bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective dosing of warfarin based on cytochrome P-450 2C9 genotype
Authors: Voora Deepak , Eby Charles , Linder Mark W. , Milligan Paul E. , Bukaveckas Bonny L. , McLeod Howard L. , Maloney William , Clohisy John , Burnett Steven R. , Grosso Leonard , Gatchel Susan K. , Gage Brian F.
Published: March 2005

Cytochrome P-450 2C9 (CYP2C9) polymorphisms (CYP2C9*2 and CYP2C9*3) reduce the clearance of warfarin, increase the risk of bleeding, and prolong the time to stable dosing. Whether prospective use of a retrospectively developed algorithm that incorporates CYP2C9 genotype and nongenetic factors can ameliorate the propensity to bleeding and delay in achieving a stable warfarin dose is unknown. We initiated warfarin therapy in 48 orthopedic patients tailored to the following variables: CYP2C9 genotype, age, weight, height, gender, race, and use of simvastatin or amiodarone. By using pharmacogenetics-based dosing, patients with a CYP2C9 variant achieved a stable, therapeutic warfarin dose without excessive delay. However compared to those without a CYP2C9 variant, patients with a variant continued to be at increased risk (hazard ratio 3.6, 95% confidence interval 1.4–9.5, p = 0.01) for an adverse outcome (principally INR > 4), despite pharmacogenetics-based dosing. There was a linear relationship (R2 = 0.42, p < 0.001) between the pharmacogenetics-predicted warfarin doses and the warfarin maintenance doses, prospectively validating the dosing algorithm. Prospective, perioperative pharmacogenetics-based dosing of warfarin is feasible; however, further evaluation in a randomized, controlled study is recommended.
Membrane type 1-matrix metalloproteinase promotes human prostate cancer invasion and metastasis
Authors: Chiarelli Christian , Kozarekar Pallavi , Adler Howard L. , Cao Jian
Published: March 2005

Development of metastases requires cancer cells to breach underlying basement membrane, migrate through interstitial stroma and gain access to blood or lymphatic vessels. Membrane type 1-matrix metalloproteinase (MT1-MMP) has been linked with these processes. Expression of MT1-MMP in human prostate cancer correlates with the stage of this disseminated disease. The mechanism underlying this observation, however, still remains to be understood. To study the role of MT1-MMP in prostate cancer dissemination, endogenous and recombinant MT1-MMP expressed in human prostate cancer cell lines (DU-145 and LNCaP) were examined. Using FITC-labeled Ma-trigel, a soluble basement membrane extract coated coverslips, LNCaP cells stably expressing a chimera of MT1-MMP and Green Fluorescent Protein (MT1-GFP) degraded Matrigel and readily migrated over degraded substrates. The degradation of Matrigel by LNCaP cells expressing MT1-GFP was sensitive to MMP inhibitors, CT-1746 and TIMP-2, but not TIMP-1. Cell migration was dramatically enhanced by expression of MT1-MMP. By employing surgical orthotopic implantation of LNCaP cells stably expressing MT1-GFP into the prostate gland of immunodeficient mice, we demonstrated that MT1-MMP promotes lymph node and lung metastasis of prostate cancer cells. Together, these results emphasize the pivotal role of MT1-MMP in prostate cancer dissemination and confirm that MT1-MMP is a suitable target to prevent cancer metastasis.
Bleeding and re-thrombosis in primary antiphospholipid syndrome on oral anticoagulation
Authors: Ciampa Antonio , Margaglione Maurizio , Scenna Giovanna , Iannaccone Luigi , Brancaccio Vincenzo , Ames Paul R. J.
Published: March 2005

The aimof this studay was to compare bleeding and re-thrombosis in primary antiphospholipid syndrome (PAPS), mitral valve replacement (MVR) and inherited thrombophilia (IT) at different oral anticoagulation intensities. It entailed a prospective 8-year follow-up on 67 patients with PAPS, 89 with IT and 24 with MVR. Anticardiolipin (aCL) antibodies detected by Elisa and lupus anticoagulant by clotting assays. At INR 2–3 minor bleeding rate was higher in MVR (33.3) than PAPS (10.9) and IT (4.2)(p<0.0001). At INR 3–4 minor bleeding rate was higher in PAPS (142) than IT (33.3) and MVR (5.8)(p<0.0001). At either INR major bleeding rate were not significantly different across the three groups, but in PAPS major and minor bleeding rates were superior at INR 3–4 than INR 2–3 (p=0.02 and p<0.0001). Re-thrombosis rate was higher in PAPS than IT at INR 2–3 (4.0 vs 0.35) (p=0.01) and at INR 3–4 (10.5 vs. nil). The hazard ratio for re-thrombosis between PAPS and IT was 13 (95% IC 1.6–102.2, p=0.015). By regression analysis, baseline IgG aCL titre (>80 GPL) (p=0.001) and male sex (p=0.03) independently predicted re-thrombosis. In conclusion, in PAPS, high intensity oral anticoagulation was not superior to conventional intensity in preventing re-thrombosis but was offset by greater bleeding rates. Male sex and elevated baseline IgG aCL predicted re-thrombosis in PAPS that is 13-fold more re-thrombogenic than IT.
Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention
Authors: Patti Giuseppe , Colonna Giuseppe , Pasceri Vincenzo , Pepe Leonardo Lassandro , Montinaro Antonio , Di Sciascio Germano
Published: March 2005

Background—

Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. Although observational data have suggested that pretreatment with a high loading dose of clopidogrel may be more effective than a conventional dose, this hypothesis has never been tested in a randomized trial.

Methods and Results—

A total of 255 patients scheduled to undergo percutaneous coronary intervention were randomized to a 600-mg (n=126) or 300-mg (n=129) loading regimen of clopidogrel given 4 to 8 hours before the procedure. Creatine kinase MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI), or target vessel revascularization. The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group (
P
=0.041) and was due entirely to periprocedural MI. Peak values of all markers were significantly lower in patients treated with the 600-mg regimen (
P
≤0.038). Safety end points were similar in the 2 arms. At multivariable analysis, the high loading regimen was associated with a 50% risk reduction of MI (OR 0.48, 95% CI 0.15 to 0.97,
P
=0.044). An incremental benefit was observed in patients randomized to the 600-mg dose who were receiving statins, with an 80% risk reduction.

Conclusions—

Pretreatment with a 600-mg loading dose of clopidogrel 4 to 8 hours before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduced periprocedural MI in patients undergoing percutaneous coronary intervention. These results may influence practice patterns with regard to antiplatelet therapy before percutaneous revascularization.
Stability of a Two-Layer Quasigeostrophic Vortex over Axisymmetric Localized Topography
Authors: Benilov E. S.
Published: March 2005

The stability of a quasigeostrophic vortex over a radially symmetric topographic feature (elevation or depression) in a two-layer ocean on the f plane is examined. This article’s concern is with compensated vortices, that is, those in which the lower layer is at rest (the disturbances, however, are present in both layers). Through numerical solution of the linear normal-mode problem, it is demonstrated that a bottom elevation is a stabilizing influence for a cyclone and a destabilizing influence for an anticyclone, whereas a bottom depression acts in the opposite way. These conclusions are interpreted using an asymptotic theory developed for the case of a thin upper layer. It is demonstrated that an elevation moves the critical level of an unstable mode toward the periphery of the cyclone, which leads to its stabilization. Estimates based on realistic oceanic parameters show that stabilization occurs for relatively small topography (5%–15% of the lower layer’s depth).
The Usefulness of In-Flight Measurements of Space Count to Improve Calibration of the AVHRR Solar Reflectance Bands
Authors: Ignatov Alexander , Cao Changyong , Sullivan Jerry , Levin Robert , Wu Xiangqian , Galvin Roy
Published: March 2005

The solar reflectance bands (SRB; centered at λ1 = 0.63, λ2 = 0.83, and λ3A = 1.61 μm) of the Advanced Very High Resolution Radiometers (AVHRR) flown on board NOAA satellites are often referred to as noncalibrated in-flight. In contrast, the Earth emission bands (EEBs; centered at λ3B = 3.7, λ4 = 11, and λ5 = 12 μm) are calibrated using two reference points: deep space and the internal calibration targets. In the SRBs, measurements of space count (SC) are also available; however, historically they are not used to specify the calibration offset [zero count (ZC)], which does not even appear in the calibration equation. A regression calibration formulation is used instead, equivalent to setting the ZC to a constant, whose value is specified from prelaunch measurements.

The analyses below, supported by a review of the instrument design and a wealth of historical SC information, show that the SC varies in-flight and differs from its prelaunch value. It is therefore suggested that 1) the AVHRR calibration equation in the SRBs be reformulated to explicitly use the ZC, consistently with the EEBs; and 2) the value of ZC be specified from the onboard measurements of SC. The ZC formulation of the calibration equation is physically solid, and it minimizes human-induced calibration errors resulting from the use of a regression formulation with an unconstrained intercept. Specifying the calibration offset improves radiances, most notably at the low end of radiometric scale, and subsequently provides for more accurate vicarious determinations of the calibration slope (gain). These calibration improvements are important for the products derived from the AVHRR low radiances, such as aerosol over ocean, and are particularly critical when generating their long-term climate data records (CDRs).
Computation of Domain-Averaged Irradiance Using Satellite-Derived Cloud Properties
Authors: Kato Seiji , Rose Fred G. , Charlock Thomas P.
Published: March 2005

The respective errors caused by the gamma-weighted two-stream approximation and the effective thickness approximation for computing the domain-averaged broadband shortwave irradiance are evaluated using cloud optical thicknesses derived from 1 h of radiance measurements by the Moderate Resolution Imaging Spectrometer (MODIS) over footprints of Clouds and the Earth’s Radiant Energy System (CERES) instruments. Domains are CERES footprints of which dimension varies approximately from 20 to 70 km, depending on the viewing zenith angle of the instruments. The average error in the top-of-atmosphere irradiance at a 30° solar zenith angle caused by the gamma-weighted two-stream approximation is 6.1 W m−2 (0.005 albedo bias) with a one-layer overcast cloud where a positive value indicates an overestimate by the approximation compared with the irradiance computed using the independent column approximation. Approximately one-half of the error is due to deviations of optical thickness distributions from a gamma distribution and the other half of the error is due to other approximations in the model. The error increases to 14.7 W m−2 (0.012 albedo bias) when the computational layer dividing the cloud layer is increased to four. The increase is because of difficulties in treating the correlation of cloud properties in the vertical direction. Because the optical thickness under partly cloudy conditions, which contribute two-thirds of cloudy footprints, is smaller, the error is smaller than under overcast conditions; the average error for partly cloudy condition is −2.4 W m−2 (−0.002 albedo bias) at a 30° solar zenith angle. The corresponding average error caused by the effective thickness approximation is 0.5 W m−2 for overcast conditions and −21.5 W m−2 (−0.018 albedo bias) for partly cloudy conditions. Although the error caused by the effective thickness approximation depends strongly on the optical thickness, its average error under overcast conditions is smaller than the error caused by the gamma-weighted two-stream approximation because the errors at small and large optical thicknesses cancel each other. Based on these error analyses, the daily average error caused by the gamma-weighted two-stream and effective thickness approximations is less than 2 W m−2.
Flexible Spending Accounts: Reducing the Regulatory Burden
Authors: O’Connell Jim
Published: March 2005

With flexible spending accounts, better known as FSAs, families can save up to 30% of the cost of their out-of-pocket medical expenses. With the exception of the new and untested health savings accounts enacted as part of the Medicare prescription drug law, FSAs are the only way workers can leverage the U.S. tax code to support their out-of-pocket expenses. However, even after 20 years, fewer than 20% of the estimated 25 million U.S. workers eligible for FSAs elect to participate. FSAs remain unappreciated and overlooked. This article discusses the FSA “use it or lose it” rule, which causes most employees to view FSAs as a gamble. This forfeiture rule prevents FSAs from winning more widespread employee interest because this regulatory obstacle requires employees to forfeit any FSA funds that remain in their account at year-end. Once this rule is modified, FSAs will become the center of employer-based U.S. health care policy.
Nursing Home Profit Status and Quality of Care: Is There Any Evidence of an Association?
Authors: Hillmer Michael P. , Wodchis Walter P. , Gill Sudeep S. , Anderson Geoffrey M. , Rochon Paula A.
Published: March 2005

This article critically reviews the association between the profit status of North American nursing homes and the quality of care. Studies were identified by searching MEDLINE (January 1990-October 2002), reference lists, letters, commentaries, and editorials. The quality indicator(s) used to measure quality of care, and its relationship to profit status, was extracted from each publication. The study design and risk-adjustment methodologies used were also extracted. The interrater reliability for the extraction of these three items was determined to be 1.0, 0.6, and 0.8, respectively. Aqualitative systematic review was performed using Donabedian’s framework of structure, process, and outcome for analyzing medical quality of care. Empirical research in the past 12 years has found that systematic differences exist between for-profit and not-for-profit nursing homes. Forprofit nursing homes appear to provide lower quality of care in many important areas of process and outcome.
Does Having Two Earners in the Household Matter for Understanding How Well Employer-Based Health Insurance Works?
Authors: Abraham Jean M. , Royalty Anne Beeson
Published: March 2005

Using the 1996 Medical Expenditure Panel Survey, the authors investigate differences between households with two earners and those with a single earner in households’ access to employer-based health insurance and the generosity of insurance options. They examine whether a household has an offer of coverage, whether a household holds coverage, and whether all household members are covered. They also explore whether two-earner households have more generous options as measured by the number and types of plans available, as well as contribution requirements. The authors find that having a second earner in the household dramatically improves both access to employer health insurance and the generosity of health plan choices, particularly for workers generally acknowledged to have little access, such as part-time workers and workers in small establishments.
An Economic Evaluation of Inpatient Residential Treatment Programs in the Department of Veterans Affairs
Authors: Wagner Todd H. , Chen Shuo
Published: March 2005

The Veterans Health Administration (VA) established psychosocial residential rehabilitation treatment programs (RTPs) to treat eligible veterans who have psychiatric and substance use disorders in a less intensive and more self-reliant inpatient setting. Fortytwo (25 percent) VA medical centers adopted RTPs in 1995. Panel regression models using data from 1993 through 1999 indicated that RTPs were associated with 8.6 and 24.4 percent decreases in the average cost per day for inpatient psychiatry and substance use care, respectively. During this time, VA transitioned much of the inpatient mental health care to ambulatory services. Yet medical centers with RTPs had smaller decreases in the number of inpatient patient days than those without RTPs. Because medical centers with RTPs provided more services, this offset the per diem savings, resulting in no significant differences in total costs between medical centers with and without RPTs.
The Impact of Private and Public Health Insurance on Medication Use for Adults with Chronic Diseases
Authors: Rice Thomas , Lavarreda Shana Alex , Ponce Ninez A. , Brown E. Richard
Published: March 2005

This article examines the impact of public and private health insurance on the use of medications for California adults with any of four chronic diseases: heart disease, high blood pressure, diabetes, and asthma. The data set used is the 2001 California Health Interview Survey. Multivariate analyses were conducted on individuals who had been diagnosed with each of these diseases. Controlling for various demographic, health status, and employment characteristics, the authors find that the uninsured are far less likely to be taking medications for each of the conditions than those with private insurance. Interestingly, those with Medicaid coverage are even more likely than those with private insurance to be taking such medications. The results of this study underscore the importance of health insurance for all persons with chronic conditions and the benefits of Medicaid in particular for low-income adults with chronic conditions.
Arginase attenuates inhibitory nonadrenergic noncholinergic nerve-induced nitric oxide generation and airway smooth muscle relaxation
Authors: Maarsingh Harm , Tio Marieke A , Zaagsma Johan , Meurs Herman
Published: March 2005

Background

Recent evidence suggests that endogenous arginase activity potentiates airway responsiveness to methacholine by attenuation of agonist-induced nitric oxide (NO) production, presumably by competition with epithelial constitutive NO synthase for the common substrate, L-arginine. Using guinea pig tracheal open-ring preparations, we now investigated the involvement of arginase in the modulation of neuronal nitric oxide synthase (nNOS)-mediated relaxation induced by inhibitory nonadrenergic noncholinergic (iNANC) nerve stimulation.

Methods

Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz)-induced relaxation was measured in tracheal preparations precontracted to 30% with histamine, in the presence of 1 μM atropine and 3 μM indomethacin. The contribution of NO to the EFS-induced relaxation was assessed by the nonselective NOS inhibitor L-NNA (0.1 mM), while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor nor-NOHA (10 μM). Furthermore, the role of substrate availability to nNOS in EFS-induced relaxation was measured in the presence of various concentrations of exogenous L-arginine.

Results

EFS induced a frequency-dependent relaxation, ranging from 6.6 ± 0.8% at 0.5 Hz to 74.6 ± 1.2% at 16 Hz, which was inhibited with the NOS inhibitor L-NNA by 78.0 ± 10.5% at 0.5 Hz to 26.7 ± 7.7% at 8 Hz (P < 0.01 all). In contrast, the arginase inhibitor nor-NOHA increased EFS-induced relaxation by 3.3 ± 1.2-fold at 0.5 Hz to 1.2 ± 0.1-fold at 4 Hz (P < 0.05 all), which was reversed by L-NNA to the level of control airways in the presence of L-NNA (P < 0.01 all). Similar to nor-NOHA, exogenous L-arginine increased EFS-induced airway relaxation (P < 0.05 all).

Conclusion

The results indicate that endogenous arginase activity attenuates iNANC nerve-mediated airway relaxation by inhibition of NO generation, presumably by limiting L-arginine availability to nNOS.
Inhibition of breathing after surfactant depletion is achieved at a higher arterial PCO2 during ventilation with liquid than with gas
Authors: Rieger-Fackeldey Esther , Sindelar Richard , Jonzon Anders , Schulze Andreas , Sedin Gunnar
Published: March 2005

Background

Inhibition of phrenic nerve activity (PNA) can be achieved when alveolar ventilation is adequate and when stretching of lung tissue stimulates mechanoreceptors to inhibit inspiratory activity. During mechanical ventilation under different lung conditions, inhibition of PNA can provide a physiological setting at which ventilatory parameters can be compared and related to arterial blood gases and pH.

Objective

To study lung mechanics and gas exchange at inhibition of PNA during controlled gas ventilation (GV) and during partial liquid ventilation (PLV) before and after lung lavage.

Methods

Nine anaesthetised, mechanically ventilated young cats (age 3.8 ± 0.5 months, weight 2.3 ± 0.1 kg) (mean ± SD) were studied with stepwise increases in peak inspiratory pressure (PIP) until total inhibition of PNA was attained before lavage (with GV) and after lavage (GV and PLV). Tidal volume (Vt), PIP, oesophageal pressure and arterial blood gases were measured at inhibition of PNA. One way repeated measures analysis of variance and Student Newman Keuls-tests were used for statistical analysis.

Results

During GV, inhibition of PNA occurred at lower PIP, transpulmonary pressure (Ptp) and Vt before than after lung lavage. After lavage, inhibition of inspiratory activity was achieved at the same PIP, Ptp and Vt during GV and PLV, but occurred at a higher PaCO2 during PLV. After lavage compliance at inhibition was almost the same during GV and PLV and resistance was lower during GV than during PLV.

Conclusion

Inhibition of inspiratory activity occurs at a higher PaCO2 during PLV than during GV in cats with surfactant-depleted lungs. This could indicate that PLV induces better recruitment of mechanoreceptors than GV.
The effects of quercetin on SW480 human colon carcinoma cells: a proteomic study
Authors: Mouat Michael F , Kolli Kumar , Orlando Ronald , Hargrove James L , Grider Arthur
Published: March 2005

Background

High fruit and vegetable intake is known to reduce the risk of colon cancer. To improve understanding of this phenomenon the action of different phytochemicals on colon cells has been examined. One such compound is quercetin that belongs to the group known as flavonoids. The purpose of this study was to determine the influence of quercetin on the proteome of the SW480 human colon adenocarcinoma cell line, specifically to identify proteins that could be the molecular targets of quercetin in its amelioration of the progression of colon cancer. To this end, two-dimensional gel electrophoresis and mass spectrometry were used to identify proteins that underwent a change in expression following treatment of the cells with 20 μM quercetin. This could elucidate how quercetin may reduce the progression of colon cancer.

Results

Quercetin treatment of the SW480 human colon cancer cells was found to result in the decreased expression of three proteins and the increased expression of one protein. The identified proteins with decreased expression were type II cytoskeletal 8 keratin and NADH dehydrogenase Fe-S protein 3. The other protein with decreased expression was not identified. The protein with increased expression belonged to the annexin family.

Conclusion

Several proteins were determined to have altered expression following treatment with quercetin. Such changes in the levels of these particular proteins could underlie the chemo-protective action of quercetin towards colon cancer.
Human macrophages limit oxidation products in low density lipoprotein
Authors: Hultén Lillemor Mattsson , Ullström Christina , Krettek Alexandra , van Reyk David , Marklund Stefan L , Dahlgren Claes , Wiklund Olov
Published: March 2005

This study tested the hypothesis that human macrophages have the ability to modify oxidation products in LDL and oxidized LDL (oxLDL) via a cellular antioxidant defence system. While many studies have focused on macrophage LDL oxidation in atherosclerosis development, less attention has been given to the cellular antioxidant capacity of these cells.

Compared to cell-free controls (6.2 ± 0.7 nmol/mg LDL), macrophages reduced TBARS to 4.42 ± 0.4 nmol/mg LDL after 24 h incubation with LDL (P = 0.022). After 2 h incubation with oxLDL, TBARS were 3.69 ± 0.5 nmol/mg LDL in cell-free media, and 2.48 ± 0.9 nmol/mg LDL in the presence of macrophages (P = 0.034). A reduction of lipid peroxides in LDL (33.7 ± 6.6 nmol/mg LDL) was found in the presence of cells after 24 h compared to cell-free incubation (105.0 ± 14.1 nmol/mg LDL) (P = 0.005). The levels of lipid peroxides in oxLDL were 137.9 ± 59.9 nmol/mg LDL and in cell-free media 242 ± 60.0 nmol/mg LDL (P = 0.012). Similar results were obtained for hydrogen peroxide. Reactive oxygen species were detected in LDL, acetylated LDL, and oxLDL by isoluminol-enhanced chemiluminescence (CL). Interestingly, oxLDL alone gives a high CL signal. Macrophages reduced the CL response in oxLDL by 45% (P = 0.0016). The increased levels of glutathione in oxLDL-treated macrophages were accompanied by enhanced catalase and glutathione peroxidase activities.

Our results suggest that macrophages respond to oxidative stress by endogenous antioxidant activity, which is sufficient to decrease reactive oxygen species both in LDL and oxLDL. This may suggest that the antioxidant activity is insufficient during atherosclerosis development. Thus, macrophages may play a dual role in atherogenesis, i.e. both by promoting and limiting LDL-oxidation.
Witch-hunt
Authors: Drucker Ernest
Published: March 2005

Beginning two years ago, the US Dept of Health and Human Services began "special reviews" of all current research grants that involved harm reduction, sex and drugs, and continues its ban on funding of needle exchange. With Bush's second term, the campaign was extended to all US funded international programs that dealt with these issues and populations. And, most recently, the US has again undertaken to dominate the discourse within international organizations charged with drug control and AIDS policies – especially those of the UN. But the international harm reduction and human rights community is fighting back in several important ways, including "An Open Letter to the delegates of the Forty-eighth session of the Commission on Narcotic Drugs (CND) of the UN" prepared by a group of 334 well respected public health experts and human rights advocates, protesting U.S. pressure on the U.N. to withdraw its support from harm reduction. This editorial includes the letter and signatures as well as French, Spanish, and Russian versions of the letter as additional files.
Are decisions using cost-utility analyses robust to choice of SF-36/SF-12 preference-based algorithm?
Authors: Pickard A Simon , Wang Zhixiao , Walton Surrey M , Lee Todd A
Published: March 2005

Background

Cost utility analysis (CUA) using SF-36/SF-12 data has been facilitated by the development of several preference-based algorithms. The purpose of this study was to illustrate how decision-making could be affected by the choice of preference-based algorithms for the SF-36 and SF-12, and provide some guidance on selecting an appropriate algorithm.

Methods

Two sets of data were used: (1) a clinical trial of adult asthma patients; and (2) a longitudinal study of post-stroke patients. Incremental costs were assumed to be $2000 per year over standard treatment, and QALY gains realized over a 1-year period. Ten published algorithms were identified, denoted by first author: Brazier (SF-36), Brazier (SF-12), Shmueli, Fryback, Lundberg, Nichol, Franks (3 algorithms), and Lawrence. Incremental cost-utility ratios (ICURs) for each algorithm, stated in dollars per quality-adjusted life year ($/QALY), were ranked and compared between datasets.

Results

In the asthma patients, estimated ICURs ranged from Lawrence's SF-12 algorithm at $30,769/QALY (95% CI: 26,316 to 36,697) to Brazier's SF-36 algorithm at $63,492/QALY (95% CI: 48,780 to 83,333). ICURs for the stroke cohort varied slightly more dramatically. The MEPS-based algorithm by Franks et al. provided the lowest ICUR at $27,972/QALY (95% CI: 20,942 to 41,667). The Fryback and Shmueli algorithms provided ICURs that were greater than $50,000/QALY and did not have confidence intervals that overlapped with most of the other algorithms. The ICUR-based ranking of algorithms was strongly correlated between the asthma and stroke datasets (r = 0.60).

Conclusion

SF-36/SF-12 preference-based algorithms produced a wide range of ICURs that could potentially lead to different reimbursement decisions. Brazier's SF-36 and SF-12 algorithms have a strong methodological and theoretical basis and tended to generate relatively higher ICUR estimates, considerations that support a preference for these algorithms over the alternatives. The "second-generation" algorithms developed from scores mapped from other indirect preference-based measures tended to generate lower ICURs that would promote greater adoption of new technology. There remains a need for an SF-36/SF-12 preference-based algorithm based on the US general population that has strong theoretical and methodological foundations.
HLA class I and II genotype of the NCI-60 cell lines
Authors: Adams Sharon , Robbins Fu-Meei , Chen Deborah , Wagage Devika , Holbeck Susan L , Morse Herbert C , Stroncek David , Marincola Francesco M
Published: March 2005

Sixty cancer cell lines have been extensively characterized and used by the National Cancer Institute's Developmental Therapeutics Program (NCI-60) since the early 90's as screening tools for anti-cancer drug development. An extensive database has been accumulated that could be used to select individual cells lines for specific experimental designs based on their global genetic and biological profile. However, information on the human leukocyte antigen (HLA) genotype of these cell lines is scant and mostly antiquated since it was derived from serological typing. We, therefore, re-typed the NCI-60 panel of cell lines by high-resolution sequence-based typing. This information may be used to: 1) identify and verify the identity of the same cell lines at various institutions; 2) check for possible contaminant cell lines in culture; 3) adopt individual cell lines for experiments in which knowledge of HLA molecule expression is relevant. Since genome-based typing does not guarantee actual surface protein expression, further characterization of relevant cell lines should be entertained to verify surface expression in experiments requiring correct antigen presentation.
Validation and test-retest reliability of the Royal Free Interview for Spiritual and Religious Beliefs when adapted to a Greek population
Authors: Sapountzi-Krepia Despina , Raftopoulos Vasilios , Sgantzos Marcos , Kotrotsiou Evangelia , Roupa-Darivaki Zoe , Sotiropoulou Kalliope , Ntourou Ioanna , Dimitriadou Alexandra
Published: March 2005

Background

The self-report version of the Royal Free Interview for Religious and Spiritual Beliefs has been confirmed as a valid and reliable scale, assessing the manner and nature in which spiritual beliefs are expressed. The aim of the present study was to evaluate the test-retest reliability and psychometric properties of the Greek version of the Royal Free Interview for Religious and Spiritual Beliefs.

Methods

A total of 209 persons (77 men and 132 women) with a mean age of 28.33 ± 9.44 years participated in the study (test group). We subsequently approached 139 participants of the test group with a mean age of 28.93 ± 9.60 years, who were asked to complete the Royal Free Questionnaire a second time two weeks later (retest group).

Results

The vast majority of participants (58.9%) reported both a religious and a spiritual belief, compared to 52 (25.1%) who told of a religious belief only. The internal consistency of the spiritual scale for the test group proved to be good, as standardized inter-item reliability / Cronbach's alpha was 0.83. Item-total correlations ranged from 0.51 to 0.73. They indicated very good levels of differentiation, thus showing that the questions were appropriate. Internal consistency of the spiritual scale for the retest group proved as good as for the test group. Standardized inter-item reliability / Cronbach's alpha was 0.84. Item-total correlations ranged from 0.52 to 0.75. The Pearson correlation coefficient for the total test-retest score of the spiritual scale was 0.754 (p < 0.001).

Conclusion

The Greek version of the Royal Free Interview for Religious and Spiritual Beliefs is reliable and thus suitable for use in Greece.
Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1
Authors: Otero Miguel , Lago Rocío , Lago Francisca , Reino Juan Jesús Gomez , Gualillo Oreste
Published: March 2005

The objective of the present study was to investigate the effect of leptin, alone or in combination with IL-1, on nitric oxide synthase (NOS) type II activity in vitro in human primary chondrocytes, in the mouse chondrogenic ATDC5 cell line, and in mature and hypertrophic ATDC5 differentiated chondrocytes. For completeness, we also investigated the signalling pathway of the putative synergism between leptin and IL-1. For this purpose, nitric oxide production was evaluated using the Griess colorimetric reaction in culture medium of cells stimulated over 48 hours with leptin (800 nmol/l) and IL-1 (0.025 ng/ml), alone or combined. Specific pharmacological inhibitors of NOS type II (aminoguanidine [1 mmol/l]), janus kinase (JAK)2 (tyrphostin AG490 and Tkip), phosphatidylinositol 3-kinase (PI3K; wortmannin [1, 2.5, 5 and 10 μmol/l] and LY294002 [1, 2.5, 5 and 10 μmol/l]), mitogen-activated protein kinase kinase (MEK)1 (PD098059 [1, 5, 10, 20 and 30 μmol/l]) and p38 kinase (SB203580 [1, 5, 10, 20 and 30 μmol/l]) were added 1 hour before stimulation. Nitric oxide synthase type II mRNA expression in ATDC5 chondrocytes was investigated by real-time PCR and NOS II protein expression was analyzed by western blot. Our results indicate that stimulation of chondrocytes with IL-1 results in dose-dependent nitric oxide production. In contrast, leptin alone was unable to induce nitric oxide production or expression of NOS type II mRNA or its protein. However, co-stimulation with leptin and IL-1 resulted in a net increase in nitric oxide concentration over IL-1 challenge that was eliminated by pretreatment with the NOS II specific inhibitor aminoguanidine. Pretreatment with tyrphostin AG490 and Tkip (a SOCS-1 mimetic peptide that inhibits JAK2) blocked nitric oxide production induced by leptin/IL-1. Finally, wortmannin, LY294002, PD098059 and SB203580 significantly decreased nitric oxide production. These findings were confirmed in mature and hypertrophic ATDC5 chondrocytes, and in human primary chondrocytes. This study indicates that leptin plays a proinflammatory role, in synergy with IL-1, by inducing NOS type II through a signalling pathway that involves JAK2, PI3K, MEK-1 and p38 kinase.
The AIB1 glutamine repeat polymorphism is not associated with risk of breast cancer before age 40 years in Australian women
Authors: Montgomery Karen G , Chang Jiun-Horng , Gertig Dorota M , Dite Gillian S , McCredie Margaret R , Giles Graham G , Southey Melissa C , Hopper John L , Campbell Ian G
Published: March 2005

Introduction

AIB1, located at 20q12, is a member of the steroid hormone coactivator family. It contains a glutamine repeat (CAG/CAA) polymorphism at its carboxyl-terminal region that may alter the transcriptional activation of the receptor and affect susceptibility to breast cancer through altered sensitivity to hormones.

Methods

We evaluated this repeat polymorphism in the context of early-onset disease by conducting a case-control study of 432 Australian women diagnosed with breast cancer before the age of 40 years and 393 population-based control individuals who were frequency matched for age. Genotyping was performed using a scanning laser fluorescence imager.

Results

There were no differences in genotype frequencies between cases and control individuals, or between cases categorized by family history or by BRCA1 and BRCA2 germline mutation status. There was no evidence that the presence of one or two alleles of 26 glutamine repeats or fewer was associated with breast cancer (odds ratio = 1.03, 95% confidence interval = 0.73–1.44), or that women with alleles greater than 29 repeats were at increased risk of breast cancer. Exclusion of women who carried a BRCA1 or BRCA2 mutation (24 cases) and non-Caucasian women (44 cases) did not alter the risk estimates or inferences. We present raw data, including that on mutation carriers, to allow pooling with other studies.

Conclusion

There was no evidence that risk of breast cancer depends on AIB1 CAG/CAA polymorphism status, even if affected women carry a mutation in BRCA1 or BRCA2.
The effect of activated protein C on experimental acute necrotizing pancreatitis
Authors: Yamenel Levent , Mas Mehmet Refik , Comert Bilgin , Isik Ahmet Turan , Aydin Sezai , Mas Nuket , Deveci Salih , Ozyurt Mustafa , Tasci Ilker , Unal Tahir
Published: March 2005

Introduction

Acute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30–40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis.

Materials and method

Forty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-α, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured.

Results

Acute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid.

Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 ± 0.47 versus 14.00 ± 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis factor--α, and IL-6 levels were also significantly decreased in comparison with positive controls (P < 0.001, P < 0.04 and P < 0.001, respectively).

Conclusion

APC improved the severity of pancreatic tissue histology, superinfection rates and serum markers of inflammation during the course of acute necrotizing pancreatitis.
From Enemy to Ally: Reconciliation Made Real in the Postwar German Maritime Sphere
Authors: Peifer Douglas
Published: March 2005

While the process of transforming West Germany from an occupied, demilitarized enemy to semi-sovereign, remilitarized ally has been scrutinized from an international and Bonn-centred perspective, a bottom-up approach as to how reconciliation was made real sheds new light on this transformation. Peifer uses the prism of the naval community to investigate the stages of reconciliation, contrasting the policies of the Royal Navy and the US Navy toward the German naval veteran community. He analyses the very different approaches of the two navies toward their former enemies, arguing that the Royal Navy was grudging and reactive while the US Navy assembled personnel, equipment and material for a new West German navy well before the diplomatic framework for German remilitarization had been clarified.
‘To Reduce Wars and Fighting to a Minimum’: Thomas Perronet Thompson on War and Peace during the 1840s and 1850s
Authors: Turner Michael J.
Published: March 2005

The purpose of this article is to describe and explain one important component of mid-nineteenth century British opinion on war and peace. The main avenues of inquiry are provided by the principles of utilitarian philosopher Jeremy Bentham and, in particular, the ways in which these were employed, modified and in some respects abandoned by one of Bentham’s followers, Thomas Perronet Thompson. The activities of Thompson during the 1840s and 1850s can be usefully explored alongside those of another Benthamite, John Bowring. Thompson and Bowring worked closely together on many issues. Their contribution to various organizations, debates and campaigns is analysed, and their outlook compared with that of other figures, notably Richard Cobden. Britain’s suspicion of France and wars against Russia and China provides useful case studies, illustrating the clash of ideas and the priorities that shaped policy and discussion. Thompson stayed closer to the Benthamite foundation than did Bowring, and the activities of both men offer valuable insights into the internal divisions and external pressures that plagued movements for peace and reform.
Mobilizing the Ottoman Nation during the Balkan Wars (1912-1913): Awakening from the Ottoman Dream
Authors: Ginio Eyal
Published: March 2005

The Balkan wars (1912-13) represent, together, the first total war of the Ottoman state. During this conflict, the Ottomans endeavoured to enlist all its citizens into the war effort. The aim of this study is twofold. First, to explore Ottoman propaganda and the set of symbols it employed to promote patriotism and cohesion among soldiers and civilians. Second, by using memoirs written by army officers, contemporary press articles, literature produced by and for non-Muslims, theatre plays, etc., it will dwell upon the responses from below to this propaganda, and the reactions of the different groups inside Ottoman society to the mobilization, to the war and to the military disaster.
C.R.W. Nevinson: Conflict, Contrast and Controversy in Paintings of War
Authors: Walsh Michael
Published: March 2005

C.R.W. Nevinson’s place in the history of art is assured as one of the key British artists of the First World War. This article analyses the nature of Nevinson’s success and the controversy which surrounded his painting, within a context of taste and acceptability in wartime Britain. It also examines public perception and official guidance in an often dichotomous socio-artistic context, where censorship and the struggle for freedom often sat very uncomfortably side by side. The initial conclusions demonstrate, perhaps surprisingly, that Nevinson’s brand of early war modernism was actually preferable to the lies and armchair patriotism of the ultra-conservative right, and preferable also to the impenetrable abstractions of the uncompromising and now discredited left. Equally surprising are the conclusions drawn from a study of his technically conservative late pictures which were deemed unacceptable, not through any breach in academic orthodoxy, but because of their potent subject matter which, it was felt, demanded censorship. The article also questions whether or not Nevinson knowingly manipulated the censorship issue to continue his quest for publicity after the armistice.
Vitamin E Mediates Cell Signaling and Regulation of Gene Expression
Authors: AZZI ANGELO , GYSIN RENÉ , KEMPNÁ PETRA , MUNTEANU ADELINA , NEGIS YESIM , VILLACORTA LUIS , VISARIUS THERESA , ZINGG JEAN‐MARC
Published: March 2005

Abstract: α‐Tocopherol modulates two major signal transduction pathways centered on protein kinase C and phosphatidylinositol 3‐kinase. Changes in the activity of these key kinases are associated with changes in cell proliferation, platelet aggregation, and NADPH‐oxidase activation. Several genes are also regulated by tocopherols partly because of the effects of tocopherol on these two kinases, but also independently of them. These genes can be divided in five groups: Group 1. Genes that are involved in the uptake and degradation of tocopherols: α‐tocopherol transfer protein, cytochrome P450 (CYP3A), γ‐glutamyl‐cysteine synthetase heavy subunit, and glutathione‐S‐transferase. Group 2. Genes that are implicated with lipid uptake and atherosclerosis: CD36, SR‐BI, and SR‐AI/II. Group 3. Genes that are involved in the modulation of extracellular proteins: tropomyosin, collagen‐α‐1, MMP‐1, MMP‐19, and connective tissue growth factor. Group 4. Genes that are connected to adhesion and inflammation: E‐selectin, ICAM‐1 integrins, glycoprotein IIb, IL‐2, IL‐4, IL‐1b, and transforming growth factor‐β (TGF‐β). Group 5. Genes implicated in cell signaling and cell cycle regulation: PPAR‐γ, cyclin D1, cyclin E, Bcl2‐L1, p27, CD95 (APO‐1/Fas ligand), and 5a‐steroid reductase type 1. The transcription of p27, Bcl2, α‐tocopherol transfer protein, cytochrome P450 (CYP3A), γ‐glutamyl‐cysteine sythetase heavy subunit, tropomyosin, IL‐2, and CTGF appears to be upregulated by one or more tocopherols. All the other listed genes are downregulated. Gene regulation by tocopherols has been associated with protein kinase C because of its deactivation by α‐tocopherol and its contribution in the regulation of a number of transcription factors (NF‐κB, AP1). A direct participation of the pregnane X receptor (PXR) / retinoid X receptor (RXR) has been also shown. The antioxidant‐responsive element (ARE) and the TGF‐β‐responsive element (TGF‐β‐RE) appear in some cases to be implicated as well.
Oxidative Stress and Antioxidant Treatment in Diabetes
Authors: SCOTT JOSHUA A. , KING GEORGE L.
Published: March 2005

Abstract: The many studies on oxidative stress, antioxidant treatment, and diabetic complications have shown that oxidative stress is increased and may accelerate the development of complications through the metabolism of excessive glucose and free fatty acids in diabetic and insulin‐resistant states. However, the contribution of oxidative stress to diabetic complications may be tissue‐specific, especially for microvascular disease that occurs only in diabetic patients but not in individuals with insulin resistance without diabetes, even though both groups suffer from oxidative stress. Although antioxidant treatments can show benefits in animal models of diabetes, negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating complications. Furthermore, it appears that oxidative stress is only one factor contributing to diabetic complications; thus, antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.