bluuebunny/crossref_metadata_2025 huggingface dataset:
Puzzling, and puzzling about puzzle development
Authors: Kuschnir Adriana Nóbrega , dos Santos Machado Beatriz
Published: May 2003

This paper has two roles in this collection. First, it illustrates Exploratory Practice (EP) in action, with two classroom investigations. Secondly, it goes further, and throws light on the key mechanism of EP (see Allwright, this issue, Sections III.1(d) and IV.2) - puzzlement. It thus presents two different puzzling processes, the EP process as set out in the introductory paper to this issue, and a meta-process of puzzling about our own puzzlement processes. First, we carried out separate research studies as EP practitioners, with one of us investigating the puzzle, ‘does the dictionary really help our students to understand the text?’, and the other investigating the puzzle, ‘why do my students translate words even when they’ve already understood their meanings in English?’ Then we puzzled about the process of puzzle development itself. This further investigation contributed, we believe, to a better understanding about how intra and inter puzzlement processes can be integrated. Our emerging understandings led us to suggest that we mentally operate in a puzzlement zone while working with our puzzles. Drawing on a possible parallel with Vygotsky’s (1984) notion of ‘zone of proximal development’ (ZPD) and on the ZPD’s levels of development (actual development level and level of potential development), we hypothesize that we mentally act at similar levels - the actual understanding level and the level of potential understanding - while working with our puzzles in this puzzlement zone.

We present our work together as one way of incorporating EP into research at Master’s level.
Exploring a world of paradoxes: an investigation of group work
Authors: Slimani-Rolls Assia
Published: May 2003

This paper has a dual role to play here. First, it presents a classroom investigation conducted within the framework of Exploratory Practice (EP) set out in the introductory paper to this volume, and secondly it illustrates EP’s potential for developing a ‘research culture’ in a university institution. Perhaps it should be possible to take such a culture of inquiry for granted at university level, but recent decades in the United kingdom have seen the rise, and fall, of many university-based language teaching units whose members’ contracts did not entail research. Now that research has become a major source of funding, such staff are increasingly being urged to undertake research as well as to teach a language. EP, with its emphasis on integrating research into pedagogy (see Allwright, this issue), offers a research model that experienced language teachers might prefer to traditional academic research, and find more manageable.

This paper illustrates how an investigation into group work arose from this interest in developing a culture of inquiry, and concludes with a note of caution concerning the pace of change.
Exploring second language communicative competence
Authors: Gunn Cindy L.
Published: May 2003

Reporting a classroom investigation within the framework of Exploratory Practice (EP) as set out in the introductory paper to this issue, this paper illustrates first how EP offers a successful and coherent approach to doctoral research, and secondly how learner and teacher/researcher understanding can be developed together.

EP principles were used to integrate teaching practices and research in an applied setting to aid both the students and myself, through a collegial process, to develop our own understandings of what happens in the language classroom. Data collected through the use of various classroom activities included both analysis of the students’ performances and the students’ reflections on their performances. The combination of the various forms of data permitted comprehensive discussion of communicative competence over time, by looking at what the students actually do, what the students say about what they do, as well as what others say about what the students do. With the data collected from a small number of students learning English at an International school in Thailand, two girls and two boys ranging in age from 11 to 13 representing four different nationalities, over a six-month period, I was able to see how their communicative competence developed over time. This information ultimately enabled me to better understand my puzzle area concerning the challenges of helping students develop communicative competence.
Exploring the written feedback dialogue: a research, learning and teaching practice
Authors: Perpignan Hadara
Published: May 2003

The final paper of this Special Issue on Exploratory Practice (EP) is another illustration of the potential of EP for doctoral research. More importantly, like the preceding paper by Gunn it emphasizes learner as well as teacher understanding, and, most importantly, it also explores ‘quality’ in interpersonal relationships.

This paper reports on research, conducted in an EFL Academic Writing context, about a written dialogue between a teacher and her learners. This dialogue consists of the learners’ written text, the teacher’s written feedback and the ongoing responses that ensue from this initial exchange.

Most past research into teachers’ written comments on student-writers’ work has examined quantitatively either the teachers’ or the learners’ perspective, and has emphasized the outcomes of the learners’ revision process. A comprehensive analysis of the intentions and interpretations of the exchange from both the teacher’s and the learners’ perspective, as well as of the dynamic nature of the dialogue within its full pedagogical context, has not yet been done. It was hoped that such an analysis could lead to some generalizations which, in turn, could lead to recommendations for improving pedagogical practice.

However, what began as a quest for a theory that could inspire guidelines for teacher effectiveness became a quest for an understanding of the conditions under which effectiveness could best be achieved. In EP terms, these conditions represent life in the classroom and the quest illustrates the aim of teacher research: to strive toward improving the quality of the life that will enable more effective use of the feedback dialogue as a crucial element in the writing process.

The paper begins by inserting the current research into the context of qualitative research literature, leading directly to EP principles. Reporting on the research itself, it shows how some of the principles were manifested in the research practices. The findings reveal that it is precisely through dialogue (the written exchange as a social enterprise) between the participants in the learning-teaching situation (in a spirit of collegiality), that an understanding of the feedback dialogue can best be reached. Herein lies the promise of an improvement in the quality of life, quality of education and ultimately quality of learning (Allwright, this issue).
Critical decision making in severe head injury management
Authors: Tolias Christos , Wasserberg Jonathan
Published: May 2003

The management of severe head injury (SHI) remains a major challenge not only for neurosurgeons but also for all other health professionals involved in the care of trauma patients. Any trauma patient with SHI is at risk of further neurological deterioration if appropriate measures are not instituted from the start of his or her treatment. Secondary insults due to ischaemic, hypotensive, and metabolic or other causes are still common, even in the most advanced neurocritical care settings. Management controversies are widespread and few decision options can be supported by Class I evidence. This article attempts to provide an up-to-date review of the published recommendations that could help health professionals in their management of SHI.
Beware the black eye
Authors: Key SJ , Dhariwal DK , Patton DW
Published: May 2003

Maxillofacial injuries are common and account for up to 5% of attendances in accident departments. Many of these are associated with a black eye. The associated swelling around the eye may hide serious injuries to the globe or facial skeleton, which, if undiagnosed, may lead to a loss of vision or unpleasant facial deformity. This article discusses some of the more common underlying injuries associated with a black eye, and illustrates the consequences of failing to diagnose them. The assessment of a black eye is described.
A simulation-based method for model evaluation
Authors: Allcroft David J. , Glasbey Chris A.
Published: May 2003

We wish to evaluate and compare models that are non-nested and fit to data using different fitting criteria. We first estimate parameters in all models by optimizing goodness-of-fit to a dataset. Then, to assess a candidate model, we simulate a population of datasets from it and evaluate the goodness-of-fit of all the models, without re-estimating parameter values. Finally, we see whether the vector of goodness-of-fit criteria for the original data is compatible with the multivariate distribution of these criteria for the simulated datasets. By simulating from each model in turn, we determine whether any, or several, models are consistent with the data. We apply the method to compare three models, fit at different temporal resolutions to binary time series of animal behaviour data, concluding that a semi-Markov model gives a better fit than latent Gaussian and hidden Markov models.
Reduced-rank vector generalized linear models
Authors: Yee Thomas W , Hastie Trevor J
Published: May 2003

Reduced-rank regression is a method with great potential for dimension reduction but has found few applications in applied statistics. To address this, reduced-rank regression is proposed for the class of vector generalized linear models (VGLMs), which is very large. The resulting class, which we call reduced-rank VGLMs (RR-VGLMs), enables the benefits of reduced-rank regression to be conveyed to a wide range of data types, including categorical data. RR-VGLMs are illustrated by focussing on models for categorical data, and especially the multinomial logit model. General algorithmic details are provided and software written by the first author is described. The reduced-rank multinomial logit model is illustrated with real data in two contexts: a regression analysis of workforce data and a classification problem.
Modelling ranks using the inverse hypergeometric distribution
Authors: D’Elia Angela
Published: May 2003

A statistical model for ranks is presented, and some results on its parameter are discussed. In particular, maximum likelihood inference is developed, with and without covariates; thus, a statistical model for rank data is introduced in order to link the expressed ranks to the main features of the raters. Some empirical evidence from a marketing survey confirms the usefulness of the proposal in the study of the preferences.
Modelling data from inside the Earth: local smoothing of mean and dispersion structure in deep drill data
Authors: Kauermann Göran , Küchenhoff Helmut
Published: May 2003

The paper describes the analysis of data originating from the German Deep Drill Program. The amount of ‘cataclastic rocks’ is modelled with data resulting from a series of measurements taken from deep drill samples ranging from 1000 up to 5000 m depth. The measurements thereby describe the amount of strongly deformed rock particles and serve as indicator for the occurrence of cataclastic shear zones, which are areas of severely‘ground’ stones due to movements of different layers in the earth crust. The data represent a ‘depth series’ as analogue to a ‘time series’, with mean, dispersion and correlation structure varying in depth. The general smooth structure is thereby disturbed by peaks and outliers so that robust procedures have to be applied for estimation. In terms of statistical modelling technology three different peculiarities of the data have to be tackled simultaneously, that is estimation of the correlation structure, local bandwidth selection and robust smoothing. To do so, existing routines are adapted and combined in new ‘two-stage’ estimation procedures.
Learning disabilities and ethnicity: achieving cultural competence
Authors: O'Hara Jean
Published: May 2003

Despite the higher prevalence of learning disabilities among some minority ethnic communities and the greater burden of care, families from minority ethnic communities with a member who has learning disabilities are doubly disadvantaged as a result of racial discrimination and culturally inappropriate forms of care and service provision. This paper looks at the issue of discrimination, as well as the generally negative attitudes towards people with learning disabilities, and synthesises these into the concept of ‘double jeopardy’. It concludes by proposing ways of developing cultural competence in the delivery of care to this population.
Invited commentary on Expert testimony in court
Authors: Blom-Cooper Sir Louis
Published: May 2003

Those who possess expertise or experience of a scientific or technical nature are often called to give evidence as a witness in a court or tribunal (in Scotland, he or she is known as a ‘skilled witness’). In so far as the expert witness expresses an opinion, that evidence is, strictly speaking, an exception to the hearsay rule. However, since the 16th century, the courts have admitted opinion evidence from anyone, not just a ‘professional’, who can assist the court on a scientific or technical matter which is an issue in the case and is beyond the knowledge of the court or tribunal. Frequently, the expert witness will be giving evidence as to fact as well as opinion. For example, the forensic pathologist who conducts a post-mortem examination will be able to give a factual description of the condition of the body and, at the same time, give an expert opinion on the cause of death. The forensic psychiatrist will similarly describe what has been determined about the patient on examination of his or her symptoms and express an opinion on the patient's mental health. There will be cases where the expert is supplied with factual data on which to express an expert opinion.
Sexual side-effects of antidepressant and antipsychotic drugs
Authors: Baldwin David , Mayers Andrew
Published: May 2003

Adequate sexual expression is essential to many human relationships and provides a sense of physical, psychological and social well-being. Epidemiological and clinical studies show that depression and schizophrenia are associated with impairment of sexual function and satisfaction, even in untreated patients. Most antidepressant and antipsychotic drugs have adverse sexual effects but it is difficult accurately to identify the incidence of treatment-emergent dysfunction, as disturbances can be reliably detected only from systematic enquiries made at baseline and during treatment. Growing awareness of the adverse effects of psychotropic drugs has led to attempts to use adjuvants or substitute treatments to resolve sexual dysfunction. More studies of the effects of antidepressant and antipsychotic drugs on sexual function are needed.
Invited commentary on Death and dying in literature
Authors: Parkes Colin Murray
Published: May 2003

John Skelton's paper (2003, this issue) reminds us that literature can put into words thoughts and feelings which we might otherwise be unable to think or articulate. This is an important attribute and one which we can make use of in our attempts to help patients and families faced with life-threatening illness. It might also help those who have been bereaved to find meaning in what seems like a meaningless experience.
Secondary uses of patient information
Authors: Lelliott Paul
Published: May 2003

The pace of development and implementation of good information management systems has been disappointingly slow and the potential benefits of using patient information for secondary purposes have not been fully realised. The secondary use of patient data might be at the level of individual practitioners or teams, or at a local-service, regional or national level. Using patient data for purposes other than direct patient care requires an understanding of the principles of case-mix, standards for recording data, the limits of accuracy of data collected in routine practice and of the principles of data security and confidentiality. The alternatives to secondary use of information are to manage the mental health service without information about the people who use it or to gather this information through channels that run in parallel to the process of clinical care.
IGDA. 1: Conceptual bases – historical, cultural and clinical perspectives
Authors:   IGDA Workgroup, WPA
Published: May 2003

Diagnostic assessment is the process of appraising a patient's condition. It involves effectively engaging the patient in order to obtain accurate information relevant to understanding health problems (mental and general medical disorders), their context (psychosocial and environmental problems) and their impact on adaptive functioning and participation in society (disablements). A comprehensive diagnostic formulation represents a summary of the clinician's judgement about the overall condition of the patient, obtained as much as possible with the latter's collaboration. The main purpose of diagnosis is to serve as the basis for clinical care. Further objectives include to communicate concisely and reliably information on health problems, to understand their biopsychosocial pathogenesis and the interaction of internal and contextual factors, to enhance training and research, and – last but not least – to inform a collaborative process of care aimed at the restoration and promotion of health, functioning and quality of life (Fig. 1.1).
IGDA. 5: Supplementary assessment procedures – psychopathological, neuropsychological and physical aspects
Authors:   IGDA Workgroup, WPA
Published: May 2003

Supplementary assessment procedures may be used to complement the psychiatric diagnostic interview. These include procedures for the comprehensive evaluation of the mental and physical state of the patient (psychosocial procedures are considered in part 6 (IGDA Workgroup, WPA 2003, this suppl.)). Psychopathological assessment instruments, biological tests and procedures and neuropsychological tests are among those used to enrich or refine data collected in a clinical interview in order to arrive at the standardised multi-axial diagnostic formulation.
IGDA. 10: Organising the clinical chart
Authors:   IGDA Workgroup, WPA
Published: May 2003

A systematic record of information collected during the process of diagnosis and care is essential to document understanding of the patient's mental, physical and social condition and the clinical service provided (Fig. 10.1).
Psychiatric disorder in veterans of the Persian Gulf War of 1991
Authors: Stimpson Nicola J. , Thomas Hollie V. , Weightman Alison L. , Dunstan Frank , Lewis Glyn
Published: May 2003

Background

Veterans of the Persian Gulf War of 1991 have reported symptoms attributed to their military service.

Aims

To review all studies comparing the prevalence of psychiatric disorders in Gulf War veterans and in a comparison group of service personnel not deployed to the Gulf War.

Method

Studies of military personnel deployed to the Gulf published between 1990 and 2001 were identified from electronic databases. Reference lists and websites were searched and key researchers were contacted for information. Atotal of 2296 abstracts and 409 complete articles were reviewed and data were extracted independently by two members of the research team.

Results

The prevalence of psychiatric disorder in 20 studies of Gulf War veterans was compared with the prevalence in the comparison group. Prevalence of post-traumatic stress disorder (PTSD) and common mental disorder were higher in the Gulf War veterans. Heterogeneity between studies was significant, but all reported this increased prevalence.

Conclusions

Veterans of the Persian Gulf War reported an increased prevalence of PTSD and common mental disorder compared with other active service personnel not deployed to the Gulf. These findings are attributable to the increase in psychologically traumatic events in wartime.
Status of neurosurgery for mental disorder in Scotland
Authors: Matthews Keith , Eljamel Muftah S.
Published: May 2003

Background

Despite the application of ablative neurosurgical treatments for intractable mental disorder throughout most of the past century, unequivocal evidence for efficacy has not been provided.

Aims

To review the status of ablative neurosurgery for mental disorder and to describe the activities of the Scottish national service.

Method

Relevant literature is reviewed alongside a description of recent clinical activity.

Results

Neurosurgical treatment is offered to a small number of patients severely disabled by otherwise intractable mental disorder. Thereareinequalitiesin the strength of evidence to support the use of some of these procedures. The frequency and severity of adverse effects remains unclear. We are collecting data that should inform future practice.

Conclusions

Modern neurosurgery can offer clinically meaningful symptom relief and improved function for ‘untreatable’ patients with chronic, severe depression and obsessive-compulsive disorder. However, follow-up studies of greater rigour are required. The potential role of non-ablative alternatives remains unclear.
Depersonalisation disorder: clinical features of 204 cases
Authors: Baker Dawn , Hunter Elaine , Lawrence Emma , Medford Nicholas , Patel Maxine , Senior Carl , Sierra Mauricio , Lambert Michelle V. , Phillips Mary L. , David Anthony S.
Published: May 2003

Background

Depersonalisation disorder is a poorly understood and underresearched syndrome.

Aims

To carry out a large and comprehensive clinical and psychopathological survey of a series of patients who made contact with a research clinic.

Method

A total of 204 consecutive eligible referrals were included: 124 had a full psychiatric examination using items of the Present State Examination to define depersonalisation/derealisation and 80 had either a telephone interview (n=22) or filled out a number of self-report questionnaires. Cases assessed were diagnosed according to DSM–IV criteria.

Results

The mean age of onset was 22.8 years; early onset was associated with greater severity There was a slight male preponderance. The disorder tended to be chronic and persistent. Seventy-one per cent met DSM–IV criteria for primary depersonalisation disorder. Depersonalisation symptom scores correlated with both anxiety and depression and a past history of these disorders was commonly reported. ‘Dissociative amnesia’ was not prominent.

Conclusions

Depersonalisation disorder is a recognisable clinical entity but appears to have significant comorbidity with anxiety and depression. Research into its aetiology and treatment is warranted.
Seasonality, negative life events and social support in a community sample
Authors: Michalak Erin E. , Wilkinson Clare , Hood Kerenza , Dowrick Chris , Wilkinson Greg
Published: May 2003

Background

Seasonal affective disorder (SAD) is now a well-described form of depressive disorder. However, relatively little research has focused upon psychosocial factors and SAD.

Aims

To determine the association between demographic/psychosocial factors and increased reported seasonal patterns of mood disorder (seasonality) and SAD in a community sample in the UK.

Method

A total of 1250 people, aged between 18 and 64 years, randomly selected from a primary care database were screened for SAD. Those above cut-off underwent diagnostic interview and completed several self-report questionnaires. Multivariate analysis was conducted to determine which variables were significantly associated with increased seasonality.

Results

Four factors (having experienced more numerous negative life events, having low levels of social support, being a woman and being non-native) were predictive of higher seasonality Being a woman was predictive of being diagnosed as a case of SAD.

Conclusions

A new association has been identified between increased seasonality, negative life events and social support. Future research should assess the psychosocial causes or consequences of SAD while continuing to examine the biology of the condition.
Mental health ‘collaborative’ challenges care culture
Authors: Kennedy Peter , Griffiths Hugh
Published: May 2003

The ‘collaborative’ method, developed by the US Institute of Health Improvement, has succeeded in motivating staff and responding to patients' concerns about acute in-patient psychiatric care across 37 trusts in the Northern, Yorkshire and Trent regions. The method puts into practice the new values underpinning government policies on ‘modernising’ and ‘shifting the balance of power’ in the NHS, i.e. seeing things through the eyes of patients, empowerment of frontline staff, learning networks and focus on measured outcomes. The evaluation suggests that organisational and management culture crucially determined the level of achievement of the trusts taking part in the collaborative. Evaluations of other collaboratives have raised doubts about the sustainability of the improvements achieved. It is argued that refining the collaborative method is less important than incorporating its principles into the existing management and organisational cultures of NHS trusts, and the leadership styles of chief executives and clinical directors.
The utility of EEG in psychiatry and aggression
Authors: Stone Jon , Moran Gregory
Published: May 2003

Aims and Method

To describe the outcomes of electroencephalography requested by general adult psychiatry over a 12-month period.

Results

187 electroencephalograms (EEGs) were performed. In 71%, the request was to look for evidence of epilepsy. In 22%, it was to determine whether there was organic brain dysfunction. In only one patient was unequivocal evidence of an epileptic focus found. A further 11 patients demonstrated a liability to epilepsy. In none of the 33 patients where aggression was mentioned on the request form were any diagnostic features found.

Clinical Implications

The yield of EEG in psychiatry is low. To diagnose epilepsy, clinicians should continue to rely on the clinical history of attacks and not the EEG. The presence of aggression is rarely associated with meaningful EEG changes.
Does having been on a ‘section’ reduce your chances of getting a job?
Authors: Fenton John , O'Hanlon Dee , Allen Danny
Published: May 2003

Aims and Method

To ascertain employers' attitudes to interviewing and hiring job applicants with a history of mental illness and, in particular, to assess the potential effect on job prospects for applicants with a history of admission under the Mental Health Act 1983. A postal tick-box questionnaire was sent to 174 companies; there was a 32% response rate.

Results

The main factors influencing employers' hiring decisions were medical opinion regarding an applicant's fitness to work and their employment and sickness records. In about three-quarters of small companies and half of large companies, questions about mental illness are simply never asked.

Clinical Implications

Approved social workers have no reason to caution people assessed under the Mental Health Act 1983 that being detained could harm their job prospects.
Selective β-Cell Loss and α-Cell Expansion in Patients with Type 2 Diabetes Mellitus in Korea
Authors: Yoon Kun Ho , Ko Seung Hyun , Cho Jae Hyoung , Lee Jung Min , Ahn Yu Bae , Song Ki Ho , Yoo Soon Jib , Kang Moo Il , Cha Bong Yun , Lee Kwang Woo , Son Ho Young , Kang Sung Koo , Kim Hee Seung , Lee In Kyu , Bonner-Weir Susan
Published: May 2003

In the presence of obesity, β-cell mass needs to be increased to compensate for the accompanying demands and maintain euglycemia. However, in Korea, the majority of type 2 diabetic patients are nonobese. We determined the absolute masses, relative volumes, and ratio of α- and β-cell in the pancreas and islets in normal and diabetic Korean subjects to correlate these findings with the clinical characteristics. Whole pancreases procured from organ donors were divided into 24 parts (control 1, n = 9). Tissue was also obtained by surgical resection after 35 partial pancreatectomies: in 25 diabetic patients, 10 age- and body mass index (BMI)-matched patients of benign or malignant pancreatic tumor without diabetes mellitus (DM) (control 2). Morphometric quantifications were performed. In control 1, the relative volume of β-cells was 2.1 ± 0.9%, and the total β-cell mass was 1.3 ± 0.3 g. The relative volume of β-cells was found to be variable (control 1, 2.1 ± 0.9%; control 2, 1.9 ± 0.7%; DM, 1.4 ± 1.0%; P < 0.05 DM vs. control 1 and 2) and showed good correlation with BMI (control 1, r2 = 0.64; DM, r2 = 0.55; all subjects, r2 = 0.38; P < 0.05). Notably, in type 2 diabetic patients, the ratio of α-cell area to β-cell area in the islet was higher than in control 1 and 2 (0.81 ± 0.4 vs. 0.29 ± 0.2, 0.20 ± 0.1, P < 0.05). Additionally, significant α-cell expansion and a decreased β-cell fraction were predominantly observed in larger islets (islet area, >6415 μm2; P < 0.05) in control 1 and diabetic patients. The relative volume of β-cell was found to be correlated with BMI in diabetic patients and normal organ donors. Moreover, decreased β-cell but increased α-cell proportion in the islets suggests for a selective β-cell loss in the pathogenesis of Korean type 2 diabetes.
Increase of Estrogen Dose Deteriorates Mood during Progestin Phase in Sequential Hormonal Therapy
Authors: Björn Inger , Sundström-Poromaa Inger , Bixo Marie , Nyberg Sigrid , Bäckström Gunnel , Bäckström Torbjörn
Published: May 2003

Previous studies have indicated that the addition of progestins during sequential hormonal replacement therapy (HRT) causes negative mood and physical symptoms. History of premenstrual syndrome, type of progestin, and dose of progestin have thus far been shown to influence the progestin-induced adverse mood symptoms during HRT.

The aim of this study was to compare adverse mood effects of two different doses of estradiol, in combination with a progestin, during postmenopausal HRT. Twenty-eight perimenopausal women were included in this randomized, double-blind, crossover study comparing 2- or 3-mg continuous estradiol, with an addition of 10 mg medroxyprogesterone acetate on d 17–28 during each treatment cycle. The main outcome measures were mood and physical symptoms kept on a daily rating scale. Together with the progestin, the higher dose of estrogen caused significantly more negative mood symptoms than the lower dose. Tension, irritability, and depressed mood were all significantly augmented during the progestin phase of cycles with 3 mg estradiol (P < 0.001). Physical symptoms also increased during the progestin phase of 3-mg estradiol cycles (P < 0.001), whereas positive mood symptoms were less affected. The only positive mood that changed with estrogen dose was friendliness, which decreased during the progestin phase of high estradiol cycles compared with cycles with lower estradiol (P < 0.05).

Our conclusion is that an increase of the estrogen dose accentuates negative mood and physical symptoms during the progestin phase of sequential hormonal therapy.
Plasma Levels of Parathyroid Hormone (1–84) Whole Molecule and Parathyroid Hormone (7–84)-Like Fragments in Pseudohypoparathyroidism Type I
Authors: Hatakeyama Yuriko , Mizunashi Kazutoshi , Furukawa Yohtaro , Yabuki Shigemitsu , Sato Yumi , Igarashi Teruo
Published: May 2003

PTH (7–84) has antagonistic effects on the calcemic and phosphaturic actions of PTH (1–84) whole molecule (bioPTH). Human plasma contains bioPTH and PTH (7–84)-like fragments. Using bioPTH-specific and nonspecific assays, we found that the patients with pseudohypoparathyroidism (PHP) type I with PTH-resistant hypocalcemia and hyperphosphatemia had the increased plasma levels of bioPTH and PTH (7–84)-like fragments than normal subjects (26.8 ± 13.2 vs. 2.37 ± 0.75 pmol/liter, P < 0.01 and 16.2 ± 8.8 vs. 0.82 ± 0.47 pmol/liter, P < 0.01, respectively). Calcitriol treatment increased phosphaturic response to PTH (1–34) (P < 0.05), and there was a negative correlation between phosphaturic response and the PTH levels (P < 0.05). These results suggested that the increased bioPTH and PTH (7–84)-like fragment levels may be related to the impaired phosphaturic response to PTH (1–34) in PHP type I. We also examined bioPTH-calcium dynamics in PHP type Ib patients and found that set-point calcium was 0.928 ± 0.045 mmol/liter and the baseline to maximal ratio of bioPTH was 0.96 ± 0.04. Calcitriol treatment increased set-point calcium to 1.129 ± 0.028 mmol/liter (P < 0.01) and suppressed baseline to maximal ratio of bioPTH to 0.35 ± 0.21 (P < 0.01). These bio-PTH calcium dynamics studies revealed the maximally stimulated baseline PTH secretion in PHP type Ib and demonstrated the effects of calcitriol on PTH-calcium curve shift and the degree of relative stimulation of baseline secretion.
Endothelial Function and Coagulant Factors in Growth Hormone-Treated Hypopituitary Adults Receiving Desmopressin
Authors: Smith J. C. , Lane H. A. , Lewis J. , Dann S. , Goodfellow J. , Collins P. , Evans L. M. , Scanlon M. F. , Davies J. S.
Published: May 2003

Although GH deficiency may underlie the increased cardiovascular risk in adult hypopituitarism, other coexisting hormonal deficiencies and/or unphysiological hormone replacement may contribute. l-Deamino-8-d-arginine (DDAVP), when administered parenterally, potentiates hemostasis by increasing plasma procoagulant factors. We investigated whether chronic intranasal DDAVP therapy influences clotting factors (plasma fibrinogen, factor VIII, and von Willebrand factor antigen) and endothelial function (flow-mediated dilation of the brachial artery) in 30 GH-treated hypopituitary subjects, including both DDAVP-treated subjects (group A) (mean age, 46 ± 11 yr) and vasopressin-sufficient subjects (group B) (mean age, 47 ± 16 yr). Fifteen healthy controls (group C) (mean age, 48 ± 12 yr) were also studied. All hypopituitary patients were receiving stable GH replacement (median duration, 19 months). Comparing the three groups, concentrations of fibrinogen (mean ± sd) (A, 3.3 ± 1.0 g/liter vs. B, 3.5 ± 0.9 vs. C, 2.6 ± 0.8, P < 0.05), factor VIII (A, 130% ± 30% vs. B, 128% ± 30% vs. C, 104% ± 35%, P < 0.05) and von Willebrand factor antigen (A, 124% ± 35% vs. B, 134% ± 45% vs. C, 93% ± 36%, P < 0.05) were higher in hypopituitary subjects, compared with controls. However, there were no differences in clotting factors between groups A and B. Flow-mediated dilation did not differ significantly between the two hypopituitary groups (A, 5.9% ± 2.0% vs. B, 4.7% ± 1.6%) and was similar to that in the control group (C, 5.7% ± 2.1%). In conclusion, although endothelium-dependent vasodilation is intact in GH-treated hypopituitary adults, elevated concentrations of hemostatic markers suggest the persistence of a prothrombotic tendency and endothelial dysfunction. Intranasal DDAVP does not appear to influence this proatherogenic profile in hypopituitary adults with vasopressin deficiency.
Antimicrobial activity of β-lactam antibiotics against clinical pathogens after molecular inclusion in several cyclodextrins. A novel approach to bacterial resistance
Authors: Athanassiou G , Michaleas S , Lada-Chitiroglou E , Tsitsa T , Antoniadou-Vyza E
Published: May 2003

Recognition and uptake by specific cellular receptors and transport systems for cyclodextrins have been demonstrated. Based on this concept, natural and synthetically modified cyclodextrins were used as drug carriers. Several β-lactam antibiotics were selected and their inclusion complexes with different cyclodextrins were prepared (molar ratio ranging from 1:1 to 1:3). The complex formation, in aqueous solution, was monitored and optimum complexation conditions were selected. The inclusion of the active molecules in the cyclodextrin cavity was confirmed by 1H NMR spectroscopy. Specific HPLC methods for the quantitation of antibiotics in the presence of cyclodextrins were developed and their chemical stability under complexation conditions was confirmed. Antimicrobial activity of drug-cyclodextrin complexes, in terms of minimum inhibitory concentration (MIC), were compared with the corresponding values of uncomplexed free molecules. A wide range of clinical pathogens and known β-lactamase-producing strains were tested. The activity of the cyclodextrin-included antibiotics was increased, particularly against Gram-negative clinical strains. The nature and degree of substitution on cyclodextrin macromolecules may be the predominant factor in the observed improvement in antimicrobial activity. We believe that the proposed methodology is a novel approach to the microbial resistance problem and will trigger research towards the development of new cyclodextrin derivatives bearing the ability to increase the uptake of included antimicrobial molecules through intensification of the corresponding molecular recognition phenomena.
Thiorphan enhances bradykinin-induced vascular relaxation in hypoxic/hyperkalaemic porcine coronary artery
Authors: Krassói Irén , Pataricza János , Papp Julius Gy
Published: May 2003

Relaxation induced by bradykinin is diminished by hypoxia in epicardial coronary arteries. The bradykinin-degrading enzyme, neutral endopeptidase (NEP, EC.3.4.24.11), is a potential target for coronary artery vasodilators. In this study, we examined the effect of thiorphan, an inhibitor of NEP, on the tone of porcine isolated coronary artery under hypoxic conditions. Endothelium-intact porcine isolated coronary artery rings were isometrically contracted with a prostaglandin F2α analogue (U46619, 0.75 μM) and potassium chloride (KCl, 30 mM), and relaxed with bradykinin (1–1000 nM) under normoxic (partial pressure of oxygen, pO2 ˜ 90–100 mmHg) and moderately hypoxic (pO2 ˜ 50–60 mmHg) conditions. Experiments were performed to study the effects of 30 min pre-treatment with the NEP-inhibitor, thiorphan (10 μM), both at physiological and at low pO2s. Hypoxia inhibited the bradykinin-induced relaxation in porcine epicardial coronary arteries. In normoxia, thiorphan significantly enhanced the decrease of coronary tone produced by bradykinin (1–10 nM) when U46619 was used as contractile agent. Under hypoxic conditions, in U46619 contracture, thiorphan did not influence, but in KCl contracture it enhanced the magnitude of relaxations induced by bradykinin. In the absence of bradykinin, thiorphan had no significant effect on the basal, KCl- and U46619-elevated tones and on the hypoxia-induced decrease of coronary artery tone. Inhibition of NEP-enzyme activity may effectively improve the relaxing capacity of epicardial coronary arteries under hypoxic/hyperkalemic conditions. This effect could be potentially utilized when the endothelial function and relaxation of the coronary arteries are impaired under clinical conditions.
Influence of co-administered antibiotics on the pharmacokinetic fate in rats of paeoniflorin and its active metabolite paeonimetabolin-I from Shaoyao-Gancao-tang
Authors: He Ju-Xiu , Akao Teruaki , Tani Tadato
Published: May 2003

The effects of orally co-administered antibiotics on the pharmacokinetics of paeoniflorin (PF) and paeonimetabolin-I (PM-I), a bioactive metabolite derived from PF by intestinal bacteria, from the traditional Chinese formulation, Shaoyao-Gancao-tang (SGT), were investigated in rats to clarify the effect of administering SGT together with some synthetic drugs. Co-administration of the antibiotics amoxicillin and metronidazole (AMPC-MET) significantly increased the area under the plasma concentration versus time curve (AUC) of PF, whereas it markedly decreased that of PM-I, to 2.6% of the normal AUC by administration of a single dose, and less than 1% by a 3-day pretreatment. Similar effects were observed using the combination of ofloxacin with SGT. The PF-metabolizing activity of intestinal bacteria was reduced to 16% and 33% of normal levels by treatment with AMPC-MET and ofloxacin, respectively, which caused alterations of that degree in the extent of absorption of PF and PM-I, but did not affect their rate of absorption or elimination. The present study suggests that it may not be appropriate to use SGT simultaneously with antibiotics such as AMPC-MET or ofloxacin, and also reveals the important role of intestinal bacteria in the pharmacokinetics of the active components of this traditional Chinese formulation.
Effects of folic acid and lamotrigine therapy in some rodent models of epilepsy and behaviour
Authors: Ali Atif , Pillai K K , Pal Shanthi N
Published: May 2003

It has been suggested that a folic acid (FA) deficiency induced by antiepileptic drugs might be the basis for the neuropsychiatric toxicity associated with these drugs. In the present study, lamotrigine (LTG), one of the newer antiepileptic drugs, was evaluated for its effect on epilepsy, mood and memory in mice. Further, the effect of the addition of FA to LTG therapy was also investigated. The increasing current electroshock seizure test was used to evaluate the anticonvulsant effect of drugs, while the forced swimming test (FST) and spontaneous alternation behaviour (SAB) models were employed for assessing the effects on mood and memory, respectively. LTG exhibited a dose-dependent increase in seizure threshold, whereas FA did not have any effect. LTG did not affect, whereas FA decreased, behavioural depression in the FST in mice. Neither LTG nor FA affected memory scores in the SAB test. The combination of LTG and FA significantly reduced depression while enhancing the effects on memory and seizure threshold. The present observations have confirmed the antiepileptic action of LTG in yet another rodent model of epilepsy. Further, the results clearly demonstrate the additional benefits on epilepsy, mood and memory brought about by the inclusion of FA in the LTG regimen.
Comparison of suppressive potency between azathioprine and 6-mercaptopurine against mitogen-induced blastogenesis of human peripheral blood mononuclear cells in-vitro
Authors: Sugiyama Kentaro , Satoh Hiroshi , Hirano Toshihiko
Published: May 2003

Azathioprine (AZ) is a prodrug of 6-mercaptopurine (6-MP), but little is known about the relative suppressive efficacy of these agents against blastogenesis of human peripheral blood mononuclear cells (PBMCs) in-vitro. We compared the pharmacological efficacy of AZ and 6-MP against T cell mitogen-induced blastogenesis of PBMCs in-vitro. PBMCs were obtained from seven healthy subjects. The potency of AZ and 6-MP to suppress PBMC-blastogenesis in-vitro was compared using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay procedures. Production of 6-MP from AZ in PBMC culture was examined by high-performance liquid chromatography. Both AZ and 6-MP dose-dependently suppressed PBMC blastogenesis. Mean ± s.d. IC50 (concentration of drug that gave 50% inhibition) values for AZ and 6-MP were 230.4 ± 231.3 and 149.5 ± 124.9 nM, respectively. Thus, the potencies of AZ and 6-MP to suppress PBMC blastogenesis were not significantly different. A significant correlation was observed between the IC50 values of AZ and 6-MP (P < 0.01, n = 6). After incubation of PBMCs with 100 μM AZ for 4 days, 35.3–92.5 μM 6-MP was liberated into the culture medium. The ratio of 6-MP liberation from AZ was influenced by the presence of PBMCs, but not by the medium or fetal bovine serum. The results suggest that the suppressive potency of the prodrug AZ and its converted form 6-MP against blastogenesis of human PBMCs in-vitro is similar, although PBMCs appeared to convert AZ to 6-MP. AZ is suggested to be effective after conversion to 6-MP to express immunosuppressive efficacy in-vitro.
Mechanical constraint imposed on plasma membrane through transverse phospholipid imbalance induces reversible actin polymerization via phosphoinositide 3-kinase activation
Authors: Bettache Nadir , Baisamy Laurent , Baghdiguian Stephen , Payrastre Bernard , Mangeat Paul , Bienvenüe Alain
Published: May 2003

Platelets were used to explore the effect of membrane curvature induced by phospholipid excess on cell shape and on organization of the actin cytoskeleton. We showed that the addition of short chain analogues of phospholipids to the outer leaflet of plasma membrane of resting platelets immediately induced a shape change with long filopodia formation containing newly polymerized actin. Cells recovered rapidly their discoid shape and their initial F-actin content only with the phosphatidylserine analogue, which was transported to the inner leaflet by aminophospholipid translocase. Filopodia formation and actin polymerization were inhibited in platelets pre-incubated with cytochalasin D. Both wortmannin and LY294002, two unrelated inhibitors of phosphoinositide 3-kinase, considerably reduced actin polymerization and filopodia formation. Phospholipid imbalance was accompanied by a reversible translocation of phosphoinositide 3-kinase from cytoplasm to plasma membrane. In agreement with a role for PI 3-kinase, when phospholipids were added to platelets, PtdIns(3,4)P2 increased two-fold and Akt protein was partly phosphorylated. A similar shape change was also observed in nocodazole-treated L929 fibroblasts which were incubated with the similar phospholipid analogues. In those nucleated cells, where the microtubule cytoskeleton was disrupted, a major actin-dependent membrane extension was induced by addition of short chain phospholipids that required the functional integrity of PI 3-kinase. We conclude that any physical constraint acting on plasma membrane and resulting on local changes in membrane curvature is sufficient to initiate transient actin polymerization via phosphoinositide 3-kinase activation.
New N-RAP-binding partners α-actinin, filamin and Krp1 detected by yeast two-hybrid screening: implications for myofibril assembly
Authors: Lu Shajia , Carroll Stefanie L. , Herrera Amy H. , Ozanne Bradford , Horowits Robert
Published: May 2003

N-RAP, a muscle-specific protein concentrated at myotendinous junctions in skeletal muscle and intercalated disks in cardiac muscle, has been implicated in myofibril assembly. To discover more about the role of N-RAP in myofibril assembly, we used the yeast two-hybrid system to screen a mouse skeletal muscle cDNA library for proteins capable of binding N-RAP in a eukaryotic cell. From yeast two-hybrid experiments we were able to identify three new N-RAP binding partners: α-actinin, filamin-2, and Krp1 (also called sarcosin). In vitro binding assays were used to verify these interactions and to identify the N-RAP domains involved. Three regions of N-RAP were expressed as His-tagged recombinant proteins, including the nebulin-like super repeat region (N-RAP-SR), the N-terminal LIM domain (N-RAP-LIM), and the region of N-RAP in between the super repeat region and the LIM domain (N-RAP-IB). We detected significant α-actinin binding to N-RAP-IB and N-RAP-LIM,filamin binding to N-RAP-SR, and Krp1 binding to N-RAP-SR and N-RAP-IB. During myofibril assembly in cultured chick cardiomyocytes, N-RAP and filamin appear to co-localize with α-actinin in the earliest myofibril precursors found near the cell periphery, as well as in the nascent myofibrils that form as these structures fuse laterally. In contrast, Krp1 is not localized until late in the assembly process, when it appears at the periphery of myofibrils that appear to be fusing laterally. The results suggest that sequential recruitment of N-RAP binding partners may serve an important role during myofibril assembly.