bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of Cortical Interneurons in Grey Matter Heterotopia in Patients with Epilepsy
Authors: Thom Maria , Martinian Lillian , Parnavelas John G. , Sisodiya Sanjay M.
Published: July 2004

Summary:  Purpose: Grey matter heterotopia are well‐defined malformations of the cortex often associated with severe epilepsy. Defects have been identified in genes, including DCX and FLN1, that influence radial migration of postmitotic cells from the ventricular zone to the cortical plate. A proportion of cortical γ‐aminobutyric acid (GABA)‐containing interneurons may arise from the ganglionic eminence of the ventral telencephalon. We aimed to identify the subtypes and localisation of interneurons within grey matter heterotopia relative to cortex.

Methods: By using quantitative immunohistochemistry, we studied the density and distribution of interneurons within six cases of grey matter heterotopia in postmortem tissue from patients with epilepsy.

Results: In many cases, a suggestion of focal rudimentary laminar arrangement and small reelin‐positive cells was identified within the heterotopia. Immunohistochemistry for glutamic acid decarboxylase65/57, parvalbumin, calbindin, and calretinin showed inhibitory neurons of all subtypes represented within the heterotopia, and of normal morphology. The mean densities of interneurons were overall similar to those of the overlying cortex, but the interneurons showed less organisation and were more randomly orientated compared with cortex.

Conclusions: Interneurons within heterotopia probably arise from the ventricular zone, but their abnormal local organization may influence the epileptogenicity of these lesions.
Effects of thermal treatments with a curling iron on hair fiber
Authors: Ruetsch S. B. , Kamath Y. K.
Published: July 2004

The effect of curling hair with a curling iron has been investigated. Possibilities of thermal damage with repeated curling according to, and in violation of, the manufacturer's specifications have been studied. The propensity of hair surface to damage depends on the moisture content of the hair, and these experiments have been conducted in both wet and dry conditions, with and without application of tension, and with short or prolonged times. Scanning electron microscopic examination revealed that fibers treated under the dry condition (50% RH) show radial and axial cracking along with scale edge fusion. Similar thermal treatment on wet hair resulted in severe damage of the type described above, as well as bubbling and buckling of the cuticle due to the formation and escaping of steam from the fiber. Fibers subjected to repeated curling in the dry condition show slight increases in tensile mechanical properties, characteristic of a cross‐linked fiber. Fibers treated with conditioners show an improvement in characteristic life, especially in the case of low‐molecular‐weight conditioners, such as CETAB, which can penetrate into the hair fiber (shown by TOF‐SIMS analysis).
Targeted delivery of salicylic acid from acne treatment products into and through skin: role of solution and ingredient properties and relationships to irritation
Authors: Rhein L. , Chaudhuri B. , Jivani N. , Fares H. , Davis A.
Published: July 2004

Salicylic acid (SA) is a beta‐hydroxy acid and has multifunctional uses in the treatment of various diseases in skin such as acne, psoriasis, and photoaging. One problem often cited as associated with salicylic acid is that it can be quite irritating at pH 3–4, where it exhibits the highest activity in the treatment of skin diseases. We have identified strategies to control the irritation potential of salicylic acid formulations and have focused on hydroalcoholic solutions used in acne wipes. One strategy is to control the penetration of SA into the skin. Penetration of the drug into various layers of skin, i.e. epidermis, dermis, and receptor fluid, was measured using a modified Franz in vitro diffusion method after various exposure times up to 24 h. A polyurethane polymer (polyolprepolymer‐15) was found to be an effective agent in controlling delivery of SA. In a dose‐dependent fashion it targeted delivery of more SA to the epidermis as compared to penetration through the skin into the receptor fluid. It also reduced the rapid rate of permeation of a large dose of SA through the skin in the first few hours of exposure. A second strategy that proved successful was incorporation of known mild nonionic surfactants like isoceteth‐20. These surfactants cleanse the skin, yet due to their inherent mildness (because of their reduced critical micelle concentration and monomer concentration), keep the barrier intact. Also, they reduce the rate of salicylic acid penetration, presumably through micellar entrapment (either in solution or on the skin surface after the alcohol evaporates). Cumulative irritation studies showed that targeting delivery of SA to the epidermis and reducing the rapid early rate of penetration of large amounts of drug through the skin resulted in a reduced irritation potential. In vivo irritation studies also showed that the surfactant system is the most important factor controlling irritancy. SA delivery is secondary, as formulations with less SA content reduced the rate of delivery to the receptor and yet were some of the most irritating formulations tested, presumably due to the action of the specific anionic surfactant on the barrier. Alcohol content also did not appreciably affect irritation and SA delivery; formulations with considerably low alcohol content but containing anionic versus nonionic surfactant systems exhibited considerably higher irritancy. Thus the surfactant type was again the predominant factor in those studies, although arguably alcohol plays some role (solubilization of SA). Results showed that both polymers and mild surfactants work in concert to provide the optimal formulation benefits of targeted delivery and reduced irritation. Synergistic relationships among hydroalcoholic formulation components will be discussed along with the mechanisms likely involved in controlling delivery of SA to skin.
Australian Thysanoptera – biological diversity and a diversity of studies
Authors: Mound Laurence A
Published: July 2004

Abstract  Studies in Australia on thrips have had extensive impacts worldwide. In behaviour, the latest definition of eusociality is derived from work on the radiation of thrips on Acacia species in central Australia, and these Acacia thrips also having been used to develop the concept of ‘model clades’ for analysing the evolution of behavioural and ecological diversity. In ecology, the concept of the lack of density dependent factors in population dynamics was elaborated through studies on the plague thrips of southern Australia. In virology, thrips were first shown in Australia to be the vectors of tospoviruses, although these viruses, their vectors and the plants attacked are all non‐native to this continent. Work in Australia has included the development of electronic methods of illustration, identification and information transfer about thrips, including the use of molecular methods for pest species recognition, and considerable advances have been made in Australia in our knowledge of the relationships between thrips and plants, from polyphagy to pollination.
Medical entomology: changes in the spectrum of mosquito‐borne disease in Australia and other vector threats and risks, 1972–2004
Authors: Russell Richard C , Kay Brian H
Published: July 2004

Abstract Our paper presents an assessment of research and operational development in relation to medically important mosquito‐borne disease, mainly the arboviruses Ross River, Barmah Forest, Murray Valley encephalitis, Japanese encephalitis, Kunjin and dengue, but also with respect to malaria. Since 1972, there have been considerable gains in research output, organisational structure, communication, surveillance including quarantine inspection and operational control. This has been due to the 1974 epidemic of Murray Valley encephalitis virus extending into temperate Australia, increasing occurrence of Ross River and the dengue viruses, the discovery of Barmah Forest virus as a disease entity in 1988, and the introduction of Japanese encephalitis in 1995. Because many of the outputs involve methodologies of global import, this has resulted in an unprecedented upsurge in publications of international standard.
Advances in the molecular and serological diagnosis of invasive fungal infection in haemato‐oncology patients
Authors: McLintock Lorna A. , Jones Brian L.
Published: July 2004

Current laboratory diagnostic methods for invasive fungal infection (IFI) in haemato‐oncology patients are insensitive, resulting in late diagnosis and contributing to high mortality. In recent years, progress has been made in the development and evaluation of sensitive sero‐diagnostic assays, including detection of genomic DNA sequences and fungal antigens, which aid in a rapid, early diagnosis of IFI. The sensitivity and specificity of the assays vary considerably between studies, highlighting the need to correlate serological results with conventional laboratory tests and clinical or radiological findings. As part of management protocols, these assays may help to confirm the diagnosis of suspected IFI; however, the impact on mortality from IFI may be greatest when they are used to screen high‐risk patients. Persistently positive screening results could direct early aggressive antifungal therapy, guided further by radiological and microbiological findings combined with regular clinical review, while the excellent negative predictive value may allow treatment to be withheld in patients with antibiotic resistant neutropenic fever but no other signs of IFI. However, this pre‐emptive approach requires evaluation in prospective randomized trials.
Complex chromosomal abnormalities in utero, 5 years before leukaemia*
Authors: Broadfield Zoë J. , Hain Richard D. W. , Harrison Christine J. , Reza Jalali G. , McKinley Mark , Michalová Kyra , Robinson Hazel M. , Zemanová Zuzana , Martineau Mary
Published: July 2004

Prenatal acquisition of leukaemia‐associated gene rearrangements is a well‐established phenomenon. This is the first report of a complex cytogenetic clone, in association with an ETV6/AML1 fusion, developing in utero. Identical twin girls, aged 4 years, developed ETV6/AML1‐positive acute lymphoblastic leukaemia (ALL) within 3 months of one another. Both demonstrated an identical four way, variant t(12;21). There was gain of an AML1 signal in twin 1 and loss of an ETV6 one in twin 2 at interphase. This unique case study demonstrates that ETV6/AML1 fusion and the associated complex chromosomal rearrangements occurred in utero. Clonal expansion of the abnormal cell in one twin was followed by metastasis to the other. There was a prolonged preleukaemic phase, which lasted well into childhood. The short time between the two diagnoses of ALL suggests a common precipitating event. The significance of the different secondary markers remains unclear.
Serum free light chains for monitoring multiple myeloma
Authors: Mead G. P. , Carr‐Smith H. D. , Drayson M. T. , Morgan G. J. , Child J. A. , Bradwell A. R.
Published: July 2004

Monoclonal immunoglobulin free light chains (FLC) are found in the serum and urine of patients with a number of B‐cell proliferative disorders, including multiple myeloma. Automated immunoassays, which can measure FLC in serum, are useful for the diagnosis and monitoring of light chain (AL) amyloidosis, Bence Jones myeloma and non‐secretory myeloma patients. We report the results of a study investigating the utility of serum FLC measurements in myeloma patients producing monoclonal intact immunoglobulin proteins. FLC concentrations were measured in presentation sera from 493 multiple myeloma patients with monoclonal, intact immunoglobulin proteins. Serial samples were assayed from 17 of these patients and the FLC measurements were compared with other disease markers. Serum FLC concentrations were abnormal in 96% of patients at presentation. FLC concentrations fell more rapidly in response to treatment than intact immunoglobulin G (IgG) and showed greater concordance with serum β2 microglobulin concentrations and bone marrow plasma cell assessments. It was concluded that serum FLC assays could be used to follow the disease course in nearly all multiple myeloma patients. In addition, because of their short serum half‐life, changes in serum FLC concentrations provide a rapid indication of the response to treatment.
Bone marrow histological patterns can predict survival of patients with grade 1 or 2 follicular lymphoma: a study from the Groupe d‘Etude des Lymphomes Folliculaires
Authors: Canioni Danielle , Brice Pauline , Lepage Eric , Chababi Myrna , Meignin Véronique , Salles Bruno , Xerri Luc , Péaud Pierre‐Yves , Rousselot Philippe , Peuchmaur Michel , Solal‐Céligny Philippe , Brousse Nicole ,   The Groupe d'Etude des Lymphomes Folliculaires
Published: July 2004

The influence of bone marrow biopsy (BMB) histology on prognosis and management of follicular lymphomas (FL) remains controversial. A total of 390 patients with grade 1 or 2 FL were prospectively included in the multicentric Groupe d'Etude des Lymphomes Folliculaires trial and their BMB reviewed in order (i) to quantify the ratio of lymphomatous foci (LFo) area to that of BMB size (LFo/BMB), (ii) to determine the BMB patterns for a practical grading of marrow infiltration, (iii) to assess the intra‐ and inter‐observer reproducibility of this grading and (iv) to analyse this grading on event‐free (EFS) and overall survival (OS), using univariate and multivariate analyses. A total of 267 patients (68%) had BMB involvement, with inter‐ and intra‐observer reproducibility for classifying the patterns of involvement of 91 and 96%, respectively. Uni‐ and multivariate analyses demonstrated the adverse influence of (i) a ratio of LFo/BMB ≥0·1, i.e. three or four nodules/medullary space or ≥1 nodule + foci of diffuse involvement on EFS (P = 0·03) and (ii) two different histological patterns in the same BMB on EFS (P = 0·004) and OS (P = 0·001). This latter finding was only significant in patients with a high tumour burden and remained significant in multivariate analysis. These results indicate that BMB histology can predict survival of FL patients with a high tumour burden, and may help in defining their treatment.
The recurrent translocation t(14;20)(q32;q12) in multiple myeloma results in aberrant expression of MAFB: a molecular and genetic analysis of the chromosomal breakpoint
Authors: Boersma‐Vreugdenhil Gienke R. , Kuipers Jeroen , Van Stralen Esther , Peeters Ton , Michaux Lucienne , Hagemeijer Anne , Pearson Peter L. , Clevers Hans C. , Bast Bert J. E. G.
Published: July 2004

Chromosomal translocations of the immunoglobulin heavy chain (IgH) gene region at 14q32 are regularly involved in B lymphoid malignancies; they may initiate transformation either by deregulation of existing (proto) oncogenes or creation of new hybrid genes with transforming properties. Previously, we reported a reciprocal novel translocation, t(14;20)(q32;q12), found in the myeloma cell line UM3. In this cell line, the t(14;20) is the only translocation involving the IgH locus. Using double colour immunofluorescence in situ hybridization, the t(14;20) was also found in the diagnostic bone marrow sample, excluding a possible in vitro artefact. We also have found this recurrent t(14;20) in four other cell lines and in additional patient material. We cloned the regions containing the breakpoints in the der(14) and der(20) chromosomes from UM3, and analysed ectopic mRNA expression of genes in the breakpoint regions of both derivative chromosomes. Ectopic gene expression was observed for the transcription factor MAFB in der(14). The breakpoint scatter in the five cell lines with a t(14;20) – all expressing MAFB– is comprised within a region of 0·8 Mb. Provisional data indicate that this t(14;20) is associated with an adverse prognosis. Aberrant expression of MAFB may be involved in the oncogenic transformation of myeloma cells that harbour the t(14;20).
Prospective evaluation of procalcitonin in adults with febrile neutropenia after haematopoietic stem cell transplantation
Authors: Ortega Mar , Rovira Montserrat , Filella Xavier , Almela Manel , Puig de la Bellacasa Jorge , Carreras Enric , Mensa Josep
Published: July 2004

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented infection and non‐infectious febrile episodes (n = 10). On first day of fever, mean (±SD) PCT level was 0·3 ng/ml (0·2) in neutropenic fever of unknown origin, 0·5 ng/ml (0·7) in microbiologically confirmed infections, 0·2 ng/ml (0·2) in clinically documented infections and 1·7 (4·2) in non‐infectious fever (P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10·1 ng/ml (6·7)] than all remaining groups (P = 0·027; Kruskal–Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values ≥3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis.
Resonance‐thrombography indices of the haemostatic process in relation to risk of incident coronary heart disease: 9 years follow‐up in the Caerphilly Prospective Heart Disease Study
Authors: Yu Shicheng , Lowe Gordon D. O. , Yarnell John W. G. , Sweetnam Peter M.
Published: July 2004

Global assays, such as resonance‐thrombography (RTG), which measure the interaction between platelets, coagulation and fibrinolysis have been used as summary measures of risk for over two decades but have not been evaluated in epidemiological studies. We examined whether RTG indices are risk indicators for incident coronary heart disease (CHD). RTG indices, related haematological variables and other risk factors were measured between 1984 and 1988 in a cohort of 2398 British men. Reaction time (r) and amplitude of fibrin leg (AF) were associated with lifestyle risk factors. During 9 years of follow‐up, 282 (12%) men developed a major new CHD event, as classified by World Health Organization criteria. On adjustment for age, only r and AF measured at baseline were related to risk of incident CHD. On multivariate adjustment in a multiple logistic regression model that included age, diastolic blood pressure, body mass index, total and high‐density lipoprotein cholesterol, lifestyle risk factors and use of prescribed medicine, these associations weakened but remained significant. Additional adjustment for fibrinogen, viscosity, white cell count and fibrin d‐dimer either reduced these associations to non‐significance (AF) or to borderline significance (r).
Phenotypic sensitivity to activated protein C in healthy families: importance of genetic components and environmental factors
Authors: Taralunga Claudia , Gueguen René , Visvikis Sophie , Regnault Véronique , Sass Catherine , Siest Gérard , Lecompte Thomas , Wahl Denis
Published: July 2004

The relative importance of environmental factors and genetic components other than factor V Leiden on the sensitivity to activated protein C (APC) in healthy nuclear families was determined. We studied 149 European families (298 parents and 278 biological offspring aged more than 6 years). APC response was measured and expressed as normalized APC‐sensitivity ratio (n‐APC‐SR). Subjects were genotyped for G1691A and G20210A polymorphisms of factor V and II genes; levels of factors II, V and VIII, antithrombin, cholesterol, high‐density lipoprotein cholesterol and triglycerides were measured. After identifying variables influencing the n‐APC‐SR by a stepwise multiple regression model, variance component analysis was used. The heritability (proportion of the overall variability of a trait due to polygenic effects) of n‐APC‐SR was determined after adjustment for all clinical and laboratory variables, including factor V Leiden. Heritability coefficients (mean ± standard deviation) were different for males (0·68 ± 0·06) and females (0·34 ± 0·12) younger than 25 years and in subjects older than 25 years: 0·37 ± 0·09. This analysis provides strong evidence for a polygenic component influencing n‐APC‐SR in addition to factor V Leiden and suggests age‐ and gender‐specific genetic effects.
Efficacy and inhibitor development in previously treated patients with haemophilia A switched to a B domain‐deleted recombinant factor VIII
Authors: Gringeri Alessandro , Tagliaferri Annarita , Tagariello Giuseppe , Morfini Massimo , Santagostino Elena , Mannucci Piermannuccio ,   the ReFacto–AICE Study Group
Published: July 2004

There have been recent reports of unexpected poor efficacy of a B‐domain‐deleted recombinant factor VIII (BDD‐rFVIII) in haemophiliacs, and inhibitor development in previously treated patients (PTPs) switched to BDD‐rFVIII. The results of a 6‐month prospective study of 25 PTPs and of a retrospective survey of 94 PTPs, all switched to BDD‐rFVIII, were used to evaluate efficacy and inhibitor development. The prospective study showed that 89% of 362 bleeds were controlled by one to two infusions, reproducing the efficacy profiles of other recombinant products (rFVIIIs). One patient, previously treated with plasma‐derived FVIII only, developed a high titre inhibitor (30 BU) after 5 days of exposure. The retrospective survey, carried out in the total Italian PTP population switched to BDD‐rFVIII, involved 19 PTPs at higher inhibitor risk due to previous exposure of ≤ 50 days and 75 PTPs at lower inhibitor risk due to previous exposure of >50 days. One patient developed an inhibitor: he was a high‐risk, severe PTP previously exposed to another rFVIII for 3 days only. Among the entire low‐risk population of severe Italian PTPs switched to BDD‐rFVIII (25 in the prospective study, 49 in the retrospective cohort) only one developed an inhibitor (1·3%). These data indirectly support the views that BDD‐rFVIII is equivalent to other rFVIIIs in term of efficacy and inhibitor development.
Intraindividual consistency of the activated protein C resistance phenotype
Authors: Tosetto Alberto , Simioni Monica , Madeo Domenico , Rodeghiero Francesco
Published: July 2004

Resistance to activated protein C (APC) has been demonstrated to be a risk factor for venous thromboembolism, but it is not known whether this phenotype is consistent over time. We reinvestigated 2580 subjects from the Vicenza Thrombophilia and Atherosclerosis (VITA) Project to evaluate the prevalence of a consistent APC resistance phenotype in the population. Among the 433 subjects with an APC resistance at first visit, the phenotype was confirmed in all the 74 factor V (FV) Leiden carriers and in 124 of 359 FV Leiden negative subjects (34%). The prevalence of a confirmed phenotype, not associated with FV Leiden, was 4·8% in our population. In a subgroup of subjects previously investigated for heritability of the APC resistance, we confirmed the APC resistance phenotype in seven of 39 (17·9%) subjects with an APC resistant sibling but only in 20 of 408 (4·9%) subjects without a sibling with the same phenotype (P = 0·005). Among the 124 FV Leiden negative subjects with a persistent APC resistance phenotype, 40 (32%) had a plasma factor VIII coagulant activity level above 150 IU/dl and eight (6·4%) were carriers of the G20210A prothrombin allele. APC resistance not due to FV Leiden is a frequent and consistent phenotype in the general population, with a possibly strong genetic influence.
Meiotic segregation of translocations during male gametogenesis
Authors: Morel Frédéric , Douet‐Guilbert Nathalie , Le Bris Marie‐Josée , Herry Angèle , Amice Véronique , Amice Jean , De Braekeleer Marc
Published: July 2004

Balanced reciprocal and Robertsonian translocations are the most common structural chromosomal abnormalities in humans. Generally, they are without consequence for the carrier, but for various degrees of oligoasthenoteratozoospermia in men. As these carriers can produce a significant percentage of gametes with an unbalanced combination of the parental rearrangement, there is a more or less significant risk, according to cases, of chromosomal imbalances for their offspring. Therefore, techniques were developed to study the meiotic segregation of these translocations in males. Direct investigation of human sperm chromosomes became possible by karyotyping spermatozoa after penetration of zona‐free hamster oocytes and, more recently, using fluorescent in situ hybridization (FISH). This paper reviews the results obtained using these techniques in Robertsonian and reciprocal translocations. The studies on spermatozoa from translocation carriers help the comprehension of the mechanisms of the meiotic segregation. They should be integrated in the genetic exploration of the infertile men, in order to give them a personalized risk assessment of unbalanced spermatozoa, specially as a correlation was found recently between the percentage of abnormal spermatozoa and that of abnormal embryos.
Glial Aromatization Decreases Neural Injury in the Zebra Finch (Taeniopygia guttata): Influence on Apoptosis
Authors: Wynne R. D. , Saldanha C. J.
Published: July 2004

Emerging evidence suggests a neuroprotective role for oestrogens following damage to the vertebrate brain. Aromatase (oestrogen synthase) is rapidly transcribed and translated in glial cells around areas of neural damage in several vertebrates. However, the potential neuroprotection afforded by locally up‐regulated glial aromatase immediately surrounding the injury remains to be tested. Towards this end, individual birds sustained penetrating mechanical injuries via a needle that contained either vehicle or the aromatase inhibitor fadrozole into contralateral hemispheres. Seventy‐two hours later, the size of neural injury (as assessed by the extent of necrotic tissue) and the number of apoptotic cells around the injuries were evaluated. The size of injury in the hemisphere injected with fadrozole was significantly larger than the injury caused by vehicle injection. Furthermore, a greater number of apoptotic nuclei were found around the fadrozole‐associated lesion relative to vehicle. Finally, constitutively expressed, neuronal aromatase close to the injury site did not differ between hemispheres. We conclude that local inhibition of glial aromatase immediately around the site of injury plays a neuroprotective role in the songbird brain and this protection involves apoptotic pathways. Local up‐regulation of glial aromatase may play a pivotal role in the limitation of secondary damage and/or the acceleration of restorative processes following injury to the vertebrate brain.
Glial Limitans Elasticity Subjacent to the Supraoptic Nucleus
Authors: Salm A. K. , Hawrylak N.
Published: July 2004

Two previous studies from our laboratory have indicated that the ventral glial limitans subjacent to the hypothalamic supraoptic nucleus (SON‐VGL) undergoes a reversible thinning upon chronic activation of the magnocellular neuroendocrine cells (MNCs) of the supraoptic nucleus (SON). Numerous other studies have shown that MNC somata hypertrophy with activation. One aim of the current study was to understand better how SON‐VGL thinning occurs. A second aim was to quantify overall changes of the MNC somata region due to cellular hypertrophy to compare relative changes in dimensions. Here, we undertook a light microscopic stereological investigation of the SON and the subjacent SON‐VGL of Nissl stained material under basal and activated conditions. Astrocyte numbers in the underlying SON‐VGL remained stable across hydration state as did the overall volume of the SON‐VGL and dendritic zone reference area. How these data are consistent with our earlier observations of SON‐VGL thinning was resolved by the finding of a highly significant, 30% increase in the mediolateral dimension of the SON‐VGL in dehydrated rats. These observations fit well with previous work from our laboratory that demonstrates a reorientation of SON‐VGL astrocytes, from vertical to horizontal, which occurs in the activated SON‐VGL. We found a significant, approximately 54%, increase in the overall volume of the MNC region of the SON. No significant rostrocaudal lengthening of the SON was detected, although a trend was evident. All the observed changes reversed with rehydration. These data indicate that elasticity of the SON‐VGL acts to accommodate the volume expansion of the MNCs and enables the SON‐VGL to continue as an interface between the underlying cerebrospinal fluid in the subarachnoid space and the expanded SON above.
Nurses’ ethical perceptions about coercion
Authors: LIND M. , KALTIALA‐HEINO R. , SUOMINEN T. , LEINO‐KILPI H. , VÄLIMÄKI M.
Published: July 2004

Purpose of the study: The purpose of this study was to describe Finnish psychiatric nurses’ ethical perceptions about coercive measures in acute psychiatric setting. Methods: The data were collected with a questionnaire developed for this study. The sample included 170 Finnish psychiatric nurses on acute wards in five psychiatric hospitals. The data were analysed using frequency and percentage distributions, mean and standard deviations. The internal consistency of the instrument was explored with Cronbach's alpha. The association between the background variables and the sum score of the items of the questionnaire was tested with Mann–Whitney U‐test and Kruskal–Wallis test. The open‐ended question was analysed with content analysis. Results: Some psychiatric nurses perceived coercive measures as ethically problematic. In particular, the implementation of forced medication (18%), four‐point restraints (16%) and patient seclusion (11%) were perceived as ethically problematic. Female nurses and nurses who worked on closed wards perceived the measures to be more problematic than male nurses and nurses who did not work on closed wards. Conclusion: In Finland, special attention has been paid to ethical questions related to the care of psychiatric patients and to the enhancement of patients’ rights, yet the majority of the nurses participating in the survey did not perceive coercive measures as ethically problematic. More research on this issue as well as further education of the personnel and more extensive teaching of ethics in nursing schools are needed to support the ability of the psychiatric personnel to identify ethically problematic situations. In addition, it is important to consider new measures for generating genuine moral reflection among the personnel on the usage of coercive measures as well as on their effectiveness and legitimacy in the psychiatric care.
An investigation into how community mental health nurses assess the risk of violence from their clients
Authors: MURPHY N.
Published: July 2004

Part of the community mental health nurse's (CMHN) role is the assessment of violence posed by clients. It explores factors such as the reduction of inpatient beds and the predictability of violent acts towards nursing staff. This study outlines how the risk of violence is assessed by generic CMHNs, by examining their awareness, understanding and perceptions of violence posed by their clients. The data were collected in one Trust, using questionnaire and focus groups. The findings emphasize the importance of historical evidence but also raise the issue of gut feelings of the nurse. They further identify that clinical judgement can be accurate in assessing for violence, and CMHNs relied upon experience and personal impressions of the presenting evidence, rather than through the use of a standardized instrument.
Evaluating the introduction of a pilot client attachment scheme in mental health nursing education
Authors: TURNER L. , CALLAGHAN P. , EALES S. , PARK A.
Published: July 2004

Client attachment (CA) allows student nurses to gain clinical experience through forming therapeutic attachments with individual clients, rather than through a series of location‐based placements. This paper describes a pilot project that evaluated CA with pre‐registration student mental health nurses. Using semi‐structured interviews, the researchers identified the students’, their supervisor’s, and their clients’ experiences of CA. Most participants agreed that students were able to learn relevant and appropriate clinical skills, and to consolidate experience‐increasing motivation, autonomy, organizational skills, and confidence.
Predicting inpatient violence in acute psychiatric wards using the Brøset‐Violence‐Checklist: a multicentre prospective cohort study
Authors: ABDERHALDEN C. , NEEDHAM I. , MISEREZ B. , ALMVIK R. , DASSEN T. , HAUG H.‐J. , FISCHER J. E.
Published: July 2004

The Norwegian Brøset‐Violence‐Checklist (BVC) is one of the few instruments that is suitable for short‐term prediction of violence of psychiatric inpatients by nursing staff in routine care. The instrument assesses the presence or absence of six behaviours or states frequently observed before a violent incident. We conducted a study to elucidate whether the predictive properties of the BVC are retained in other psychiatric settings than the original north‐Norwegian validation dataset. During their admission period, 219 consecutive patients admitted to six acute psychiatric wards were assessed as to the risk for attack using a German version of the BVC (BVC‐G). Data on preventive measures were concurrently collected. Aggressive incidents were registered using an instrument equivalent to the Staff Observation of Aggression Scale (SOAS‐R). Fourteen attacks towards staff were observed with incident severity ranging from 5 to 18 of a possible 22 points. BVC‐G sensitivity was 64.3%, the specificity 93.9%, the positive predictive value 11.1%, and the area under the receiver operating characteristic curve 0.88. In some false positive cases intense preventive measures had been implemented. The predictive accuracy of the BVC‐G proved consistent with the Norwegian original.
Ignoring the evidence dictating the practice: sexual orientation, suicidality and the dichotomy of the mental health nurse
Authors: McANDREW S. , WARNE T.
Published: July 2004

International epidemiological studies demonstrate that gay and bisexual males are four times more likely to report a serious suicide attempt than their heterosexual counterparts. Data on completed suicides, usually derived from mortality statistics misrepresent the rate of suicides among homosexual populations. However, an increasing number of studies comparing representative samples of gay, lesbian and bisexual youths with heterosexual controls demonstrate increased rates of mental health problems and subsequent suicide among the homosexual population. Homosexual orientation must therefore be considered a risk factor for mental distress and as such should be a focus for any contemporary public health agenda. One of the difficulties of addressing the problem through a public health agenda is the juxtaposition proffered by our political and social environment. The Diagnostic and Statistical Manual of Mental Disorder ceased to define homosexuality as pathological in 1973 replacing it with a new ‘illness’ of ‘gender identity disorder’. Until recently in England, Section 28 of the Local Government Act (1988), forbidding the promotion of homosexuality, further reinforced negativity towards this group of people. This compounded the negative mental health consequences for those developing a gay sexual orientation in a climate of heterosexism. Current health care policy in England concerns itself with the rising number of suicides among young people but fails to acknowledge the importance of the research findings relating to gay people by integrating them into the development of mental health policy. This paper reviews the literature relating to homosexual people and suicidality, and addresses the seriousness of a policy rhetoric which results from ignoring the evidence while dictating mental health nursing practice.
Exercise: a neglected intervention in mental health care?
Authors: CALLAGHAN P.
Published: July 2004

This paper reports the results of a literature review examining the effects of exercise on mental health and well‐being. Throughout history many societies, ancient and modern, have used exercise as a means of preventing disease, and promoting health and well‐being. There is evidence that exercise is beneficial for mental health; it reduces anxiety, depression, and negative mood, and improves self‐esteem and cognitive functioning. Exercise is also associated with improvements in the quality of life of those living with Schizophrenia. However, exercise is seldom recognized by mainstream mental health services as an effective intervention in the care and treatment of mental health problems. There is evidence to suggest that exercise may be a neglected intervention in mental health care.
A concept analysis of forensic risk
Authors: KETTLES A. M.
Published: July 2004

Forensic risk is a term used in relation to many forms of clinical practice, such as assessment, intervention and management. Rarely is the term defined in the literature and as a concept it is multifaceted. Concept analysis is a method for exploring and evaluating the meaning of words. It gives precise definitions, both theoretical and operational, for use in theory, clinical practice and research. A concept analysis provides a logical basis for defining terms through providing defining attributes, case examples (model, contrary, borderline, related), antecedents and consequences and the implications for nursing. Concept analysis helps us to refine and define a concept that derives from practice, research or theory. This paper will use the strategy of concept analysis to find a working definition for the concept of forensic risk. In conclusion, the historical background and literature are reviewed using concept analysis to bring the term into focus and to define it more clearly. Forensic risk is found to derive both from forensic practice and from risk theory. A proposed definition of forensic risk is given.
Novel mutations in the EXT1 gene in two consanguineous families affected with multiple hereditary exostoses (familial osteochondromatosis)
Authors: Faiyaz‐Ul‐Haque M , Ahmad W , Zaidi SHE , Hussain S , Haque S , Ahmad M , Cohn DH , Tsui L‐C
Published: July 2004

Multiple hereditary exostoses (HME) is an autosomal dominant developmental disorder exhibiting multiple osteocartilaginous bone tumors that generally arise near the ends of growing long bones. Here, we report two large consanguineous families from Pakistan, who display the typical features of HME. Affected individuals also show a previously unreported feature – bilateral overriding of single toes. Analysis using microsatellite markers for each of the known EXT loci, EXT1, EXT2, and EXT3 showed linkage to EXT1. In the first family, mutation analysis of the EXT1 gene revealed that affected individuals were heterozygous for an in‐frame G‐to‐C transversion at the conserved splice donor site in intron 1. This mutation is predicted to disrupt splicing of the first intron and produce a frameshift that leads to a premature termination codon. In the second family, an insertion of an A in exon 8 is predicted to produce a frameshift at codon 555 followed by a premature termination, a further 10 codons downstream. In both families, an increased number of affected male subjects were observed. In affected females in family 2, phenotypic variability and incomplete penetrance were noted.
Enzyme replacement therapy with agalsidase β improves cardiac involvement in Fabry's disease
Authors: Spinelli L , Pisani A , Sabbatini M , Petretta M , Andreucci MV , Procaccini D , Lo Surdo N , Federico S , Cianciaruso B
Published: July 2004

Fabry's disease is an X‐linked lysosomal storage disease caused by a deficiency of α‐galactosidase that results in an accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system. Fabry cardiomyopathy, characterized by progressive severe concentric left ventricular (LV) hypertrophy, is very frequent and is the most important cause of death in affected patients. Enzyme replacement therapy (ERT) allows a specific treatment for this disease, however, there are very few data on the effectiveness of therapy on cardiac involvement. Nine patients with Fabry cardiac disease were studied on basal condition and after 6 and 12 months of treatment with algasidase β (Fabrazyme®). A complete clinical, electrocardiographic and echocardiographic evaluation was performed in all patients. Interpretable Doppler recordings of transmitral flow and pulmonary flow velocity curves were also acquired. At baseline, the patients with Fabry's disease had increased LV septum and posterior wall thickness, normal LV fractional shortening, LV ejection fraction, normal Doppler parameters of mitral inflow but a duration of pulmonary vein flow velocity wave exceeding that of the mitral wave at atrial systole. ERT did not affect heart rate and arterial pressure. LV internal diameters did not change, there was a slight but not significant decrease in the LV posterior wall thickening and a progressive decrease in the interventricular septum thickening (p < 0.025) and in LV mass (p < 0.001) The difference in duration between pulmonary vein flow velocity wave and mitral wave at atrial systole significantly decreased (p < 0.001). These results suggest that ERT in patients with Fabry cardiomyopathy is able to reduce the LV mass and ameliorate the LV stiffness.
Genome‐wide screening using automated fluorescent genotyping to detect cryptic cytogenetic abnormalities in children with idiopathic syndromic mental retardation
Authors: Borck G , Rio M , Sanlaville D , Redon R , Molinari F , Bacq D , Raoul O , Cormier‐Daire V , Lyonnet S , Amiel J , Merrer M Le , De Blois M‐C , Prieur M , Vekemans M , Carter NP , Munnich A , Colleaux L
Published: July 2004

Mental retardation (MR) is the most common developmental disability, affecting approximately 2% of the population. The causes of MR are diverse and poorly understood, but chromosomal rearrangements account for 4–28% of cases, and duplications/deletions smaller than 5 Mb are known to cause syndromic MR. We have previously developed a strategy based on automated fluorescent microsatellite genotyping to test for telomere integrity. This strategy detected about 10% of cryptic subtelomeric rearrangements in patients with idiopathic syndromic MR. Because telomere screening is a first step toward the goal of analyzing the entire genome for chromosomal rearrangements in MR, we have extended our strategy to 400 markers evenly distributed along the chromosomes to detect interstitial anomalies. Among 97 individuals tested, three anomalies were found: two deletions (one in three siblings) and one parental disomy. These results emphasize the value of a genome‐wide microsatellite scan for the detection of interstitial aberrations and demonstrate that automated genotyping is a sensitive method that not only detects small interstitial rearrangements and their parental origin but also provides a unique opportunity to detect uniparental disomies. This study will hopefully contribute to the delineation of new contiguous gene syndromes and the identification of new imprinted regions.
Interstitial deletion of 10p and atrial septal defect in DiGeorge 2 syndrome
Authors: Yatsenko SA , Yatsenko AN , Szigeti K , Craigen WJ , Stankiewicz P , Cheung SW , Lupski JR
Published: July 2004

We present molecular genetic investigations of a 4‐year‐old boy with craniofacial dysmorphism and developmental delay. Trivial mitral and tricuspid regurgitation without gross structural abnormality was diagnosed by echocardiography. High‐resolution chromosome analysis revealed an interstitial deletion, del(10)(p12.1p12.32). To characterize the deletion size and breakpoints, we performed fluorescence in situ hybridization analysis using 27 BAC clones. Our data demonstrate an approximately 5.5 Mb deletion del(10)(p12.1p12.31). Surprisingly, the BAC clone RP11‐56H7 that contains NEBL, an apparent downstream gene of the cardiogenic transcription factor HAND2 previously shown to be deleted in the patients with DiGeorge 2 syndrome and 10p13 deletion, was deleted in our patient with 10p12.1‐p12.31 deletion. In addition, we provide clinical data and results of molecular analysis for a patient with multiple congenital anomalies including Ebstein's anomaly, kidney malformations, and 10p13‐p14 deletion. We also reviewed 19 patients with congenital heart defects and deletions involving 10p and propose that atrial septal defect (ASD) is a common cardiac anomaly associated with DiGeorge 2 syndrome. Based on genotype–phenotype analysis of published patients and those reported herein, we propose an approximately 1.0 Mb critical region between loci D10S547 and D10S2176 in 10p14 to be associated with ASD. Considering that septal defects are the most frequent congenital heart anomaly, we suggest that further investigations in the 10p critical region are important to identify gene(s) responsible for this common birth defect.
All‐Units Discounts in Retail Contracts
Authors: Kolay Sreya , Shaffer Greg , Ordover Janusz A.
Published: July 2004

All‐units discounts in retail contracts refer to discounts that lower a retailer's wholesale price on every unit purchased when the retailer's purchases equal or exceed some quantity threshold. These discounts pose a challenge to economic theory because it is difficult to understand why a manufacturer ever would charge less for a larger order if its intentions were benign. In this paper, we show that all‐units discounts may profitably arise absent any exclusionary motive. All‐units discounts eliminate double marginalization in a complete information setting, and they extract more profit than would a menu of two‐part tariffs in the standard incomplete information setting with two types of buyers. All‐units discounts may improve or may reduce welfare (relative to menus of two‐part tariffs) depending on demand parameters.