole plasma concentrations on days 1 and 7. Safety and toleration were assessed by monitoring of both laboratory safety tests and adverse events.Results Administering voriconazole with food significantly decreased both day 7 AUCτandCmaxby approximately 35% (9598–7520 ng·h  ml−1;P = 0.003) and 22% (2038–1332 ng ml−1;P = 0.008), respectively. Administering voriconazole with food statistically significantly delayed absorption, evident fromtmaxvalues; the mean difference fortmaxon day 7 was 1.1 h. The terminal phase rate constant was unchanged by administering voriconazole with food. The fasted terminal phase half‐life was 7.3 h compared with 6.6 h for the fed state. Visual inspection ofCminvalues suggests that steady state was achieved after 5 days in both dietary states. Voriconazole accumulation, as assessed by ratios ofCmaxand AUCτon days 1 and 7, was statistically significantly greater when administered with food (Cmax,P = 0.010, AUCτ,P = 0.006). MeanCmaxaccumulation in the fasted state was 2.1‐fold compared with 3.5‐fold in the fed state. AUCτaccumulation in the fasted state was 3.1‐fold compared with 4.2‐fold in the fed state. There were no discontinuations due to adverse events or laboratory abnormalities. Treatment‐related mild‐to‐moderate visual disturbances were experienced by six out of 12 subjects.Conclusions The bioavailability of twice‐daily 200 mg voriconazole is reduced by approximately 22% as measured by AUCτafter multiple dosing when taken with food, compared with fasting.
The production of tissue inhibitors of metalloproteinases (TIMPs) in megakaryopoiesis: possible role of platelet‐ and megakaryocyte‐derived TIMPs in bone marrow fibrosis
Authors: Murate Takashi , Yamashita Kyoko , Isogai Chiho , Suzuki Hitoshi , Ichihara Masatoshi , Hatano Sonoko , Nakahara Yosuke , Kinoshita Tomohiro , Nagasaka Tetsuro , Yoshida Shonen , Komatsu Norio , Miura Yasusada , Hotta Tomomitsu , Fujimoto Noboru , Saito Hidehiko , Hayakawa Taro 
Published: November 2003

We quantified tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2 in serum and plasma in normal control subjects and patients with a low or high platelet count, using one‐step sandwich enzyme immunoassays. The serum levels of TIMP‐1 and TIMP‐2 were 101.1 ± 13.3 ng/ml, and 82.7 ± 26.3 ng/ml, respectively, in normal subjects. In patients with an elevated platelet count, such as in essential thrombocytosis, polycythaemia vera, and myelofibrosis, serum levels of TIMP‐1 and TIMP‐2 were 351.6 ± 200.9 ng/ml and 148.9 ± 84.0 ng/ml, respectively. Serum levels of TIMP‐1 and TIMP‐2 in patients with a low platelet count, such as in aplastic anaemia and idiopathic thrombocytopenic purpura, were 57.2 ± 25.8 ng/ml and 19.7 ± 7.68 ng/ml, respectively. The serum level of TIMP‐1 was significantly correlated with the platelet count in all subjects. The correlation between the serum level of TIMP‐2 and the platelet count was not as strong. The level of TIMP‐1 in platelet‐depleted plasma was not correlated with the platelet count.Immunohistochemical staining using monoclonal antibodies against TIMP‐1 and TIMP‐2 showed that megakaryocytes and platelets were positive for both TIMP‐1 and TIMP‐2, confirming that they are rich sources of TIMPs. TIMP‐1 and TIMP‐2 stimulated the proliferation of bone marrow fibroblasts, although their effect was less potent than that of TGF‐β and PDGF.Erythroleukaemia and megakaryoblastic cell lines showed the highest secretion of TIMP‐1 among the leukaemia cell lines examined. There was no lineage specificity for TIMP‐2 secretion. These results suggest that TIMPs released from megakaryocytes or from local platelet coagulation may be important in the development of bone marrow fibrosis.
MDR 1 expression is an independent prognostic factor for response and survival in de novo acute myeloid leukaemia
Authors: Van Den Heuvel‐Eibrink Marry M. , Van Der Holt Bronno , Te Boekhorst Peter A. W. , Pieters Rob , Schoester Martijn , Löwenberg Bob , Sonneveld Pieter 
Published: November 2003

The Multidrug Resistance gene (MDR 1) is frequently expressed in acute myeloid leukaemia (AML). MDR 1 is associated with resistance to chemotherapy in vitro and with a poor response rate in AML. We have investigated the prognostic value of MDR 1 expression in relation to other patient characteristics with respect to response and survival.One hundred and thirty patients aged 0–88 years were treated for de novo AML with standard induction and consolidation chemotherapy. MDR 1 expression was determined by immunocytochemistry. Univariate and multivariate analyses were conducted to identify prognostic factors for reaching complete remission (CR) and for overall survival from diagnosis, in order to compare MDR 1 with known prognostic factors. Univariate analysis showed that higher MDR 1 expression was an adverse prognostic factor for CR (P < 0.001), as was higher age (P < 0.001) and unfavourable karyotype (P < 0.01). These factors were also negative prognostic factors for overall survival (P < 0.001, P < 0.05 and P < 0.005, respectively). In the multivariate analysis MDR 1 (P < 0.001), higher age (P < 0.001) and karyotype (P < 0.01) were independent adverse prognostic factors for CR as well as for overall survival (P < 0.001, P < 0.005, P < 0.001, respectively). Our data indicate that MDR 1 expression is a disease‐related unfavourable prognostic factor which has a significant impact on complete remission and overall survival in AML. Analysis of MDR 1 may be used to determine prognosis in individual patients.
Prevalence of hepatitis G virus RNA in a monocentric population of French haemophiliacs
Authors: Gerolami V. , Halfon P. , Chambost H. , Sicardi F. , Thuret I. , Planells R. , Halimi G. , Fossat C. , Michel G. , Cartouzou G. 
Published: November 2003

Hepatitis G virus (HGV) and hepatitis GB virus (GBV‐C) have been reported as possible causes of non‐A–E transfusional hepatitis. To assess the prevalence of hepatitis G virus infection in haemophiliacs we retrospectively investigated the presence of viral RNA in 92 patients with and without HCV infection. HGV/GBV‐C RNA was reverse transcribed and amplified with primers from the 5′ non‐coding region of the genome. RNA was detected in 16/92 patients (17.4%). Restriction enzyme analysis revealed that the 16 patients belonged to the HGV‐like genotype. Serology with E2‐specific antibodies demonstrated that HGV viraemia underestimates previous infection by HGV. 33 patients were positive for HGV; all but two have cleared HGV RNA. 47/92 patients had a marker of prior infection by HGV.No difference between HGV RNA positive and negative patients was observed concerning age, diagnosis, HIV and HCV status. Previous HBV infection correlated with the frequency of HGV infection. There was no difference in alanine aminotransferase levels between HGV positive and negative patients. All 18 patients exposed to only virally inactivated plasma‐derived concentrates were negative for both HGV RNA and anti E2 antibodies.Prior exposure to untreated concentrates correlated with HGV viraemia (P=0.03), HGV seropositivity (P=0.0002), and markers of HGV infection (P<0.0001).In haemophiliacs with a past exposure to non‐inactivated concentrates, persistence of HCV RNA (53/74 patients) was more frequent than HGV RNA persistence (16/74 patients) although HGV viraemia is more frequent than HCV viraemia in blood donors. This may be related to a greater ability of individuals to clear HGV infection and suggests that hepatitis G virus infection in multi‐transfused patients has a better outcome than infection with other blood‐borne viruses.
Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X
Authors: Chessells J. M. , Swansbury G. J. , Reeves B. , Bailey C. C. , Richards S. M. ,   on behalf of the Medical Research Council Working Party in Childhood Leukaemia
Published: November 2003

We have analysed the prognostic influence of cytogenetic findings at diagnosis in a group of 502 children with acute lymphoblastic leukaemia (ALL), treated on MRC UKALL X, in whom clonal cytogenetic abnormalities were detected at diagnosis. Despite the overall improvement in outcome in children treated on this protocol compared with previous trials, some cytogenetically‐defined groups were still associated with a poor outcome and ploidy retained some prognostic significance. Patients with high hyperdiploid ALL (39% of those with clonal abnormalities) had a favourable outcome with event free survival of 71% at 5 years. Those with near haploidy (1%), hypodiploidy (9%) and low hyperdiploidy (16.5%) had a relatively poor prognosis with event‐free survival at 5 years of 17%, 42% and 49% respectively. Only two of 12 children with Ph‐positive leukaemia are alive in remission and abnormalities of chromosome 11q23 were also associated with a high risk of treatment failure. In contrast, the t(1;19) was associated with improved event‐free survival of 87.5% at 5 years. A number of other non‐random abnormalities were identified with no clear prognostic significance.We conclude that identification of certain genetic changes remains important in the management of acute lymphoblastic leukaemia, although whether molecular diagnosis of clinically relevant abnormalities can now supplant cytogenetics in the clinical trials context remains to be determined.