bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral outcome including attention deficit hyperactivity disorder/hyperactivity disorder and minor neurological signs in perinatal high‐risk newborns at 4−6 years of age with relation to risk factors
Authors: Sato Masuko , Aotani Hirofumi , Hattori Ritsuko , Funato Masahisa
Published: May 2004

Abstract
Background
: Diagnostic problems with the criteria of attention deficit hyperactivity disorder (ADHD) in the Diagnostic Statistical Manual, 4th edn, have been identified. The aim of this study was to clarify whether the minor neurological signs test (MNT) the authors had previously reported was a predictor for the criteria of ADHD or hyperactivity disorder (HD) in perinatal risk children at 4−6 years of age and what kind of risk factors related to MNT1.

Methods
: A total of 136 children discharged from neonatal intensive care units were examined at the age of 4−6 years by a developmental neuropediatrician using both MNT and diagnostic criteria of DSM‐IV ADHD/ICD‐10 (International Classification of Diseases, 10th edn) HD. SPSS base and professional were used for statistical analysis.

Results
: On comparison of diagnostic criteria between ADHD (11.0%) and HD (27.5%), the incidence in the same subjects showed significant difference. MNT scores showed significant correlation with criteria of ADHD (P < 0.01) and HD (P < 0.05). Diagnostic validity of MNT for predicting ADHD was demonstrated with 78% sensitivity and 79% specificity. High positive rates on MNT did not show a significant difference between the very low birthweight (VLBW) and non‐low birthweight (NLBW) groups. Behavioral outcome with relation to risk factors were analyzed using multiple regression analysis. Apgar 5 in the NLBW group and toxemia of pregnancy and small for gestational age (SGA) in VLBW group were highly correlated with behavioral outcome.

Conclusions
: Minor neurological signs test score was a significant predictor for criteria of ADHD and HD. High incidences of positive MNT were suspected in not only VLBW children but also NLBW children and Apgar 5 in NLBW children and toxemia of pregnancy and SGA in VLBW children influenced behavioral outcome.
Water and electrolyte absorption from hypotonic oral rehydration solution in rat small intestine and colon
Authors: Nishinaka Daisuke , Kishino Fumiharu , Matsuura Akihiro
Published: May 2004

Abstract
Background
: The authors evaluated and compared the efficacy of hypotonic oral rehydration solutions (ORS), isotonic ion solutions, and distilled water to elucidate the relation between net water absorption and osmolality, or between electrolyte absorption and their ion concentrations in rat small intestine and colon.

Methods
: Water and electrolyte absorption from two hypotonic ORS (Solita‐T granules No. 2 [STG2]; sodium 60 mEq/L, osmolality 249 mOsm/L, Solita‐T granules No. 3 [STG3]; sodium 35 mEq/L, osmolality 199 mOsm/L), two isotonic ion solutions (Aqualight [AL]; sodium 30 mEq/L, osmolality 290 mOsm/L, Pocarisweat [PS]; sodium 21 mEq/L, osmolality 300 mOsm/L), and distilled water, were evaluated by an in vivo perfusion technique with the small intestine and colon of anesthetized rats.

Results
: In the small intestine and colon, two hypotonic ORS significantly promoted net water absorption much greater than did two isotonic ion solutions (P < 0.05). Net sodium absorption from two hypotonic ORS was significantly greater than that from two isotonic ion solutions (P < 0.05). Sodium absorption from all solutions was greater in the colon than in the small intestine. Distilled water did not contribute to give net water absorption in the small intestine, but in the colon, it caused almost equivalent net water absorption to that by two hypotonic ORS. The largest amount of sodium secretion from the small intestine and colon was induced by distilled water.

Conclusions
: These data indicate that low osmolality is a crucial factor to facilitate water absorption, and the electrolytes, sodium and chloride, can effectively be salvaged in the colon.
Natural immunity to Haemophilus influenzae type B in children of Ankara, Turkey
Authors: Ocaktan Esin , Özyurda Ferda , Akar Nejat
Published: May 2004

Abstract
Background
: Haemophilus influenzae type b (Hib) infection has a high morbidity and mortality rate especially in children under 5 years of age. The incidence of Hib disease in Turkey is not known, and Hib vaccine is not included in the National Immunization Program. The aim of this study was to determine the natural immunity to Hib of children 6−60 months of age living in the Park Health Center region of Ankara, Turkey.

Methods
: A total of 270 children were selected by layered random sampling method, and 242 of them (89.6%) participated in the study. A questionnaire was given to the parents of the children who were included in the study and blood samples were taken from those children. Anti‐Hib IgG antibody (anti‐PRP) level was determined in the serum by using anti‐Haemophilus influenzae IgG EIA kit and anti‐PRP antibody levels of 0.15 µg/mL and over were accepted as the natural immunity.

Results
: Natural immunity was determined in 65.3% of the children. A relationship was determined statistically between the history of disease with possible Hib agent and with natural immunity.

Conclusions
: The exposure rate of children with Hib was higher than expected, even in children who were just a few months old. Our data revealed that multicentric, national studies should be done to define the burden of Hib disease before making a decision for Hib vaccine to be included in the National Immunization Program.
Clinical spectrum of acute abdominal pain in Turkish pediatric patients: A prospective study
Authors: Erkan Tülay , Çam Halit , Özkan Hilda Çerçi , Kiray Evrim , Erginoz Ethem , Kutlu Tufan , Tastan Yucel , Çullu Fugen
Published: May 2004

Abstract
Background
: The aim of the present study was to determine the prevalence, associated symptoms, and clinical outcomes of children with acute abdominal pain who had been admitted to an emergency department.

Methods
: Children aged between 2 and 16 years who presented to the emergency department of Cerrahpaşa Medical School, Istanbul University between July 2001 and August 2002 with acute abdominal pain were enrolled in this study. A questionnaire was completed each patient admitted to our pediatric emergency unit for acute abdominal pain. Data collected included presenting signs and symptoms, the hospital follow up for all children who returned within 10 days, test results, and telephone follow up.

Results
: The number of children referred to the emergency department was 7442, with 399 (5.4%) of these having acute abdominal pain. The mean age of the study population was 6.9 ± 3.5 years, and 201 of the patients were male. The five most prevalent diagnoses were: (i) upper respiratory tract infection and/or complicated with otitis media or sinusitis (23.7%); (ii) abdominal pain with uncertain etiology (15.4%); (iii) gastroenteritis (15.4%); (iv) constipation (9.4%); and (v) urinary tract infection (8%). The most common associated symptoms were decreased appetite, fever and emesis. Because of follow‐up deficiency the progress of 28 patients was not obtained. Eighty‐two children were referred to the department of pediatric surgery, but only 17 of 82 (20.7%) required surgical intervention (15 of these 17 for appendicitis). Eleven patients returned within 10 days for re‐evaluation, but the initial diagnosis was not changed. The complaints of 57 patients with uncertain etiology were resolved within 2 days.

Conclusions
: An acute complaint of abdominal pain was usually attributed to a self‐limited disease. However, the percentage of surgical etiology is not negligible.
A questionnaire survey on the use of quick‐acting insulin analog in Japanese children and adolescents with type 1 diabetes
Authors: Urakami Tatsuhiko , Kawamura Tomoyuki , Sugihara Shigetaka , Miyamoto Shigeki , Amemiya Shin , Sasaki Nozomu , Matsuura Nobuo
Published: May 2004

Abstract
Background
: The aim of this study was to investigate the actual condition of quick‐acting insulin analog (Q) in Japanese children and adolescents with type 1 diabetes.

Methods
: Forty‐seven physicians who managed 944 patients under 18 years of age with type 1 diabetes, were requested to complete questionnaires in May 2002 regarding the use of Q.

Results
: Q was administered to 417 out of 944 (44%) patients. The details of the daily insulin regimens were as follows: three doses of Q with basal insulin in 116 of 403 (29%), three doses of Q with more than twice the basal insulin in 69 of 403 (17%), and other modifications using either Q or regular insulin (R) depending on the patients’ lifestyles in 213 of 403 (53%). Q dose was equal to R after the change of insulin regimens in 232 of 290 (80%). After switching to Q from R, the basal insulin dosage increased in 113 of 341 (33%) and the number of basal insulin injections increased in 42 of 341 (12%). After the transfer to Q from R, glycemic control was judged to improve in 179 of 372 (48%), to have no significant change in 162 of 372 (44%), and to aggravate in 31 of 372 (8%). The majority of patients, (305/389; 78%), noted an improvement of quality of life (QOL) following the administration of Q.

Conclusions
: Q was considered to be useful in flexibility of daily insulin therapy and improvement of QOL in children and adolescents with type 1 diabetes. Insulin therapy for type 1 diabetes during childhood and adolescence should be tailored to meet individual needs.
Ineffective erythropoiesis underlies the clinical heterogeneity of congenital dyserythropoietic anemia type II (CDA II)
Authors: Kostaridou Stavroula , Polychronopoulou Sophia , Premetis Evangelos , Papassotiriou Ioannis , Stamoulakatou Alexandra , Haidas Stavros
Published: May 2004

Abstract
Background
: Congenital dyserythropoietic anemia type II (CDA II) is an autosomal recessive disease, and is the most common CDA. The qualitative and quantitative defects of erythropoiesis in CDA II, as estimated by the hematological and biochemical parameters at the time of diagnosis, may not reflect the heterogeneity of the disease course of each patient.

Methods
: Three pediatric patients with CDA II are herein presented, having an heterogeneous clinical course. In addition to bone marrow morphology, Ham test and SDS‐PAGE of erythrocyte membrane protein, the present study also examined erythroid marrow activity, by measuring serum Erythropoietin (Epo), soluble Transferrin Receptors (sTfR) concentrations and Reticulocyte Production Index (RPI).

Results
: All patients demonstrated the same pattern of ineffective erythropoiesis, having increased Epo (350−389 IU/L), sTfR concentrations (6.2−7.8 mg/L) and low RPI values (0.8−1.3). Erythron expansion was expressed by RPI values nearly twofold higher than normal values in parallel to raised sTfR and high Epo production. Despite the same degree of ineffective erythropoiesis seen in all patients, the severity of the clinical course was diverse in terms of frequency and clinical relevance of transfusion needs.

Conclusion
: An analysis of the parameters expressing ineffective erythropoiesis in CDA II can provide a better understanding of the degree of dyserythropoiesis, however it is not useful for predicting the clinical course of disease in patients, because the underlying genetic heterogeneity of this disorder remains obscure.
Analysis of factors that influence body mass index from ages 3 to 6 years: A study based on the Toyama cohort study
Authors: Sugimori Hiroki , Yoshida Katsumi , Izuno Takashi , Miyakawa Michiko , Suka Machi , Sekine Michikazu , Yamagami Takashi , Kagamimori Sadanobu
Published: May 2004

Abstract
Background
: The aim of the present study was to elucidate both environmental and behavioral factors that influence body mass index (BMI, kg/m2) among Japanese children from ages 3−6.

Methods
: In 1992 (at age 3) and 1995 (at age 6), 8170 6‐year‐old children (4176 boys and 3994 girls) were surveyed using a questionnaire on both body build (height and weight) and lifestyle. The correlation between BMI for 3‐year‐olds and for 6‐year‐olds were analyzed. From the temporal changes of body build between age 3 and 6 years, we categorized children into four groups: group 1, normal at both age 3 years and 6 years (normal/normal); group 2, overweight at age 3 years and normal at age 6 years (overweight/normal); group 3, normal at age 3 years and overweight at age 6 years (normal/overweight); and group 4, overweight at both age 3 years and 6 years (overweight/overweight). The authors compared the four groups with each other according to sex, concerning frequencies of children who matched the categories of environmental and behavioral factors. Each factor was tested using the χ2 test. Overweight children were defined as those whose BMI value was age‐sex specific in the 90th percentile or more.

Results
: A significant correlation was found between body builds for children aged 3 and 6 years in both genders (boys, r = 0.559, P < 0.01; girls, r = 0.584, P < 0.01). Significant factors associated with overweight children were diet (eating rice, green tea, eggs, meat, but less breads and juice), rapid eating, short sleep duration, early bedtime, long periods of television viewing, avoidance of physical activity, and frequent bowel movement.

Discussion
: Temporal changes in BMI from age 3 years to 6 years are significantly associated with both environmental and behavioral factors at age 6 years. The results of this study may be useful for health promotion programs designed to prevent obesity during the early stages of childhood.
Relation between predischarge auditory brainstem responses and clinical factors in high‐risk infants
Authors: Suzuki Naomitsu , Suzumura Hiroshi
Published: May 2004

Abstract
Background
: Advances in perinatal medicine have increased the survival rate of infants admitted to neonatal intensive care units (NICU). Some of the infants will have health problems including hearing disorder and/or brainstem dysfunction, and may have associated communicative and cognitive difficulties and/or repeated apnea attacks that require therapy or care.

Methods
: In this study, the authors measured mean thresholds and mean I−V interpeak latencies in 56 high‐risk infants and 30 controls who were about to be discharged from NICU. The authors retrospectively investigated whether predischarge auditory brainstem response (ABR) data, which seem to be related to a number of clinical factors affecting neonates, are useful for detecting hearing disorder and/or brainstem dysfunction, and we investigated six clinical factors.

Results
: The results showed that the positive risk factors for hearing impairment in infants who are about to be discharged from the NICU are: receiving mechanical ventilation (including for a period of <1 day) and the administration of five or more different antibiotics, especially in extremely low‐birthweight (ELBW) infants. Another result showed that the high‐risk mature infants had a significant high risk factor for brainstem dysfunction.

Conclusions
: The findings of the study emphasize the importance of performing ABR examinations in high‐risk infants, even in infants who are about to be discharged from an NICU. ABR examinations are especially important in ELBW infants or mature infants who have received mechanical ventilation or who have received five or more different antibiotics.
Facilitation of visuo‐motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans
Authors: Antal Andrea , Nitsche Michael A. , Kincses Tamás Z. , Kruse Wolfgang , Hoffmann Klaus‐Peter , Paulus Walter
Published: May 2004

Performance of visuo‐motor tasks requires the transfer of visual data to motor performance and depends highly on visual perception and cognitive processing, mainly during the learning phase. The primary aim of this study was to determine if the human middle temporal (MT)+/V5, an extrastriate visual area that is known to mediate motion processing, and the primary motor cortex are involved in learning of visuo‐motor coordination tasks. To pursue this, we increased or decreased MT+/V5, primary contralateral motor (M1) and primary visual cortex excitability by 10 min of anodal or cathodal transcranial direct current stimulation in healthy human subjects during the learning phase of a visually guided tracking task. The percentage of correct tracking movements increased significantly in the early learning phase during anodal stimulation, but only when the left V5 or M1 was stimulated. Cathodal stimulation had no significant effect. Also, stimulation of the primary visual cortex was not effective for this kind of task. Our data suggest that the areas V5 and M1 are involved in the early phase of learning of visuo‐motor coordination.
GABAergic synapses of the suprachiasmatic nucleus exhibit a diurnal rhythm of short‐term synaptic plasticity
Authors: Gompf Heinrich S. , Allen Charles N.
Published: May 2004

We examined synaptic plasticity at intrasuprachiasmatic nucleus (SCN) γ‐aminobutyric acid (GABA)ergic synapses by measuring the paired‐pulse ratio between pairs of evoked inhibitory postsynaptic currents (IPSCs). Interstimulus intervals were chosen to represent the range of spontaneous action potential firing frequencies found in SCN neurons. A majority of synapses studied during the day exhibited paired‐pulse depression (PPD), whereas a majority of synapses studied during the night showed no PPD. Two types of PPD were found. Type 1 PPD expresses the greatest inhibition at shorter interstimulus intervals, is predominant in the early morning and is likely to be a result of vesicle depletion. Type 2 showed the greatest inhibition at interstimulus intervals between 175 and 225 ms, is found throughout the day yet rarely at night and is likely to be a result of a Ca2+‐dependent mechanism that is independent of pertussis toxin‐sensitive G‐proteins. Thus, multiple mechanisms of synaptic plasticity modulate intra‐SCN communication throughout the diurnal cycle.
Thapsigargin‐induced mobilization of dendritic dense‐cored vesicles in rat supraoptic neurons
Authors: Tobin Vicky A. , Hurst Gillian , Norrie Linda , Dal Rio Francesco P. , Bull Philip M. , Ludwig Mike
Published: May 2004

Dense‐cored vesicles (DCVs) containing oxytocin or vasopressin are secreted from both the nerve terminals in the posterior pituitary and dendrites in the hypothalamus of magnocellular supraoptic neurons. Dendritic secretion can be enhanced (primed) by pretreatment with either thapsigargin or oxytocin for subsequent activity‐dependent release. Here, we determined whether priming involves a translocation of DCV closer to the dendritic membrane. To reduce total vesicle content, rats were salt‐loaded for 24 h before application of thapsigargin or vehicle onto the ventrally exposed surface of the supraoptic nucleus in vivo. Tissues were then prepared for quantitative electron microscopic analysis of the total incidence of DCVs within supraoptic dendritic cross‐sections, and of the incidence and distance (within a 500‐nm margin) of each DCV to the dendritic plasma membrane. Salt loading per se did not alter the frequency distribution or average proportion of DCVs found in the 500‐nm margin but significantly decreased the average incidence of DCVs per dendrite by 30% (P < 0.05). However, thapsigargin treatment resulted in a significant increase in the total incidence of DCVs within the 500‐nm margins and a higher incidence of DCVs within the first 200 nm of the plasma membrane (P < 0.05), indicating that the thapsigargin‐induced priming involves a relocation of DCVs closer to sites of secretion.
Re‐visioning the spider woman archetype in Kiss of the Spider Woman
Authors: Wiegmann Mira
Published: May 2004

The article examines the transformation of spider woman archetype from Manuel Puig's adaptation of his novel to a play, and other adaptations into a film and a musical. The paper examines how the archetype's image and function shift when ‘re‐visioned’ by various artists and performed in disparate social contexts.
Knowing What You Don’t Know? Discourses and Contradictions in Knowledge Management Research
Authors: Schultze Ulrike , Stabell Charles
Published: May 2004

ABSTRACTEven though knowledge management scholars generally advocate explicit management of knowledge, there is research that cautions against the unintended consequences of such efforts. Some researchers go as far as arguing that knowledge and management are contradictory concepts (Alvesson and Kärreman, 2001). This paper explores the apparent double‐edged nature of knowledge management by developing a theory‐based framework that highlights different fundamental assumptions about knowledge and its management. This framework, which is an adaptation of Burrell and Morgan's four paradigms of social and organizational inquiry, distinguishes among a neo‐functionalist, a constructivist, a critical and a dialogic discourse.

We use the contradiction of managing tacit knowledge, which has been highlighted in the knowledge management literature, as an analytical device to explore the four discourses in more detail. We show how notions of knowledge, and what it means to manage knowledge, vary across the four discourses. We conclude that all four discourses need to be appreciated, understood and represented in knowledge management research for this area of inquiry to deal with the rich and problematic nature of managing knowledge in practice.
When Production and Consumption Meet: Cultural Contradictions and the Enchanting Myth of Customer Sovereignty
Authors: Korczynski Marek , Ott Ursula
Published: May 2004

ABSTRACT The central cultural contradiction of capitalism, argued Bell some 25 years ago, was the existence of rationalized, disciplined production alongside free and hedonistic consumption. This paper argues that this thesis, although overstated, has resonance within contemporary capitalism. The paper then considers the question of how this contradiction is managed when production and consumption meet directly within the service interaction. On the production‐side rationalization is joined by customer‐orientation, and on the consumption‐side management promotes consumption of the enchanting myth of sovereignty. Here the customer is meant to experience a sense of being sovereign. At the same time the space is created for the customer to be, potentially, substantively directed and influenced to follow the requirements that flow from the rationalized elements of production. Key aspects of the service interaction, including the menu and its presentation, the display of empathy and aesthetic labour, and the use of naming within the service interaction, are analysed in terms of the promotion of the enchanting myth of sovereignty. Consumption, however, is a fragile process, and remains, to an important degree, ‘unmanageable’. The analysis, therefore, also examines how the promotion of the enchanting myth of sovereignty systematically creates the conditions for the myth's negation.
Management Control as an Employee Resource: The Case of Front‐line Service Workers
Authors: Rosenthal Patrice
Published: May 2004

ABSTRACT This paper argues that the conception of management control as an employee resource can enhance critical understandings of front‐line service work. The argument is developed first through a critique of the contemporary control literature and its prominent worker images of smiling docility and haggard exhaustion. Seeking to encourage accounts more sensitive to the subjectivity and agency of service workers, the paper calls for more research attention to the question of how these employees experience and evaluate management control in relation to their self‐defined interests. Analysis of the nature of contemporary service work suggests that one such perceived interest is likely to be interactive control, or the capacity of workers to control and influence those parties with whom they directly interact. Based on a close reading of the emerging empirical literature on services, the article explores various ways in which the bureaucratic, technical and normative regulation designed by management to control service workers is used in turn by workers to further their own control and influence over managers and customers.
Resourceful Sensemaking in an Administrative Group
Authors: Wright Charles R. , Manning Michael R.
Published: May 2004

ABSTRACT In this study, we present the concept of resourceful sensemaking as an extension of Weick's sensemaking theory. Resourceful sensemaking extends Weick's theory by carefully examining the influence of the lifeworld on organizational sensemaking practices. Lifeworld factors that affect organizational sensemaking are brought out in a dialectical method wherein a working definition of the resourceful sensemaking concept is compared with the sensemaking practices of an administrative group. We then show how this dialectical method can help develop a more robust formulation of the resourceful sensemaking concept. The paper ends by discussing the strengths and shortcomings of the concept and suggesting directions for future organizational sensemaking research.
Corporate Entrepreneurship and Real Options in Transitional Policy Environments: Theory Development
Authors: Doh Jonathan P. , Pearce John A.
Published: May 2004

ABSTRACT We develop a theoretical framework for describing, modelling, and predicting entrepreneurial strategies by corporations in transitional public policy environments. Drawing on research in entrepreneurship, real options, and strategic management under uncertainty, we demonstrate how corporations affected by government policy can use entrepreneurial strategies to exploit discontinuities generated by uncertain and unstable public policy environments. We argue that specific strategies will be effective depending on the degree and slope/inflection profile of policy change. Four strategies are identified: preemptive, optioned, synchronized, and adaptive. We develop propositions and provide illustrations to show how each of these strategies has helped firms respond to transitional policy environments. We conclude by offering a discussion of the utility and limitations of the framework and its potential application to other managerial circumstances in which uncertainty is pervasive, and by describing opportunities for further research, including empirical testing of our model.
East Meets West: A Cross‐Cultural Comparison of Charismatic Leadership Among Canadian and Iranian Executives
Authors: Javidan Mansour , Carl Dale E.
Published: May 2004

ABSTRACT This study first develops an empirically based Western charismatic leadership profile. Using confirmatory factor analysis, the profile is compared with a profile of Iranian managers. The results demonstrate that despite major cultural differences in the two countries, there are core similarities in the profiles across the two cultures. The Canadian charismatic profile of vision, tenacity, intellectual challenge, self‐sacrifice, and eloquence is substantially confirmed within the Iranian sample. But we also show that Iranian managers’ ratings are significantly lower than those of the Canadian managers, indicating potentially different behavioural manifestations. The paper speculates that while the differences are probably due to cultural differences, the similarities may be due to universal intrinsic human desire for morality, autonomy, and achievement.
The Problem of Abortion: Essentially Contested Concepts and Moral Autonomy
Authors: Gibson Susanne
Published: May 2004

When one thinks about the ethics of abortion, one inevitably thinks about rights, since it is in terms of the concept of rights that much of the debate has been conducted. This is true of overtly feminist as well as non‐feminist accounts. Indeed, some early feminist writers – Judith Jarvis Thomson and Mary Ann Warren, for example – employ a model of rights that is indistinguishable, or virtually indistinguishable, from that of their non‐feminist counterparts. However, more recent feminist writers have developed a different understanding of ‘a woman's right to choose.’

In this paper, I will begin by outlining the non‐feminist debate over the moral permissibility of abortion. I will suggest that this debate is irresolvable, since at its heart is an ‘essentially contested concept’, that of personhood. I will then consider the way in which some feminist writers have attempted to reconceive the terms of the abortion debate and suggest an expanded account of women's right to abortion, drawing on the work of Susan Sherwin. Finally, I will argue that there is a further element to a ‘woman's right to choose’ that expands on and provides a conceptual link between the feminist and non‐feminist understanding of abortion.
Adequate Conscious Life and Age‐Related Need: F.M. Kamm's Approach to Patient Selection
Authors: Waring Duff
Published: May 2004

Kamm's approach to patient selection qualifies the notion that fairness makes need for scarce, transplantable organs inversely proportional to age. She defines need as how much adequate conscious life a person will have had before death. Length of adequate conscious life correlates highly with age. If so, then younger persons are usually needier than older ones. Since Kamm allows for past periods of non‐adequate conscious life, I argue that this correlation may be neither as close, nor as easy to apply, as she wants it to be. Fairness should require assessment of experiential content in determining how long one's life has been adequately conscious. I argue that such assessments involve some of the goods of experience and quality of life judgements that Kamm thinks a reliance on adequate conscious life will avoid.
What Happened to the Japanese Model?
Authors: Schaede Ulrike
Published: May 2004

Japan's steep postwar growth was nested in a political economy built around producer‐oriented policies: by fostering the growth of large firms using the tools of industrial policy, the government could jumpstart development. Many large firms, and their employees, benefited indirectly from this growth program, and very small firms and industries not included in the growth model were compensated through preferential policies or subsidies. Japan's social contract evolved around this system, having as its centerpiece lifetime employment. The government spent more resources on supporting exporting industries and compensating domestic ones than on building a forward‐looking welfare system. Japan's decade‐long economic downturn marks a structural transition towards a postindustrial society. While excelling in producing tangibles, Japan has fallen behind in fostering modern industries, including services; the country also lacks a welfare system to handle increasing structural unemployment that this transition brings about. Without a commitment towards a welfare system and a welfare society, and a reorientation of the social contract towards citizens, Japan is unlikely to transition successfully.
Choice of designs and doses for early phase trials
Authors: Zhou Yinghui
Published: May 2004

This paper reviews state‐of‐art statistical designs for dose‐escalation procedures in first‐into‐man studies. The main focus will be on studies in oncology, as most statistical procedures for phase I trials have been proposed in this context. Extensions to situations such as the observation of bivariate outcomes and healthy volunteer studies are also discussed. The number of dose levels and cohort sizes used in early phase trials are considered. Finally, this paper raises some practical issues for dose‐escalation procedures.
Assessment of patient‐reported outcomes in clinical trials: the example of health‐related quality of life
Authors: Wiklund Ingela
Published: May 2004

As the patient is the primary recipient of treatment, there is a need to recognize and value the patient's perception of change in response to treatment in clinical trials. A new outcomes classification, patient‐reported outcomes (PROs), has been proposed by regulators. The PROs are used as an umbrella term and include, for example measures of subjective symptoms, health‐related quality of life (HRQL) and treatment satisfaction. In this sense, the PROs are unique and complementary indicators of disease activity as well as of treatment efficacy. Frequently, pharmaceutical companies desire to include PRO benefits in the product label in order to reach a broad range of customers, including prescribers as well as patients. Therefore such information must be based on results that are scientifically valid. The measurement strategy, i.e. the thinking about and decision‐making related to PRO and HRQL evaluations, needs to be explicit for clinical trials. First of all it is necessary to specify and provide the rationale for measuring the PROs. Similarly, the reason for selecting particular instruments should be stated and, for the selected instruments, the psychometric evidence should be summarized. The key PRO domains must be prespecified and evidence of their importance to patients should be provided. The research question under study and potential claims need to be clearly delineated. Hence, instrument selection is a key initial step for planning successful and scientifically adequate clinical trials intended to support labelling and promotional claims of PRO benefits to patients. The scientific criteria and design issues of clinical trials are the same for clinical and PRO endpoints. However, important issues of particular relevance to PRO assessments, such as missing values, multiple outcomes, and the statistical analysis, require careful attention. The thinking and planning involved in developing the PRO component of the clinical trial need to be articulated. Successful evaluation of PROs in clinical trials relies on careful planning provided the treatment shows sufficient effectiveness.
Effects of differential blockade of the renin‐angiotensin system in postinfarcted rats
Authors: Lacour Colette , Roccon Alain , Galindo Gérard , Canals Françoise , Hogie Manuela , Segondy Danielle , Briand Danielle , Roque Claude , Herbert Jean‐Marc , Nisato Dino
Published: May 2004

The present study compared short‐term effects of the AT1‐receptor antagonist, irbesartan with the angiotensin‐converting enzyme (ACE) inhibitor, enalapril on systemic haemodynamics and cardiac remodelling in post‐myocardia‐infarcted (MI) rats. MI Sprague–Dawley rats were orally treated for 4 weeks with irbesartan (50 mg/kg/day) or enalapril (10 mg/kg/day). Then, cardiac and systemic haemodynamics were measured. Compared with the sham‐operated group, left ventricular end‐diastolic pressure (LVEDP), diastolic pressure (LVDP), heart weight to body weight ratio were all significantly increased in the MI group while the LV contractility (dP/dt) and pulsatile arterial pressure were significantly reduced. Both drugs reduced the elevated LVEDP and LVDP and prevented cardiac hypertrophy. Furthermore, irbesartan attenuated the right shift of the pressure–volume curves, prevented postinfarction‐induced increase in urinary cyclic guanosine monophosphate and reduced urinary aldosterone excretion. Although both drugs were able to prevent further cardiac hypertrophy and improved cardiac filling pressure, only irbesartan limited LV dilatation. These data indicate that blockade of the renin‐angiotensin system at the level of AT1 receptors may have a better cardioprotective benefit than reducing angiotensin II levels by ACE inhibition.
Physiological and metabolic actions of mycophenolate mofetil on cultured newborn rat cardiomyocytes in normoxia and in simulated ischemia
Authors: Bès Sandrine , Tatou Etienne , Vandroux David , Tissier Cindy , Rochette Luc , Athias Pierre
Published: May 2004

Mycophenolate mofetil (MMF) is a new immunosuppressive drug used to reduce acute rejection after heart transplantation. As with other immunosuppressive drugs, MMF therapy is associated with several adverse effects. However, the direct effects of MMF on myocardial tissue has not been yet evaluated. The aim of the work was thus to evaluate the effects of MMF on isolated cardiomyocytes (CM) in normal conditions and in an in vitro model of simulated ischemia (SI; substrate‐free hypoxia) and reperfusion (R; reoxygenation). Myocyte‐enriched cultures were prepared from newborn rat heart ventricles. The transmembrane potentials were recorded using conventional microelectrodes and the cell contractions were monitored with a photoelectric device. In basal conditions, MMF (10−6and 10−5 m) exerted no significant effects on the survival and on the electrical and contractile activities of CM in culture, even during long‐term exposure (up to 48 h). SI per se led to a gradual decrease and then an abortion of the spontaneous automaticity and electromechanical activity of CM. Pretreating CM with either 10−6or 10−5 mMMF was able to reduce the SI‐induced cell dysfunctions. The presence of MMF at these concentrations did not hamper the post‐SI functional recovery of CM during reoxygenation. At 10−5 m, MMF applied during reoxygenation only permitted a better recovery of CM. However, the mitochondrial function after reoxygenation, as assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl‐tetrazolium bromide (MTT) test, was not significantly influenced by the addition of MMF before as well as after ischemia. Conversely, MMF was able to reduce in this model the postischemic rise in xanthine and hypoxanthine. These data from CM‐enriched model show that MMF: (i) had no cytotoxic effect, (ii) displayed a cytoprotective effect during SI, and (iii) exerted its beneficial effect at least partly through the decrease in the xanthine oxidase‐dependent free radical production.
Level of evidence and therapeutic evaluation: need for more thoughts
Authors: Bossard Nadine , Boissel François‐Henri , Boissel Jean‐Pierre
Published: May 2004

The practice of evidence‐based medicine requires a tool to assess and discriminate available data based on objective grounds, thus facilitating access to reliable information. The level of evidence, conceptually and practically embedded in scientific activity, allows comparing the results from multiple studies testing an identical hypothesis along the lines of at least two dimensions. The first dimension deals with the design of the study, i.e. the extent to which bias is avoided or managed, the second with the quality of incorporated data. A third dimension specific to therapeutic evaluation focuses on the clinical relevance of the tested hypothesis. The concern of the final user of the information is thus put to the fore. Indeed, a general practitioner will be interested in the benefit for its patients whereas the concern of a biologist might significantly diverge from the former matter. The bulk of existing scales of level of evidence concentrate on methodology. Some may include the second dimension but none embrace the three of them. Seldom considered are matters regarding reproducibility and procedure. This is all the more unfortunate as reproducibility is a cornerstone of scientific progress. Moreover, scales used for overviews fail to take into account the methodology designed to produce the synthesis. Inconsistent existing scales prevent the emergence of a generally agreed standard. Therefore, there is a need to further specify the concept of level of evidence in therapy evaluation and design scales encompassing the three above‐mentioned dimensions: methodology of experiment, quality of data, and clinical relevance of the primary criterion.
Polyphenolic compounds from Cognac induce vasorelaxation in vitro and decrease post‐ischaemic cardiac infarction after an oral administration
Authors: Ralay Ranaivo H. , Diebolt M. , Schott C. , Andriantsitohaina R.
Published: May 2004

The effects of Cognac polyphenolic compounds (CPC) on aorta and isolated heart, the consequences of oral administration on haemodynamic parameters, vascular reactivity and cardiac recovery after ischaemia were investigated. CPC induced an endothelium‐dependent vasorelaxation on rat‐isolated aorta. This effect was prevented by the nitric oxide (NO) synthase inhibitor, NG‐nitro‐l‐arginine‐methyl ester, but not by the cyclo‐oxygenase inhibitor, indomethacin, suggesting the implication of NO pathway. On isolated rat hearts, CPC induced positive inotropic, chronotropic, and lusitropic effect at 10−4–10−2 g/L while at 10−1 g/L, it had negative lusitropic effect and other parameters returned to baseline values. Oral administration of 40 mg/kg of CPC for 2 weeks did not modify systolic blood pressure and heart rate of rats throughout the treatment. CPC treatment did not affect ex vivo response of isolated thoracic aorta either to the contractile agent noradrenaline or to the endothelial‐relaxant agent, acetylcholine. Isolated hearts from treated rats were submitted to 30‐min global ischaemia followed by 120 min of reperfusion. Post‐ischaemic recovery of functional cardiac parameters was not modified by treatment with CPC. Infarct size measured after the reperfusion in heart from CPC‐treated rats was significantly decreased in comparison with hearts from control group. We conclude that in vitro, CPC had NO‐dependent vasorelaxant effects and stimulated cardiac function. Oral treatment with CPC appeared to have no impact in vivo on blood pressure, heart rate of the rats or on cardiac contractility ex vivo; however, it could decrease the infarct size after an ischaemia–reperfusion.
Endothelium‐dependent contractions to acetylcholine, ATP and the calcium ionophore A 23187 in aortas from spontaneously hypertensive and normotensive rats
Authors: Yang Di , Gluais Pascale , Zhang Ji Nan , Vanhoutte Paul M. , Félétou Michel
Published: May 2004

The present study was designed to determine whether or not an increase in endothelial intracellular concentration of calcium ([Ca2+]i) evokes endothelium‐dependent contractions in the aorta from normotensive Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR). Acetylcholine, adenosine triphosphate (ATP) and the calcium ionophore, A 23187, produced endothelium‐dependent relaxations in isolated aortic rings of both WKY and SHR. These relaxations in response to the three agonists were significantly smaller in the SHR when compared with the WKY. Endothelium‐dependent contractions to acetylcholine, ATP and A 23187 were observed only in the aorta isolated from the SHR. In the presence of NG‐nitro‐L‐arginine, an NO synthase inhibitor, the endothelium‐dependent contractions in response to acetylcholine, ATP and A 23187 were potentiated significantly in the aorta SHR and were unmasked in that of WKY. However, the contractions were still significantly greater in SHR than in WKY. These contractions were abolished by indomethacin and valeryl salicylate (two cyclo‐oxygenase inhibitors) as well as by S 18886 (a TP‐receptor antagonist), indicating that the endothelium‐dependent contraction produced by the three agonists share the same characteristics. The results of the present study indicate that the release/generation of endothelium‐derived contracting factor, requires an increase in endothelial [Ca2+]i.
ERRATUM
Authors: Yang J. Q. , Morin S. , Verstuyft C. , Fan L. A. , Zhang Y. , Xu ChP. , Barbu V. , Funck‐Brentano C. , Jaillon P. , Becquemont L.
Published: May 2004

FCP 17:3 (2003); pp. 373–376.

The name of one of the contributing authors to this paper was omitted from the list of authors that appeared on page 373. The correct list of authors and affiliations are printed below:
Adenosine decreases both presynaptic calcium currents and neurotransmitter release at the mouse neuromuscular junction
Authors: Silinsky Eugene M.
Published: May 2004

A controversy currently exists as to the mechanism of action by which adenosine, an endogenous mediator of neurotransmitter depression, reduces the evoked release of the neurotransmitter acetylcholine (ACh) at the skelelal neuromuscular junction. Specifically, it is uncertain whether adenosine inhibits ACh release from mammalian motor nerve endings by reducing Ca2+ calcium entry through voltage‐gated calcium channels or, as is the case at amphibian motor nerve endings, by an effect downstream of Ca2+ entry. In an attempt to address this controversy, the effects of adenosine on membrane ionic currents and neurotransmitter release were studied at neuromuscular junctions in adult mouse phrenic nerve hemidiaphragm preparations. In wild‐type mice, adenosine (500 μm–1 mm) reduced prejunctional Ca2+ currents simultaneously with a reduction in evoked ACh release. In Rab3A knockout mice, which have been shown to have an increased sensitivity to adenosine, the simultaneous reduction in Ca2+ currents and ACh secretion occurred at significantly lower adenosine concentrations (≤ 50 μm). Measurements of nerve terminal Na+ and K+ currents made simultaneously with evoked ACh release demonstrated that the decreases in Ca2+ currents were not attributable to changes in cation entry through voltage‐gated Na+ or K+ channels. Furthermore, no effects of adenosine on residual ionic currents were observed when P/Q‐type calcium channels were blocked by Cd2+ or ω‐agatoxin‐IVA. The results demonstrate that inhibition of evoked neurotransmitter secretion by adenosine is associated with a reduction in Ca2+ calcium entry through voltage‐gated P/Q Ca2+ channels at the mouse neuromuscular junction. Whilst it may be that adenosine inhibits ACh release by different mechanisms at amphibia and mammalian neuromuscular junctions, it is also possible that the secretory apparatus is more intimately coupled to the Ca2+ channels in the mouse such that an effect on the secretory machinery is reflected as changes in Ca2+ currents.
Prenatal glucocorticoid exposure alters hypothalamic–pituitary–adrenal function and blood pressure in mature male guinea pigs
Authors: Banjanin Sonja , Kapoor Amita , Matthews Stephen G.
Published: May 2004

Pregnant guinea pigs were treated with dexamethasone (1 mg kg−1) or vehicle on days 40–41, 50–51 and 60–61 of gestation, after which animals delivered normally. Adult male offspring were catheterized at 145 days of age and subjected to tests of hypothalamic–pituitary–adrenal (HPA) axis function in basal and activated states. Animals exposed to dexamethasone in utero (mat‐dex) exhibited increased hippocampus‐to‐brain weight ratio, increased adrenal‐to‐body weight ratio and increased mean arterial pressure. There were no effects on gestation length, birth weight and postnatal growth. There were no overall differences in diurnal plasma adrenocorticotropic hormone (ACTH) and cortisol profiles, though there were subtle differences during the subjective afternoon between control and mat‐dex offspring. A significant decrease in initial ACTH suppression was observed following dexamethasone injection in mat‐dex offspring compared to control offspring. Molecular analysis revealed significantly increased MR mRNA expression in the limbic system and particularly in the dentate gyrus in mat‐dex offspring. In the anterior pituitary, both pro‐opiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA levels were significantly elevated in mat‐dex offspring. In conclusion, (1) repeated prenatal treatment with synthetic glucocorticoid (sGC) permanently programmes organ growth, blood pressure and HPA regulation in mature male offspring and these changes involve modification of corticosteroid receptor expression in the brain and pituitary; (2) the effects of prenatal sGC exposure on HPA function appear to change as a function of age, indicating the importance of investigating HPA and cardiovascular outcome at multiple time points throughout life.