bluuebunny/crossref_metadata_2025 huggingface dataset:
Laryngeal cancer patients: Analysis of patient delay at different tumor stages
Authors: Brouha Xavier D. R. , Tromp Debbie M. , de Leeuw J. Rob J. , Hordijk Gert‐Jan , Winnubst Jacques A. M.
Published: January 2005

Background.

The aim of this study was to determine the length of stages (appraisal, illness, behavioral, and scheduling) of patient delay in patients with head and neck cancer and to find out whether these delays were related to the stage of the disease at diagnosis.

Methods.

Before treatment, 117 newly diagnosed patients with laryngeal cancer were interviewed about their prediagnostic period. To determine the length of the different stages of patient delay, patients were asked about their symptoms, attributions of symptoms, and reasons to postpone medical consultation. A questionnaire was sent to the general practitioner and to a close relative to verify their answers.

Results.

There was no significant difference in the length of patient delay between early‐ (T1–T2) and advanced‐ stage (T3–T4) disease (9 vs 5 weeks; p = .07). Only tumor site was significantly associated with patient delay. The median total patient delays for glottic and supraglottic tumors were 10 and 4 weeks, respectively (p = .00). Hoarseness/voice change was the most commonly mentioned symptom. Patients attributed their symptom most frequently to a common cold/infection or had no idea about the cause. Medical attention was postponed because symptoms were interpreted as innocuous/benign or the symptom was thought not to be serious enough. The main reason to visit the general practitioner was persistent hoarseness. Behavioral and scheduling delays were of minor importance.

Conclusions.

Patient delay was significantly longer in cases of glottic cancer, but diagnosis at an early stage of the disease was more frequent among these patients than among patients with supraglottic cancer. Advanced supraglottic cancer probably has a late onset of symptoms. Thus, earlier intervention will probably not result in a significantly higher proportion of small supraglottic cancers being diagnosed. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Psychosocial effects in long‐term head and neck cancer survivors
Authors: Holloway Richard L. , Hellewell James L. , Marbella Anne M. , Layde Peter M. , Myers Katherine B. , Campbell Bruce H.
Published: January 2005

Background.

To identify and rate the importance of several psychosocial and physiologic influences on quality of life (QOL) among a cohort of 5‐year head and neck cancer survivors, we conducted a cross‐sectional study of a convenience sample that used both questionnaires and physiologic evaluations.

Methods.

QOL was assessed by the Functional Assessment of Cancer Therapy (FACT) and the FACT Head and Neck additional concerns (FACT‐H&N) questionnaires. Psychosocial characteristics (or risk factors) potentially influencing QOL were measured by the Millon Behavioral Health Inventory (MBHI) and the Social Support Questionnaire (SSQSR). Physiologic risk factors were measured in examinations that included shoulder and neck range of motion, whole and stimulated saliva measurements, and oropharyngeal swallowing efficiency. We evaluated the association of selected QOL measures with three groups of potential risk factors: psychosocial factors, consisting of selected MBHI and SSQSR scales; physiologic factors, consisting of selected physical ability measures; and a combination of psychosocial/physiologic factors.

Results.

The entire study population of 105 subjects completed the FACT and FACT‐H&N questionnaires; 86 of these completed the physiologic tests as well. Combined psychosocial/physiologic models best predicted all QOL measures considered. Psychosocial models alone, compared with physiologic models alone, better predicted FACT physical and social/family well‐being measures. Physiologic models alone, compared with psychosocial models alone, better predicted FACT‐H&N additional concerns measures. Premorbid pessimism (MBHI) was consistently the best predictor of QOL measures.

Conclusions.

Both psychosocial and physiologic factors influence QOL in patients with head and neck cancer, but many QOL measures are most strongly influenced by psychosocial considerations. Physicians and surgeons caring for long‐term head and neck cancer survivors should be cognizant of the importance of psychosocial risk factors in the QOL of their patients. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Spatiotemporal analysis of NO production upon NMDA and tetanic stimulation of the hippocampus
Authors: Takata Norio , Harada Tokiko , Rose John A. , Kawato Suguru
Published: January 2005

Nitric oxide (NO) is a gaseous neuromessenger. Although increasing evidence reveals significant physiological effects of NO in the hippocampal synaptic plasticity, the spatial distribution of NO production has remained largely uncharacterized due to the poor development of techniques for real‐time NO imaging. In this work, using a NO‐reactive fluorescent dye, diaminorhodamine‐4M (DAR‐4M), time‐dependent heterogeneous NO production is demonstrated in hippocampal slices upon N‐methyl‐D‐aspartate (NMDA) stimulation or tetanic stimulation. NMDA‐induced DAR fluorescence increase in the CA1 was found to be twice that in the CA3 and the dentate gyrus (DG). Intracellular Ca2+ concentration was also investigated. NMDA induced similar Ca2+ responses both in the CA1 and DG, which were approx. 13% greater than that in the CA3. Subsequently, spatial distribution of NO production in the CA1 upon a tetanic stimulation of Schaffer collateral was investigated, because there are contradictory reports on the effect of NO on long‐term potentiation (LTP), and that NO is known to exert various physiological effects depending on its concentration. In the stratum radiatum (sr), DAR fluorescence increase upon tetanus was largest at the vicinity of a stimulating electrode and decreased as a function of increasing distance from the stimulating electrode, suggesting the possibility that the effect of NO in LTP is dependent on the distance between stimulating and recording electrodes. The tetanus‐induced Ca2+ response observed in the sr showed the same but weak distant dependence from the stimulating electrode. Taken together, the observed heterogeneity in the distribution of NO production is suggestive of region‐specific effects of NO in the hippocampus. © 2005 Wiley‐Liss, Inc.
Synthesis of N‐Acetylglucosamine‐Derived Nagstatin Analogues and Their Evaluation as Glycosidase Inhibitors
Authors: Terinek Miroslav , Vasella Andrea
Published: January 2005

The gluco‐configured analogue 15 of nagstatin (1) and the methyl ester 14 were synthesized via condensation of the thionolactams 17 or 18 with the β‐amino ester 19. The silyl ethers 20 and 21 resulting from 17 were desilylated to 22 and 23; these alcohols were directly obtained by condensing 18 and 19. The attempted substitution of the C(8)OH group of 22 by azide under Mitsunobu conditions led unexpectedly to the deoxygenated α‐azido esters 24. The desired azide 25 was obtained by treating the manno‐configured alcohol 23 with diphenyl phosphorazidate. The azide was transformed to the debenzylated acetamido ester 14 that was hydrolyzed to the nagstatin analogue 15. The imidazole‐2‐acetates 14 and 15 are nanomolar inhibitors of the N‐acetyl‐β‐glucosaminidases from Jack beans and from bovine kidney, submicromolar to micromolar inhibitors of the β‐glucosidase from Caldocellum saccharolyticum, and rather weak inhibitors of the snail β‐mannosidase. In all cases, the ester was a stronger inhibitor than the corresponding acid. As expected from their gluco‐configuration, both imidazopyridines 14 and 15 are stronger inhibitors of the β‐N‐acetylglucosaminidase from bovine kidney than nagstatin.
Synthesis of Dendritic Metalloporphyrins with Distal H‐Bond Donors as Model Systems for Hemoglobin
Authors: Felber Beatrice , Diederich François
Published: January 2005

We report the synthesis of the first‐ (G1) and second‐generation (G2) dendritic FeII porphyrins 1⋅Fe–4⋅Fe (G1) and 6⋅Fe (G2) bearing distal H‐bond donors ideally positioned for stabilization of FeIIO2 adducts by H‐bonding (Fig. 1). A first approach towards the construction of these novel biomimetic systems failed unexpectedly: the Suzuki cross‐coupling between appropriately functionalized ZnII porphyrins and ortho‐ethynylated aryl derivatives, serving as anchors for the distal H‐bond donor moieties, was unsuccessful (Schemes 1, 3, and 5), presumably due to steric hindrance resulting from unfavorable coordination of the ethynyl residue to the Pd species in the catalytic cycle (Scheme 6). The target molecules were finally prepared by a route in which the ortho‐ethynylated meso‐aryl ring is introduced during porphyrin construction in a mixed condensation involving the two dipyrrylmethanes 33 and 34, and aldehyde 36 (Schemes 7 and 8). Following attachment of the dendrons (Scheme 11), the distal H‐bond donors were introduced by Sonogashira cross‐coupling (Scheme 12), and subsequent metallation afforded the dendritic FeII porphyrins 1⋅Fe–6⋅Fe. 1H‐NMR Spectroscopy proved the location of the H‐bond donor moiety atop the porphyrin surface, and X‐ray crystal‐structure analysis of model system 45 (Fig. 2) revealed that this moiety would not sterically interfere with gas binding. With 1,2‐dimethyl‐1H‐imidazole (DiMeIm) as ligand, the dendritic FeII porphyrins formed five‐coordinate high‐spin complexes (Figs. 3 and 4) and addition of CO led reversibly to the corresponding stable six‐coordinate gas complexes (Fig. 6). Oxygenation, however, did not result in defined FeIIO2 complexes as rapid decomposition to FeIII species took place immediately, even in the case of the G2 dendrimer 6⋅Fe(DiMeIm) (Fig. 7). In contrast, stable gas adducts are formed between dendritic CoII porphyrins and O2 in the presence of DiMeIm as axial ligand, as revealed by electron paramagnetic resonance (EPR). The possible stabilization of these complexes through H‐bonding involving the distal ligand is currently under investigation in multidimensional and multifrequency pulse EPR experiments.
Rationale on the Abnormal Effect of Temperature on the Enantioselectivity in the Asymmetric Borane Reduction of Ketones Catalyzed by L‐Prolinol
Authors: Xu Jiaxi , Wei Tiezheng , Lin Shrong‐Shi , Zhang Qihan
Published: January 2005

The effect of temperature on the enantioselectivity of the oxazaborolidine‐catalyzed asymmetric borane reduction of ketones was investigated in the presence of (5S)‐3‐oxa‐1‐aza‐2‐borabicyclo[3.3.0]octane (=(3aS)‐tetrahydro‐1H,3H‐pyrolo[1,2‐c][1,3,2]oxazaborole; 1a) and its 2‐methoxy derivative (1b) as catalysts, which were synthesized from L‐prolinol with borane and trimethyl borate, respectively. The results indicate that the two catalysts induce a different temperature‐dependent enantioselectivity. The enantioselectivity of the B‐unsubstituted (5S)‐3‐oxa‐1‐aza‐borabicyclo[3.3.0]octane (1a) increases with increasing temperature, while its B‐methoxy‐substituted derivative 1b shows the highest enantioselectivity at ca. 50°. (5S)‐3‐Oxa‐1‐aza‐2‐borabicyclo[3.3.0]octane (1a) is more likely to dimerize than its 2‐methoxy derivative 1b. The conversion rates of L‐proline to L‐prolinol in the presence of different amounts of borane were also determined in this study.
Occurrence of Stilbene Glucosides in Upuna borneensis
Authors: Ito Tetsuro , Ali Zulfiqar , Iliya Ibrahim , Furusawa Miyuki , Tanaka Toshiyuki , Nakaya Ken‐ichi , Takahashi Yoshikazu , Sawa Ryuichi , Murata Jin , Darnaedi Dedy , Iinuma Munekazu
Published: January 2005

Four new stilbene glucosides, upunosides A (1), B (5), C (6), and D (7), were isolated from the stem of Upuna borneensis (Dipterocarpaceae) together with the three known glucosides 3, 4, and 8. Upunoside A (1) is the first natural instance of a glucoside of a resveratrol pentamer, and its aglycone has a dibenzo‐fused bicyclo[5.3.0]octadiene and two dihydrobenzofuran moieties. The relative structure of the aglycone was determined by spectral analysis including 1D and 2D NMR experiments.
Synthesis of Indolones via Radical Cyclization of N‐(2‐Halogenoalkanoyl)‐Substituted Anilines
Authors: Nishio Takehiko , Iseki Kyoko , Araki Norihito , Miyazaki Takenori
Published: January 2005

The radical reactions of N‐(2‐halogenoalkanoyl)‐substituted anilines (anilides) of type 1 have been investigated under various conditions. Treatment of compounds 1a–1o with Bu3SnH in the presence of (2,2′‐azobis(isobutyronitrile) (AIBN) afforded a mixture of the indolones (oxindoles) 2a–2o and the reduction products 5a–5o (Table 1). In contrast, the N‐unsubstituted anilides 1p–1s, 1u, and 1v gave the corresponding reduction products exclusively (Table 1). Similar results were obtained by treatment of 1 with Ni powder (Table 2) or wth Et3B (Table 3). Anilides with longer N‐(phenylalkyl) chains such as 6 and 7 were inert towards radical cyclization, with the exception of N‐benzyl‐2‐bromo‐N,2‐dimethylpropanamide (6b), which, upon treatment with Ni powder in i‐PrOH, afforded the cyclized product 9b in low yield (Table 4). Upon irradiation, the extended anilides 6, 7, 10, and 11 yielded the corresponding dehydrobromination products exclusively (Table 5).
Graphite/Methanesulfonic Acid (GMA) as a New Reagent for Sulfonylation of Phenols and Thia‐Fries Rearrangement of Aryl Sulfonates to Sulfonylphenols
Authors: Sharghi Hashem , Shahsavari‐Fard Zahra
Published: January 2005

A new facile method for direct sulfonylation of phenols was developed. Graphite in methanesulfonic acid (GMA) was used to prepare sulfonylphenols by sulfonylation of phenol and naphthalene derivatives with p‐toluenesulfonic acid (=4‐methylbenzenesulfonic acid) (Table 1) and the thia‐Fries rearrangement of aryl sulfonates (Table 4). Mechanistic studies showed that the sulfonylation reaction of phenols in GMA occurred through an initial sulfonate formation followed by a thia‐Fries rearrangement of the aryl sulfonate by an intermolecular mechanism (Scheme 3).
Protonation Equilibria of Hoechst 33258 in Aqueous Solution
Authors: Ladinig Manfred , Leupin Werner , Meuwly Markus , Respondek Michal , Wirz Jakob , Zoete Vincent
Published: January 2005

The bis‐benzimidazole derivative Hoechst 33258 (2′‐(4‐hydroxyphenyl)‐5‐(4‐methylpiperazin‐1‐yl)‐2,5′‐bi‐1H‐benzimidazole) binds to the minor groove of DNA duplexes and is widely used as fluorescent cytological stain for DNA. The neutral compound, 1, is amphiphilic with four basic and three acidic sites. We have determined all seven acidity constants by spectrophotometric titration to define the pH‐dependent distribution of species, from the fully protonated tetracation 14+ to the fully deprotonated trianion 13−, in aqueous solution. The structures of the intermediate protonation states were assigned with the aid of density‐functional calculations. Electrostatic interaction free energies were calculated to adjust the acidity constants of the molecular subunits of 1 to their environment in the species 14+ to 13−. The experimental and theoretical pKa values agree well, but they differ substantially from previous estimates given in the literature.
New Clerodane Diterpenoids from Casearia membranacea
Authors: Shen Ya‐Ching , Lee Cheng Lin , Khalil Ashraf Taha , Cheng Yuan‐Bin , Chien Ching‐Te , Kuo Yao‐Haur
Published: January 2005

Bioassay‐guided fractionation of an AcOEt extract of Casearia membranacea resulted in the isolation of six new clerodane diterpenes, caseamembrins G–L (1–6). The structures of the new compounds, including their relative configurations, were established by an extensive study of their spectral data, especially 2D NMR. The cytotoxic activities of the isolated diterpenes against human oral epidermoid (KB), cervical epitheloid (Hela), and liver (Hep59T/VGH) carcinoma cell lines were investigated.
Suberoretisteroids A–E, Five New Uncommon Polyoxygenated Steroid 24‐Ketals from the Hainan Gorgonian Suberogorgia reticulata
Authors: Zhang Wen , Guo Yue‐Wei , Gavagnin Margherita , Mollo Ernesto , Cimino Guido
Published: January 2005

Five new uncommon polyoxygenated steroids, namely suberoretisteroids A–E (1–5), were isolated from the gorgonian Suberogorgia reticulata, never studied so far. The structures and relative configurations of these new compounds were elucidated on the basis of extensive spectral analysis. This work led to the structural revision of some steroids previously found in the Indian gorgonian Gorgonella umbraculum.
Paneth, IUPAC, and the Naming of Elements
Authors: Koppenol Willem H.
Published: January 2005

The procedure for assigning names to elements by the International Union of Pure and Applied Chemistry involves establishing priority of discovery, then inviting the discoverers to suggest a name. This protocol is in contrast with the suggestions of Friedrich A. Paneth form 1947, who believed that the discoverers of an element have the undisputed right to name it. This difference in philosophy came to light during a workshop convened 10 years ago for the purpose of naming elements 104–109, when the discoverers of these elements contended that they were solely entitled to name them. During the debate, and in support of the name seaborgium for element 106, it was argued that gadolinium, samarium, gallium, einsteinium and fermium had been named after living scientists. The history of the naming of these elements demonstrates that this is not the case; Glenn T. Seaborg is the first scientist for whom an element was named during his lifetime.
Erythropoietin for the treatment of anemia associated with hematological malignancy
Authors: Littlewood T. J.
Published: January 2005

Anemia is common in patients with hematological malignancy. Most patients will have their anemia attributed to the anemia of chronic disease. The anemia of chronic disease is caused by cytokine mediated suppression of erythropoiesis and low serum erythropoietin levels are found in the majority of patients with cancer. Many of these anemic patients will be symptomatic with fatigue. Data from many studies indicates that treatment of anemic patients with erythropoietin will increase their hemoglobin concentration, decrease transfusion need and also improve their quality of life. A recent study also suggests that improving the hemoglobin level may improve the patients' prognosis but this finding needs to be confirmed. Copyright © 2001 John Wiley & Sons, Ltd.
Application of activity‐based costing (ABC) for a Peruvian NGO healthcare provider
Authors: Waters Hugh , Abdallah Hany , Santillán Diana
Published: January 2005

This article describes the application of activity‐based costing (ABC) to calculate the unit costs of the services for a health care provider in Peru. While traditional costing allocates overhead and indirect costs in proportion to production volume or to direct costs, ABC assigns costs through activities within an organization. ABC uses personnel interviews to determine principal activities and the distribution of individual's time among these activities. Indirect costs are linked to services through time allocation and other tracing methods, and the result is a more accurate estimate of unit costs.

The study concludes that applying ABC in a developing country setting is feasible, yielding results that are directly applicable to pricing and management. ABC determines costs for individual clinics, departments and services according to the activities that originate these costs, showing where an organization spends its money. With this information, it is possible to identify services that are generating extra revenue and those operating at a loss, and to calculate cross subsidies across services. ABC also highlights areas in the health care process where efficiency improvements are possible. Conclusions about the ultimate impact of the methodology are not drawn here, since the study was not repeated and changes in utilization patterns and the addition of new clinics affected applicability of the results.

A potential constraint to implementing ABC is the availability and organization of cost information. Applying ABC efficiently requires information to be readily available, by cost category and department, since the greatest benefits of ABC come from frequent, systematic application of the methodology in order to monitor efficiency and provide feedback for management. The article concludes with a discussion of the potential applications of ABC in the health sector in developing countries. Copyright © 2001 John Wiley & Sons, Ltd.
Utilization of district health services by injured persons in a rural area of Ghana
Authors: Mock Charles , Ofosu Anthony , Gish Oscar
Published: January 2005

Introduction

Injury is a significant health problem in many less developed countries. However, strategies for dealing with it have been only minimally addressed.

Goals

We ought to assess the pattern of health care utilization by injured persons in rural Ghana. We thus hoped to provide data that would assist in strengthening injury treatment in this setting.

Methods

Using household interviews, we surveyed 9442 person. We sought information on any injury during the previous year that resulted in one or more days of disability. Injured persons were interviewed regarding the mechanism of injury, treatment obtained and length of disability.

Results

During the previous year, 923 nonfatal injuries were reported. Half the injured persons (49%) received no formal medical care. When treatment was received, it was primarily delivered by a non‐doctor staffed primary health care (PHC) clinic. Such clinics provided treatment for 30% of all injured persons (58% of those receiving formal medical care). Twenty percent of the injured received hospital‐based care (39% of those receiving formal medical care). Among those using hospitals, the majority (92%) used district hospitals.

Conclusions

In this setting, efforts to improve injury treatment should include district hospitals and PHC clinics. At both there is a need to advance the concept of ‘essential’ injury treatment services, addressing equipment, supplies and training. Copyright © 2001 John Wiley & Sons, Ltd.
The concept of effectiveness—a blind alley? A study of different interpretations in a Swedish county council
Authors: Axelsson Lilian , Engström Agneta Kullén
Published: January 2005

Swedish health care organizations are experiencing pressure to make ever greater efforts to rationalize and to increase effectiveness in the way they plan and provide services. In order to gain a better understanding of the current practice of the three groups of key actors in Swedish health care—politicians, senior civil servants and operational managers—and their perception of effectiveness, a study was carried out in a Swedish county council using both qualitative and quantitative methods. While in general the concept of effectiveness is thought of as crucial, it is not clearly or uniformly defined within the organization. Each of the three groups defines the concept in a way that reflects their own function, which may lead efforts to achieve effectiveness into a blind alley. Copyright © 2001 John Wiley & Sons, Ltd.
Coordination and integration of disability services for the elderly: a viewpoint
Authors: Al Mahdy Husayn
Published: January 2005

The provision of disability services for the elderly in Australia is fragmented with areas of duplication arising chiefly from disorganized planning with the States and Territories providing certain services independent of Commonwealth contribution. It is suggested that the Commonwealth should be responsible for the complete provision of disability services for the elderly comprising community services and residential care. Private providers competing with each other for efficient provision of such services should be sought with financial incentives in funding arrangements encouraging healthy ageing thereby reducing expenditure in health care in the next decades. Copyright © 2001 John Wiley & Sons, Ltd.
Can a purchaser be a partner? nursing education in the English universities
Authors: Meerabeau E.
Published: January 2005

Since the early 1990s, public sector management in England has been exhorted to follow the example of the private sector, and ‘quasi‐markets’ have been established, for example in the health service. A quasi‐market also exists between the NHS and higher education for the purchasing (or procurement) of nursing education. This paper uses policy documents such as the National Health Service Executive Circular (March 1999) on ‘Good Contracting Guidelines’ for Non‐Medical Education and Training, plus other relevant literature on the commodification of higher education, quasi‐markets and contract theory to examine this market, and the confusion of two rhetorics, those of competition and partnership. Nursing occupies a marginal place in higher education in England, having only recently become part of it. The emphasis of the quasi‐market on the output of a trained ‘fit for purpose’ labour force combines with professional attempts to create an academic discipline, in complex ways which are as yet underanalysed. Copyright © 2001 John Wiley & Sons, Ltd.
Clinical guidelines: attitudes, information processes and culture in English primary care
Authors: Dowswell George , Harrison Stephen , Wright John
Published: January 2005

The application to clinical medicine of evidence‐based clinical guidelines is an increasingly international policy prescription, yet research on how such guidelines might be implemented has tended to focus on change initiatives without seeking to understand change processes. This paper reports an empirical study of guideline implementation in UK general practice. Most GPs welcome guidelines as a means of improving care, though have reservations about their authority, relevance and effect on professional autonomy. ‘Clan’ organizational culture predominates and general practices do not generally have well‐functioning internal arrangements for the management of clinical evidence and related information. We found no coherent relationships between these variables and practices' actual uptake of guidelines. Copyright © 2001 John Wiley & Sons, Ltd.
The practice characterization model: the importance of organizational life cycles and targeted interventions in general medical practice
Authors: Atkins E. M. , Duffy M. C. , Bain D. J.
Published: January 2005

In response to a climate of constant change and increasing demand for services, general practice in the UK has undergone significant modification over the last 10 years. It has become a multi‐disciplinary organisation encouraged by funding bodies to plan for service delivery using a more structured team based approach.

In Tayside in 1996, practices were charged with producing formal Practice Development Plans (PDPs) which would focus on priority areas aligned with the Health Boards own strategic plan–those were teamwork, information management and technology, and clinical service delivery.

The University of Dundee's Department of General Practice successfully applied for funding to develop ways of facilitating practices so that they could a) identify their own development priorities, and b) plan and implement action and learning to see these priorities through.

Using action research methodology, the project attempted to create a climate for change, provide support and training to see the changes implemented, and ensure commitment to the changes from all members of the practice team. The Facilitator adopted a flexible style varying her role between expert, guide and support.

Analysis of progress made by different practices, coupled with the Facilitator's in depth knowledge of them, suggested the importance of certain key aspects of practice organisation and culture. A practice characterisation model identified practices which were stable, currently coping, proactive and ready to face the challenge of change as best placed to engage in a full scale development programme. Other profiles suggested a range of alternative interventions as more likely to be acceptable and productive.
On a hiding to nothing? assessing the corporate governance of hospital and health services in New Zealand 1993–1998
Authors: Barnett Pauline , Perkins Rod , Powell Michael
Published: January 2005

In New Zealand the governance of public sector hospital and health services has changed significantly over the past decade. For most of the century hospitals had been funded by central government grants but run by locally elected boards. In 1989 a reforming Labour government restructured health services along managerialist lines, including changing governance structures so that some area health board members were government appointments, with the balance elected by the community. More market oriented reform under a new National government abolished this arrangement and introduced (1993) a corporate approach to the management of hospitals and related services. The hospitals were established as limited liability companies under the Companies Act. This was an explicitly corporate model and, although there was some modification of arrangements following the election of a more politically moderate centre‐right coalition government in 1996, the corporate model was largely retained. Although significant changes occurred again after the election of a Labour government in 1999, the corporate governance experience in New Zealand health services is one from which lessons can, nevertheless, be learnt. This paper examines aspects of the performance and process of corporate governance arrangements for public sector health services in New Zealand, 1993–1998. Copyright © 2001 John Wiley & Sons, Ltd.
Regulation effects on the lower Peace River, Canada
Authors: Peters Daniel L. , Prowse Terry D.
Published: January 2005

The headwaters of the Peace River, Canada became regulated in 1968 by a major hydroelectric facility and associated reservoir located in the Rocky Mountains. This paper examines the change to the downstream hydrographs that have resulted from regulation. To facilitate the comparison, a naturalized (without regulation effects) flow regime (1972–1996) was generated using a combination of hydrologic and hydraulic flow models. The results showed that even some 1100 km downstream, there have been significant changes to the hydrograph. Specifically, average winter flows were 250% higher, annual peaks (1‐day, 15‐day, 30‐day highs) were in the order of 35–39% lower, and overall variability in daily flows decreased. Despite the reduction in peaks and variability, however, the downstream hydrograph is far from flat and has retained the basic shape of the pre‐regulation hydrograph. This is primarily due to the strong influence of tributary inflow below the point of regulation. Recommendation for improvements to the model and future application of these data are also discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Job access at labour market entry and occupational achievement in the life course
Authors: van Ham Maarten
Published: January 2005

This paper addresses the question of the extent to which job access at labour market entry influences socio‐economic status later in life. Multivariate models of workers' socio‐economic status at the ages of 30, 40 and 50 were estimated using longitudinal data. The results show that job access at labour market entry is indeed instrumental in career advancement over the life course. The importance of job access at labour market entry increases significantly with age. Good job access at the beginning of the labour career evidently gives workers an advantage over others who start in less favourable labour markets. Copyright © 2003 John Wiley & Sons, Ltd.
Protection of endotoxin‐induced oxidative renal tissue damage of rats by vitamin E or/and EGb 761 treatment
Authors: Coskun Omer , Armutcu Ferah , Kanter Mehmet , Kuzey Gamze Mocan
Published: January 2005

The aim of the present study was to evaluate the possible protective effects of vitamin E and EGb 761 treatments, alone or in combination, against oxidative renal tissue damage in experimentally induced endotoxaemic rats. Fifty healthy male Wistar albino rats, weighing 150–250 g and averaging 12 weeks old, were allotted randomly into one of ﬁve experimental groups: A (untreated), B (endotoxaemic), C (endotoxaemic + vitamin E treated), D (endotoaxemic + EGb 761 treated) and E (endotoxaemic + vitamin E and EGb 761 treated), each containing ten animals. Group A received only an intraperitoneal (i.p.) injection of 2 ml of normal saline solution and served as the control. Groups B, C, D and E were administrated a single i.p. injection of 0.5 ml of endotoxin solution. In addition, groups C, D and E received i.p. injections of 600 mg kg−1 body mt. of vitamin E and oral extract of 50 mg kg−1 body wt. of EGb 761, alone or in combination, immediately after the endotoxin injection. The experiment lasted for 24 h. At the end of the experiment blood and tissue samples were obtained for biochemical and histopathological investigation. Endotoxin injection produced renal damage, increased lipid peroxidation and decreased antioxidant enzyme activity. Vitamin E or/and EGb 761 treatment decreased lipid peroxidation, increased antioxidant enzyme activity and also prevented renal tissue damage in experimentally induced endotoxaemic rats. In conclusion, vitamin E and EGb 761 treatment, alone or in combination, appears to be beneﬁcial in preventing endotoxin‐induced oxidative renal tissue damage and therefore shows potential for clinical use. Copyright © 2005 John Wiley & Sons, Ltd.
Segmentary effects on the renal proximal tubule due to hexachloro‐1,3‐butadiene in rats: biomarkers related to gender
Authors: Trevisan Andrea , Cristofori Patrizia , Beggio Michela , Venturini Matteo Borella , Marco Livio Di , Zanetti Edoardo
Published: January 2005

Renal tissue biomarkers (glutamine synthetase and p‐aminohippuric acid uptake) were studied in male and female rats after treatment with hexachloro‐1,3‐butadiene. Reduced glutathione content also was also determined in liver and kidney. Histopathological examination (light microscopy) was then performed. The aim was to deﬁne sex differences in nephrotoxic effects caused by the solvent injected i.p. at 50, 100 and 200 mg kg−1 dose. The rats were sacriﬁced 24 and 48 h after treatment; after 24 h a signiﬁcant (P < 0.05) dose‐dependent depletion of liver reduced glutathione was observed in male rats only; after 48 h male and female rats showed a signiﬁcant (P < 0.05) increase at 50 and 100 mg kg−1 doses. Reduced glutathione in the kidney was increased in male but not in female rats 24 and 48 h after treatment. Glutamine synthetase activity in renal tissue showed a signiﬁcant (P < 0.05) dose‐dependent decrease 24 and 48 h after treatment in both sexes, but is was signiﬁcantly (P < 0.05) greater in female rats after 48 h. p‐Aminohippuric acid uptake in renal cortical slices appeared signiﬁcantly (P < 0.05) decreased in both sexes at the higher dose 24 h after treatment but this was signiﬁcantly (P < 0.05) greater in female rats. A further signiﬁcant (P < 0.05) impairment was observed after 48 h in males treated with a 200 mg kg−1 dose. In addition, a slight but signiﬁcant (P < 0.05) loss of p‐aminohippuric acid uptake was observed 48 h after treatment with a 100 mg kg−1 dose in both sexes. Light microscopy showed that the pars recta of the proximal tubule was mainly affected and tubular damage increased according to dose and time, involving the inner medulla and cortex. In conclusion, female rats show a signiﬁcantly earlier and higher susceptibility of the kidney to toxic effects of hexachloro‐1,3‐butadiene. Copyright © 2005 John Wiley & Sons, Ltd.
Protective effects of MESNA (2‐mercaptoethane sulphonate) against acetaminophen‐induced hepatorenal oxidative damage in mice
Authors: Şener Göksel , Sehirli Özer , Cetinel Şule , Yeğen Berrak G. , Gedik Nursal , Ayanoğlu‐Dülger Gül
Published: January 2005

Acetaminophen, a widely used analgesic and antipyretic, is known to cause hepatic and renal injury in humans and experimental animals when administered in high doses. It was reported that these toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. In this study we aimed to investigate the possible beneﬁcial effect of 2‐mercaptoethane sulphonate (MESNA), an antioxidant agent, against acetaminophen toxicity in mice.

Balb‐c mice were injected i.p. with: vehicle (the control group); a single dose of 150 mg kg−1 MESNA (MES group); a single dose of 900 mg kg−1 i.p. acetaminophen (AA4h and AA24h groups); and MESNA, at a dose of 150 mg kg−1 after acetaminophen injection (AA4h‐MES and AA24h‐MES groups). The MESNA injection was repeated once more 12 h after the ﬁrst injection in the AA24h‐MES group. Blood urea nitrogen, serum creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in blood and glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver and kidney tissues were measured. Tissues also were examined microscopically.

Blood urea nitrogen and serum creatinine, which were increased signiﬁcantly (P < 0.001) following acetaminophen treatment were decreased signiﬁcantly (P < 0.05–0.001) after treatment with MESNA. The ALT and AST levels were also increased signiﬁcantly (P < 0.001) after acetaminophen treatment but were not reduced with MESNA. Acetaminophen treatment caused a signiﬁcant (P < 0.05–0.001) decrease in GSH levels whereas MDA levels and MPO activity were increased in both tissues. These changes were reversed by MESNA treatment. Collagen contents of the liver and kidney tissues were increased by acetaminophen treatment (P < 0.001) and reversed back to the control levels with MESNA. Our results imply that acetaminophen causes oxidative damage in hepatic and renal tissues and that MESNA, via its antioxidant effects, protects these tissues. Therefore, its therapeutic role as a ‘tissue injury‐limiting agent’ must be elucidated further in drug‐induced oxidative damage. Copyright © 2005 John Wiley & Sons, Ltd.
Characterization of the binding of cholera toxin to ganglioside GM1 immobilized onto microtitre plates
Authors: Dawson R. M.
Published: January 2005

Ganglioside GM1 is the receptor for cholera toxin on cell surfaces, and the binding of cholera toxin to GM1 immobilized on microtitre plates has been reported previously by several authors as an assay for the toxin (GM1‐ELISA). This assay has been examined in detail. Results were independent of the adsorption solvent for GM1 (methanol or phosphate‐buffered saline), the pH of aqueous solvents (7.4–10.2) and the temperature (4–37 °C). High and near‐maximal rates of absorbance change in the assay were found for lower concentrations of GM1 (100 ng ml−1) and for shorter incubation times (a few hours) than reported in the literature. A method was devised to provide a semi‐quantitative estimate of the amount of GM1 bound to the plate; this was found to be in the low nanogram range. Binding of cholera toxin to the immobilized GM1 required ≥1.5 h for maximal assay results. The failure of free GM1 in solution to displace cholera toxin once bound to immobilized GM1 indicated that binding to immobilized GM1 is irreversible in the time frame of the experiment. Data from the literature support the very slow dissociation rates of the toxin–GM1 complex. Copyright © 2005 John Wiley & Sons, Ltd.
Role of molecular geometry, valence charge distribution and vibrational modes in bioactivity of cyclodiene insecticides
Authors: Saxena P. N. , Gupta V. D.
Published: January 2005

Fourier transform infrared spectral measurement and complete normal mode calculations have been carried out for heptachlor and wedge modes have been identiﬁed. In addition, valence charge distributions have been obtained for aldrin, endrin, heptachlor, beta‐endosulfan, cis‐chlordane, trans‐chlordane, photo‐cis‐chlordane and photo‐trans‐chlordane using CNDO/2 (complete neglect of differential overlap) molecular orbital calculations. A toxicity parameter has been deﬁned as the product of the charge distribution and surface area of the corresponding active wedges, depending on the interacting structural features. The variation of this toxicity parameter is generally in order and in agreement with the reported measurements based on the corresponding order of observed ld50 values. Because of the structural features, the toxicity in these cases is a surface phenomenon rather than a volume effect as in the case of Gammexane, wherein the insecticide binds itself to membrane channels. Because the biological activity is a dynamic rather than a static phenomenon, it is expected that the normal modes involving the wedge atoms play an important role. Copyright © 2005 John Wiley & Sons, Ltd.
Effects of a single intratracheal administration of phenanthraquinone on murine lung
Authors: Hiyoshi Kyoko , Takano Hirohisa , Inoue Ken‐ichiro , Ichinose Takamichi , Yanagisawa Rie , Tomura Shigeo , Cho Arthur K. , Froines John R. , Kumagai Yoshito
Published: January 2005

Although several studies have reported that diesel exhaust particles (DEP) affect cardiorespiratory health in animals and humans, the responsible components in DEP for the effects remain to be deﬁned. Diesel exhaust particles contain quinones that can catalyse the generation of reactive oxygen species, resulting in the induction of oxidative stress. Oxidative stress can correlate with a variety of diseases and health effects. In the present study, we investigated the effects of phenanthraquinone — a relatively abundant quinone in DEP — on lung inﬂammation and the local expression of cytokine proteins in mice as a measure of oxidative damage. The animals were randomized into two experimental groups that received vehicle or phenanthraquinone by intratracheal instillation. The cellular proﬁles of bronchoalveolar lavage ﬂuid (BALF) and local expression of cytokines were evaluated 24 and 48 h after the instillation. Phenanthraquinone challenge revealed an increase in the numbers of neutrophils and eosinophils in BALF as compared to vehicle challenge (P < 0.05 at 48 h post‐instillation). Phenanthraquinone induced the lung expression of interleukin (IL)‐5 and eotaxin 48 h and 24 h after the challenge, respectively. These results indicate that intratracheal exposure to phenanthraquinone induces recruitment of inﬂammatory cells, at least partly, through the local expression of IL‐5 and eotaxin. Copyright © 2005 John Wiley & Sons, Ltd.
Weak inhibitors protect cholinesterases from strong inhibitors (paraoxon): in vitro effect of ranitidine
Authors: Petroianu G. A. , Arafat K. , Schmitt A. , Hasan M. Y.
Published: January 2005

Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition MCP is a weak and reversible inhibitor of cholinesterases. We have shown that MCP has a cholinesterase protective effect against inhibition by organophosphates. The putative mode of protective action of MCP is competition for the active site of the enzyme with the more potent organophosphate. In the present paper we present our results using another weak inhibitor of cholinesterases: ranitidine (RAN).

The purpose of the study was to quantify in vitro the extent of RAN‐conferred protection, using paraoxon (POX) as an inhibitor. Paraoxon is a non‐neuropathic organophosphate responsible for a large number of accidental or suicidal exposures.

Red blood cell (RBC) acetylcholinesterase (AChE) activities in whole blood and butyrylcholinesterase (BChE) activities in human plasma were measured photometrically in the presence of different POX and RAN concentrations and the ic50 was calculated. Determinations were repeated in the presence of increasing RAN concentrations. The ic50 shift induced by the presence of RAN increases with the RAN concentration in a linear manner. The shift was more pronounced with RBC‐AChE.

The protective effect of RAN on cholinesterase could be of practical relevance in the treatment of POX poisoning. We conclude that in vivo testing of RAN as an organophosphate protective agent is warranted. Copyright © 2005 John Wiley & Sons, Ltd.
Protective agents in acute high‐dose organophosphate exposure: comparison of ranitidine with pralidoxime in rats
Authors: Petroianu G. A. , Hasan M. Y. , Nurulain S. M. , Arafat K. , Shaﬁullah M. , Naseer O.
Published: January 2005

Weak and reversible inhibitors of cholinesterase, when coadministred in excess with a more potent inhibitor such as organophosphates, can act in a protective manner. Ranitidine (RAN) is a clinically widely used histamine type 2 (H2) receptor blocker. Ranitidine is also the most potent inhibitor of acetylcholinesterase among H2 blockers (inhibitory constant K in the low micromolar range) but roughly three orders of magnitude less potent than paraoxon. This study evaluates RAN‐conferred protection in acute high‐dose organophosphate (paraoxon, POX) exposure in rats in direct comparison with the therapeutic gold‐standard pralidoxime (PRX).

Group 1 received 1 µM POX, group 2 received 50 µM RAN, group 3 received 50 µM PRX, group 4 received 1 µM POX + 50 µM RAN and group 5 received 1 µM POX + 50 µM PRX. All substances were applied intraperitoneally. The animals were monitored for 48 h and mortality was recorded at 30 min and 1, 2, 3, 4, 24 and 48 h. Blood was taken for red blood cell acetylcholinesterase (RBC‐AChE) measurements at baseline, 30 min and 24 and 48 h. Mortality occurred mainly in the ﬁrst 30 min after POX administration, with minimal changes occurring thereafter. Mortality (in %) at 30 min in groups 1, 4 and 5 was 52 ± 18, 37 ± 20 and 17 ± 18, respectively, and mortality at 48 h was 59 ± 12, 39 ± 20 and 28 ± 20, respectively. The RBC‐AChE activities (in % of baseline values) at 30 min in groups 1, 4 and 5 were 18 ± 16, 47 ± 23 and 48 ± 20, respectively. At 24 h the values were 46 ± 16, 65 ± 24 and 86 ± 17, respectively, and at 48 h the values were 71 ± 19, 78 ± 21 and 110 ± 27, respectively.

Coadministration of PRX signiﬁcantly decreases mortality in the described model at all points in time. Coadministration of RAN statistically signiﬁcantly decreases mortality at 24 and 48 h. The extent of protection conferred by RAN is less (but not statistically signiﬁcantly so) than that conferred by the gold‐standard PRX. Coadministration of PRX statistically signiﬁcantly increases RBC‐AChE activities in the described model at all points in time. Ranitidine confers a statistically signiﬁcant protection for the enzyme at 30 min only.

We conclude that RAN is potentially of clinical use in reducing mortality in acute high‐dose organophosphate exposure. Further studies involving different organophosphates and dosages, as well as different animal species, will be needed both to conﬁrm these initial ﬁndings and to address the issue of the optimal timing for RAN preadministration. Copyright © 2005 John Wiley & Sons, Ltd.
Benzene increases the ratio of arachidonic acids to docosahexaenoic acids and inhibits the de novo synthesis of ceramide in the rat liver
Authors: Sul Donggeun , Shim Ilsub , Im Hosub , Won NamHee , Kim Hae‐Joon , Lee Eunil
Published: January 2005

The present study investigated the effects of inhalation exposure of benzene at 0, 10, 200 and 600 ppm for 1, 2 and 4 weeks on n‐6 and n‐3 fatty acids and ceramide levels in the rat liver. No signicant difference in the ratio of saturated fatty acid to unsaturated fatty acid was found on increasing benzene exposure levels, but the ratio of saturated fatty acid to unsaturated fatty acid decreased with increasing benzene exposure times, with the exception of the phospholipids of rats exposed to 200 and 600 ppm of benzene. A signicant increase in the ratio of arachidonic acid to docosahexaenoic acid was found in the phospholipids of rats exposed to 200 and 600 ppm of benzene for 4 weeks. In our study, no change in the relative amounts of sphingomyelin in phospholipids, due to benzene exposure at 600 ppm for 4 weeks resulted in the lack of sphingomyelin turnover. However, ceramide levels in the livers of rats exposed to 600 ppm of benzene for 4 weeks were signicantly reduced upon increasing the benzene concentration. This result shows that the de novo synthesis of ceramide was signicantly inhibited at higher levels of benzene and that the ratio of arachidonic acid to docosahexaenoic acid in phospholipids is dose‐dependently related to benzene exposure. Copyright © 2005 John Wiley & Sons, Ltd.