bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-Drug Interactions Among Elderly Patients Hospitalized for Drug Toxicity
Authors: Juurlink David N. , Mamdani Muhammad , Kopp Alexander , Laupacis Andreas , Redelmeier Donald A.
Published: April 2003

Context

Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized.

Objective

To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission.

Design

Three population-based, nested case-control studies.

Setting

Ontario, Canada, from January 1, 1994, to December 31, 2000.

Patients

All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors).

Main Outcome Measure

Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date.

Results

During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively).

Conclusions

Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.
Cereal, Fruit, and Vegetable Fiber Intake and the Risk of Cardiovascular Disease in Elderly Individuals
Authors: Mozaffarian Dariush , Kumanyika Shiriki K. , Lemaitre Rozenn N. , Olson Jean L. , Burke Gregory L. , Siscovick David S.
Published: April 2003

Context

People older than 65 years are the fastest-growing segment of the population and account for the majority of cardiovascular disease (CVD) morbidity, mortality, and health care expenditures. Additionally, the influence of dietary habits on risk may be less pronounced in elderly persons, when atherosclerosis is more advanced. However, few data address the influence of diet on CVD risk in this population.

Objective

To determine whether fiber consumption from fruit, vegetable, and cereal sources (including whole grains and bran) is associated with incident CVD in elderly persons.

Design

Prospective cohort study conducted from 1989 to June 2000.

Setting and Participants

Population-based, multicenter study among 3588 men and women aged 65 years or older and free of known CVD at baseline in 1989-1990. Usual dietary fiber consumption was assessed at baseline (mean participant age, 72 years) using a 99-item food frequency questionnaire.

Main Outcome Measure

Incident CVD (combined stroke, ischemic heart disease death, and nonfatal myocardial infarction).

Results

During 8.6 years mean follow-up, there were 811 incident CVD events. After adjustment for age, sex, education, diabetes, ever smoking, pack-years of smoking, daily physical activity, exercise intensity, alcohol intake, and fruit and vegetable fiber consumption, cereal fiber consumption was inversely associated with incident CVD (P for trend = .02), with 21% lower risk (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62-0.99) in the highest quintile of intake, compared with the lowest quintile. In similar analyses, neither fruit fiber intake (P for trend = .98) nor vegetable fiber intake (P for trend = .95) were associated with incident CVD. When CVD events were separately evaluated, higher cereal fiber intake was associated with lower risk of total stroke and ischemic stroke and a trend toward lower risk of ischemic heart disease death. In a post hoc analysis, dark breads such as wheat, rye, or pumpernickel were associated with a lower risk of incident CVD (HR, 0.76; 95% CI, 0.64-0.90) rather than cereal fiber from other sources.

Conclusions

Cereal fiber consumption late in life is associated with lower risk of incident CVD, supporting recommendations for elderly individuals to increase consumption of dietary cereal fiber.
Blood Mercury Levels in US Children and Women of Childbearing Age, 1999-2000
Authors: Schober Susan E. , Sinks Thomas H. , Jones Robert L. , Bolger P. Michael , McDowell Margaret , Osterloh John , Garrett E. Spencer , Canady Richard A. , Dillon Charles F. , Sun Yu , Joseph Catherine B. , Mahaffey Kathryn R.
Published: April 2003

Context

Humans are exposed to methylmercury, a well-established neurotoxin, through fish consumption. The fetus is most sensitive to the adverse effects of exposure. The extent of exposure to methylmercury in US women of reproductive age is not known.

Objective

To describe the distribution of blood mercury levels in US children and women of childbearing age and the association with sociodemographic characteristics and fish consumption.

Design and Setting

The 1999-2000 data from the National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population.

Participants

In 1999-2000, 1250 children aged 1 to 5 years and 2314 women aged 16 to 49 years were selected to participate in the survey. Household interviews, physical examinations, and blood mercury levels assessments were performed on 705 children (56% response rate) and 1709 women (74% response rate).

Main Outcome Measure

Blood concentration of total mercury.

Results

Blood mercury levels were approximately 3-fold higher in women compared with children. The geometric mean concentration of total blood mercury was 0.34 µg/L (95% confidence interval [CI], 0.30-0.39 µg/L) in children and 1.02 µg/L (95% CI, 0.85-1.20 µg/L) in women. Geometric mean mercury levels were almost 4-fold higher among women who ate 3 or more servings of fish in the past 30 days compared with women who ate no fish in that period (1.94 µg/L vs 0.51 µg/L; P<.001).

Conclusions

Measures of mercury exposure in women of childbearing age and young children generally fall below levels of concern. However, approximately 8% of women had concentrations higher than the US Environmental Protection Agency's recommended reference dose (5.8 µg/L), below which exposures are considered to be without adverse effects. Women who are pregnant or who intend to become pregnant should follow federal and state advisories on consumption of fish.
Association of Nitrotyrosine Levels With Cardiovascular Disease and Modulation by Statin Therapy
Authors: Shishehbor Mehdi H. , Aviles Ronnier J. , Brennan Marie-Luise , Fu Xiaoming , Goormastic Marlene , Pearce Gregory L. , Gokce Noyan , Keaney John F. , Penn Marc S. , Sprecher Dennis L. , Vita Joseph A. , Hazen Stanley L.
Published: April 2003

Context

Formation of nitric oxide–derived oxidants may serve as a mechanism linking inflammation to development of atherosclerosis. Nitrotyrosine, a specific marker for protein modification by nitric oxide–derived oxidants, is enriched in human atherosclerotic lesions and low-density lipoprotein (LDL) recovered from human atheroma.

Objectives

To determine whether systemic levels of nitrotyrosine are associated with the prevalence of coronary artery disease (CAD) and are modulated by hydroxymethylglutaryl coenzyme-A reductase inhibitor (statin) therapy.

Design, Setting, and Patients

A case-control and interventional study at 2 urban tertiary-care referral centers; recruitment for each was from June 1, 2001, until January 1, 2002. For the case-control study, 100 case-patients with established CAD and 108 patients with no clinically evident CAD were recruited consecutively. In the interventional study, participants aged 21 years or older with hypercholesterolemia (LDL cholesterol ≥130 mg/dL [≥3.5 mmol/L]) underwent nutrition and exercise counseling. Those whose levels did not decrease with 6 to 8 weeks were enrolled in the study (n = 35). For 12 weeks, they received 10 mg/d of oral atorvastatin therapy.

Main Outcome Measures

In the case-control study, the association between systemic levels of protein-bound nitrotyrosine, CAD risk, and presence of CAD. In the interventional study, the change in nitrotyrosine, lipoprotein, and C-reactive protein (CRP) levels.

Results

Nitrotyrosine levels were significantly higher among patients with CAD (median 9.1 µmol/mol [interquartile range, 4.8-13.8 µmol/mol] tyrosine vs 5.2 µmol/mol [interquartile range, 2.2-8.4 µmol/mol]; P<.001). Patients in the upper quartile of nitrotyrosine (29%; P<.001) had a higher odds of CAD compared with those in the lowest quartile (unadjusted odds ratio, 6.1; 95% confidence interval, 2.6-14.0; P<.001). In multivariate models adjusting for Framingham Global Risk Score and CRP, upper quartiles of nitrotyrosine remained associated with CAD (odds ratio, 4.4; 95% confidence interval, 1.8-10.6; P<.001). Statin therapy reduced nitrotyrosine levels significantly (25%; P<.02) with a magnitude similar to reductions in total cholesterol levels (25%; P<.001) and LDL particle number (29%; P<.001) yet were independent of alterations in lipoproteins and inflammatory markers like CRP.

Conclusions

The findings from this preliminary study indicate that nitrotyrosine levels are associated with the presence of CAD and appear to be modulated by statin therapy. These results suggest a potential role for nitric oxide–derived oxidants as inflammatory mediators in CAD and may have implications for atherosclerosis risk assessment and monitoring of anti-inflammatory actions of statins.
Statin-Associated Myopathy
Authors: Thompson Paul D. , Clarkson Priscilla , Karas Richard H.
Published: April 2003

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are associated with skeletal muscle complaints, including clinically important myositis and rhabdomyolysis, mild serum creatine kinase (CK) elevations, myalgia with and without elevated CK levels, muscle weakness, muscle cramps, and persistent myalgia and CK elevations after statin withdrawal. We performed a literature review to provide a clinical summary of statin-associated myopathy and discuss possible mediating mechanisms. We also update the US Food and Drug Administration (FDA) reports on statin-associated rhabdomyolysis. Articles on statin myopathy were identified via a PubMed search through November 2002 and articles on statin clinical trials, case series, and review articles were identified via a PubMed search through January 2003. Adverse event reports of statin-associated rhabdomyolysis were also collected from the FDA MEDWATCH database. The literature review found that reports of muscle problems during statin clinical trials are extremely rare. The FDA MEDWATCH Reporting System lists 3339 cases of statin-associated rhabdomyolysis reported between January 1, 1990, and March 31, 2002. Cerivastatin was the most commonly implicated statin. Few data are available regarding the frequency of less-serious events such as muscle pain and weakness, which may affect 1% to 5% of patients. The risk of rhabdomyolysis and other adverse effects with statin use can be exacerbated by several factors, including compromised hepatic and renal function, hypothyroidism, diabetes, and concomitant medications. Medications such as the fibrate gemfibrozil alter statin metabolism and increase statin plasma concentration. How statins injure skeletal muscle is not clear, although recent evidence suggests that statins reduce the production of small regulatory proteins that are important for myocyte maintenance.
Hormones and competitive aggression in women
Authors: Cashdan Elizabeth
Published: March 2003

This study used diaries of competitive interactions to explore the relationship between hormones and competitive aggression in women. Thirty women completed approximately 10 diary entries each. In each entry, the women described a recent competitive interaction they had engaged in and noted whether it was expressed aggressively or through other tactics. Each woman received a score for the fraction of her competitive interactions that were expressed using physical aggression, verbal aggression, nothing overt, and so on. Hormones (total testosterone, free testosterone, androstenedione, estradiol, and cortisol) were measured in serum early in the follicular phase. Results indicate that women with low levels of androstenedione and total testosterone were less likely to express their competitive feelings overtly, while women with high levels of androstenedione were more likely than other women to express their competitive feelings through verbal aggression. Estradiol was unrelated to competitive tactics, but women with high estradiol levels reported fewer competitive interactions over athletics than did other women. Aggr. Behav. 29:107–115, 2003. © 2003 Wiley‐Liss, Inc.
Sex differences in social representations of aggression: Men justify, women excuse?
Authors: Astin Sarah , Redston Phillip , Campbell Anne
Published: March 2003

Women tend to hold an expressive social representation of aggression (as a loss of self‐control) while men tend to hold an instrumental representation (as a means of imposing control over others). Because expressive beliefs correspond to excuses and instrumental beliefs to justifications, it may be a sex difference in moral acceptability of aggression that informs social representation. Participants completed the Expagg questionnaire with reference to an episode of same‐sex or cross‐sex physical aggression and rated the moral acceptability of their behaviour. Women scored higher on Expagg (specifically lower than men on the instrumental scale) but there was no effect of target sex or participant‐by‐target interaction. Contrary to expectation, women rated their own aggression as more acceptable than did men and hence this could not explain their lower levels of instrumentality relative to men. Aggr. Behav. 29:128–133, 2003. © 2003 Wiley‐Liss, Inc.
“She is not actually bullied.” the discourse of harassment in student groups
Authors: Teräsahjo Timo , Salmivalli Christina
Published: March 2003

Bullying is a considerable problem in schools. It has various negative effects on the children involved. The purpose of this qualitative study was to explore how children themselves interpret and construct bullying. Three elementary school classes with a high number of victim nominations were chosen among the 48 classes taking part in a larger study. The pupils from selected classes were interviewed in small groups. The interviews were tape‐recorded, transcribed and analyzed using the discourse analytical methodology described by Potter and Wetherell [1987]. Various recurrently used systems of terms (e.g., interpretative repertoires) were found. The results suggest that bullying can be construed as unproblematic and justified among children. For example, the ‘interpretative repertoire of underestimation’ constructs bullying as a game or some other harmless action, the ‘odd student repertoire’ describes the victim as a negatively deviant student who cannot behave as he/she should and the ‘interpretative repertoire of deserving’ constructs meaningful reasons for hostility towards the victim. These and other interpretative repertoires are described and discussed. Aggr. Behav. 29:134–154. © 2003 Wiley‐Liss, Inc.
On the terminal region of model predictive control for non‐linear systems with input/state constraints
Authors: Chen Wen‐Hua , O'Reilly John , Ballance Donald J.
Published: April 2003

This paper addresses the terminal region of model‐based predictive control (MPC) for non‐linear systems with control input and state constraints. Based on a stability condition of non‐linear MPC, a method to determine the terminal weighting term in the performance index and the terminal stabilizing control law to enlarge the terminal region and thus the domain of attraction of the non‐linear MPC is proposed. An LMI based optimization approach is developed to choose the terminal weighting item and fictitious terminal stabilizing control law so as to enlarge the terminal region of the non‐linear MPC method. The proposed method is illustrated by a numerical example and compares favourably with existing results. Copyright © 2003 John Wiley & Sons, Ltd.
Adaptive control for non‐negative and compartmental dynamical systems with applications to general anesthesia
Authors: Haddad Wassim M. , Hayakawa Tomohisa , Bailey James M.
Published: April 2003

Non‐negative and compartmental dynamical system models are composed of homogeneous interconnected subsystems or compartments which exchange variable non‐negative quantities of material with conservation laws describing transfer, accumulation, and elimination between the compartments and the environment. These models are widespread in biological and physiological sciences and play a key role in understanding these processes. In this paper, we develop a direct adaptive control framework for linear uncertain non‐negative and compartmental systems. The proposed framework is Lyapunov‐based and guarantees partial asymptotic set‐point regulation; that is, asymptotic set‐point stability with respect to part of the closed‐loop system states associated with the plant. In addition, the adaptive controller guarantees that the physical system states remain in the non‐negative orthant of the state space. Finally, a numerical example involving the infusion of the anesthetic drug propofol for maintaining a desired constant level of depth of anesthesia for non‐cardiac surgery is provided to demonstrate the efficacy of the proposed approach. Copyright © 2003 John Wiley & Sons, Ltd.
Fixed‐point steady‐state analysis of adaptive filters
Authors: Yousef Nabil R. , Sayed Ali H.
Published: April 2003

The steady‐state performance of adaptive filters can vary significantly when they are implemented in finite precision arithmetic, which makes it vital to analyse their performance in a quantized environment. Such analyses can become difficult for adaptive algorithms with non‐linear update equations. This paper develops a feedback and energy‐conservation approach to the steady‐state analysis of quantized adaptive algorithms that bypasses some of the difficulties encountered by traditional approaches. Copyright © 2003 John Wiley & Sons, Ltd.
Crane‐Heise syndrome: A second familial case report with elaboration of phenotype
Authors: Zand Dina J. , Carpentieri David , Huff Dale , Medne Livija , Napierala Dobrawa , Lee Brendan , Zackai Elaine
Published: March 2003

The constellation of features in Crane‐Heise syndrome (CHS) includes 1) poorly mineralized calvarium, 2) characteristic facial anomalies, and 3) extracranial skeletal anomalies that involve both vertebral anomalies and absent clavicles. Since the original report of Crane and Heise [1981: Pediatrics 68:235–237] describing three affected siblings, there have been few isolated cases published. We present two siblings from a second pedigree with features strikingly similar to those presented in the original publication, and distinct clinical differences, including distal phalangeal hypoplasia and mild cardiac and GI abnormalities that may represent familial variation. Despite extensive cytogenetic, molecular, and biochemical analyses, we could not elucidate a molecular mechanism for this rare phenotype. © 2003 Wiley‐Liss, Inc.
Ten years follow up of a boy with a complex chromosomal rearrangement: Going from a > 5 to 15‐breakpoint CCR
Authors: Houge Gunnar , Liehr Thomas , Schoumans Jacqueline , Ness Gro O. , Solland Kjetil , Starke Heike , Claussen Uwe , Strømme Petter , Åkre Bjug , Vermeulen Stefan
Published: March 2003

A moderately mentally retarded 10‐year‐old boy of very short stature was found initially to have a complex chromosomal rearrangement (CCR) involving chromosome 1, 2, 3, 4, and 8. A balanced twelve‐breakpoint CCR was suggested after extensive investigations including subtelomere FISH, whole chromosome paints, comparative genomic hybridization (CGH), multicolor FISH (MFISH), and spectral karyotyping (SKY). SKY and MFISH gave slightly discrepant results. For further clarification of the karyotype, multicolor banding (MCB) analysis and FISH with region‐specific YAC probes were done. This allowed clarification of a sixteen‐fragment CCR to be made, the most complex constitutional chromosomal rearrangement reported so far. Remarkably, two ‘secondary’ insertions originated from the interior of a ‘primary’ insertion by an excision/duplication event. The randomness of the fragments and the complexity of the derivative chromosomes suggest that this CCR is the result of a single meiotic event, e.g., faulty repair of a five‐chromosome knot. © 2003 Wiley‐Liss, Inc.
New heritable fragile site at 15q13 in both members of a nonconsanguineous couple
Authors: Karadeniz Nadide Nilüfer , Tunca Yusuf , Imirzalıoğlu Necat
Published: March 2003

The detection of a fragile site in a patient often causes concerns due to its potential significance and the necessity to be followed‐up properly with genetic counseling. Here we present a new heritable fragile site at 15q13, which was spontaneously expressed at a high frequency in lymphocytes culture of both members of a nonconsanguineous couple with recurrent abortions. The fragile site was not detected in the parents of the female, while the male had inherited it from his father. The fragile site was seen ≥85% of cells in all the carriers. To the best of our knowledge, the presence of this fragile site is being described for the first time under different culture conditions. While it looks like the fragile site is harmless in all carriers, having heterozygosity in the couple may lead to homozygous offspring that could result in fetal loss. © 2003 Wiley‐Liss, Inc.
Intrachromosomal insertion translocation resulting in duplication of chromosome band Yq11.2 in two fertile brothers
Authors: Engelen J.J.M. , Arens Y.H.J.M. , Gondrie E.T.C.M. , Alofs M.G.P. , Loneus W.H. , Hamers A.J.H.
Published: March 2003

Chromosome analysis in a couple referred because of two spontaneous abortions showed a normal 46,XX karyotype in the 28‐year‐old female and an aberrant Y chromosome with an enlarged short arm in the 30‐year‐old male. Subsequent chromosome analysis showed that his 33‐year‐old brother was carrier of the same Y chromosome aberration. Further characterization of the aberrant Y chromosome with FISH using probes specific for chromosome bands Yp11.32, Yq11.2, the centromere and the subtelomeric region of the p‐arm of the Y chromosome showed that chromosome band Yq11.2 was duplicated and inserted in the p‐arm of the Y chromosome. Combining the results of the analysis of GTG‐banded chromosomes and of the FISH analysis we conclude that both patients have a 46,X,ins dup(Y)(pter → p11.23::q12 → q11.1::p11.23 →) karyotype. The clinical and cytogenetical findings are reported and discussed. © 2003 Wiley‐Liss, Inc.
Noonan‐like syndrome with loose anagen hair: A new syndrome?
Authors: Mazzanti Laura , Cacciari Emanuele , Cicognani Alessandro , Bergamaschi Rosalba , Scarano Emanuela , Forabosco Antonino
Published: March 2003

We present three children with short stature, the same facial phenotype, macrocephaly, enlarged cerebral spinal fluid spaces, short neck with redundant skin, severe GH deficiency, mild psychomotor delay with attention deficit/hyperactivity disorder (ADHD), mild dilatation of the pulmonary root in two of them, and a unique combination of ectodermal abnormalities. Their appearance, not completely typical of Noonan syndrome, the behavioral phenotype, GH deficiency, darkly pigmented and hairless skin, and the unusual aspect of the hair, defined as loose anagen hair syndrome did not fit any known condition. We postulate that these children may represent a distinct, previously unreported syndrome that we would name “Noonan‐like syndrome with loose anagen hair”. © 2003 Wiley‐Liss, Inc.
Toward a genetic etiology of CHARGE syndrome: I. A systematic scan for submicroscopic deletions
Authors: Lalani Seema R. , Stockton David W. , Bacino Carlos , Molinari Laura M. , Glass Nancy L. , Fernbach Susan D. , Towbin Jeffrey A. , Craigen William J. , Graham John M. , Hefner Margaret A. , Lin Angela E. , McBride Kim L. , Davenport Sandra L. , Belmont John W.
Published: March 2003

CHARGE syndrome is a distinctive subgroup within the more heterogeneous group of patients with CHARGE association. While significant progress has been made in the clinical delineation of this syndrome, the molecular basis of the disorder remains unknown. Based on the complex phenotype, some overlap with DiGeorge/velocardiofacial syndrome (DGS/VCFS), and its estimated population incidence, we hypothesized that CHARGE syndrome could be caused by an unidentified genomic microdeletion. In order to address this hypothesis, we carried out a genome‐wide screen for loss of expected heterozygosity using 811 microsatellite markers in ten CHARGE syndrome subjects and their unaffected parents. Eight markers gave results suggestive of failure to inherit one parental allele. These loci were tested with fluorescence in situ hybridization (FISH), but none showed evidence of deletion. This screen sets upper limits on the length of a CHARGE‐related microdeletion, should that be the genetic mechanism underlying the phenotype. © 2003 Wiley‐Liss, Inc.
Pathogenic role of mtDNA duplications in mitochondrial diseases associated with mtDNA deletions
Authors: Odoardi Francesca , Rana Michele , Broccolini Aldobrando , Mirabella Massimiliano , Modoni Anna , D'Amico Adele , Papacci Manuela , Tonali Pietro , Servidei Serenella , Silvestri Gabriella
Published: March 2003

We estimated the frequency of multiple mtDNA rearrangements by Southern blot in 32 patients affected by mitochondrial disorders associated with single deletions in order to assess genotype‐phenotype correlations and elucidate the pathogenic significance of mtDNA duplications. Muscle in situ hybridization studies were performed in patients showing mtDNA duplications at Southern blot. We found multiple rearrangements in 12/32 (37.5%) patients; in particular, mtDNA duplications were detected in 4/4 Kearns‐Sayre syndrome (KSS), in 1 Pearson's syndrome, in 1/3 encephalomyopathies with progressive external ophthalmoplegia (PEO), and in 2/23 PEO. In situ studies documented an exclusive accumulation of deleted mtDNAs in cytochrome c oxidase negative fibers of patients with mtDNA duplications. The presence of mtDNA duplications significantly correlated with onset of symptoms before age 15 and occurrence of clinical multisystem involvement. Analysis of biochemical data documented a predominant reduction of complex III in patients without duplications compared to patients with mtDNA duplications. Our data indicate that multiple mtDNA rearrangements are detectable in a considerable proportion of patients with single deletions and that mtDNA duplications do not cause any oxidative impairment. They more likely play a pathogenic role in the determination of clinical expression of mitochondrial diseases associated with single mtDNA deletions, possibly generating deleted mtDNAs in embryonic tissues by homologous recombination. © 2003 Wiley‐Liss, Inc.
Recycling of high density polyethylene/poly(vinyl chloride)/polystyrene ternary mixture with the aid of high energy radiation and compatibilizers
Authors: Elmaghor Fathi , Zhang Liye , Li Hangquan
Published: March 2003

Ternary mixtures of waste plastics of high density polyethylene (HDPE), poly(vinyl chloride) (PVC), and polystyrene (PS) was recycled using a single‐screw extruder. Poly(ethylene‐co‐vinyl acetate) and poly(styrene‐b‐ethylene/butylenes‐b‐styrene) were introduced as compatibilizers for HDPE/PVC and HDPE/PS, respectively. After the polymer blends was prepared via extrusion, they were subjected to high energy irradiation. The morphology and the mechanical properties of the hybrid blends were examined. Scanning electron micrographs and transmission electron micrographs showed that both compatibilizers and irradiation improved the uniformity and dispersion of the system. The heterogeneous crosslinking generated by irradiation resulted in an optimum impact strength. High elongation at break was achieved by using compatibilizers. The improvement of tensile strength was moderate. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 12: 2756–2762, 2003
Rheological properties of semidilute solutions of poly(acrylic acid) modified with hydrocarbon and fluorocarbon end‐capped poly(ethylene glycol) macromonomer
Authors: Zhuang Dongqing , Zhang Hongdong , Yang Yuliang , Zhang Yunxiang
Published: March 2003

Hydrocarbon and fluorocarbon end‐capped poly(ethylene glycol) (PEG) macromonomers with 9, 23, and 45 ethylene oxide units were synthesized by the esterification method. Copolymerization of these macromers with acrylic acid (AA) resulted in hydrophobically grafted poly(AA)s (PAAs) containing different lengths of PEG spacers. Their solution properties were investigated by rheological measurements and compared to those without hydrocarbon and fluorocarbon groups and without PEG spacers. Evident hydrophobic association was found to exist in the aqueous solution of these hydrophobically grafted copolymers, and the associating efficiency was improved by the flexible PEG spacer compared to those counterparts without them. However, the intramolecular association became predominant with the spacer length increase and the solution viscosity decreased. A wide viscosity plateau was observed for macromer modified polyelectrolytes in the alkalization process, which was unavailable for hydrophobically modified ones without PEG spacers. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 12: 2777–2783, 2003
Self‐interference flow of an isotactic polypropylene melt in a cavity during injection molding. I. Effect of the self‐interference flow on the properties
Authors: Dai Wenli , Liu Pengsheng , Wang Xiayu
Published: March 2003

The self‐interference flow (SIF) of a melt in a cavity during injection molding is introduced. It comes from two streams of the melt being split by a patented mold gate called a twin gate. The effects of this flow on the static and dynamic mechanical properties, thickness distribution, and shrinkage in the transverse direction (TD) of injection‐molded isotactic polypropylene parts are discussed. SIF has an influence on the static mechanical properties, especially the impact strength. There are slight increases in the tensile strength and Young's modulus and an increase of approximately 70–90% in the impact strength in comparison with the properties of samples obtained by a conventional flow process with a common pin gate. Dynamic mechanical thermal analysis studies show an increase in the storage modulus for SIF samples. Results obtained from research into the effect of the mold temperature and injection pressure on the impact strength show that the impact strength of SIF specimens has a weaker dependence on the mold temperature and injection pressure. In addition, the flow brings a more uniform thickness distribution and a smaller shrinkage in the TD to SIF samples. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2784–2790, 2003
Water and temperature response of semi‐IPN hydrogels composed of chitosan and polyacrylonitrile
Authors: Kim Seon Jeong , Shin Su Ryon , Lee Song Min , Kim In Young , Kim Sun I.
Published: March 2003

Temperature‐responsive semi‐interpenetrating polymer networks (semi‐IPNs) constructed with chitosan and polyacrylonitrile (PAN) were crosslinked with glutaraldehyde. The semi‐IPN determined the sorption behavior of water at several temperatures and at a relative humidity (RH) of 95% using a dynamic vapor sorption (DVS) system. Water diffusion coefficients of semi‐IPNs were calculated according to the Fickian Law at several temperatures and exhibited a relatively water uptake, 0.1–0.4 at room temperature. The water uptake of hydrogels depended on temperature. The apparent activation energy was dependent of the composition of the semi‐IPN with value of 32.8–34.8 kJmol−1. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 12: 2721–2724, 2003
Chemorheological study of compatibilized blends of low‐density polyethylene and polydimethyl siloxane rubber
Authors: Jana R. N. , Nando G. B.
Published: March 2003

Compatibilization of the blends of polydimethyl siloxane (PDMS) rubber and low‐density polyethylene (LDPE) was achieved through reactive processing during extrusion in a Monsanto Processability Tester (MPT). The chemorheological characteristics of 50 : 50 LDPE : PDMS blends with varying proportions (0–8 wt %) of ethylene comethyl acrylate (EMA) were investigated at three different temperatures (170, 190, and 210°C) and four different shear rates (61.3, 122.6, 306.6, and 613.1 s−1). It was found that EMA reacts with vinyl groups of PDMS rubber at a temperature of 190°C during extrusion through the capillary of MPT, forming EMA‐grafted‐PDMS rubber (EMA‐g‐PDMS), which acts as the compatibilizer for the blend systems. The results are based on IR spectroscopy, melt rheology, and phase morphology of the blends. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 12: 2810–2817, 2003
Self‐interference flow of an isotactic polypropylene melt in a cavity during injection molding. II. Morphology and crystallinity
Authors: Dai Wenli , Lui Pengsheng , Wang Xiayu
Published: March 2003

This article is principally concerned with the morphology and crystallinity of isotactic polypropylene (iPP) parts molded by injection molding, during which a self‐interference flow (SIF) occurs for the melt in the cavity. Scanning electron microscopy shows that a transverse flow takes place in SIF samples. Wide‐angle X‐ray diffraction and differential scanning calorimetry show that SIF moldings exhibit a γ phase, in addition to α and β phases, and high crystallinity. Meanwhile, the results for iPP moldings made by the conventional flow process, that is, conventional injection molding, are reported for comparison. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2791–2796, 2003
Microcellular foam of polymer blends of HDPE/PP and their composites with wood fiber
Authors: Rachtanapun P. , Selke S. E. M. , Matuana L. M.
Published: March 2003

In this study, the effects of batch processing conditions (foaming time and temperature) and blend composition as well as the effect of incorporating wood fiber into the blends on the crystallinity, sorption behavior of CO2, void fraction, and cellular morphology of microcellular foamed high‐density polyethylene (HDPE)/polypropylene (PP) blends and their composites with wood fiber were studied. Blending decreased the crystallinity of HDPE and PP and facilitated microcellular foam production in blend materials. The void fraction was strongly dependent on the processing conditions and on blend composition. Foamed samples with a high void fraction were not always microcellular. The addition of wood fiber inhibited microcellular foaming. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2842–2850, 2003
Effect of amphiphilic surfactant agents on the gastrointestinal absorption of albendazole in cattle
Authors: Virkel Guillermo , Imperiale Fernanda , Lifschitz Adrián , Pis Alejandra , Alvarez Ana , Merino Gracia , Prieto Julio , Lanusse Carlos
Published: April 2003

Albendazole (ABZ) is a widely used broad‐spectrum benzimidazole (BZD) anthelmintic. Low hydrosolubility and poor/erratic gastrointestinal (GI) absorption play against the systemic availability and resultant clinical efficacy of BZD compounds. Different strategies are currently investigated to improve their bioavailability and efficacy in different animal species and humans. Surfactant agents facilitate dissolution of lipophilic drugs and increase membrane permeability. The influence of amphiphilic surfactants on the pattern of absorption and systemic availability of ABZ and its metabolites in cattle was characterized in the current trial. Twenty (20) parasite‐free Holstein calves (100–120 kg) were randomly allocated into four groups and treated intraruminally (10 mg/kg) using one of the following ABZ suspensions: control without surfactant (75/25 dimetyl sulphoxide/saline solution) (group A), 5 mM sodium taurocholate (STC) in saline solution (group B), 8.27 mM sodium lauryl sulphate (SLS) in saline solution (group C) and a commercial formulation (Valbazen®, Pfizer Inc. SA) (group D). Jugular blood samples were taken over 72 h post‐treatment and plasma analysed by HPLC. Albendazole sulphoxide (ABZSO) and sulphone were the metabolites found in plasma. STC did not affect ABZ absorption while increased ABZSO peak plasma concentration (Cmax) (158% higher, P<0.001) was observed following co‐administration of ABZ plus SLS, compared to the control group without surfactant. ABZSO plasma availability was significantly greater after the ABZ–SLS (164%) co‐administration compared to that obtained in the control group without surfactant. A similar ABZSO plasma availability was obtained following the treatments with the ABZ‐SLS and the commercially available formulation. SLS‐mediated enhanced dissolution and absorption of ABZ accounted for the observed increased systemic availability of the active ABZSO metabolite in cattle. These results should be considered among strategies to improve the use of BZD anthelmintics. Copyright © 2003 John Wiley & Sons, Ltd.
Potentiation of domperidone‐induced catalepsy by a P‐glycoprotein inhibitor, cyclosporin A
Authors: Tsujikawa Kenji , Dan Yukihiko , Nogawa Kiyoko , Sato Hitoshi , Yamada Yasuhiko , Murakami Hideyasu , Ohtani Hisakazu , Sawada Yasufumi , Iga Tatsuji
Published: April 2003

The distribution of domperidone (DOM), a peripheral dopamine D2 receptor antagonist, to the brain is restricted by P‐glycoprotein (P‐gp) at the blood–brain barrier (BBB) and for this reason, DOM rarely causes parkinsonian symptoms, such as extrapyramidal side effects (EPS), unlike other dopamine D2 antagonists. In this study, we aimed to investigate whether cyclosporin A (CsA), a P‐gp inhibitor, potentiates EPS induced by DOM.

The intensity of EPS was assessed in terms of the duration of catalepsy in mice. D1, D2 and mACh receptor occupancies at the striatum were measured in vivo and in vitro. Moreover, the distribution of DOM to the brain was investigated by using an in situ brain perfusion technique. The intensity of DOM‐induced catalepsy was significantly potentiated by the coadministration of CsA. The in vivo occupancies of D1, D2 and mACh receptors, as well as the brain distribution of DOM, were increased by CsA. These results suggest that CsA increases the brain distribution of DOM by inhibiting P‐gp at the BBB, and potentiates catalepsy by increasing the occupancies of the D1 and D2 receptors. The risk of DOM‐induced parkinsonism may be enhanced by the coadministration of CsA. Copyright © 2003 John Wiley & Sons, Ltd.
Pharmacokinetics and allometric scaling of levormeloxifene, a selective oestrogen receptor modulator
Authors: Østerberg O. , Kiehr B. , Erichsen L. , Poulsen H.E. , Ingwersen S.H.
Published: April 2003

The pharmacokinetics of a new selective oestrogen receptor modulator levormeloxifene was investigated in mice, rats, cynomolgus monkeys and humans by compartmental pharmacokinetics. Levormeloxifene was administered as an oral solution in all studies. Allometric scaling was used to predict human pharmacokinetic parameters and the performance of the approach was evaluated. Mean values of clearance confounded by F(CL/F) were 0.073, 0.29, 3.18 and 2.4 l/h in mice, rats, monkeys and humans, respectively. Values of distribution volume at steady state confounded by F(Vss/F) were 0.073 and 7.5 l in mice and rats. In monkeys, values of the central volume F(Vc/F) and volume at steady state F(Vss/F) were 28.9 and 57.9 l, respectively. In humans, values of Vc/F and Vss/F were 106 and 587 l, respectively. Predicted CL/F and Vss/F showed a linear relationship when plotted vs BW on a log–log scale; for CL/F, r was 0.95–0.98 and for Vss/F, r was 0.99. Using allometric scaling the predicted human Vss/F deviated 3‐fold from the experimentally determined values. Observed values of CL/F deviated 21–25 fold from the predicted, the latter depending on the scaling method. Confidence intervals for the predicted parameters showed major lack of precision for all the allometric scaling methods. Copyright © 2003 John Wiley & Sons, Ltd.
Evaluation of the pharmacokinetic profiles of the new testosterone topical gel formulation, Testim™, compared to AndroGel®
Authors: Marbury T. , Hamill E. , Bachand R. , Sebree T. , Smith T.
Published: April 2003

A two‐period, randomized, complete crossover study was performed to evaluate the pharmacokinetic profiles of Testim™ (AA2500), a new 1% testosterone topical gel formulation, compared to AndroGel®, an already available 1% testosterone topical gel. Twenty‐nine hypogonadal subjects received a single dose (50 mg testosterone) of each formulation seven days apart. Cmax estimates for total testosterone, dihydrotestosterone and free testosterone were greater (30, 19 and 38%, respectively) following the application of Testim™ compared to AndroGel®. Similarly, AUC0−24 estimates for total testosterone, dihydrotestosterone, and free testosterone were greater (30, 11 and 47%, respectively) following the application of Testim™ compared to AndroGel®. Confidence intervals for Cmax and AUC0−24 were not wholly contained within the bioequivalence limits for testosterone, therefore Testim™ and AndroGel® are not bioequivalent with Testim™ providing higher serum levels and greater bioavailability than AndroGel®. Copyright © 2003 John Wiley & Sons, Ltd.
Gastrointestinal transit of liquids in unfed cynomolgus monkeys
Authors: Kondo Hiromu , Takahashi Yutaka , Watanabe Takashi , Yokohama Shigeharu , Watanabe Jun
Published: April 2003

In this study, the gastric emptying rate and oro‐caecal transit time of two liquid volumes (20 and 60 ml) were compared in unfed cynomolgus monkeys. First, the acetaminophen method was used to determine the gastric half‐emptying time (t50%). The mean t50% from seven monkeys was 21.2 min for the 20‐ml volume and 27.8 min for the 60‐ml volume. This mean t50% in monkeys is similar to that reported previously in fasting humans. Next, the sulfasalazine‐sulfapyridine method was used to determine median oro‐caecal transit times for the 2 liquid volumes; these times were 2.5 h for the 20‐ml volume and 2.3 h for the 60‐ml volume, which are about 1.5 h shorter than previously reported transit times in humans. An increase in volume administered did not significantly change either the t50% or oro‐caecal transit time. The data also show that variability in both t50% and oro‐caecal transit time within each monkey is not as great as the large variability between monkeys. Consequently, cynomolgus monkeys are good model animals to use for studies on the gastric emptying of drug‐containing liquids after fasting; however, analysis of results from bioavailability studies must compensate for differences in the oro‐caecal transit time between monkeys and humans. Copyright © 2003 John Wiley & Sons, Ltd.
Deep thoughts and shallow frames: on the susceptibility to framing effects
Authors: LeBoeuf Robyn A. , Shafir Eldar
Published: March 2003

This paper examines the occurrence of framing effects when more thought is given to problems. In Study 1, participants were presented with one of two frames of several decision problems. Participants' Need for Cognition (NC) scores were obtained, and half the participants were asked to justify their choices. Substantial framing effects were observed, but the amount of thought purportedly given to a problem, whether manipulated by justification elicitation or measured by NC scores, did not reduce the incidence of framing effects. In Study 2, participants responded to both frames of problems in a within‐subjects design. Again, NC scores were unrelated to responses on the first frame encountered. However, high‐NC, compared to low‐NC, participants were more consistent across frames of a problem. More thought, as indexed here, does not reduce the proclivity to be framed, but does promote adherence to normative principles when the applicability of those principles is detectable. Copyright © 2003 John Wiley & Sons, Ltd.
Searching for certainty in an uncertain world: the difficulty of giving up the experiential for the rational mode of thinking
Authors: Schul Yaacov , Mayo Ruth
Published: March 2003

Our research explores predictions that people make in a simple environment consisting of sequences of a binary signal followed by two possible outcomes. In order to optimize their prediction success, respondents should use a very simple decision rule, called maximization, whereby they consistently predict according to the signal. In line with past research, our findings show that even respondents who realized after the experiment that maximization is optimal failed to use it during the experiment itself. We discuss conditions that weaken or reinforce behaving according to the optimal rule in a repeated choice situation. Experiment 1 shows that individuals who are forced to plan their strategy and justify their actions are more likely to discover and use the optimal rule than those not forced to do so. Thinking about the appropriateness of one's performance can be done in two different orientations: focusing on the past (justifying past actions) or on the future (planning future action). Experiment 2 shows that planning induces rule‐base thinking, while justifying fails to do so. These findings are discussed within a theoretical framework which suggest an interplay between the experiential and the rational modes of processing. Copyright © 2003 John Wiley & Sons, Ltd.
The influence of reasons on interpretations of probability forecasts
Authors: Flugstad Annette R. , Windschitl Paul D.
Published: March 2003

When providing a probability estimate for an event, experts often supply reasons that they expect will clarify and support that estimate. We investigated the possible unintended influence that these reasons might have on a listener's intuitive interpretation of the event's likelihood. Experiments 1 and 2 demonstrated that people who read positive reasons for a doctor's probability estimate regarding a hypothetical surgery were more optimistic than those who read negative reasons for the identical estimate. Experiment 3 tested whether a doctor's failure forecast for a surgery would result in differing levels of pessimism when the potential risk was attributed to one complication that had a probability of 0.30 versus three complications that had a disjunctive probability of 0.30. Overall, the findings are consistent with the argument that a probability estimate, albeit numerically precise, can be flexibly interpreted at an intuitive level depending on the reasons that the forecaster provides as the basis for the estimate. Copyright © 2003 John Wiley & Sons, Ltd.