bluuebunny/crossref_metadata_2025 huggingface dataset:
The expression of p63 in basal cell carcinomas and association with histological differentiation
Authors: Bircan Sema , Candir Ozden , Kapucoglu Nilgun , Baspinar Sirin
Published: March 2006

Background:  We aim to examine p63 expression in basal cell carcinomas (BCCs) and to investigate association with their histopathological differentiation subtypes.

Methods:  Eighty‐four BCCs were classified according to the histopathologic differentiation subtypes. Immunohistochemistry using monoclonal antibody against p63 was performed.

Results:  In nontumoral skin, p63 expression was consistently seen in basal/suprabasal cells of epidermis, hair matrix cells, and outer root sheath of the hair follicle. In BCCs, the cases were distributed as 47 undifferentiated, 28 differentiated (16 adenoid and 12 keratotic), and nine superficial. The nuclear p63 expression was negative in two cases, whereas 64 BCCs (76.2%) showed homogeneous p63 immunostaining. There was no statistically significant difference between p63 expression and histological differentiation subtypes (p > 0.05). The expression of p63 was found strongly and diffuse in 72.3% of solid undifferentiated and 82.1% differentiated and in 77.8% of superficial type BCCs.

Conclusions:  p63 is consistently expressed in epidermal basal/suprabasal and adnexal basal cells. Most BCCs have higher homogeneous p63 expression than nontumoral epidermis, which is not changed according to histological differentiation subtypes. Thus, overexpression of p63 in all histological subtypes may confirm that basaloid progenitor cells are linked tumor‐cell lineage and have a role in the tumorigenesis of BCC.
Oral malignant melanoma associated with pseudoepitheliomatous hyperplasia. Report of a case
Authors: Meleti Marco , Mooi Wolter J. , Van Der Waal Isaäc
Published: March 2006

Background:  Pseudoepitheliomatous hyperplasia (PEH), a histological mimic of squamous cell carcinoma, is an exuberant reactive epithelial proliferation that may be induced by a variety of infectious, traumatic, inflammatory and neoplastic conditions of the skin and mucous membranes. PEH has been described in association with Spitz nevi and intramucosal nevi but not with oral malignant melanoma.

Methods and results:  A case of PEH in malignant melanoma of the palate in a 46‐year‐old female patient has been described. A search of the English literature did not disclose any previously reported case of such event.

Conclusions:  PEH associated with oral malignant melanoma is apparently very rare and most likely originates from the surface epithelium. This is in contrast with PEH in cutaneous melanoma where follicular or eccrine units have been suggested to be the origin.
IgG4 as the predominant IgG subclass in pemphigoides gestationis
Authors: Patton T. , Plunkett R. W. , Beutner E. H. , Deng J. S. , Jukic D. M.
Published: March 2006

Background:  Pemphigoides gestationis (PG) is a blistering disorder of pregnancy caused by antibodies against basement membrane proteins. They are directed against the 180 kD bullous pemphigoid antigen (BPAg2), towards the epitopes within the NC 16A domain. There are many similarities between pemphigoid gestationis and bullous pemphigoid (BP), but the literature so far indicated different immunofluorescence results in regards with C3 and IgG, and IgG subclasses (IgG4 vs. IgG1).

Methods:  We evaluated staining patterns and IgG subclasses, as well as C5b‐9 membrane attack complex (MAC) in 10 pregnant patients with PG, using sandwich double antibody immunofluorescence (SDAI) and direct immunofluorescence (DIF).

Results:  All ten specimens stained with C3 by DIF, but only five had trace amount of IgG reactants by this method. By SDAI, 100% were positive for the IgG4 and C5b‐9 MAC, 70% for IgG2, 50% for IgG1, and 40% for IgG3.

Conclusion:  IgG4 was the predominant IgG subtype identified. This finding has not been reported for PG, but it mimics results reported for BP. One explanation is prolonged disease course, as well as blocking of antigenic domains by IgG4. Understanding this completely will help develop therapies and prevention strategies for immunobullous and other autoimmune diseases, and perhaps aid in an exact classification.
t(14;18)(q32;q21) involving IGH and MALT1 is uncommon in cutaneous MALT lymphomas and primary cutaneous diffuse large B‐cell lymphomas
Authors: Wongchaowart Nicholas T. , Kim Bong , Hsi Eric D. , Swerdlow Steven H. , Tubbs Raymond R. , Cook James R.
Published: March 2006

Background:  t(14;18)(q32;q21) involving IGH and MALT1 has been demonstrated in cutaneous MALT lymphomas and in one case of primary cutaneous diffuse large B‐cell lymphoma (DLBCL). However, the incidence of IGH/MALT1 translocations in these forms of cutaneous lymphoma remains unclear.

Methods:  We performed paraffin section interphase fluorescence in situ hybridization (FISH) analysis using MALT1 and IGH break‐apart probes on 16 cutaneous MALT lymphomas and 16 primary cutaneous DLBCL in order to assess the frequency of IGH/MALT1 translocations and to screen for other potential translocations involving the IGH or MALT1 loci.

Results:  Translocations involving MALT1 were not detected in any of 16 cutaneous MALT lymphomas or 16 primary cutaneous DLBCL. Of the 12 MALT lymphomas that could be analyzed for an IGH translocation, all were negative. In contrast, four of the 13 cases (31%) of primary cutaneous DLBCL that could be analyzed for translocations involving IGH were positive. Subsequent FISH analysis demonstrated one of these to be an IGH/BCL2 translocation and one to be a CMYC/IGH translocation, while the translocation partners in the remaining two cases are currently unidentified.

Conclusions:  This study demonstrates that translocations involving MALT1, including IGH/MALT1, are uncommon in cutaneous MALT lymphomas and primary cutaneous DLBCL. Other translocations involving IGH also are not involved in the pathogenesis of at least most cutaneous MALT lymphomas. In contrast, primary cutaneous DLBCL may contain one of several IGH translocations in a minority of cases.
Genetic polymorphism of cholesterol 7α‐hydroxylase (CYP7A1) and colorectal adenomas: Self Defense Forces Health Study
Authors: Tabata Shinji , Yin Guang , Ogawa Shinsaku , Yamaguchi Keizo , Mineshita Masamichi , Kono Suminori
Published: March 2006

Bile acids have long been implicated in colorectal carcinogenesis, but epidemiological evidence is limited. Cholesterol 7α‐hydroxylase (CYP7A1) is the rate‐limiting enzyme producing bile acids from cholesterol. A recent case‐control study showed a decreased risk of proximal colon cancer associated with the CC genotype of the CYP7A1 A‐203C polymorphism. The present study examined the relationship between the CYP7A1 A‐203C polymorphism and colorectal adenoma, which is a well‐established precursor lesion of colorectal cancer. The study subjects comprised 446 cases of colorectal adenomas and 914 controls of normal total colonoscopy among men receiving a preretirement health examination at two hospitals of the Self Defense Forces (SDF). The CYP7A1 genotype was determined by the polymerase chain reaction–restriction fragment length polymorphism method. Statistical adjustment was made for age, hospital, rank in the SDF, smoking, alcohol use, body mass index, physical activity and parental history of colorectal cancer. The CYP7A1 polymorphism was not measurably related to the overall risk of colorectal adenomas. However, the CC genotype was associated with a decreased risk of proximal colon adenomas, but not of distal colon and rectal adenomas. Adjusted odds ratios of proximal colon adenomas (95% confidence intervals) for the AC and CC genotype versus AA genotype were 0.82 (0.54–1.24) and 0.56 (0.34–0.95), respectively. The findings add to evidence for the role of bile acids in colorectal carcinogenesis. The CC genotype of the CYP7A1 A‐203C polymorphism probably renders lower activity of the enzyme synthesizing bile acids. (Cancer Sci 2006)
Anti‐tumor effect of the anti‐KL‐6/MUC1 monoclonal antibody through exposure of surface molecules by MUC1 capping
Authors: Doi Mihoko , Yokoyama Akihito , Kondo Keiichi , Ohnishi Hiroshi , Ishikawa Nobuhisa , Hattori Noboru , Kohno Nobuoki
Published: March 2006

Human polymorphic epithelial mucin (MUC1) is a heavily glycosylated large protein that is frequently overexpressed on the surface of many human adenocarcinomas. Studies using monoclonal antibodies (mAb) identified MUC1 as a tumor‐associated antigen that has been intensely studied as a target for cancer immunotherapy. We previously identified a mouse IgG1 mAb that recognizes a sialylated sugar chain, designated as KL‐6, classified in ‘Cluster 9 (MUC1)’. Using the anti‐KL‐6 mAb, we investigated antitumor effects of anti‐MUC1 mAb on breast cancer cell lines expressing MUC1 abundantly. We showed that anti‐KL‐6 mAb induced capping of MUC1 and facilitated E‐cadherin‐mediated cell–cell interaction in the breast cancer cell lines YMB‐S and ZR‐75‐1S, which proliferate in suspension culture without aggregation. Moreover, anti‐KL‐6 mAb enhanced the cytotoxic activity of lymphokine‐activated killer cells. These results indicate that the capping of MUC1 restores cell surface proteins, such as adhesion molecules and tumor antigens, to work in cell–cell interactions, leading to inhibition of tumor proliferation due to cell–cell adhesion and increased accessibility to effector cells that are needed to kill tumor cells. (Cancer Sci 2006)
Upstream open reading frames of the barley Mla13 powdery mildew resistance gene function co‐operatively to down‐regulate translation
Authors: HALTERMAN DENNIS A. , WISE ROGER P.
Published: March 2006

To protect themselves against pathogen infection, plants have evolved multifarious defence mechanisms that include the production of antimicrobial compounds and hypersensitive cell death. This defence includes the regulation of expression of resistance proteins, which function to detect pathogen effectors and control the response. Barley Mla is one of several Ml genes that confer specific resistance to the powdery mildew fungus, Blumeria graminis f. sp. hordei. The Mla13 allele contains a long (523 nt) transcript leader region with three upstream open reading frames (uORFs) and two alternatively spliced introns. The lengths of the Mla13 uORFs, which encode up to 70 amino acid peptides, are directly influenced by the splicing of these introns. We have used in vivo and in vitro translation assays to show that Mla13 uORFs function co‐operatively to down‐regulate translation of the parent cistron up to 13‐fold. However, resistance conferred by constitutively transcribed Mla appears to be unaffected by removal of these uORFs, signifying that a potential increase in MLA13 protein is innocuous to barley cells. In addition, cells that possess a predicted increase in MLA13 translation via over‐expression and uORF mutation retain their requirement for RAR1, suggesting that this increase is not sufficient to overcome the concentration threshold required for activation of RAR1‐independent resistance.
A qualitative investigation of changes in the belief systems of families of children with autism or Down syndrome
Authors: King G. A. , Zwaigenbaum L. , King S. , Baxter D. , Rosenbaum P. , Bates A.
Published: March 2006

Background  There have been few reports of the world views, values and priorities of families of children with autism or Down syndrome, despite the fact that family belief systems are considered to be among the most important factors affecting the adaptation and resilience of families.

Methods  Transcripts from three focus groups involving 19 key informants (15 parents of children with autism or Down syndrome, and 4 service providers) were analysed using qualitative methods.

Results  The themes indicated that raising a child with a disability can be a life‐changing experience that spurs families to examine their belief systems. Parents can come to gain a sense of coherence and control through changes in their world views, values and priorities that involve different ways of thinking about their child, their parenting role, and the role of the family. Although parents may grapple with lost dreams, over time positive adaptations can occur in the form of changed world views concerning life and disability, and an appreciation of the positive contributions made by children to family members and society as a whole. Parents’ experiences indicate the importance of hope and of seeing possibilities that lie ahead.

Conclusions  The information from this study may be used to provide families with an advance understanding of the changes in beliefs that they might undergo, and assists service providers in providing individualized and family‐centred services and supports to families.
Satisfaction with formal support and education for children with autism spectrum disorder: the voices of the parents
Authors: Renty J. , Roeyers H.
Published: March 2006

Introduction  The aim of the present study was to identify and describe factors associated with variations in the level of parental satisfaction with formal support and education for children with autism spectrum disorder (ASD) in Flanders.

Methods  Participants were recruited by a mailing from a diagnostic centre for pre‐schoolers and by advertisements dispersed in the Flemish parent organization for ASD and in services and special schools. The sample consisted of 244 parents of children with ASD (age range: 2.69–17.81 years, male/female sex ratio 4 : 1). The data were collected using a questionnaire on experiences with education and support, which was compiled for the purpose of this study. The data resulting from the questionnaire were supplemented with information obtained from semi‐structured in‐depth interviews with a stratified sample of 15 parents.

Results and conclusions  The study revealed that parents experienced difficulties with the diagnostic process, with support and education provided by mainstream settings and with the accessibility of autism‐specific service provisions. Conversely, parents reported to be satisfied with the quality of autism‐specific support and education. Predictors of overall satisfaction were parental involvement in formal support, knowledge of available service provisions and time between first consultation and final diagnosis. Practical implications of the results are discussed.
Perceptions of child labour among working children in Ibadan, Nigeria
Authors: Omokhodion F. O. , Omokhodion S. I. , Odusote T. O.
Published: March 2006

Background  The adverse effects of child labour on the children's psychological development continue to raise concerns about this public health problem worldwide. Several views have been presented by child health authorities, non‐governmental organizations (NGOs) and international agencies. Few studies have focused on the children themselves. This study sought to determine working children's perspective of child labour, its benefits and disadvantages and the working children's perceptions of themselves, and their aspirations for the future.

Methods  A cross‐sectional study was carried out among working children in a large market in Ibadan, south‐west Nigeria. Questionnaires were administered to all consenting children.

Results  A total of 225 children, 132 females and 93 males, participated in the survey. Their age range was 8–17 years. A total of 103 respondents (46%) were currently in school while 117 (52%) were out of school. Five respondents (2%) had never attended school. A total of 104 (46%) thought that children should not work. However, when asked about the benefits of working, 81 working children (36%) felt that work provided a source of income for them, 52 (23%) indicated that it was a way of helping their parents and 39 (17%) thought it was part of their training to be responsible adults. Bad company, ill health and road traffic accidents were the perceived ill effects of child labour. The majority of the children interviewed were aspiring towards artisan trades and very few towards professional or office jobs. A total of 106 (47%) children perceived themselves as less fortunate than their peers. Fifty‐five children (24%) thought that child labour was a sign of deprivation. The perception that child labour is a sign of deprivation was more prevalent among child workers whose highest educational attainment was primary school, child workers who had worked for more than 6 months and those whose earnings were small.

Conclusion  We recommend that school education for children should be a priority even when the harsh economic realities in their families force parents to send them to work outside the home.
Do maternal depressive symptoms, stress and a lack of social support influence whether mothers living in deprived circumstances adopt safety practices for the prevention of childhood injury?
Authors: Mulvaney C. , Kendrick D.
Published: March 2006

Background  Maternal depressive symptoms are common, as are childhood injuries, particularly among the socio‐economically disadvantaged. Maternal depression may be associated with lesser engagement in injury prevention practices. Providing support to mothers can reduce the risk of child injury, but the mechanism by which this occurs is unclear. The aim of this study was to examine the relationship between maternal depressive symptoms, social support and stress, and engagement in home safety practices to prevent injuries to pre‐school children living in socio‐economically deprived families in the UK.

Methods  Three questionnaires were posted to mothers of young children living in deprived areas in the city of Nottingham, UK, who were enrolled in the control group of a randomized controlled trial (RCT). The questionnaires assessed socio‐demographic characteristics at baseline; depressive symptoms, perceived social support and self‐reported stress 21 months later and engagement in home safety practices 24 months post baseline. The mothers in the control group received no intervention. Main outcome measures were the use of fireguards, stair gates, smoke alarms, window locks and safe storage of medicines, sharp objects and cleaning products.

Results  One‐third (36.4%) of mothers reported depressive symptoms. The most widely adopted safety practices were safe storage of medicines (93.5%) and use of smoke alarms (86.2%). The majority of mothers did not use fireguards (60.7%) or store sharp objects safely (63.8%). Depressive symptoms were not independently associated with any of the seven safety practices. Mothers reporting some lack of social support were more likely not to store medicines safely [odds ratio, OR, 4.08 (95% confidence interval, CI, 1.79–9.30) compared with those reporting no lack of social support] and mothers reporting moderate or large amounts of stress were more likely not to store sharp objects safely [OR 1.77 (95% CI 1.11–2.83) compared with mothers reporting no or little stress] after controlling for confounders.

Conclusions  Our results suggest that depressive symptoms, stress and a lack of social support are not important influences on the adoption of safety practices by mothers living in deprived areas in the UK, at least in the short term. Further work is required to explore the effects of chronic maternal depressive symptoms on the adoption of safety practices.
Childhood unintentional injuries: the perceived impact of the environment, lack of supervision and child characteristics
Authors: Munro S.‐A. , Van Niekerk A. , Seedat M.
Published: March 2006

Background  Investigations into the context and causation of injury, including injury risks, are an essential part of the injury prevention knowledge base. Caregiver perceptions of childhood injury risks may assist in the design of safety interventions and influence the way in which an intervention is received within a community.

Methods  Focus groups and individual interviews were conducted in two low‐income neighbourhoods in South Africa to collect information on caregiver perceptions of injury risks. The data were analysed via thematic content analysis.

Results  The results revealed that injury risks are perceived as multifaceted and as contributing synergistically to an injury event. Parents of children also tended to attribute most risks to the environment instead of individual action.

Conclusions  Interventions including passive strategies and less activity from the parent may be welcomed in communities. Attention should be given to child injury prevention methods specifically for low‐income contexts.
The association between information and communication technology exposure and physical activity, musculoskeletal and visual symptoms and socio‐economic status in 5‐year‐olds
Authors: Straker L. M. , Pollock C. M. , Zubrick S. R. , Kurinczuk J. J.
Published: March 2006

Background Increasing use of computers by children has raised concerns over the potential impact on their cognitive, social, educational, visual and physical development. Despite this concern, there are no large‐scale studies relating the use of computers to specific health indicators in children as they reach school age.

Methods A cross‐sectional analysis of 1600 5‐year‐old Western Australian children participating in a longitudinal cohort study was conducted to ascertain their computer use, other activities (watching television and videos, playing electronic games, reading and looking at books, drawing on paper and moderate to vigorous physical activity), and specific health indicators.

Results More than half (56%) of the children used computers each week. Computer use was significantly related to TV viewing (OR 1.97 weekday) and electronic game use (console games OR 2.48 weekday, 1.81 weekend; hand‐held games OR 1.88 weekend) and negatively associated with vigorous physical activity on weekends (OR 0.72). Computer use was also significantly related to socio‐economic indicators such as the mother being older (40+ years, OR 1.70 weekend, 1.73 weekday), tertiary educated (OR 1.63 weekend) and studying (OR 1.52 weekend, 1.41 weekday). Almost 1% children were reported to have complained of tired or sore muscles, and 2.2% had complained of tired or sore eyes, after watching television or using a computer.

Conclusion A substantial proportion of 5‐year‐old Western Australian children are using computers. Computer use was related to other sedentary activities and less vigorous activity. While musculoskeletal and vision problems are not widespread, their presence and the sedentary nature of computer use is of public health concern.
Health‐related issues in individuals with agenesis of the corpus callosum
Authors: Doherty D. , Tu S. , Schilmoeller K. , Schilmoeller G.
Published: March 2006

Objectives  To explore and compare the prevalence and expression of specific health‐related variables in a large survey sample of persons with agenesis of the corpus callosum (ACC) and their siblings.

Methods  Caregiver surveys of individuals with ACC (n = 189) and their siblings (n = 189) provided data regarding diagnoses, physical features, neurological and sensory information, feeding, elimination and sleep concerns, and some behavioural features.

Results  Compared with their siblings, individuals with ACC had more concurrent conditions and were more likely to have altered pain perception and sensitivity to touch. In addition, individuals with ACC had more sensory deficits and abnormalities as well as altered patterns of feeding/eating, elimination and sleep.

Conclusions  These data raise important questions for future research and suggest the need for increased vigilance by caregivers and health‐care professionals of individuals with callosal disorders. Early detection and intervention may help prevent or ameliorate health problems in this population.
Operationalizing the concept of resilience in child neglect: case study research
Authors: Daniel B.
Published: March 2006

Background  There is a considerable amount of interest in resilience as a concept for child care and protection practice. This paper describes an exploratory project that drew on a set of case studies to explore the extent to which the concept of resilience can be operationalized for use with neglected children in the context of statutory social work.

Method  The study was carried out within a local authority in Scotland and focused on the value of the concept as an aid to assessment and planning. The study built on a published workbook that provides a structure for the assessment of potential areas of resilience and gives detailed suggestions for intervention in six domains of a child's life. Eight neglected children aged between five and 11 were recruited. Six training days on the concept were held. Questionnaires were used to gather information about the theoretical frameworks already being used. At the end of the study, semi‐structured interviews were carried out with the social workers about the value of the concept. Assessment reports completed before and after the training were analysed.

Results  Findings indicated that participants were familiar with the concept of resilience and that the training helped enhance their understanding of the concept. Training assisted with the provision of a more structured approach to assessment and planning. Respondents reported that the approach enhanced their knowledge of the child and they were able to identify areas for development in the six domains.

Conclusion  The study indicated that the concept of resilience can be operationalized for use with neglected children. Further, the case studies raised the issue of the extent to which the need for a secure base underpins other domains. The domain of positive values was also highlighted as an important area for further exploration.
Out‐of‐home day care for families living in a disadvantaged area of London: economic evaluation alongside a RCT
Authors: Mujica Mota R. , Lorgelly P. K. , Mugford M. , Toroyan T. , Oakley A. , Laing G. , Roberts I.
Published: March 2006

Background  Children born into poverty have lifelong disadvantages compared with those more fortunate; social interventions seek to break this cycle of poverty and deprivation. Early Years Centres are one such intervention. These were established in deprived areas in the UK to provide high quality out‐of‐home day care. This paper reports the results of an economic evaluation conducted alongside a randomized controlled trial of one of these centres in the Borough of Hackney, London.

Methods  Participants were randomized to receive either high quality day care as provided by the centre or to other child care that they secured for themselves where they chose to do so. Information on resource use (early years education and care, as well as health and social care) was collected over an 18‐month period; this was valued using appropriate unit costs. The cost of education, social and health care together with the value of productivity gains and out‐of‐pocket costs were then compared with the effectiveness of the intervention, increased labour force participant in mothers.

Results  From the societal perspective, the value of employment outweighs the costs of health and social services used, and in both groups there are cost savings. These are greater in the intervention group, therefore Early Years day care is an efficient use of resources. However, there is a net cost to the public sector of providing the intervention. The cost of achieving an additional mother in the labour force at 18 months is £38 550 (85% CI of –£1273, £416 172).

Conclusion  From the societal perspective, over an 18‐month period, all child care is cost saving, but high quality day care provided by the Early Years Centre is a cost‐effective alternative to day care provided by other local services in Hackney. The public sector, however, incurs added expense from this intervention.
Potential medication dosing errors in outpatient pediatrics
Authors: Jacobson Robert M.
Published: March 2006

.
 
McPhillips H.A.,
Stille C.J.,
Smith D.,
Hecht J.,
Pearson J.,
Stull J.,
Debellis K.P.,
Andrade S.,
Miller M.,
Kaushal R.,
Gurwitz J. &
Davis R.L.
(
2005
)

,
147
,
761
–
767
.

Objective  To determine the prevalence of potential dosing errors of medication dispensed to children for 22 common medications.

Study design  The investigators used automated pharmacy data from three health maintenance organizations. Children were eligible if they were less than 17 years old at the time of dispensing. The investigators randomly selected up to 120 children with a new dispensing prescription for each drug of interest, giving 1933 study subjects. Errors were defined as potential overdoses or potential under‐doses. The error rate in two health maintenance organizations that use paper prescriptions was compared with one health maintenance organization that uses an electronic prescription writer.

Results  Approximately 15% of children were dispensed a medication with a potential dosing error: 8% were potential overdoses and 7% were potential under‐doses. Among children weighing less than 35 kg, only 67% of doses were dispensed within recommended dosing ranges, and more than 1% were dispensed at more than twice the recommended maximum dose. Analgesics were most likely to be potentially overdosed (15%), whereas anti‐epileptics were most likely potentially under‐dosed (20%). Potential error rates were not lower at the site with an electronic prescription writer.

Conclusions  Potential medication dosing errors occur frequently in outpatient paediatrics. Studies on the clinical impact of these potential errors and effective error prevention strategies are needed.
Non‐accidental burns in children – are we neglecting neglect?
Authors: Reading Richard
Published: March 2006

Chester D.L.,
Jose R.M.,
Aldlyami E.,
King H. &
Moiemen N.S.
(
2006
)

,
32
,
222
–
228
.
Are paediatric burns more common in asylum seekers? An analysis of paediatric burn admissions
Authors: Reading Richard
Published: March 2006

.
 
Dempsey M.P. &
Orr D.J.A.
(
2006
)

,
32
,
242
–
245
.
Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta‐analysis
Authors: Reading Richard
Published: March 2006

.
 
Buscemi N.,
Vandermeer B.,
Hooton N.,
Pandya R.,
Tjosvold L.,
Hartling L.,
Vohra S.,
Klassen T.P. &
Baker G.
(
2006
)

,
332
,
385
–
393
.

Objective  To conduct a systematic review of the efficacy and safety of exogenous melatonin in managing secondary sleep disorders and sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder.

Data sources  Thirteen electronic databases and reference lists of relevant reviews and included studies; Associated Professional Sleep Society abstracts (1999–2003).

Study selection  The efficacy review included randomized controlled trials; the safety review included randomized and non‐randomized controlled trials.

Quality assessment  Randomized controlled trials were assessed by using the Jadad Scale and criteria by Schulz et al., and non‐randomized controlled trials by the Downs and Black checklist.

Data extraction and synthesis  One reviewer extracted data and another reviewer verified the data extracted. The inverse variance method was used to weigh studies and the random effects model was used to analyse data.

Main results  Six randomized controlled trials with 97 participants showed no evidence that melatonin had an effect on sleep onset latency in people with secondary sleep disorders [weighted mean difference −13.2 (95% CI −27.3 to 0.9) min]. Nine randomized controlled trials with 427 participants showed no evidence that melatonin had an effect on sleep onset latency in people who had sleep disorders accompanying sleep restriction [−1.0 (−2.3 to 0.3) min]. Seventeen randomized controlled trials with 651 participants showed no evidence of adverse effects of melatonin with short‐term use (3 months or less).

Conclusions  There is no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. There is evidence that melatonin is safe with short‐term use.
Inter‐relationships between airway inflammation, reticular basement membrane thickening and bronchial hyper‐reactivity to methacholine in asthma; a systematic bronchoalveolar lavage and airway biopsy analysis
Authors: Ward C. , Reid D. W. , Orsida B. E. , Feltis B. , Ryan V. A. , Johns D. P. , Walters E. H.
Published: March 2006

Background
Asthma is accepted as a disease characterized by airway inflammation, with evidence that airway structural changes, or ‘remodelling’ occurs. There are few studies relating airway physiology, inflammation and remodelling, however. We have carried out a study of inter‐relationships between airway inflammation, airway remodelling, reticular basement membrane (RBM) thickening, and bronchial hyper‐reactivity (BHR), before and after high‐dose inhaled corticosteroid (fluticasone propionate 750 μg b.d.), in a group of relatively mild but symptomatic, steroid naïve asthma patients.

Methods
Double‐blind, randomized, placebo‐controlled, parallel group study of inhaled corticosteroid (ICS) in 35 asthmatics, with bronchoalveolar lavage (BAL) and airway endobronchial biopsy (EBB) for inflammatory cell profiles and EBB for airway remodelling carried out at baseline, 3 and 12 months.

Results
At baseline RBM thickening was related to BAL mast cells and EBB eosinophil counts. In turn baseline log EBB EG2 eosinophil count, log%BAL epithelial cells and log RBM thickness explained 55% of the variability in BHR.

Conclusion
We provide new information that airway inflammation, remodelling, and BHR in asthma are inter‐related and improved by ICS therapy. Our data potentially support the need for early and long‐term intervention with ICS even in relatively mild asthmatics, and the need to further assess the potential merit of longitudinal BHR testing in management of some patients, as this may reflect both airway inflammation and remodelling.
Co‐stimulatory molecules as potential targets for therapeutic intervention in allergic airway disease
Authors: Kallinich T. , Beier K. C. , Gelfand E. W. , Kroczek R. A. , Hamelmann E.
Published: March 2006

Airway inflammation is a characteristic feature of allergic asthma. Central to the initiation and progression of the inflammatory process are allergen‐specific T lymphocytes that attract eosinophils, mast cells, and B cells to the airways by the secretion of specific cytokines. The direction of T cell responses is influenced by co‐stimulatory signals that modulate the antigen‐specific signal delivered by the T cell receptor. In addition to the prototypic co‐stimulatory molecule, CD28, a number of newly identified co‐stimulatory molecules and their ligands have now been characterized. Over the past 5 years, the role of these molecules in the pathophysiology of allergen‐mediated sensitization and airway inflammation has been extensively studied in animal models of allergic asthma. The aim of this review is to provide a detailed overview on recent studies in mice and preliminary findings in man and to discuss the potential therapeutic and preventive treatment strategies offered by interactions with co‐stimulatory molecules for patients with allergic airway diseases.
In chronic idiopathic urticaria autoantibodies against FcɛRII/CD23 induce histamine release via eosinophil activation
Authors: Puccetti A. , Bason C. , Simeoni S. , Millo E. , Tinazzi E. , Beri R. , Peterlana D. , Zanoni G. , Senna G. , Corrocher R. , Lunardi C.
Published: March 2006

Background
Chronic idiopathic urticaria is a common skin disorder characterized by recurrent, transitory, itchy weals for more than 6 weeks. An autoimmune origin has been suggested based on the findings of auto‐antibodies (Abs) directed against either the α subunit of the high‐affinity IgE receptor or the IgE molecule in nearly half of the patients.

Objective
To identify other autoantigen targets in patients with chronic idiopathic urticaria.

Methods
We used pooled IgG derived from 133 patients with chronic idiopathic urticaria to screen a random peptide library to identify disease‐relevant autoantigen peptides. Among the identified peptides, one was recognized by the vast majority of patients' sera. Abs against this peptide were affinity purified from the patients' sera and assayed for their ability to induce histamine release from basophils.

Results
We identified a peptide that showed similarity with the low‐affinity IgE receptor (FcɛRII/CD23) expressed on lymphomonocytes and eosinophils. Anti‐peptide IgG Abs purified from the patients' sera bound cell surface CD23 and were able to induce histamine release from basophils. This effect appeared to be mediated by the release of major basic protein from eosinophils upon engagement of CD23. The same effects were obtained with the sera from mice immunized with the CD23 peptide.

Conclusion
Our results indicate that patients with chronic idiopathic urticaria have Abs against CD23 and that eosinophils, which infiltrate the skin of these patients, play a crucial role in maintaining the disease through the release of major basic protein upon engagement of the low‐affinity IgE receptor by such auto‐Abs.
Topical corticosteroid inhibits interleukin‐4, ‐5 and ‐13 in nasal secretions following allergen challenge
Authors: Erin E. M. , Zacharasiewicz A. S. , Nicholson G. C. , Tan A. J. , Higgins L. A. , Williams T. J. , Murdoch R. D. , Durham S. R. , Barnes P. J. , Hansel T. T.
Published: March 2006

Background
Cytokines and chemokines produced by allergen‐reactive T‐helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders.

Objective
This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods.

Methods
Patients with grass pollen seasonal‐allergic rhinitis (n=13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 μg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC.

Results
Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL‐4, IL‐5, IL‐6 and IL‐13 responses in the filter paper taken in the late phase (P<0.05 for IL‐4 and IL‐13, P<0.01 for IL‐5 and IL‐6). Levels of chemokines (eotaxin, RANTES, MCP‐1, MIP‐1α, IL‐8 and IP‐10) were also reduced in the late phase (P<0.01 at 8 h). However, levels of IL‐2, IL‐3, IL‐7, IL‐12 (p40 and p70), ‐15, TNF‐α, IFN‐γ and GM‐CSF were not affected.

Conclusion
Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.
Expression of CXCR6 and its ligand CXCL16 in the lung in health and disease
Authors: Morgan A. J. , Guillen C. , Symon F. A. , Huynh T. T. , Berry M. A. , Entwisle J. J. , Briskin M. , Pavord I. D. , Wardlaw A. J.
Published: March 2006

Background
Chemokine receptors (CR) play an important role in T cell migration, but their contribution to lung trafficking is unclear.

Objective
We hypothesized that if a particular CR was involved in T cell homing its expression would be enriched on lung T cells compared with peripheral blood T cells (PBT).

Methods
We have measured the CR expression on BAL T cells from patients with sarcoid, other interstitial lung diseases (ILD), asthma and healthy volunteers.

Results
Of 14 CR studied in sarcoid, CXCR6 expression was the most markedly increased in the lung compared with the blood, a finding that was also seen in ILD patients. A striking although lesser increase was also seen in asthmatics and healthy controls. Analysis of expression of the CXCR6 ligand, CXCL16, by immunohistochemistry suggested that alveolar macrophages (AM) were the major source of CXCL16 in the lung. AM expressed mRNA for CXCL16 and released nanogram quantities after adhesion to plastic as shown by RT‐PCR, Western blotting and ELISA. Bronchoalveolar lavage (BAL) fluid from all subjects contained large amounts of CXCL16. The full‐length CXCL16 was the predominant isoform in AM lysates, supernatants and BAL.

Conclusion
This data suggests that CXCR6 and CXCL16 may play a role in T cell recruitment to the lung.
Agents causing occupational asthma in Finland in 1986–2002: Cow epithelium bypassed by moulds from moisture‐damaged buildings
Authors: Piipari R. , Keskinen H.
Published: March 2006

Background
Occupational asthma is an avoidable form of asthma. In Finland, the diagnosis of occupational asthma entitles substantial compensation to the employee. The diagnostics are based on symptoms, exposure assessment, allergologic investigations, follow‐up of peak expiratory flow (PEF) at work and at home and, in many cases, specific challenge tests.

Objective
To study the causative agents of occupational asthma in Finland.

Methods
The causative agents and the numbers of new occupational asthma cases notified to the Finnish Register of Occupational Diseases (FROD) during 1986–2002 are reported.

Results
The number of occupational asthma cases increased from 1986 until 1995, after which a downward trend, stabilizing during the last few years, has been observed. The majority of the cases (59%) in the beginning of the period (1986–1990) were associated with agriculture, but the percentage has fallen thereafter (42% of the cases in 1998–2002) along with the fall in the total number of cases. Since 1995, indoor moulds from water‐damaged buildings have caused an increasing number of cases and have become the most important causative agents (0.5% cases, in 1986–1990 and 18% of the cases in 1998–2002). Chemicals have caused 10–30% of the cases, a decreasing number since 1990. The most important chemicals causing occupational asthma have been diisocyanates and welding fumes, followed by hairdressing chemicals and formaldehyde.

Conclusions
The number of occupational asthma cases in Finland reached its height in the mid‐1990s. The decrease in the number of total cases is because of the decrease in agriculture‐associated cases, reflecting the number of employees in agriculture‐associated occupations, which has greatly decreased since Finland joined the EU in 1995. An epidemic of mould‐induced asthma, affecting mostly white‐collar employees working in moisture‐damaged buildings, has taken place since 1995.
Chlamydia pneumoniae infection enhances cellular proliferation and reduces steroid responsiveness of human peripheral blood mononuclear cells via a tumor necrosis factor‐α‐dependent pathway
Authors: Cho Y. S. , Kim T.‐B. , Lee T.‐H. , Moon K.‐A. , Lee J. , Kim Y.‐K. , Lee K.‐Y. , Moon H.‐B.
Published: March 2006

Background
Although epidemiological studies have found an association between Chlamydia pneumoniae infection and severe asthma, the causality and underlying mechanism are largely unknown. We hypothesized that C. pneumoniae infection increases the proliferation and enhances the survival of immune and inflammatory cells, resulting in reduced responsiveness to corticosteroids and suggesting that the underlying mechanism is related to a TNF‐α‐dependent pathway.

Methods
Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro in the presence or absence of C. pneumoniae infection. Responsiveness to corticosteroids was assayed by adding dexamethasone, and the underlying mechanism was investigated by treating cells with infliximab that is a chimeric anti‐TNF‐α monoclonal antibody. Cellular proliferation and apoptosis was assessed by thymidine uptake and counting apoptotic cells using flow cytometry.

Results
Cellular proliferation was significantly higher in C. pneumoniae‐infected PBMCs than in uninfected PBMCs, which is more prominent in Th2‐dominant microenvironment. The anti‐proliferative and pro‐apoptotic effect of corticosteroid were significantly reduced in C. pneumoniae‐infected PBMCs compared with uninfected PBMCs. The proliferative effect of C. pneumoniae infection and the reduced response to corticosteroid were effectively reversed by blocking the TNF‐α pathway at least partially.

Conclusion
C. pneumoniae infection enhanced the proliferation and survival of immune and inflammatory cells, resulting in steroid resistance. The reversal of these phenomena by the TNF‐α inhibitor suggests that TNF‐α may play an important role in the induction of steroid dependence or resistance. A TNF‐α inhibitor may therefore be a candidate agent for managing steroid‐dependent or ‐resistant severe asthma.
Parity and decreased use of oral contraceptives as predictors of asthma in young women
Authors: Jenkins M. A. , Dharmage S. C. , Flander L. B. , Douglass J. A. , Ugoni A. M. , Carlin J. B. , Sawyer S. M. , Giles G. G. , Hopper J. L.
Published: March 2006

Background
Asthma is more prevalent among males in childhood, but females report higher rates in adulthood. The reasons are unknown; although it has been hypothesized that hormonal factors may explain this sex‐dependent risk of adult‐onset asthma.

Objective
To determine whether a woman's reproductive history or use of oral contraceptives is associated with adult‐onset asthma.

Methods
In 1991–1993, we surveyed 681 women aged 29–32 years randomly sampled from participants first surveyed at age 7 years by the 1968 Tasmanian Asthma Survey, a study of all children born in 1961 and attending school. Current asthma was defined as reporting asthma or wheezy breathing in the past 12 months.

Results
In women who did not have asthma or wheezy breathing by age 7 years, 13% had current asthma. The risk of current asthma in these who were parous increased with the number of births (odds ratio (OR) 1.50 per birth, 95% confidence interval (CI) 1.01–2.23 P=0.04) while women with one birth were at a lower risk than nulliparous women (OR 0.46 95% CI 0.2–1.06, P=0.07). Independent of parity, the risk decreased by 7% (95% CI 0–13%) per year of oral contraceptive pill use in all women. In women who did have asthma or wheezy breathing by age 7 years, neither reproductive history nor oral contraceptive pill use predicted current asthma.

Conclusion
Our observation that parity and decreased oral contraceptive use predict asthma in women, is consistent with the hypothesis that the asthma that develops after childhood is in part a response to endogenous and exogenous female hormones. This may be due to alterations of cytokine responses by the pregnant state, triggering adult‐onset asthma in women.