bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the physical properties of endoscopic retrieval systems
Authors: Singhvi S K , Allan W , Williams E D , Small P K
Published: March 2003

Background

A reliable method of retrieval of laparoscopically resected organs is required. The physical properties of three commercial systems available for clinical use (two plastic, one woven fabric) were examined.

Methods

Pig abdominal walls and gallbladders containing steel balls to represent gallstones were used to simulate organ retrieval on 60 occasions. The performance of retrieval bags was measured in terms of the temporal profile of pressure developed inside the bag, the force on the bag during withdrawal, and whether or not the bag could be retrieved intact. The force versus elongation relationship was also determined for each bag.

Results

Although there was a wide range of maximum pressures recorded (14–320 mmHg) with each retrieval system, the mean pressures in the plastic systems were significantly higher. The forces recorded during attempted withdrawal of both plastic bags were significantly lower than those with the fabric system (BERT bag: mean (range) 87 (25–165) N; Endocatch: 40 (7–123) N; Endopouch: 40 (14–68) N; P = 0·005 Endocatch versus BERT, P = 0·004 Endopouch versus BERT). The BERT bags tore more easily at the site of the grasper.

Conclusion

Plastic retrieval systems were less likely to burst than fabric systems when subjected to simulated retrieval, and required less force for withdrawal. Plastic systems may therefore be associated with less tumour seeding or gallstone spillage as a consequence of bag disruption.
Morbidity and mortality associated with pancreatogastrostomy and pancreatojejunostomy following partial pancreatoduodenectomy
Authors: Schlitt H J , Schmidt U , Simunec D , Jäger M , Aselmann H , Neipp M , Piso P
Published: March 2003

Background

The pancreatic anastomosis is still the Achilles heel in partial pancreatoduodenectomy (PPD).

Methods

This study describes retrospectively a series of 441 patients who underwent standard or extended PPD and reconstruction by either pancreatogastrostomy or pancreatojejunostomy over a period of 13 years (1988–2000).

Results

Reconstruction of the pancreatic remnant was achieved by pancreatogastrostomy in 250 patients (56·7 per cent) and by pancreatojejunostomy in 191 patients (43·3 per cent). The leakage rate of the pancreatic anastomosis was 2·8 per cent after pancreatogastrostomy versus 12·6 per cent after pancreatojejunostomy (P < 0·001), whereas other surgical complications (bile leakage, haemorrhage, pancreatitis) were identical in the two groups. The leakage rate after standard PPD with or without vascular reconstruction was 2·0 per cent (four of 205 patients) after pancreatogastrostomy and 11·5 per cent (18 of 156) after pancreatojejunostomy (P < 0·001); following extended PPD it was 6·7 per cent (three of 45) after pancreatogastrostomy and 17·1 per cent (six of 35) after pancreatojejunostomy. The mortality rate due to leakage was 1·6 per cent (four of 250 patients) after pancreatogastrostomy versus 5·2 per cent (ten of 191) after pancreatojejunostomy (P = 0·037).

Conclusion

Pancreatogastrostomy is a safe and reliable method of reconstruction after PPD that may be associated with a lower leakage and mortality rate than pancreatojejunostomy.
Scintigraphic assessment of antegrade colonic irrigation through an appendicostomy or a neoappendicostomy
Authors: Christensen P , Olsen N , Krogh K , Laurberg S
Published: March 2003

Background

The aim of this study was to evaluate large bowel transport following antegrade colonic irrigation with a new scintigraphic technique.

Methods

Ten patients (eight with severe constipation, two with faecal incontinence; median age 47 (range 41–66) years) treated with antegrade colonic irrigation took 111In-labelled polystyrene pellets to label the bowel contents. 99mTc-labelled diethylenetriamine penta-acetate was mixed with the irrigation fluid to map its distribution within the large bowel. Scintigraphy was performed before and after a standardized irrigation procedure. The large bowel was divided into four segments. Assuming ordered evacuation of the large bowel, the contribution of each colonic segment to total evacuation was expressed as a percentage of original segmental count. The segmental contributions were added to reach a total defaecation score (range 0–400).

Results

The median defaecation score was 350, corresponding to complete emptying of the rectosigmoid, descending colon, transverse colon, and half of the caecum and ascending colon. The retained irrigation fluid was located throughout the large bowel. Back-flow to the ileum was observed in four patients.

Conclusion

This study used a new scintigraphic technique to assess large bowel transport following antegrade colonic irrigation. Antegrade colonic irrigation induces highly effective emptying even in patients with severe constipation.
Association of pS2 (TFF1) release with breast tumour proliferative rate: in vitro and in vivo studies
Authors: Potten Christopher , Darzynkiewicz Zbigniew , Sasaki Kohsuke , Reshkin S. J. , Tedone T. , Correale M. , Mangia A. , Casavola V. , Paradiso A.
Published: March 2003

Abstract. Although cytosolic expression of the protein pS2 (TFFl) is considered to be a marker of oestrogen receptor (OR) function, there exists some clinical data to suggest an inverse relationship of cytosolic pS2 to tumour proliferation. Although secreted from breast cancer cells, the relationship of pS2 secretion to tumour natural history has been little studied. The mechanisms and kinetics of pS2 release and its relation to tumour cell proliferation were studied in a human breast cancer cell line MCF‐7 and verified in a preliminary clinical study. Stimulation by stripped serum or oestradiol resulted in parallel increases of proliferation and pS2 release in both time course and dose–response experiments. Direct pharmacological alterations of proliferation were followed by identical changes in pS2 release. The relationship between serum pS2 levels and tumour proliferative activity when analysed as a function of steroid status showed a slope of 0.56 in OR+ vs. 0.19 in OR– tumours. It is concluded that pS2 release from breast cancer cells is associated with their proliferation and measurement of serum pS2 levels might be a good predictor of tumour proliferative state and could permit noninvasive monitoring of this tumour parameter.
Optimized fluorescent probe combinations for evaluation of proliferation and necrosis in anthracycline‐treated leukaemic cell lines
Authors: Boutonnat J. , Barbier M. , Muirhead K. , Mousseau M. , Ronot X. , Seigneurin D.
Published: March 2003

Abstract. Proliferation and multidrug resistance status are key predictors of therapeutic outcome in acute myeloid leukaemia (AML). Anthracyclines such as daunorubicin (DNR) are typically used to treat AML and can induce drug resistance. The goal of the studies described here was to select a combination of fluorescent probes that could be used in combination with flow cytometry to monitor cell proliferation vs. cell death/necrosis as a function of anthracycline uptake. Propidium iodide (PI), the most commonly used marker of membrane integrity, cannot be used to evaluate necrosis in DNR‐containing cells because of spectral overlap. A membrane integrity probe compatible with the use of a dye dilution method using PKH67 to study cell proliferation was also selected. The results show that DAPI and Cascade Blue (CB), like PI, were able to detect necrotic cells when no DNR was present, although CB gave less resolution between viable and necrotic cells than PI or DAPI. In the presence of DNR, DAPI cannot be used owing to the fluorescence quenching by DNR. However, it was found that a combination of DNR, CB, and PKH67 allows simultaneous identification of chemoresistant cells, based on reduced DNR accumulation, necrotic cells based on CB incorporation, and proliferating cells based on partitioning of PKH67 fluorescence between daughter cells. It was also found that unless a marker of necrosis is used in combination with the dye dilution assay, a moderate decrease of fluorescence as a result of necrosis may be incorrectly interpreted as proliferation.
Cell cycle‐dependent regulation of the DNA‐dependent protein kinase
Authors: Nilsson A. , Sirzén F. , Lewensohn R. , Wang N. , Skog S.
Published: March 2003

Abstract. Human DNA‐dependent protein kinase (DNA‐PK) is a nuclear‐localized serine/threonine protein kinase. The holoenzyme consists of a catalytic subunit with a molecular mass of 465 kDa and a DNA‐binding heterodimer Ku86/70. The kinase has been implicated in a variety of nuclear processes including V(D)J recombination, double‐strand break repair, and transcription. Cells with defective DNA‐PK activity show increased radiosensitivity and lack of V(D)J recombination. To study DNA‐PK activity during the cell cycle, HeLa cells were separated by elutriation centrifugation into different cell cycle compartments based on cellular size. DNA‐PK activity was found to vary during the cell cycle. The kinase activity was lowest during G1 phase and increased dramatically as the cells entered S phase and remained high during the G2‐phase. The subcellular distribution of DNA‐PKcs is relocalized from the cytoplasm during M and G1 phases to the nucleus during G1–S phase transition and S phase. Expression of both the catalytic subunit and the Ku86/70 heterodimer was found to be constant throughout the cell cycle. This study demonstrates that DNA‐PK activity as well as its subcellular localization fluctuates during the cell cycle. In addition, the distribution of DNA‐PK during M phase corresponds with low DNA‐PK activity.
Influence of irradiation and pentoxifylline on histone H3 phosphorylation in human tumour cell lines
Authors: Binder A. , Bohm L.
Published: March 2003

Phosphorylation of histone H3 at Ser‐10 correlates with chromatin condensation and this amino terminal modification is now recognized as a specific marker of mitosis. We have monitored the appearance of cells showing histone H3 phosphorylation in four human tumour cell lines to identify cell cycle progression after irradiation. In the human melanoma cell lines Be11 and MeWo and in the squamous cell carcinoma lines 4197 and 4451 a dose of 7 Gy of Co‐γ irradiation increases the number of cells binding anti‐histone H3‐P antibody 1–8‐fold in a p53‐independent manner. In the p53 mutant cell lines MeWo and 4451 H3‐P phosphorylated cells can be detected as early as 30 min and show a maximum 1 h post‐irradiation. In the cell lines Be11, 4197 and 4451 the early wave of H3 phosphorylated cells is followed by a second wave, which reaches a maximum 4.5–7 h post‐irradiation and then declines. These events are attributed to damage‐induced cell cycle blocks in the G1 and G2 phase of the cell cycle. Addition of the dose modifying drug pentoxifylline before irradiation increases the appearance of cells showing early and the late H3 phosphorylation. When pentoxifylline is added 12–24 h post‐irradiation when the cell cycle blocks have reached their maximum the appearance of cells with phosphorylated H3 increases 3–5‐fold in the p53 mutant cell lines MeWo and 4451. These observations are consistent with the function of the drug as a G2 block abrogator. The large H3 phosphorylation signal in p53 mutant cells is consistent with early entry of a cohort of G2 cells into mitosis. The smaller H3‐P signal in p53 wild type cells correlates with the lower proportion of stable G2 populations in G1 blocked cells. These results indicate that pentoxifylline influences the appearance of histone H3 phosphorylated cells in a manner strongly dependent on the number of cells in G2 phase. This suggests that addition of pentoxifylline indeed abrogates the G2 block and thereby facilitates early entry into mitosis.
Nitric oxide inhibits irreversibly P815 cell proliferation: involvement of potassium channels
Authors: Costa R. S. A. , Assreuy J.
Published: March 2003

Abstract. Nitric oxide (NO) has been shown to inhibit both normal and cancer cell proliferation. Potassium channels are involved in cell proliferation and, as NO activates these channels, we investigated the effect of NO on the proliferation of murine mastocytoma cell lines and the putative involvement of potassium channels. NO (in the form of NO donors) caused dose‐dependent inhibition of cell proliferation in the P815 cell line inducing growth arrest in the mitosis phase. Incubation with NO donor for 4 or 24 h had a similar inhibitory effect on cell proliferation, indicating that this effect is irreversible. The inhibitory effect of NO was completely prevented by the blockade of voltage‐ and calcium‐dependent potassium channels, but not by blockade of ATP‐dependent channels. NO inhibition of cell proliferation was unaffected by guanylate cyclase and by cytoskeleton disruptors. Therefore, NO inhibits cell proliferation irreversibly via a potassium channel‐dependent but guanylate cyclase‐independent pathway in murine mastocytoma cells.
Growing up with a parent who has a chronic mental illness: one child’s perspective
Authors: Hindle
Published: March 2003

This paper describes a growing understanding of one adolescent boy’s experience of living with a parent with a chronic mental illness. The way in which services were organized and delivered to address the needs of either adults or children made it difficult to comprehend the impact of parental psychiatric disorder on the family as a whole. The case study illustrates the problems for the ‘not‐noticed child’, the process of internalization and enmeshment that affected his internal world, his relationships with others, and his development in adolescence. The need for all professionals to focus on interactive processes both within the family and in the professional network is emphasized, as is the importance of collaborative work.
‘The past, the present, but never the future’: thematic representations of fostering disruption
Authors: Butler  , Charles
Published: March 2003

The paper discusses some of the findings of a small‐scale explor‐atory research project which analysed the dynamics involved in substitute family care placements for young people, and assessed the processes demonstrated in fostering breakdowns in terms of the interactions, negotiations and adjustments between the re‐spective parties over time. The paper concentrates on three core and interlocking themes: first, the perception of foster placements as ‘second best’; secondly, the ‘images of family life’ permeating placements; and finally, the ‘nature vs. nurture’ debate which affected the ability of users and carers to sustain placements. These themes were selected for their significance in the development of an explanatory framework for understanding the interactional dynamics involved in placement disruption. The paper concludes with a discussion of the key implications for social work practice, considering foster carer training, sustaining placements, and part‐nership arrangements between the young people, their natural families, foster carers and social work professionals.
Evaluation of therapeutic play: a challenge for research
Authors: Carroll
Published: March 2003

There is increased pressure on practitioners offering therapy to troubled children to provide evidence of efficacy of their interventions. However, current research has not yet provided the necessary evidence. There are considerable difficulties creating a quantitative research design which excludes all relevant variables and produces unequivocal data. Quantitative research, which mainly takes the form of narrative case studies, provides ample anecdotal evidence, but there is, as yet, no comprehensive review of these data nor clear conclusions drawn. It is also necessary to consider the purpose of a narrative case study: few claim to be objective or provide a comparative analysis of a given intervention. None of the research currently available includes the opinions of experiences of children.
The feminizing of neglect
Authors: Turney
Published: March 2003

This paper is concerned with understandings of neglect in child care social work. It is a theoretical discussion in which the social construction of neglect is examined through an analysis of the relationship between ‘care’ and neglect. In particular, I explore the gendered nature of ‘care’ and the possible feminizing of its correlate, neglect. I consider the links between gender, race and caring, and how these interact in ‘achieving’ femininity, and go on to look at the relationship between ideas of care and the ‘natural’ mother. This, in turn, is linked to a discussion of social work responses to neglect. I argue the need for feminist analyses of neglect as a significant area of abuse – analyses that can parallel the important insights that have been offered in relation to other areas of child abuse, and can contribute to the development of effective social work intervention strategies.
Identifying and implementing pathways for organizational change – using the Framework for the Assessment of Children in Need and their Families as a case example
Authors: Horwath  , Morrison
Published: March 2003

Change within social work organizations is incessant. This has implications for senior managers and elected members who have to manage these changes. The Department of Health has introduced new guidance entitled the Framework for the Assessment of Children in Need and their Families (
Department of Health 1999a). The guidance is based on a number of principles that require an attitudinal shift in terms of assessing ways of safeguarding children and promoting their welfare. This paper describes strategic approaches to the effective introduction of the framework within social services departments and other child welfare organizations. Two models have been adapted from practice: the actual framework for assessing children and their families and the Protchaska and DiClementi model of change. These models complement each other. The adapted Assessment Framework provides a structure to assess the readiness of the organization for the implementation of the new framework. The model of change provides a schema for planning, implementing and reviewing the introduction and operation of the Framework for the Assessment of Children in Need and their Families. Although the focus of the paper is the introduction of the new guidance, the models can be utilized by senior managers in any social care organization who are facilitating major changes in the organization.
Spiralling up and spiralling down: implications of a long‐term study of temperament and conduct disorder for social work with children
Authors: Bagley C. , Mallick K.
Published: March 2003

A model of social work grounded in the integration of the social sciences is presented. In social work with children this is exemplified by the importance of difficult childhood temperament and the goodness of fit between parenting practices in the evolution of conduct disorders. A professional model in which the social worker is an equal status member of a cooperative team of professionals engaged in treatment and research is stressed. The basis for this model of social work is that of the person‐in‐environment in which loopbacks from the child’s environment reinforce or diminish the evolution of conduct disorder in the process of spiralling down or spiralling up. This process is illustrated by two extensive case histories. In one the spiralling down process has been checked through intensive social work inputs. Nevertheless, in a longitudinal study it is shown that without such interventions difficult temperament observed at age 3 has significant links to conduct disorders, and movement into care or institutional life at age 17. Severe conduct disorders which lead to permanent school exclusion are likely to be expensive.
Training foster carers in challenging behaviour: a case study in disappointment?
Authors: Pithouse Andrew , Hill‐Tout Jan , Lowe Kathy
Published: March 2003

This paper sets out key features of a semi‐experimental investigation conducted between March 1999 and April 2001 into the impact of training foster carers in techniques to manage challenging behaviour. We identified a sample of children (n = 103) in foster care in four authorities in South Wales who were selected by a checklist as showing behaviours that could be defined as challenging. From this search procedure we identified their foster carers (n = 106) and created a training intervention group for 53 carers looking after 49 children and a non‐intervention comparison group of 53 carers looking after 54 children. Both groups of carers were interviewed using a range of measures before and after the delivery of the training in order to identify any changes they perceived in the conduct of children and changes they perceived in their own capacities as carers. The training was delivered in small groups and evaluative feedback was gathered from carers and from training officers in those agencies that participated in the study. The results suggested that training, as designed and delivered in this study, had limited impact on child conduct and carer capacity. The reasons for this are discussed in light of selected findings. We spend some time on describing our methods in order to expose our approach to the critical scrutiny of readers, whose views would be welcome as we make our future research plans in this field.
Promising practices in understanding and treating child neglect
Authors: Berry Marianne , Charlson Renae , Dawson Kari
Published: March 2003

Child neglect is the most common type of child maltreatment in the United States. However, services provided to families who neglect often fail to address and treat the primary concerns associated with child neglect. The information provided in this paper identifies the primary problems contributing to child neglect, and some promising practices in child welfare casework that address these problems and show positive outcomes for the children and families who experience child neglect. Knowledge pertaining to assessment skills, treatment abilities, and model programmes is provided.
What is community‐based rehabilitation? A view from experience
Authors: Crishna B.
Published: March 2003

This paper argues that unless community‐based rehabilitation (CBR) programmes acknowledge the complexities of working in diverse communities with their unique cultural, religious, social and economic conditions, they will not be able to meet the needs of service provision for people in developing countries. An examination of some of the main aspects that form the essential components of CBR, the realities of the manner in which they interact, and the way they should interact is presented from experiences of CBR services initiated by the Spastics Society of Eastern India, in West Bengal, India.Keywords: community‐based, unique cultures, integration, demystify, flexible, partnerships, nurture, marganalized, beliefs, challenging
Using a model of transactional developmental regulation to evaluate the effectiveness of an early intervention programme for pre‐school children with motor impairments
Authors: Woolfson L. H.
Published: March 2003

This study investigates how early intervention programme benefits may operate beyond the traditional parameters of child developmental progress by exploring family outcomes too. Sameroff & Fiese's (1990) model of transactional developmental regulation is applied to provide a conceptual framework for the evaluation of an interdisciplinary intervention programme for pre‐school children with motor impairments. Qualitative and quantitative methods were combined by using standardized assessment of child progress and interviews. Fifteen children, 11 mothers and five staff participated in the study. Triangulation of data was carried out to obtain evidence of remediation (child progress), re‐education (parent learning) and redefinition (changes in parental perceptions and expectations of their child's difficulties that allowed parents to apply usual, rather than special, caregiving practices) as described in Sameroff and Fiese's model. Findings point to the effectiveness of the programme as indicated by evidence of child developmental progress, parental re‐education and redefinition. The study suggests that redefinition may be at least as important a programme outcome as remediation or re‐education, challenging established notions of the goals of pre‐school programmes for disabled children. Implications of a broader‐based, family‐focused approach are discussed.Keywords: programme evaluation, disabilities, early intervention, transactional developmental regulation
Multidisciplinary assessment of children with deficits relating to attention, motor activity and perception: evaluation of the ANSER model
Authors: Isberg E. , Kjellman B.
Published: March 2003

This study describes a process for multidisciplinary assessment of children having deficits in attention, motor activity and perception (DAMP) with an evaluation of that process based on the opinions of parents, teachers and team members. The process named the ‘ANSER model’ consists of six steps (I to VI) conducted over a 2‐month period and a follow‐up 2 years later (step VII). Parents and teachers are fully involved early in the process and their participation is considered essential for a good result. Particular consideration is given to directly helping a child understand him/herself and become aware of his/her own difficulties. Strategies to overcome those difficulties are developed together with the child, the parents and the teacher. A specific aspect of the assessment is the aim to provide therapy through discussion of the questions, thoughts and feelings evoked during, and by the process. The expectations of parents and teachers regarding the assessment, and their completion of six steps of the process were ascertained from questionnaires. A large majority of both parents and teachers had high expectations of the assessment. Slightly more parents than teachers were convinced of its necessity. Their expectations were satisfied. Parents, teachers and team members emphasized the importance of the participation of parents and teachers in the process. The average time required for a complete assessment according to the process and including the work of all the specialists was 33 hours.
Conceptual frameworks in evaluation of multidisciplinary services for children with disabilities
Authors: McConachie H. R.
Published: March 2003

Child disability services are under pressure to evaluate what they provide. Evaluation encompasses both the procedures they adopt and the outcomes for their clients, that is, for children and families. This paper presents practical frameworks for service evaluation, with examples from experience and from published literature. Individual services cannot carry out evaluation of the clinical effectiveness of particular interventions, but they can clarify their goals, institute regular audit projects, develop guidelines for their practice through participatory evaluation, and sample parents' views of the quality of the services they provide. Practical suggestions are made for the measurement of outcomes for individual children and families.
The measurement of quality of life in young children
Authors: Eiser C , Mohay H , Morse R
Published: March 2003

The purpose of this paper is to argue for a measure of quality of life (QoL) for children aged between 4 and 8 years, describe the obstacles in developing such a measure, and provide evidence that it is possible to elicit directly information from children. Finally we summarize and critique measures that are currently available for this purpose.
Measuring health‐related quality of life in adolescents: agreement between raters and between methods of administration
Authors: Verrips G H W , Vogels A G C , Ouden A L den , Paneth N , Verloove‐Vanhorick S P
Published: March 2003

The aim of this study was to evaluate the agreement between children and proxies as well as the agreement between methods of administration in assessing Health‐Related Quality of Life (HRQoL) using the TNO AZL Children's Quality Of Life (TACQOL) questionnaire. A random sample from a Dutch cohort of 14‐year‐old very low birth weight children and their parents were invited to participate in a face‐to‐face (n= 150) or telephone interview (n= 150). Participants were also sent a questionnaire by mail. The response rate was 83%. Inter‐rater and intermethod agreement were generally good in observable HRQoL domains, and moderate in less readily observable, and possibly less stable, domains such as moods, pain and physical symptoms, and social functioning. In measuring children's HRQoL using the TACQOL, the results and their interpretation are dependent on the source of information and the method of administration.
Culture, stress and the parent–child relationship: a qualitative study of parents’ perceptions of parenting
Authors: Sidebotham P ,   the ALSPAC Study Team
Published: March 2003

This qualitative research project, based on the principles of grounded theory, has used a series of semi‐structured interviews with parents to explore parental understanding of the culture in which today’s children are growing up, the influences of that culture on their parenting and the potential impact on their child.

MethodsSixteen mothers and one father whose children are participating in the Avon Longitudinal Study of Parents and Children were interviewed. The interviews covered various aspects of parenting and culture. Data from the transcribed interviews were analysed for emerging themes relating to parenting and areas where parenting can go wrong. These themes were developed further through an understanding of the literature on parenting and families.

ResultsAnalysis of the data suggested several key areas in which our culture imposes particular stresses on parents and, as such, does not support families or children. Prominent areas of stress were time pressures, particularly in the work–home arena, expectations of children to be active and achieving, financial pressures and the impact of consumerism on families.

ConclusionsThese data suggest that parents, although holding a very positive view of their children, do perceive parenting as being stressful. This is exacerbated by social structures and attitudes that do not value or support children and their families.
A prospective study of absence for illness and injury in childcare children
Authors: Slack‐Smith L. M. , Read A. W. , Stanley F. J.
Published: March 2003

Objectives  This population‐based study investigated prospectively collected absence episodes to describe patterns and rates of absences for illness and other reasons in two types of formal childcare.

Design Centre day care and family day care homes were selected at random from licensing lists. All centres (n = 11) and 95% of family day care caregivers (n = 130) agreed to participate. The results are based on absence information from carers and on questionnaires to the parents of participating children (n = 846).

Results The major reason for absence was respiratory illness with 48% of all children absent at least once during the year with some form of respiratory illness. Although the absence rate for children in centre care was higher than that in family care (3.34 episodes per 52 child–weeks compared with 2.41), the difference was not statistically significant.

Conclusion Investigating patterns of absences from childcare allows a better understanding of needs in childcare. The major reason for absence for illness was respiratory illness.
Neuropeptide innervation and neuroendocrine cells in allergic rhinitis and chronic hypertrophic rhinitis
Authors: Fang S.‐Y. , Shen C.‐L.
Published: March 2003

Background

The neuropeptides and neuroendocrine cells are proven to exist in the human nasal mucosa. However, the pathophysiological and neuroimmunological roles of regulatory peptides in human nasal diseases require further investigation.

Objectives

To investigate and compare the functional morphology and quantify the tissue concentration of regulatory peptides in the nasal mucosas of normal, allergic rhinitis (AR) and chronic hypertrophic rhinitis (CHR) subjects.

Methods

Human inferior turbinate mucosa specimens from 28 patients with AR, 25 patients with CHR and 15 patients without any nasal diseases were investigated. Using immunohistochemistry and radioimmunoassays, we detected the presence, distribution and concentrations of various neuropeptides (vasoactive intestinal peptides [VIP], neuropeptide Y [NPY], substance P [SP], calcitonin gene‐related peptides [CGRP]) and general neuroendocrine markers (neuronee‐specific enolase, chromogranin A and somatostatin). Quantitative analysis of the stained fibres and cells were performed using a graphic AutoCAD program.

Results

The presence and distribution of NPY, CGRP, and SP nerve fibres and neuroendocrine cells were similar among the three subject groups. AR subjects had significantly higher VIP and SP tissue concentrations. VIP fibres had highest density in AR subjects and these fibers predominantly innervated vessels. In CHR, VIP fibres primarily innervated glands.

Conclusions

VIP and SP may play an important neuroimmunological role in the pathogenesis of AR. VIP may lead to the hypertrophic changes of submucosal glands in the pathogenesis of CHR.
Evolution of lymphocyte transformation to wasp venom antigen during immunotherapy for wasp venom anaphylaxis
Authors: Stevens W. J. , Ebo D. G. , De Clerck L. S. , Bridts C. H. , De Gendt C. M. , Mertens A. V.
Published: March 2003

Background

Venom immunotherapy (VIT) has proven to be safe and effective in wasp venom anaphylaxis. However, there are no good parameters to indicate when to stop venom immunotherapy.

Objective

To evaluate the relationship of the lymphocyte transformation test (LTT) to history and specific IgE determination, and to address the time course of lymphocyte transformation responses to wasp (Vespula) venom during VIT and the possible utility of LTT to determine the duration of therapy.

Methods

Peripheral blood mononuclear cells (PBMCs) of 18 individuals with a history of wasp sting anaphylaxis and a positive serum‐venom‐specific IgE, were stimulated with wasp venom before immunotherapy, at the end of a 5‐day semi‐rush immunotherapy and at 24 months during venom immunotherapy. Results, expressed as stimulation index (SI), were compared with the SI in seven asymptomatic stung controls.

Results

In controls the median (minimum–maximum) of the SI were 2.39 (0.52–3.39) before therapy and 2.39 (1.12–6.02) when repeated after 24 months. For patients the median (minimum–maximum) of the SI were 10.13 (1.19–44.88) before immunotherapy (d0), 2.73 (0.67–12.03) at the end of the build‐up immunotherapy (d5) and 4.21 (0.88‐14.66) at the end of 24 months of maintenance therapy (m24). The proliferation responses in vespid‐allergic patients were significantly higher than in stung controls (P = 0.006) but only13/18 patients showed a positive LTT result before the start of immunotherapy (sensitivity of the LTT 72%). When the LTT was repeated after a 5 day build‐up hyposensitization course the SI significantly dropped as compared to the pre‐treatment levels (P = 0.002). The SI of the LTT was negative in eight out of 18 patients at 24 months and the median values were significantly lower than before therapy (P = 0.03).

Conclusions

Although, in the absence of sting challenge data it is not possible to draw conclusions about the predictive value of the LTT, our data may suggest that abolition of the LTT during VIT might indicate clinical insensitivity. Further studies, comparing the results of sting challenges, with the results of lymphocyte transformation will be necessary in order to evaluate the role of LTT in stopping immunotherapy.
Analysis of T‐cell reactive regions and HLA‐DR4 binding motifs on the latex allergen Hev b 1 (rubber elongation factor)
Authors: Raulf‐Heimsoth  , Chen  , Rihs  , Kalbacher  , Liebers  , Baur
Published: March 2003

Background

The rubber elongation factor in Hevea rubber (Hev b 1) is one of the important latex‐allergenic proteins inducing the production of specific IgE antibodies in latex‐exposed subjects. In addition, Hev b 1 induces lymphocyte proliferation responses. A study about detailed T‐cell epitope analysis of major latex allergens has not been published yet.

Objective

The aim of this study was to define the T‐cell reactive regions on the latex allergen Hev b 1.

Methods

Nine overlapping peptides with 19 or 17 amino acid lengths representing the complete sequence of Hev b 1 were used for T‐cell epitope mapping. Peripheral blood mononuclear cells (PBMCs) of latex‐sensitized patients and healthy subjects were isolated and stimulated with the synthetic peptides to determine the specific proliferation response. The examined patients were sensitized to latex by occupational exposure (n = 14) and suffered from rhinitis, conjunctivitis, contact urticaria and/or asthma. Two control groups of non‐sensitized subjects were studied, one occupationally exposed to latex (n = 4), the other one not exposed to latex (n = 4).

Results

Positive proliferation response induced by one or more peptides was detected in 10 of the latex‐sensitized patients and in two of the latex‐exposed non‐sensitized subjects. Each patient exhibited an individual epitope reactivity pattern. The whole protein was found to be immunogenic, but the intensity of lymphocyte responses induced by the peptides was different. The majority of the patients' PBMCs (more than 66%) responded to the peptides 31–49 and 91–109. Using the peptide selection of Stille's algorithms, three epitopes were predicted covering region 38–74 and two others covering region 82–104; the two peptides 31–49 and 91–109 are part of these regions. A strong HLA‐DR4Dw4 (DRB1*0401)‐binding motif according to published DR4w4 binding motifs was predicted in the region of 102–110 including peptide 91–109 to which the majority of tested HLA‐DR4‐positive patients responded.

Conclusions

Our data indicate that the whole 14 kDa protein Hev b 1 is immunogenic having regions that demonstrate individual and varying PBMC stimulation. Experimental data of T‐cell reactive regions based on PBMC‐stimulation complement the information on T‐cell epitope prediction. In addition, the Hev b 1 molecule contains a HLA‐DR4Dw4 (DRB1*0401)‐binding motif.
Symptom control in patients with hay fever in UK general practice: how well are we doing and is there a need for allergen immunotherapy?
Authors: White  , Smith  , Baker  , Davis  , Frew
Published: March 2003

Background

Seasonal allergic rhinitis is often regarded as a trivial condition which patients should treat themselves. However, a significant proportion of sufferers are not fully controlled on standard hay fever medication, either because they do not use it properly or because their symptoms are resistant to standard therapy. The latter group may be suitable for allergen immunotherapy, which was once widely available in UK general practice but is now only available through specialist centres.

Aims

To describe the symptom control of patients with hay fever, to assess concordance with prescribed medication, and to estimate the number of patients who may benefit from referral for allergen immunotherapy.

Setting

General practices in Hampshire and Dorset, UK.

Method

Survey of adult hay fever sufferers prescribed a non‐sedating antihistamine and nasal steroid spray by their general practitioner. A postal questionnaire was sent to all eligible patients aged 16–64 registered with 16 general practices. Self‐assessment of symptom control and reported compliance with medication were used to identify those patients who were suboptimally controlled and might therefore benefit from immunotherapy.

Results

Eight hundred and forty‐six out of 62 500 registered patients aged 16–64 (1.4%) were receiving both drugs, and responses were received from 627 (74.1%); 526 of these met the full entry criteria. One hundred and forty‐two patients (27.0%) were using both types of drug regularly. Of the 142 patients using optimum pharmacotherapy, 54 (38.0%) reported good control of their hay fever symptoms. The remaining 62.0% experienced troublesome residual symptoms and described symptom control as partial or poor. Among those using suboptimal pharmacotherapy, 181/376 (48.1%) reported good control.

Conclusion

Many patients are using treatment inappropriately. Current guidelines need to be applied better but there is also a significant burden of residual symptoms, even among those receiving current optimal therapy. This indicates a need for patients with severe summer hay fever to receive specialist assessment.
Leflunomide, a novel immunomodulating agent, prevents the development of allergic sensitization in an animal model of allergic asthma
Authors: Eber  , Uhlig  , Mcmenamin  , Sly
Published: March 2003

Background

Leflunomide is a new anti‐inflammatory and immunomodulating agent which is showing promise in several immune disorders, especially rheumatoid arthritis. Its activity profile suggests it may be of use in modulating allergic sensitization.

Objective

To investigate the effectiveness of leflunomide in preventing the development of allergic sensitization.

Methods

Fifty‐three brown Norway rats were sensitized by intraperitoneal injection of ovalbumin and adjuvant (ricin) on day 0. To determine the ability of leflunomide to inhibit primary allergic sensitization six rats were treated with A77 1726, the active metabolite of leflunomide, from day 0 through day 5, six were treated from day 5 through day 10, and nine rats acted as controls. On day 14, ovalbumin‐specific serum antibody levels and the magnitude of the early‐phase airway response (EAR) after inhalation allergen challenge were assessed. To determine the ability of acute topical treatment with leflunomide to inhibit mast cell degranulation, three groups of five animals received either vehicle, 100 μg A77 1726, or 1000 μg A77 1726 60 min prior to aerosol allergen challenge. To determine the effects of leflunomide treatment in vivo on mast cell function in vitro, mast cells were obtained by bronchoalveolar lavage from 17 rats (nine treated with leflunomide and eight controls). Allergen‐specific and non‐specific degranulation (48/80 induced) were studied.

Results

In the leflunomide treated rats both ovalbumin‐specific IgE and IgG levels were significantly reduced, and the increases in lung resistance and lung elastance were essentially abolished, compared to those of the control group. Non significant differences were found in any of the parameters between the two leflunomide treated groups. Topical pre‐treatment with leflunomide did not prevent the allergen‐induced EAR. Treatment with leflunomide in vivo prevented allergen‐induced mast cell degranulation in vitro because the mast cells lacked IgE on their surface. Non allergen‐specific degranulation was normal and allergen‐induced degranulation could be restored by passive sensitization.

Conclusions

These data suggests that leflunomide can prevent primary allergic sensitization and prevent allergen‐induced EAR by inhibiting production of allergen‐specific IgE antibodies. Further studies in atopic conditions are warranted.
Mite‐antigen avoidance can reduce bronchial epithelial shedding in allergic asthmatic children
Authors: Piacentini  , Vicentini  , Mazzi  , Chilosi  , Martinati  , Boner
Published: March 2003

Background

Asthma is characterized by bronchial hyperresponsiveness (BHR), bronchial mucosa inflammation and airway epithelial damage.

Objective

This study was designed to evaluate the effect of mite avoidance on bronchial epithelial shedding in asthmatic children sensitized to Dermatophagoides.

Methods

The percentages of airway epithelial cells and eosinophil have been counted in samples obtained by hypertonic saline‐induced sputum before and after a period of antigen avoidance in an Alpine environment (1756 m). The degree of bronchial hyperresponsiveness to methacholine was also evaluated.

Results

After avoidance the median (lower, Q1, and upper, Q3, quartile) percentage of epithelial cells in the sputum decreased significantly from 3.50 [0.50;6.98] to 0 [0;0.5] (P = 0.012) and eosinophil percentage decreased from 1 [0;5.25] to 0 [0,1.5] (P < 0.05). Median (Q1,Q3) PC20 increased significantly from 2.75 [1.53;7.5] to 3.25 [1.65;15.25] mg/mL (P = 0.038). After 3 weeks of re‐exposure to mite the epithelial median (Q1,Q3) percentage raised to 3.90 [1.5;6] (P = 0.027), eosinophils to 1.5 [0;3.00] (NS) and PC20 was 5.25 [1.68;14.50] (NS).

Conclusion

Exposure to house dust mite antigen can induce airway epithelial shedding even in subjects with low eosinophil airway infiltration, thus supporting the idea that epithelial damage in asthmatics sensitized to Dermatophagoides may be due to a proteolytic activity of the mite major antigens.
Inhaled corticosteroid reduced lamina reticularis of the basement membrane by modulation of insulin‐like growth factor (IGF)‐I expression in bronchial asthma
Authors: Hoshino  , Nakamura  , Sim  , Yamashiro  , Uchida  , Hosaka  , Isogai
Published: March 2003

Background

Pathological studies of bronchial biopsy specimens have confirmed the apparent thickening of lamina reticularis of the epithelial basement membrane. Corticosteroids have proven to be most effective in modifying airway inflammation. However, there is not much data on the effects of corticosteroid‐treatment on the basement membrane.

Objective

To investigate the effects of inhaled beclomethasone dipropionate (BDP) on the thickness of basement membrane and cellular infiltration into the bronchial mucosa, and the expression of growth factors in patients with asthma.

Methods

We studied bronchial biopsies from 24 asthmatic patients before and after treatment with inhaled BDP, 400 μg twice a day or placebo, for 6 months in a double‐blind manner. Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured before and after treatment. The thickness of the basement membrane was determined by electron microscopy. Inflammatory cells and the expression of growth factors were examined by immunohistochemistry in endobronchial biopsy specimens.

Results

After 6 months of treatment, we observed a significant improvement of asthma symptoms (P < 0.01), PEF (P < 0.01), diurnal variation of PEF (P < 0.05), and airway responsiveness (P < 0.05) in the BDP group compared with the placebo group. This was accompanied by a significant decrease in the thickness of the lamina reticularis (P < 0.001), and in the number of activated eosinophils (P < 0.01), T‐lymphocytes (P < 0.01), and fibroblasts (P < 0.05) in BDP‐treated patients. There was also a reduction in the expression of insulin‐like growth factor (IGF)‐I (P < 0.01). Significant correlation was found between the IGF‐I expression and collagen thickening (rs = 0.34, P < 0.01), and the number of fibroblasts (rs = 0.45, P < 0.01).

Conclusion

These results suggest that corticosteroid treatment in asthma can reduce the lamina reticular thickness by modulation of IGF‐I expression with consequent inhibition of the airway infiltration by inflammatory cells, and therefore may help to prevent remodelling of the airways.