bluuebunny/crossref_metadata_2025 huggingface dataset:
The Classroom as a Place of Formation: Purposefully Creating a Transformative Environment for Today's Diverse Seminary Population
Authors: Winkelmes Mary‐Ann
Published: September 2004

Abstract.  This essay draws on insights from studies on learning to explore the role of formation in the classroom. Studies of intellectual development, learning styles, and the physiology of learning are reviewed. Methodologies and models for encouraging formative learning in seminary classrooms are explored. This essay was written to address one of the issues that have focused the attention of the participants in the Lexington Seminar on Theological Teaching for the Church's Ministries, a project sponsored by Lexington Theological Seminary and supported by the Lilly Endowment, Inc. It will be included in Practical Wisdom: On Theological Teaching and Learning, edited by Malcolm L. Warford, a collection of essays intended to (1) affirm the teaching ministry of theological educators, (2) raise up and discern the diverse ways in which issues of teaching and learning present themselves in institutional contexts, (3) evoke new perspectives on the challenges facing individual schools, and (4) encourage faculty to make conversations about teaching and learning a crucial part of faculty life. Peter Lang Publishing will release the book in fall 2004. Additional information about the work of the Lexington Seminar is available on the Lexington Seminar's Web site .
Thinking Developmentally: The Bible, the First‐Year College Student, and Diversity
Authors: Solvang Elna K.
Published: September 2004

Abstract.  The Bible is a non‐western text subject to a variety of interpretations and applications – constructive and destructive. The academic study of the Bible, therefore, requires critical thinking skills and the ability to engage with diversity. The reality is that most first‐year college students have not yet developed these skills. Rather than bemoan students’lack of development, the essay explores ways of teaching and applying critical thinking within the context of an introductory Religion course. The essay claims that first‐year college students can better learn the content of the discipline and function in a pluralistic world if the teaching of critical thinking skills is a part of the pedagogy.
Preachers and Prophets: Using Film to Teach American Religious History
Authors: Rowe David L.
Published: September 2004

Abstract. Can students learn religious history from movies? While using film as text is likely to attract students’ interest, will such a course be able to negotiate the complex intertwining of film with religion and history to provide students with more than mere entertainment? Will students respond to a challenge to move beyond a movie's surface visual experience to address the core lessons history posits: it's not always been this way, we are the product of what has come before us, I/we are being called to change? This article discusses one attempt to answer these questions and examines both the opportunities and difficulties of using movies to teach religious history.
Emerging Hispanic English: New dialect formation in the American South
Authors: Wolfram Walt , Carter Phillip , Moriello Beckie
Published: September 2004

Although stable Hispanic populations have existed in some regions of the United States for centuries, other regions, including the mid‐Atlantic South, are just experiencing the emergence of permanent Hispanic communities. This situation offers an ideal opportunity to examine the dynamics of new dialect formation in progress, and the extent to which speakers acquire local dialect traits as they learn English as a second language. We focus on the production of the /ai/ diphthong among adolescents in two emerging Hispanic communities, one in an urban and one in a rural context. Though both English and Spanish have the diphthong /ai/, the Southern regional variant of the benchmark local dialect norm is unglided, thus providing a local dialect alternative. The instrumental analysis of /ai/ shows that there is not pervasive accommodation to the local norm by Hispanic speakers learning English. There is, however, gradient, incremental adjustment of the /ai/, and individual speakers who adopt local cultural values may accommodate to the local dialect pattern.
Supply, Factor Shares and Inflation Persistence: Re‐examining Euro‐area New‐Keynesian Phillips Curves*
Authors: McAdam Peter , Willman Alpo
Published: September 2004

Using euro‐area data, we re‐examine the empirical success of New‐Keynesian Phillips curves (NKPCs). We re‐estimate with a suitably specified optimizing supply side (which attempts to treat non‐stationarity in factor income shares and mark‐ups) that allows us to derive estimates of technology parameters, marginal costs and ‘price gaps’. Our resulting estimates of the euro‐area NKPCs are robust, provide reasonable estimates for fixed‐price durations and discount rates and embody plausible dynamic properties. Our method for identifying the underlying determinants of NKPCs has general applicability to a wide set of countries as well as of use for sectoral studies.
Inferring Policy Objectives from Economic Outcomes*
Authors: Dennis Richard
Published: September 2004

Estimated policy rules are reduced‐form equations that are silent on many important policy questions. However, a structural understanding of monetary policy can be obtained by estimating a policymaker's objective function. The paper derives conditions under which the parameters in a policymaker's policy objective function can be identified and estimated. We apply these conditions to a New Keynesian sticky‐price model of the US economy. The results show that the implicit inflation target and the relative weight placed on interest rate smoothing both declined when Paul Volcker was appointed Federal Reserve chairman.
Protective effects of Munziq and Mushil of Abnormal Savda to mitochondrial oxidative damage
Authors: Yusup Abdiryim , Upur Halmurat , Umar Anwar , Moore Nicholas
Published: September 2004

Munziq and Mushil of Abnormal Savda are traditional Uighur herbal medicinal products, which could have antioxidant properties protecting mitochondria against oxidative damage. Mitochondria were isolated from rat livers. A FeSO4/VitC hydroxyl radical‐generating system was used to induce mitochondrial oxidative damage. Alterations in mitochondrial membrane structure were observed by electron microscopy, and mitochondrial superoxide dismutase (SOD) activity, malondialdehyde (MDA) level and Ca2+–Mg2+‐ATPase activity were measured. Muziq or Mushil were added, at concentrations ranging from 10−5 to 10−1 g/mL. Mitochondrial membrane structure was damaged after exposure to hydroxyl radical; mitochondrial SOD and Ca2+–Mg2+‐ATPase activities decreased (by 80 and 55%, respectively, both P < 0.01), and MDA level increased 4.6‐fold (P < 0.01). Munziq and Mushil protected mitochondrial membranes from structural damage. They inhibited the changes in mitochondrial functions in a dose‐dependent manner. At the highest concentrations, values were equal to initial normal values. Munziq and Mushil of Abnormal Savda can reduce the oxidative damage induced by hydroxyl radical and protect the mitochondrial membrane structure and its functions.
Statins but not fibrates are associated with a reduced risk of venous thromboembolism: a hospital‐based case–control study
Authors: Lacut Karine , Oger Emmanuel , Le Gal Grégoire , Couturaud Francis , Louis Stéphanie , Leroyer Christophe , Mottier Dominique
Published: September 2004

Previous studies of selected patients have suggested a reduction in the risk of venous thromboembolism with the use of statins. The objective of this study is to evaluate the influence of statin use on the risk of venous thromboembolic (VTE) events. The study is a case–control study (EDITH: Etude des Déterminants et Interactions de la Thrombose Veineuse), designed to investigate the genetic and environmental risk factors of VTE. A total of 377 patients consecutively hospitalized in the Brest University Hospital for a documented VTE event, between May 2000 and May 2002, and 377 age‐ and sex‐matched controls were studied. Statin use was associated with a 58% decreased risk of VTE [odds ratio (OR) 0.42; 95% confidence interval (CI) 0.23–0.76; P = 0.002]. Adjustment for age, gender, coronary heart disease, atherosclerothrombotic disease or current use of aspirin did not alter the result. Neither fibrates (OR 1.38; 95% CI 0.76–2.52; P = 0.26), nor thienopyridines (OR 1.07; 95% CI 0.48–2.41; P = 0.85) were associated with a reduced risk of VTE. Aspirin use tended to decrease the risk of VTE, but this result was not significant (OR, 0.66; 95% CI, 0.42–1.05). The use of statins is associated with a significant reduction in the risk of VTE, irrespective of age, gender, and past history of atherosclerothrombotic disease, as well as the use of aspirin. This possible protective effect of statins warrants further investigations.
Comparison of pharmacokinetics and metabolism of desloratadine, fexofenadine, levocetirizine and mizolastine in humans
Authors: Molimard M. , Diquet B. , Benedetti M. Strolin
Published: September 2004

Absorption, distribution, metabolism and excretion of desloratadine, fexofenadine, levocetirizine, and mizolastine in humans have been compared. The time required to reach peak plasma levels (tmax) is shortest for levocetirizine (0.9 h) and longest for desloratadine (≥3 h). Steady‐state plasma levels are attained after about 6 days for desloratadine, 3 days for fexofenadine, 2–3 days for mizolastine and by the second day for levocetirizine. The apparent volume of distribution is limited for levocetirizine (0.4 L/kg) and mizolastine (1–1.2 L/kg), larger for fexofenadine (5.4–5.8 L/kg) and particularly large for desloratadine (≈ 49 l/kg). Fexofenadine and levocetirizine appear to be very poorly metabolized (≈ 5 and 14% of the total oral dose, respectively). Desloratadine and mizolastine are extensively metabolized. After administration of 14C‐levocetirizine to healthy volunteers, 85 and 13% of the radioactivity are recovered in urine and faeces, respectively. In contrast, faeces are the preferential route of excretion for 14C‐fexofenadine (80% vs. 11% of the radioactive dose in urine). The corresponding values are 41% (urine) and 47% (faeces) for 14C‐desloratadine, 84–95% (faeces) and 8–15% (urine) for 14C‐mizolastine. The absolute bioavailability is 50–65% for mizolastine; it is high for levocetirizine as the percentage of the drug eliminated unchanged in the 48 h urine is 77% of the oral dose; the estimation for fexofenadine is at least 33%; no estimation was found for desloratadine. Fexofenadine is a P‐glycoprotein (P‐gp) substrate and P‐gp is certainly involved both in the poor brain penetration by the compound and, at least partially, in a number of observed drug interactions. An interaction of desloratadine with P‐gp has been suggested in mice, whereas the information on mizolastine is very poor. The fact that levocetirizine is a substrate of P‐gp, although weak in an in vitro model, could contribute to prevent drug penetration into the brain, whereas it is unlikely to be of any clinical relevance for P‐gp‐mediated drug interactions.
Selenium diet‐supplementation improves cocaine‐induced myocardial oxidative stress and prevents cardiac dysfunction in rats
Authors: Moritz Fabienne , Monteil Christelle , Isabelle Marc , Mulder Paul , Henry Jean‐Paul , Derumeaux Geneviève , Richard Vincent , Muller Jean‐Michel , Thuillez Christian
Published: September 2004

Chronic cocaine abuse causes cardiac dysfunction and induces oxidative stress. The goal of this study was to evaluate whether an enhanced antioxidant pool, induced by the administration of selenium, may prevent the myocardial dysfunction induced by cocaine. Cocaine was administered for 7 days (15 mg/kg/day, i.p.) to rats pretreated for 4 weeks with selenium (1.16 mg/L/day, p.o.). Cardiac function was evaluated by cardiac index and left ventricular (LV) fractional shortening (FS) measured by echocardiography. The redox ratio and enzymatic activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured in the LV myocardium. Cocaine administration induced a cardiac dysfunction, as evidenced by a decrease in cardiac index and LV FS as well as by an increase in LV diameters. Moreover, antioxidant markers and redox ratio were altered in rats after cocaine exposure. Selenite supplementation induced a significant limitation of cardiac index and FS alterations observed after cocaine administration. This improvement in cardiac function was associated with a redox ratio recovery while SOD and GPX activities remained unchanged. Thus, selenite reversed both the oxidative stress and the contractile dysfunction induced by cocaine administration. These results suggest a major role of oxidative stress in the cocaine‐induced cardiotoxicity.
The hemostatic agent ethamsylate promotes platelet/leukocyte aggregate formation in a model of vascular injury
Authors: Hernandez Maria Rosa , Alvarez‐Guerra Miriam , Escolar Ginés , Chiavaroli Carlo , Hannaert Patrick , Garay Ricardo P.
Published: September 2004

The hemostatic agent ethamsylate enhances membrane expression of P‐selectin in human platelets, but whether this promotes platelet–leukocyte aggregate formation is unknown. Here we investigated this point by flow cytometry determination of human platelet–leukocyte aggregates under basal conditions and after whole‐blood perfusion through a damaged rabbit aorta segment. Actions of ethamsylate on adhesive molecules of platelets and leukocytes were investigated in parallel. Under basal conditions, ethamsylate was unable to modify whole‐blood platelet–leukocyte aggregation, but following whole‐blood perfusion through a damaged vessel, ethamsylate produced a modest, but significant increase in platelet–leukocyte aggregates (48 ± 21 and 45 ± 26% above control levels at ethamsylate 20 and 40 μm respectively). In isolated leukocyte plasma membranes, 14C‐ethamsylate specifically bound up to an amount of 660 pmol/mg protein. Moreover, at concentrations ≥1 μm, ethamsylate induced an important (100–200%) and significant increase in the P‐selectin glycoprotein ligand 1 (PSGL‐1) fluorescence signal in isolated leukocytes and was unable to significantly modify the percentage of CD11b‐positive cells. However, no significant changes in aggregate formation were found when ethamsylate was incubated with isolated leukocytes and blood was reconstituted and perfused. In isolated platelet cell membranes, anti‐P‐selectin antibody and the anti‐integrin RGD‐containing pentapeptide (GRDGS) were unable to displace 14C‐ethamsylate binding. In conclusion, ethamsylate specifically binds to plasma membranes of leukocytes, enhances membrane PSGL‐1 expression and promotes leukocyte–platelet aggregation in whole‐blood perfused through a damaged vascular segment. These results together with the previously observed enhancement of platelet P‐selectin membrane expression [Thromb. Res. (2002)107:329–335] confirms and extends the view that ethamsylate acts on the first step of hemostasis, by improving platelet homo‐ and heterotypic adhesiveness.
Proliferative response to phenytoin and nifedipine in gingival fibroblasts cultured from humans with gingival fibromatosis
Authors: Sano Masakazu , Ohuchi Nozomi , Inoue Tomio , Tono Kayoko , Tachikawa Tetsuhiko , Kizawa Yasuo , Murakami Hajime
Published: September 2004

The response of gingival fibroblasts cultured from humans with gingival fibromatosis to phenytoin (PHT) and nifedipine (NIF) was investigated. PHT and NIF induced proliferation, and increased the expression of immunoreactive endothelin‐1 (ET‐1). ET‐1 (0.1 nm–1 μm) itself also induced proliferation in a concentration‐dependent manner. The proliferation was inhibited by BQ‐123 (ETA receptor antagonist; 1 μm) and TAK044 (ETA/ETB receptor antagonist; 1 μm), but not by BQ‐788 (ETB receptor antagonist; 1 μm). The proliferation induced by PHT (0.25 μm) and NIF (0.25 μm) was inhibited by BQ‐123 (1 μm). In addition, the results of Western blot analysis indicated the presence of ETA and ETB receptors in/on the fibroblasts. These findings suggest that PHT‐ and NIF‐induced gingival proliferation may be mediated by endogenously generated ET‐1, possibly via ETA receptors.
Pharmacoproteomic approach to the study of drug mode of action, toxicity, and resistance: applications in diabetes and cancer
Authors: Chapal Nicolas , Molina Laurence , Molina Franck , Laplanche Marion , Pau Bernard , Petit Pierre
Published: September 2004

Proteomics is a powerful technique for investigating protein expression profiles in biological systems and their modifications in response to stimuli or to particular physiological or pathophysiological conditions. It is therefore a technique of choice for the study of drug mode of action, side‐effects, toxicity and resistance. It is also a valuable approach for the discovery of new drug targets. All these proteomic applications to pharmacological issues may be called pharmacoproteomics. The pharmacoproteomic approach could be particularly useful for the identification of molecular alterations implicated in type 2 diabetes and for further characterization of existing or new drugs. In oncology, proteomics is widely used for the identification of tumour‐specific protein markers, and pharmacoproteomics is used for the evaluation of chemotherapy, particularly for the characterization of drug‐resistance mechanisms. The large amount of data generated by pharmacoproteomic screening requires the use of bioinformatic tools to insure a pertinent interpretation. Herein, we review the applications of pharmacoproteomics to the study of type 2 diabetes and to chemoresistance in different types of cancer and the current state of this technology in these pathologies. We also suggest a number of bioinformatic solutions for proteomic data management.
Long‐term protection of obese Zucker rat kidneys from fibrosis and renal failure with an angiotensin‐converting enzyme inhibitor/diuretic combination
Authors: Renaud Isabelle M. , Chainey Angele , Belair Marie‐France , Mandet Chantal , Michel Odile , Myara Isaac , Chevalier Jacques , Plante Gerard E.
Published: September 2004

Some combinations of antihypertensive agents were shown to reduce proteinuria in patients with renal failure. However, preventive effects of such combinations on renal structure and function are presently unknown when treatment is administered before the onset of renal abnormalities. We thus investigated the long‐term effects of an angiotensin‐converting enzyme (ACE) inhibitor (perindopril)/diuretic (indapamide) combination (per/ind) in the Zucker rat, a classical model of chronic renal failure associated with obesity, hyperlipidemia, and insulin resistance. Two‐month‐old lean and obese Zucker rats, presenting normal renal structure and function at this young age, received per/ind (0.76 + 0.24 mg/kg of body weight/day) or the vehicle of this combination by daily gavage. After 8.5 consecutive months of treatment, those 10.5‐month‐old rats were used for determination of renal structural and functional parameters which were examined using standard renal clearance experiments and kidney tissue analysis. Per/ind prevented focal and segmental glomerular hyalinosis and tubulo‐interstitial damage in obese rats. Treatment was also associated with a significant reduction in several staining markers of glomerular and interstitial fibrosis. The hypertrophy of superficial glomeruli and the mesangial expansion of deep glomeruli observed in control rats were reduced in per/ind‐treated obese rats. The severe proteinuria observed in 10.5‐month‐old control obese rats was prevented by per/ind, while glomerular filtration and renal hemodynamic parameters reached similar values to those obtained in lean animals. These results show that long‐term treatment with this ACE inhibitor/diuretic combination protects renal structure and function in the obese Zucker rat, emphasizing the potential efficiency of such therapy in renal failure prevention.
Bioactivation of nitroglycerin to nitric oxide (NO) and S‐nitrosothiols in the rat liver and evaluation of the coexisting hypotensive effect
Authors: Sokołowska Maria , Bednarski Marek , Kwiecień Inga , Filipek Barbara , Włodek Lidia
Published: September 2004

The aim of the present study was to investigate nitroglycerin (NTG) bioactivation pathways in the liver after various periods of its administration. We also attempted to elucidate the relationship between nitric oxide (NO) and S‐nitrosothiol (SNT) levels, and concentration of nonprotein thiols (NPSH) and intensity of peroxidative processes. Intravenous injections of NTG cause an increase in NO and SNT levels in the rat liver. The same intravenous NTG injections in the rats pretreated with 5‐day i.p. NTG administrations lead to a drop in the levels of the biologically active NO, SNT and NPSH, with no concomitant changes in the rate of lipid peroxidation. This indicates that after such period of nitroglycerin pretreatment, levels of pharmacologically active NO and SNT decrease. However, during longer periods of NTG administration (for 10 and 17 days) NO, SNT and NPSH concentrations remain at the control level in spite of a considerably enhanced lipid peroxidation, which indicates that tolerance did not develop. Effects of NTG bioactivation in the liver, i.e. the levels of NO and SNT released from it, after different periods of drug administration correspond with hypotensive effects, which are known to be dependent on NTG biodegradation in vascular endothelial cells. The changes in NO and SNT levels observed in the rat liver after different periods of NTG administration parallel alterations in the hypotensive effect. In conclusion, NTG treatment for 10 and 17 days does not lead to tolerance, however, a transient loss of its pharmacological activity occurs after 5‐day NTG pretreatment.
Conjugation with taurine prevents side‐chain desaturation of ursodeoxycholic and β‐muricholic acids in bile fistula rats
Authors: Guitaoui Mustapha , Parquet Michel , Aubert Claude , Montet Anne‐Marie , Montet Jean‐Claude
Published: September 2004

The metabolism of intravenously infused bile salts, tauroursodeoxycholate, tauro‐β‐muricholate and their corresponding unconjugated forms in the liver was investigated in bile salt‐depleted bile fistula rats. The biliary bile salt composition was determined by gas chromatography–mass spectrometry using chemical positive ionization and electron‐impact methods. For an infusion rate of 2 μmol/min/kg, all bile salts were efficiently secreted in bile, inducing similar choleresis. Only tauroconjugated bile salts were recovered; no glucuronide or glyco derivatives were detected. The infusion of free ursodeoxycholate led to the appearance of a metabolite identified as a Δ22 derivative (12%). A similar biotransformation rate (11%) was observed following free β‐muricholate infusion. In contrast, no metabolite was observed after infusion of the tauroconjugated form of ursodeoxycholate and β‐muricholate. The unsaturation process probably depends on the availability of the carboxyl group for the starting step of the β‐oxidation mechanism. In conclusion, the current in vivo study demonstrates a hepatic origin for Δ22 bile salts. It also shows that free bile salts were sensitive to Δ22 formation while conjugation with taurine totally prevented the side‐chain oxidation of the two 7β‐hydroxylated bile salts.
Differential time effect profiles of amlodipine, as compared to valsartan, revealed by ambulatory blood pressure monitoring, self blood pressure measurements and dose omission protocol
Authors: Radauceanu Anca , Boivin Jean‐Marc , Bernaud Corine , Fay Renaud , Zannad Faiez ,   the CIC General Practitioners Investigators’ Group
Published: September 2004

Amlodipine and valsartan are once‐daily antihypertensive agents. To date, no comparison between these agents given as monotherapies was reported. This study was aimed to evaluate the therapeutic coverage and safety of amlodipine and valsartan in mild‐to‐moderate hypertensive patients. Multicenter, double‐blind, randomized, comparative study. After a 4‐week placebo wash‐out period, 246 outpatients with office diastolic blood pressure 95 ≤ DBP ≤110 mmHg and systolic blood pressure (SBP) < 180 mmHg, in addition to a mean daytime SBP and/or DBP > 135/85 mmHg on 24‐h ambulatory blood pressure monitoring (ABPM), were randomly allocated to once‐daily amlodipine 5–10 mg or valsartan 40–80 mg, for 12 weeks. In a subgroup of patients, 48‐h ABPM were performed at the end of the treatment period. Dose omission was simulated by a single‐blind placebo dosing. The primary efficacy end‐point was the 24‐h trough office BP after 12 weeks of active therapy. The reductions in 24‐h trough BP were more pronounced in amlodipine compared with valsartan group as well in office [SBP: −17.8 ± 10.9 vs. −14.6 ± 11.2, P = 0.025, DBP: −12.7 ± 7.2 vs. −10.9 ± 7.8 mmHg, P = 0.06) as in ambulatory BP (SBP/DBP: −13.0 ± 13.7/−10.8 ± 9.1 vs. −7.2 ± 19.4/−4.9 ± 13.4 mmHg, P < 0.05). Forty‐eight hours after the last active dose, the slope of the morning BP surge (4–9 h) was less steep with amlodipine vs. valsartan [DBP (P < 0.04), SBP (n.s.)]. Ankle edema were more often reported in amlodipine group. These results suggest a superior BP lowering and a longer duration of action with amlodipine compared with valsartan.
New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humans
Authors: Trellu M. , Filali‐Ansary A. , Françon D. , Adam R. , Lluel P. , Dubruc C. , Thénot J.P.
Published: September 2004

Thiocolchicoside (TCC) has been prescribed for several years as a muscle relaxant drug, but its pharmacokinetic (PK) profile and metabolism still remain largely unknown. Therefore, we re‐investigated its metabolism and PK, and we assessed the muscle relaxant properties of its metabolites. After oral administration of 8 mg (a therapeutic dose) of 14C‐labelled TCC to healthy volunteers, we found no detectable TCC in plasma, urine or faeces. On the other hand, the aglycone derivative obtained after de‐glycosylation of TCC (M2) was observed and, in addition, we identified, as the major circulating metabolic entity, 3‐O‐glucuronidated aglycone (M1) obtained after glucuro‐conjugation of M2. One hour after oral administration, M1 plus M2 accounted for more than 75% of the circulating total radioactivity. The pharmacological activity of these metabolites was assessed using a rat model, the muscle relaxant activity of M1 was similar to that of TCC whereas M2 was devoid of any activity. Subsequently, to investigate the PK profile of TCC in human PK studies, we developed and validated a specific bioanalytical method that combines liquid chromatography and ultraviolet detection to assay both active entities. After oral administration, TCC was not quantifiable with an lower limit of quantification set at 1 ng/mL, whereas its active metabolite M1 was detected. M1 appeared rapidly in plasma (tmax = 1 h) and was eliminated with an apparent terminal half‐life of 7.3 h. In contrast, after intramuscular administration both active entities (TCC and M1) were present; TCC was rapidly absorbed (tmax = 0.4 h) and eliminated with an apparent terminal half‐life of 1.5 h. M1 concentration peaked at 5 h and this metabolite was eliminated with an apparent terminal half‐life of 8.6 h. As TCC and M1 present an equipotent pharmacological activity, the relative oral pharmacological bioavailability of TCC vs. intramuscular administration was calculated and represented 25%. Therefore, to correctly investigate the PK and bioequivalence of TCC, the biological samples obtained must be assayed with a bioanalytical method able to specifically analyse TCC and its active metabolite M1.
Intraoperative Extracorporeal Irradiation for Limb Sparing in 13 Dogs
Authors: Liptak Julius M. , Dernell William S. , Lascelles B. Duncan X. , Larue Susan M. , Jameson Vicki J. , Powers Barbara E. , Huber Douglas J. , Withrow Stephen J.
Published: September 2004

Objective— To evaluate extracorporeal intraoperative radiation therapy (IORT) as a treatment method for limb and joint sparing in dogs with appendicular sarcomas in sites other than the distal aspect of the radius.

Study Design— Retrospective study.

Animals— Thirteen client‐owned dogs.

Methods— The bone tumor database and medical records (1998–2002) were reviewed for dogs with primary appendicular bone tumors treated with IORT limb‐sparing surgery and adjuvant chemotherapy. The segment of bone containing the tumor was isolated from adjacent soft tissue and an osteotomy performed distant to the tumor. The bone segment was exteriorized, irradiated (70 Gy single fraction), and then stabilized with internal fixation. Adjuvant chemotherapy was administered. Lameness was graded and local and distant tumor control was determined. Associations between intra‐ and postoperative variables with complications and Kaplan–Meier survival analysis for median disease‐free interval and survival time were calculated.

Results— Limb function was good or excellent in 10 dogs (77%). Postoperative complications (9 dogs, 69%) included deep infection, fracture of the irradiated bone, and implant failure. Surgical failure was more likely if a single implant was used to stabilize the osteotomized bone and if deep infection developed postoperatively. In 3 dogs, tumors recurred locally within bone in the radiation field. The disease‐free and overall success rates of extracorporeal IORT for limb and joint preservation were 46% and 54%, respectively.

Conclusions— Extracorporeal IORT provides a novel alternative to traditional techniques for preservation of joint and limb function in dogs with primary appendicular sarcomas. A minimum of 2 implants and intramedullary bone cement should be used to stabilize the osteotomized bone to minimize postoperative complications. Extracorporeal IORT should be used with caution in dogs with tumors of the distal tibia because of a high complication rate. Dogs with tumors in areas of good soft‐tissue coverage, such as the humerus and femur, may be good candidates for limb and joint‐sparing surgery using extracorporeal IORT.

Clinical Relevance— Extracorporeal IORT is a surgical technique that can be used for limb and joint salvage in dogs with primary appendicular sarcomas in sites usually not amenable to traditional limb‐sparing techniques.
Evaluation of Primary Critical Ischemia Time for the Deep Circumflex Iliac Cutaneous Flap in Cats
Authors: Teunissen Brian D. , Walshaw Richard , Hauptman Joe G. , Degner Daniel A. , Jackson Andrew H.
Published: September 2004

Objective—To evaluate the primary critical ischemia time for the deep circumflex iliac (DCI) cutaneous flap in cats.

Study Design—In vivo model.

Animals—Thirteen young adult female cats.

Methods—An island skin flap was created on the right side of each cat based on the angiosome of the ventral branches of the DCI vessels. The cats were randomly assigned to a flap ischemia time ranging from 1 to 3 hours in 10‐minute intervals. Microvascular clamps were used to occlude the artery and vein for the designated time. Flaps were sutured into position after the ischemic period. On day 3, fluorescein dye was administered and the flaps were evaluated under ultraviolet light to assess percent area of perfusion. On days 7 and 14, the percent area of survival was determined for each flap based on cutaneous morphometry.

Results—All flaps had 100 percent area of survival throughout the study. On day 3, all flaps fluoresced uniformly compared with the surrounding skin. On days 7 and 14, all flaps were uniformly viable as confirmed by skin color, consistency, bleeding, and hair re‐growth.

Conclusion—The DCI cutaneous flap in cats can withstand up to 3 hours of ischemia with predictable survival.

Clinical Relevance—In a clinical setting, high success rates can be expected with microvascular transfer of the DCI cutaneous flap in cats when the ischemia time is <3 hours and precise surgical technique is used.
Evaluation of Arthrocentesis Site Bacterial Flora before and after 4 Methods of Preparation in Horses with and without Evidence of Skin Contamination
Authors: Zubrod Chad J. , Farnsworth Kelly D. , Oaks J. Lindsay
Published: September 2004

Objective—To evaluate the effectiveness of four methods of povidone–iodine preparation on skin bacterial flora of arthrocentesis sites, in horses, with and without evidence of skin contamination.

Study Design—Prospective randomized study.

Animals—Twenty‐four adult horses.

Methods—Horses were assigned to either the clean or contaminated group based on housing environment and visual evidence of contamination. Using a moist sterile swab, microbial culture samples were obtained from the skin over the distal interphalangeal joints immediately before and after preparation. Each site was aseptically prepared with 1 of 4 povidone–iodine techniques: 10‐minutes scrub, 5‐minutes scrub, three 30‐second scrubs, or commercial one‐step iodophor surgical solution. Colony forming units (CFUs) were determined for each sample, 24 hours after inoculation, on blood agar plates.

Results—Mean (±SD) pre‐scrub CFUs/mL was significantly higher in the contaminated group (9588.33±1223.65) compared with the clean group (4489.00±3842.03) (P<.01). After preparation of the arthrocentesis sites, there were no significant differences in post‐scrub CFUs/mL among the 10 minutes (mean clean, 46.00±64.36; mean contaminated, 28.67±18.04), 5 minutes (mean clean, 84.17±109.80; mean contaminated, 40.33±44.52), three 30 seconds povidone–iodine scrubs (mean clean, 95.50±172.29; mean contaminated, 46.67±56.94), or application of a commercial one‐step iodophor surgical solution (mean clean, 102.17±161.78; mean contaminated 117.67±143.78); or between the clean (81.96±131.69) and contaminated groups (58.33±85.90) (P<.01).

Conclusions—Preparation of the distal interphalangeal joint arthrocentesis site with each of these techniques significantly reduces the bacterial flora to a similar level for arthrocentesis in horses with and without evidence of skin contamination.

Clinical Relevance—Aseptic preparation of the skin over the distal interphalangeal joint may be accomplished with any of these techniques.
An In Vitro Study to Determine the Effectiveness of a Patellar Ligament/Fascia Lata Graft and New Tibial Suture Anchor Points for Extracapsular Stabilization of the Cranial Cruciate Ligament–Deficient Stifle in the Dog
Authors: Harper Tisha A. M. , Martin Robert A. , Ward Daniel L. , Grant J. Wallace
Published: September 2004

Objective—(1) To determine whether an extracapsular patellar ligament/fascia lata graft would provide stability in the cranial cruciate ligament (CrCL)‐deficient stifle comparable with that of the intact stifle. (2) To determine if different tibial anchor points would enhance stability of the CrCLdeficient stifle when compared with the standard fabellar‐tibial suture (FTS) placement.

Study Design—Experimental.

Animals—Twenty‐eight canine cadaver hind limbs.

Methods—Stifles were mounted in a jig and tested between loads of −65 and 80 N. After testing the intact CrCL, 4 stabilization techniques were tested after CrCL transection: lateral graft technique (LGT) and 3 FTS with different tibial anchor points.

Results—There were no significant differences in displacement between the LGT and standard FTS, between the LGT and the intact CrCL, or between the FTS and the intact CrCL, in either the Securos™ or the Screw–washer experiments. Stiffness of the intact CrCL was significantly greater than that of any stabilization technique and the cut CrCL. The standard FTS showed the least displacement of all suture stabilization techniques. Differences in stiffness were not significant between the suture stabilization techniques.

Conclusions—Securely anchored, the LGT results in a reduction in drawer motion similar to that of the intact CrCL and the standard FTS. Altering the tibial anchor point for the FTS does not improve stiffness or enhance stabilization of the CrCL‐deficient stifle.

Clinical Relevance—The LGT could be used for the treatment of CrCL ruptures in the dog. A clinical study is recommended.
Accuracy and reproducibility of two manual periodontal probes
Authors: Buduneli Eralp , Aksoy Okay , Köse Timur , Atilla Gül
Published: September 2004

Background: Periodontal probe is the standard instrument for assessment of probing pocket depth and clinical attachment level. However, probing measurements have inherent measurement errors from a wide range of sources, such as instrument, patient, examiner and disease status.

Aim: The purpose of the present study was to create an in vitro model simulating gingival sulcus/pocket and investigate the accuracy and reproducibility of two different manual probes.

Methods: Thirty‐three aluminium blocks with dimensions of 2 × 2 cm and thickness ranging from 2.00 to 10.00 mm were constructed. Holes with a diameter of 1.00 mm were made in the blocks through the whole thickness. These 33 aluminium blocks were then carefully stucked together so that the probing faces would be on the same level. A plastic material, which shows deformation with forces >45 g was placed at the base of the blocks. Two conventional manual probes (Williams and WHO probes) were used in the present study. Seventeen periodontists were selected to perform duplicate measurements on the blocks over two visits using both of the probes. The intra‐ and inter‐examiner percentage accuracy (with regard to 0.25 mm) and reproducibility for each of the duplicate measurements was calculated and analysed using repeated measure analysis of variance (anova) (three factor experiments with repeated measure on two factors; probe and probing session).

Results: anova showed statistically significant differences between the examiners (p=0.000) and between the two readings of each probe (p=0.002), while the differences between the two probes were not statistically significant (p=0.098). The overall percentage of accuracy was higher with WHO probe compared with Williams probe. Kappa analysis revealed better reproducibility percentages for WHO probe in comparison with Williams probe.

Conclusions: This in vitro study, using a metal construction and a plastic material with a deformation coefficient similar to that of gingival pocket, may be suggested as a good model to test intra‐ and inter‐examiner differences in periodontal probing. Our findings emphasise the importance of inter‐examiner calibration for probing, particularly in longitudinal studies.
The influence of reactivation of the telomerase in tumour tissue on the prognosis of squamous cell carcinomas in the head and neck
Authors: Koscielny S. , Eggeling F. v. , Dahse R. , Fiedler W.
Published: September 2004

Background:  The reactivation of the telomerase seems to be an important step in the carcinogenesis of most human cancer types. Cell clones, which express this enzyme, get the ability of indefinite proliferation, means become immortal.

Methods:  In this study, 80 patients with squamous cell carcinomas (SSC) in oral cavity, oropharynx, hypopharynx and larynx were recorded prospectively concerning a possible correlation of telomerase activity and clinical and prognostic factors. Telomerase activity was analysed by a modified telomeric repeat amplification protocol (TRAP) assay.

Results:  In 75% of the tumour tissues the telomerase was demonstrated independently of the localization of the tumour. The known clinical prognostic factors did not show any correlation to the expression rate of the telomerase activity in the tumour tissues. Also, reactivated telomerase did not affect the tumour‐dependent survival. Only the number of lymph node metastases was in tendency higher in patients with telomerase‐positive tumours. The number and timeframe of local and regional recurrences was not influenced by the telomerase status.

Conclusions:  Although telomerase seems to be an important part of the carcinogenesis of SCC our data show that the reactivation of telomerase in tumour tissue did not have any prognostic significance for these tumours. The tendency that tumours with active telomerase developed lymph node metastases in a higher number should be evaluated by further enlarged studies for its clinical relevance.
Health Care Cost Implications of Sildenafil Citrate
Authors: Miner Martin
Published: September 2004

Introduction

As prescription drug expenditures increase, third-party payors are increasingly scrutinizing costs and reimbursement guidelines, such as for medications that treat chronic conditions that are not necessarily directly life threatening (i.e., obesity, nicotine addiction, and erectile dysfunction).

Aim

To review the costs and consequences of pharmacy benefit reimbursement policies related to erectile dysfunction therapies, using sildenafil citrate as the case study.

Methods

Data and references were found through searches of PubMed and Google.

Results and Conclusions

To meet the varied health needs of a defined population under reasonable resource constraints requires analysis of cost and of the economic and non-economic consequences of a treatment. Based on analysis of sildenafil data, oral therapy of erectile dysfunction provides substantial cost savings when compared with other treatment options and contributes insignificant overall costs to health plans. Regardless, health plans impose controls to limit reimbursement. Because erectile dysfunction is often a precursor to other conditions, such limitations could compromise detection and management of underlying disease (e.g., depressive, cardiovascular, and urogenital). Reimbursement restrictions may also decrease membership satisfaction and re-enrollment rates.
Duration of Action of Sildenafil Citrate in Men with Erectile Dysfunction
Authors: Gingell Clive , Sultana Stefan R. , Wulff Maria B. , Gepi-Attee Sam
Published: September 2004

Introduction

Viagra® (sildenafil citrate) has a rapid onset of action for the treatment of erectile dysfunction (ED). However, its duration of action has not been thoroughly investigated. Practical knowledge of the time window available for sexual intercourse would be valuable for couples planning sexual activity.

Aim

We investigated the duration of action of sildenafil in men with ED.

Methods

This was a double-blind, randomized, placebo-controlled, four-way crossover study of 16 men, mean age of 55 years (range, 36–68 years) with ED of no known organic cause. Participants received oral sildenafil (100 mg) or placebo 1, 8, or 12 hours before visual sexual stimulation (VSS). Measurements included the duration of erections of ≥ 60% rigidity, assessed by penile plethysmography (RigiScan®), and the proportion of sildenafil responders, defined as patients with erections of ≥ 60% rigidity for ≥ 4 minutes and ≥ 50% improvement over erections achieved in their placebo arm. Self-assessed duration of grade 3 (hard enough for penetration) or grade 4 (fully hard) erections was also recorded.

Results

At 1, 8, and 12 hours after dosing with sildenafil, the mean duration of erections with ≥ 60% rigidity was 26, 11, and 8 minutes, respectively, compared with only 3 minutes after placebo dosing (P < 0.05). However, the mean duration of self-assessed erections was 33, 23, and 16 minutes, respectively, compared with 7 minutes after placebo dosing (P < 0.05), and was greater than that assessed by RigiScan. Of the 69% sildenafil responders at 1 hour, 82% responded at 8 hours and 45% responded at 12 hours after sildenafil administration.

Conclusion

Sildenafil improved objective and self-assessed erectile function in men with ED, and the duration of action of sildenafil was longer than that previously reported. These data suggest that sildenafil may be effective in a significant proportion of men with ED up to 12 hours after being taken.
Loss Reduction Using Riblets on a Supersonic Through-Flow Fan Blade Cascade
Authors: Ninnemann Todd , Ng Wing F.
Published: September 2004

An experimental and computational study to determine the effects of riblets on the performance of the Supersonic Throughflow Fan (STF) cascade blades was performed. The cascade was tested in the Virginia Tech intermittent wind tunnel facility, where the Mach and Reynolds (based on chord) numbers were 2.36 and 4.8×106, respectively. The riblet sheets were symmetric v-grooved type and were applied onto the blade surfaces. Three different riblet heights were tested: 0.023, 0.033, and 0.051 mm. Riblet testing was conducted at design incidence as well as at off-design conditions (incidence angles: +5, −10 deg). Loss coefficients were measured and compared with a control test case where an equivalent thickness of smooth material was applied to the blade. Results show that at the design incidence, the riblet sheet with a height of 0.033 mm provides the optimal benefit, with a reduction of 8.5% in loss coefficient compared to the control case. Smaller effects were measured at the off-design conditions. In addition to the experimental study, a numerical investigation of the riblet effect on the STF cascade was conducted at design incidence. A simple method was developed to model riblet effects due to decrease in turbulent viscous drag and the delay of turbulent transition on the blades. Conclusions from numerical study indicate the 2/3 of the total decrease in losses are the result of delaying the transition location. The final 1/3 decrease in loss coefficient comes from the decrease in turbulent viscous losses.
Output ratio in air for MLC shaped irregular fields
Authors: Zhu Timothy C. , Bjärngard Bengt E. , Xiao Ying , Bieda Mike
Published: September 2004

For accurate monitor unit calculation, it is important to calculate the output ratio in air, for an irregular field shaped by MLC. We have developed an algorithm to calculate based on an empirical model [Med. Phys. 28, 925–937 (2001)] by projecting each leaf position to the isocenter plane. Thus it does not require the exact knowledge of the head geometry. Comparisons were made for three different types of MLC: those with MLC replacing the inner collimator jaws; those with MLC replacing the outer collimator jaws; and those with MLC as a tertiary attachment. When the MLC leaf positions are substantially different from the secondary collimators (or the rectangular field encompassing the irregular field), one observes an up to 5% difference in the value of headscatter correction factor, HCF, defined as the ratio of output ratio in air between the MLC shaped irregular field and that of the rectangular field encompassing the irregular field. No collimator exchange effect was observed for rectangular fields shaped by MLC (e.g., 5×30 and 30×5 cm2 diagonal) when the secondary collimators are fixed, unlike that for the rectangular fields shaped by the inner and outer collimator jaws, where it can be 1–2%. For the same MLC shaped irregular field, the value of increases from the Elekta, to the Siemens, to the Varian accelerators, with an up to 4% difference. The calculation agrees with measurement to within 1.2% for points both on and off the central‐axis. The fitting parameters used in the algorithm are derived from measurements for square field sizes on the central‐axis.