Journeys of adjustment: the experiences of adolescents living with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is one of the most common diseases of childhood causing pain, swelling of joints and reduced mobility. Previous research has focused on the challenges and psychosocial impact of JIA, but there has been limited attention given to how young people adjust and adapt to living with a long-term condition such as JIA. The aim of this qualitative study was therefore to explore adolescents' experiences of living with JIA, with particular focus on the process of adjustment. METHODS: Ten adolescents (7 female, 3 male) aged 13-17 years with good treatment adherence were recruited from an adolescent arthritis clinic. In-depth interviews were conducted, and data were analysed by two researchers independently using interpretative phenomenological analysis. RESULTS: These adolescents described the physical and psychosocial 'burden of living with JIA' and the challenges faced by an underlying preoccupation 'to be a normal teenager'. However, their accounts also revealed ways in which they regained agency and developed 'resilience through taking control' over their lives. This resilience helped the adolescents re-establish a sense of well-being through an ongoing process of 'acceptance and self-growth'. CONCLUSIONS: Although much research has adopted a deficit model that focuses on adjustment problems, the current study highlights the resourcefulness of young people in managing the challenges of living with a long-term condition. These experiences of successful adjustment can be used as the basis of positive, strength-based intervention approaches for adolescents with arthritis to enhance resilience and well-being.

Doing qualitative research in dentistry and dental education.

The purpose of this paper is to assist dental researchers to develop their expertise in qualitative research. It sketches the key characteristics of qualitative research; summarises theoretical perspectives; outlines the core skills of qualitative data collection and the procedures which underlie three methods of qualitative research: interviewing, focus groups and concept maps. The paper offers some guidance on writing qualitative research and provides examples of qualitative research drawn from dentistry and dental education.

Detection of reciprocal quantitative trait loci for acute ethanol withdrawal and ethanol consumption in heterogeneous stock mice.

RATIONALE: Previous studies have suggested that there is an inverse genetic relationship between ethanol consumption (two-bottle choice, continuous access) and ethanol withdrawal (e.g., Metten et al., Behav Brain Res 95:113-122, 1998a). OBJECTIVES: The current study used short-term selective breeding from heterogeneous stock (HS) animals to examine this relationship. The primary goal of the current study was to determine if reciprocal quantitative trait loci (QTLs) could be found in the selectively bred lines. The advantage of detecting QTLs in HS animals is that it is possible to extract a haplotype signature for the QTL, which in turn can be used to narrow the number of candidate genes generated from gene expression and sequence databases (see, e.g., Hitzemann et al., Mamm Genome 14:733-747, 2003). RESULTS: Seven reciprocal QTLs were detected on chromosomes (Chr) 1 (two), 3, 6, 11, 16, and 17 that exceeded the nominal LOD threshold of 10; genetic drift, which occurs during selection, dramatically increases the LOD threshold. The proximal Chr 1 QTL was examined in some detail. The haplotype structure of the QTL was such that the LP/J allele was associated with low withdrawal and high consumption. The QTL appears to be located in a gene-poor region between 170 and 173 Mbp. Based on available sequence data, two plausible candidate genes emerge-Nos1ap and Atf6alpha. CONCLUSIONS: The data presented here confirm some aspects of the negative genetic relationship between acute ethanol withdrawal and ethanol consumption. The QTL data point to the potential involvement of NO signaling and/or the unfolded protein response.

Physical activity and psychological well-being in children with Type 1 diabetes.

Physical activity and psychological well-being contribute to positive lifestyle and well-being in youngsters who have Type 1 diabetes. The aims of this study were to objectively assess the physical activity levels of children with Type 1 diabetes, and investigate associations between physical activity levels, psychological well-being and HbA(1c). Thirty-six children, mean age 12.8 years, participated in the investigation. Physical activity was assessed using heart rate monitoring over four days. Children further completed the Diabetes Quality of Life for Youths Questionnaire, the Physical Self-Perception Profile for Children and the Self-Efficacy for Diabetes Scale. Routine outpatient HbA(1c) measurements were recorded. There were no significant associations between psychological well-being and physical activity, or HbA(1c) and physical activity, thus suggesting physical activity does not directly relate to psychological well-being in children with Type 1 diabetes. It may be that the effect of physical activity differs from that in children without Type 1 diabetes because of the place of physical activity within diabetes management and the need to balance this with insulin dosage and dietary intake to maintain blood glucose levels.

Child Health Assessment at School Entry (CHASE) project: evaluation in 10 London primary schools.

AIMS: To assess the feasibility of implementing the Child Health Assessment at School Entry (CHASE) questionnaire, developed to capture the multiple dimensions of the health of children in their first year at school, and to evaluate data quality, reliability and validity. METHODS: Parents of 278 year-1 children, from 10 primary schools in two London boroughs, received a parent questionnaire and school nurses completed a separate questionnaire from health and education records for children whose parents consented. Additional data on free school meal eligibility and ethnicity were obtained from the two Local Education Authorities. The parent questionnaire included the Strengths and Difficulties Questionnaire (SDQ) and four dimensions of the Child Health Questionnaire Parent Form-28 (CHQ-PF28). RESULTS: Response rate was 61%. The association between school free school meals eligibility and response rate in each school approached significance (r = -0.62, P = 0.05). Data completeness of the parent questionnaire was high (mean 98%). Data completeness of the school nurse questionnaire was more variable (mean 82%). Cronbach's Alpha was greater than 0.6 for four of the five SDQ scales and greater than 0.7 for the two CHQ-PF28 multi-item scales. Relative to parents with qualifications, parents with no qualifications rated their children as having significantly more conduct problems, peer problems, and overall mental health problems (P < 0.01) as assessed by the SDQ, and significantly lower global health (P < 0.01) as assessed by the CHQ-PF28. Children with special educational needs and children with long-standing illness or disability were rated as having significantly lower global health (P < 0.05) than children without these. Sample tables of inter-school and inter-borough comparison of key findings demonstrate considerable differences in physical and mental health status. DISCUSSION: The questionnaire was acceptable to parents and school nurses, and feasible to implement within existing school resources. Initial tests of internal reliability and validity are satisfactory. These data have the potential to inform interventions and service provision at school and borough level, and public health trends over time.

Development of a questionnaire to collect public health data for school entrants in London: Child Health Assessment at School Entry (CHASE) project.

BACKGROUND: To develop a multiprofessional consensus about the relative contributions of the components of children's health and well-being and to develop a questionnaire that can be used to assess these in London's children. METHODS: Semi-structured interviews with health, education and social services professionals were used to identify areas to include in the questionnaire. These ideas were used as the basis for a wider Delphi consultation, with 79 experts in the area of child health. Round 1 of the Delphi asked panelists to rate 54 items as to whether they should be included in the questionnaire or not. Responses were divided into four categories: item to be included measurement method agreed, item to be included measurement method not agreed, no consensus, or excluded. In round 2, consensus was sought for the categories where there was none following round 1. RESULTS: Themes identified by the interviews were: economic factors, ethnicity, environment, nutrition, hygiene and physical activity, growth, suffers from chronic/serious illness, development, disability and learning, accidents and hospital attendances, self-regulation, psychological well-being, significant life events. After Delphi round 1, items included, where quality measurement method was agreed, were: deprivation index (from postcode), child's ethnicity, temporary accommodation, care status, registered with general practitioner, dental visits, height, weight, special educational needs status, baseline educational assessment result, immunization status, visual and hearing function. Following round 2, items relating to chronic illness, mental health, physical functioning, general health, self-esteem, family cohesion and accident status were agreed for inclusion with a measurement method also agreed. The questionnaire was acceptable to parents. CONCLUSION: The validity, reliability and feasibility of this questionnaire must now be examined. This data set, if collected across London, would substantially increase the public health data available and allow trends in health to be monitored.

Preoperative assessment of pancreatic malignancy using endoscopic ultrasound.

BACKGROUND: Endoscopic ultrasound (EUS) has been regarded as the most accurate modality for locoregional staging of pancreatic malignancy. However, several recent studies have questioned this. The current study assessed the accuracy of EUS in determining preoperative resectability of pancreatic neoplasia. METHODS: A retrospective review was performed of patients with pancreatic malignancy who had preoperative EUS and underwent surgery. EUS-predicted resectability was compared with surgical resectability. Where available, accuracies of vascular and nodal staging were also assessed. RESULTS: Forty-five patients were identified (mean age 60 years, age range = 36-79 years). All patients underwent surgical exploration; vascular staging was available in 32 cases and 17 cases underwent surgical resection. The sensitivity, specificity, and accuracy of EUS in determining unresectability were 66%, 100%, and 78% respectively. Overall EUS stage concurred with surgical stage in 56%, greater than surgical stage in 4%, and less than surgical stage in 40%. Vascular staging on EUS had a sensitivity of 69% and a specificity of 100%. Accuracy of nodal staging was 71%. CONCLUSION: EUS had a high specificity for assessing unresectable pancreatic malignancy. This technique should be used to avoid unnecessary surgical exploration of incurable lesions. However, EUS had only a moderate sensitivity, and a proportion of patients staged preoperatively as having resectable disease will not be surgically resectable.

Absence of BRAF gene mutations in uveal melanomas in contrast to cutaneous melanomas.

The recent discovery of activating mutations in the BRAF gene in many cutaneous melanomas led us to screen the genomic sequence of BRAF exons 11 and 15 in a series of 48 intraocular (uveal) melanomas, together with control samples from three cutaneous melanomas and the SK-Mel-28 cell line, which has a BRAF mutation. The same mutation was detected in two-thirds of our cutaneous melanoma samples, but was not present in any uveal melanomas. This finding further underlines the distinction between uveal and cutaneous melanomas, and suggests that BRAF inhibitors are unlikely to benefit patients with uveal melanoma.

An audit of metal stent palliation for malignant biliary obstruction.

BACKGROUND AND AIMS: Endoscopic stent insertion is the optimum method of palliation for malignant biliary obstruction. Metal stents have several advantages over the polyethylene alternatives, but are significantly more expensive. It has been reported that patients need to survive beyond 6 months to make metal stents more cost-effective. The aim of this study was to audit the performance of expanding metal biliary stents in our endoscopy unit, and to identify factors that might help with patient selection. METHODS: The records of all patients who were selected for endoscopic metal stent insertion at the Royal Perth Hospital for malignant biliary obstruction between September 1994 and November 1998 were reviewed. RESULTS: Thirty-two patients (16 males, mean age 71 years (range 34-88 years) were identified and followed up for a mean 201 days (range 3-810 days). Fifteen (47%) had cholangiocarcinoma, 13 (41%) had pancreatic cancer, and four had metastatic disease as the cause of obstruction. Mortality rates after metal stent insertion were 16, 41 and 55% at 30, 90 and 180 days, respectively. In total, 24 (75%) patients died during the follow-up period. Eleven (34%) stents became obstructed during follow up with a median time to occlusion of 125 days (range 44-729 days). Patients with cholangiocarcinoma had significantly longer survival than pancreatic cancer cases (median 286 vs 58 days, P = 0.04). No other factors were found to correlate with the survival or stent complications. CONCLUSIONS: Less than half of this mixed cohort survived beyond 6 months. Metal stent palliation of malignant biliary obstruction should probably be targeted at those with cholangiocarcinoma, as these patients tend to survive longer.

Extubation failure in a large pediatric ICU population.

OBJECTIVE: To review a large population of children receiving mechanical ventilation to establish a baseline rate of extubation success and failure and to identify those characteristics that place a patient at greater risk of failing planned extubation. DESIGN: Retrospective chart review. SETTING: University-affiliated children's hospital with a 20-bed pediatric ICU. PATIENTS: All 632 patients receiving mechanical ventilation during the 2-year period from July 1, 1996, to June 30, 1998. METHOD: Patients receiving mechanical ventilation were identified via a computerized database. Charts were reviewed of all patients who were reintubated within 72 h of extubation. MEASUREMENTS AND RESULTS: There were 548 planned extubation events, of which 521 were successful. Twenty-seven patients failed planned extubation at least once; only the first attempt at extubation was included in the analysis. The failure rate of planned extubations was 4.9%. Including only patients who had received mechanical ventilation for > 24 h before extubation, the failure rate was 6.0%. For patients intubated > 48 h, the failure rate was 7.9%. The patients who failed extubation were found to be significantly younger and to have received mechanical ventilation longer than those who succeeded, in both the analysis of all patients receiving mechanical ventilation and the subgroup of those receiving mechanical ventilation > 24 h. When only patients who had received mechanical ventilation for > 48 h were analyzed, the difference in age was no longer significant, but the duration of ventilation before extubation was still significantly longer for those who failed. CONCLUSION: We determined the overall failure rate of planned extubations in a large population of pediatric patients to be 4.9%. Those patients who were younger and had received mechanical ventilation longer were more at risk for extubation failure.

Pancreatic islet cell tumours presenting as recurrent acute pancreatitis: imaging features in three cases.

We present three cases of recurrent pancreatitis that occurred in patients with small islet cell tumours of the pancreas which were obstructing the main pancreatic duct. This is a very uncommon presentation of pancreatic islet cell tumours. The radiological findings in these cases are shown and the implications for imaging of 'idiopathic' relapsing pancreatitis are discussed.

Malignant melanoma metastatic to the common bile duct.

Metastatic melanoma is renowned for its propensity to spread to almost every organ of the body; however, symptomatic metastases within the biliary tree are very rare. We report two cases of bile duct obstruction from metastatic melanoma. The first case was caused by an intraluminal metastatic melanoma to the common bile duct, while the second case was caused by extraluminal involvement. The unique aspects of these cases include clinical presentations masquerading as biliary colic, cholangitis and obstructive jaundice. Management and follow up for 3 years is presented. Aspects of medical and surgical management, as well as a review of the world's literature are discussed.

Distinct localization and function of (1,4,5)IP(3) receptor subtypes and the (1,3,4,5)IP(4) receptor GAP1(IP4BP) in highly purified human platelet membranes.

Platelet activation is associated with an increase of cytosolic Ca(++) levels. The (1,4,5)IP(3) receptors [(1,4,5)IP(3)R] are known to mediate Ca(++) release from intracellular stores of many cell types. Currently there are at least 3 distinct subtypes of (1,4, 5)IP(3)R-type I, type II, and type III-with suggestions of distinct roles in Ca(++) elevation. Specific receptors for (1,3,4,5)IP(4) belonging to the GAP1 family have also been described though their involvement with Ca(++) regulation is controversial. In this study we report that platelets contain all 3 subtypes of (1,4,5)IP(3)R but in different amounts. Type I and type II receptors are predominant. In studies using highly purified platelet plasma (PM) and intracellular membranes (IM) we report a distinct localization of these receptors. The PM fractions were found to contain the type III (1,4,5)IP(3)R and GAP1(IP4BP) in contrast to IM, which contained type I (1,4,5)IP(3)R. The type II receptor exhibited a dual distribution. In studies examining the labeling of surface proteins with biotin in intact platelets only the type III (1,4,5)IP(3)R was significantly labeled. Immunogold studies of ultracryosections of human platelets showed significantly more labeling of the PM with the type III receptor antibodies than with type I receptor antibodies. Ca(++) flux studies were carried out with the PM to demonstrate in vitro function of inositol phosphate receptors. Ca(++) release activities were present with both (1,4,5)IP(3) and (1, 3,4,5)IP(4) (EC(50) = 1.3 and 0.8 micromol/L, respectively). Discrimination of the Ca(++)-releasing activities was demonstrated with cyclic adenosine monophosphate (cAMP)-dependent protein kinase (cAMP-PK) specifically inhibiting (1,4,5)IP(3) but not (1,3,4, 5)IP(4)-induced Ca(++) flux. In experiments with both PM and intact platelets, the (1,4,5)IP(3)Rs but not GAP1(IP4BP) were found to be substrates of cAMP-PK and cGMP-PK. Thus the Ca(++) flux property of (1,3,4,5)IP(4) is insensitive to cAMP-PK. These studies suggest distinct roles for the (1,4,5)IP(3)R subtypes in Ca(++) movements, with the type III receptor and GAP1(IP4BP) associated with cation entry in human platelets and the type I receptor involved with Ca(++) release from intracellular stores.

Localization of M(2) muscarinic acetylcholine receptor protein in cholinergic and non-cholinergic terminals in rat hippocampus.

The muscarinic receptor family (M(1)-M(4)) mediates cholinergic modulation of hippocampal transmission. Pharmacological and physiological studies have indicated that a presynaptic receptor on cholinergic terminals plays a key role in regulating ACh release, although the molecular identity of this subtype is uncertain. In this study, the localization of the M(2) receptor is described in detail for the pyramidal cell layer in the CAl region of the hippocampus. Electron microscopic analysis of M(2) immunoreactivity in this area revealed mainly presynaptic expression of this subtype. Double-labeling experiments using antibodies to M(2) and to the vesicular acetylcholine transporter, a novel, specific marker of cholinergic terminals, were used to investigate the nature of these presynaptic receptors. These studies have revealed that M(2) is located in cholinergic and non-cholinergic terminals. This is the first direct anatomical evidence that suggests that M(2) may indeed function as a cholinergic autoreceptor in the hippocampus. The distribution of the M(2) receptor in non-cholinergic terminals also suggests functional roles for M(2) as a presynaptic heteroreceptor.

Granular cell tumour of the oesophagus: endoscopic ultrasound appearances.

A case of granular cell tumour of the oesophagus in a middle-aged woman is reported. The pathological features and appearances on endoscopic ultrasound (EUS) are described, and the role of EUS in the characterization of intramural oesophageal tumours is discussed.

Continuous arterial gas monitoring: initial experience with the Paratrend 7 in children.

OBJECTIVE: To describe clinical usage of the Paratrend 7 continuous arterial blood gas monitor in children. DESIGN: Children older than 24 months of age who required significant ventilatory intervention were eligible for sensor placement. INTERVENTIONS: The sensor was placed via the arterial catheter to measure pH, PCO2, PO2, and temperature. The simultaneous arterial blood gas value was recorded along with the sensor reading. RESULTS: The sensor functioned for as long as seven days and provided the clinicians with data on the patient's respiratory status. The statistical validity of the device when compared to the arterial blood gas showed that the bias/precision for pH was 0.006/0.024, for PCO2 -0.78/4.68 mmHg, and for PO2 1.9%/17.1% (mmHg). CONCLUSIONS: This report demonstrates actual clinical use of continuous blood gas monitoring in children. The information obtained is a major asset to the management of critically ill children in the intensive care unit.

Pre-operative staging of gastro-oesophageal junction carcinoma: comparison of endoscopic ultrasound and computed tomography.

Fifteen patients with carcinoma of the gastro-oesophageal junction were pre-operatively staged with endoscopic ultrasound (EUS) and computed tomography (CT). The accuracy of tumour and nodal staging using both modalities was compared to the final histological staging of the resected specimens. In staging depth of tumour growth, EUS was significantly more accurate (87% of lesions correctly staged) than CT (40% correctly staged). In staging nodal involvement, EUS was again significantly more accurate (73% correctly staged) than CT (33%). Two-thirds of the lesions were traversable with the endoscopic probe, but most of the nontraversed lesions were correctly staged on EUS. In this study, CT has performed poorly as a staging modality for carcinoma at the gastro-oesophageal junction. Other studies have shown CT to be less accurate at this location than at other oesophageal sites. The orientation of the gastro-oesophageal junction, lack of surrounding fat planes, proximity of adjacent organs and patient motion contribute to the poor staging performance of CT at this location. In contrast, EUS has been an accurate staging modality at the gastro-oesophageal junction in this study and compares well with other studies evaluating EUS in the more proximal oesophagus. Endoscopic ultrasound is therefore a necessary modality if accurate pre-operative staging of gastro-oesophageal junction carcinoma is to be achieved.

Expression of m1-m4 muscarinic acetylcholine receptor proteins in rat hippocampus and regulation by cholinergic innervation.

A family of muscarinic ACh receptor genes are expressed in hippocampus, but little is known about the localization of the encoded proteins and their regulation by cholinergic innervation. Subtype-specific antibodies were used to localize m1-m4 proteins in the hippocampal formation by immunocytochemistry and to determine the alterations in the subtypes following deafferentation. Each of the receptors is differentially localized in Ammon's horn and dentate gyrus, with highly complementary distributions. m1 is widely expressed in somata and dendrites of pyramidal neurons and granule cells in dentate gyrus. m2 immunoreactivity is expressed mostly in nonpyramidal neurons, and in several discrete bands of fibers and puncta surrounding pyramidal neurons and other layers. m3 is enriched in pyramidal neurons, the neuropil in stratum lacunosum-moleculare and the outer third of the molecular layer of dentate gyrus. m4 is enriched in nonpyramidal neurons, in fiber pathways (alveus, fimbria, and hippocampal commissure), and in the inner third of the molecular layer. Fimbria-fornix lesions decreased ipsilateral m2- and m4-immunoreactive axons in the fimbria, with no apparent changes in the distribution of any of the receptors in hippocampus. 192-IgG immunotoxin lesions of the cholinergic septohippocampal projections, which spare noncholinergic projections, produced a small decrease in m2-immunoreactive fibers in the fimbria with no other major changes in the distribution of subtypes. Immunoprecipitation studies at 3-28 d following fimbria-fornix lesions revealed a 25% loss of m2 at 3 d in hippocampus, and upregulation of both m1 (20-29% at 7-14 d) and m4 (44% at 28 d). Thus, the vast majority of muscarinic receptor subtypes are intrinsic to the hippocampal formation and/or nonseptal hippocampal afferents. A subset of m2 and m4 are presynaptically localized, with m2 in cholinergic axons and m2 and m4 possibly in noncholinergic axons that comprise the septohippocampal pathway. The unique laminar and regional distributions of m1-m4 in the hippocampus reflect differential cellular and subcellular distributions of the subtypes and/or selective association of receptor subtypes with certain afferent and intrinsic connections. These results indicate that each subtype likely has a different role in cholinergic modulation of excitatory and inhibitory hippocampal circuits.

Light and electron microscopic study of m2 muscarinic acetylcholine receptor in the basal forebrain of the rat.

The m2 muscarinic acetylcholine receptor gene is expressed at high levels in basal forebrain, but the paucity of information about localization of the encoded receptor protein has limited the understanding of cellular and subcellular mechanisms involved in cholinergic actions in this region. The present study sought to determine the cellular localization of m2 protein, its relationship to cholinergic neurons, and its pre- and postsynaptic distribution in the rat medial septum-diagonal band complex using immunocytochemistry with polyclonal rabbit antibodies and a newly developed rat monoclonal antibody specific to the m2 receptor. Light microscopic colocalization studies demonstrated that m2 was present in a subset of choline acetyltransferase immunoreactive neurons, in choline acetyltransferase-negative neurons, and in more neuropil elements than was choline acetyltransferase. Intraventricular injections of 192 IgG-saporin, an immunotoxin directed to the low-affinity nerve growth factor receptor, resulted in depletion of choline acetyltransferase-immunoreactive neurons in the medial septum-diagonal band complex, whereas m2 immunoreactivity in neurons and in the neuropil was unchanged. By electron microscopy, m2 receptor in medial septum-diagonal band complex was localized to the plasmalemma of a small population of small to medium-sized neurons, and it was also found in dendrites, axons, and axon terminals in the neuropil. Neurons expressing m2 immunoreactivity received synaptic contacts from unlabelled axon terminals. A small distinct subpopulation of large neurons, unlabelled by m2 immunoreactivity, received synaptic contacts from m2-immunoreactive terminals. Thus, m2 receptor is situated to mediate the local effects of acetylcholine on basal forebrain cholinergic and noncholinergic neurons and, also, at both pre- and postsynaptic sites.