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Biomedical subjects

J E Powell

Publications and source records attributed to J E Powell.

At least 19 recordsLinked to original sources
PubMed2006

Caring for survivors of childhood cancers: the size of the problem.

Many survivors of childhood cancer have significant health problems due to their illness or treatment. This population-based study examines the number of long-term survivors, their disabilities and consequent long-term care needs. Survival rates for children diagnosed with cancer between 1960 and 1999 in the West Midlands, United Kingdom (UK), were used to estimate future long-term survivor numbers. Treatment and late effects data on a cohort of patients surviving for more than 5 years were used to consider continuing care needs. Between the 1960s and 1990s, 5-year survival increased from 23% to 70%. There were 98 5-year survivors in 1970, and numbers may exceed 2,100 by the end of 2005. Most (at least 61%) survivors in the West Midlands Region have one or more chronic medical problems and may require multidisciplinary care. We conclude that, in order to determine how to provide cost-effective care for this increasing population, protocol delivered management with audit is needed.

Adolescent↗
PubMed2005

Free-grafting of mandibular condyle fractures: clinical outcomes in 10 consecutive patients.

"Free-grafting" of the superior segment, either alone or in combination with a posterior ramus osteotomy, is occasionally required when managing displaced condylar neck fractures. This allows ideal reduction and fixation, but carries the risk of proximal segment resorption, possibly requiring secondary reconstruction. The purpose of this study was to evaluate the clinical and radiographic outcomes of this technique in all patients who underwent this procedure during a seven-year period at a tertiary care centre. Ten patients who had undergone 11 free graft procedures were included in the study. Three patients required secondary costochondral reconstruction due to advanced resorption of the free-grafted condylar segment, this occurring from 3 to 9 months following the initial trauma surgery. All but one of the remaining patients exhibited varying degrees of condylar resorption/flattening radiographically, occurring within the first year only. However, no occlusal changes occurred in this group either objectively or subjectively during this year or during the subsequent follow-up period. The mean inter-incisal opening was 47mm (range 40-56). With the exception of one patient that had a non-painful reciprocal click of the treated side, no patients demonstrated either objective or subjective signs of TMJ pathology. No patients reported dietary limitations, and all reported satisfaction with treatment to date. Based on objective and subjective evaluation, free grafting of the fractured condylar segment in this patient population had a 70% success rate. All failures occurred within 9 months and required secondary costochondral reconstruction.

Adolescent↗
PubMed2004

Welfare rights services for people disabled with arthritis integrated in primary care and hospital settings: set-up costs and monetary benefits.

OBJECTIVE: To quantify the set-up costs and monetary benefits of a welfare rights service integrated within an NHS service provider, that selects eligible patients using the Health Assessment Questionnaire (HAQ) and offers welfare rights advice to assist in application for Disability Living Allowance and Attendance Allowance. METHOD: (1) DESIGN: a cost evaluation of a social intervention, screening with the HAQ and welfare rights advice in primary care and hospital settings. (2) SETTING: Eight general practices and four hospital rheumatology out-patient departments were selected from four localities in the southwest of England. (3) PARTICIPANTS: Two hundred and sixty-eight eligible patients with arthritis accepted an interview with a welfare rights officer (WRO) from a sample of 1989 service users identified from GPs' records and hospital out-patient lists. Two hundred and forty two service users expressed an interest in take up of the social intervention. (4) Service users with a HAQ score >/=1.5 were contacted by telephone and offered an appointment with an experienced WRO to help them complete a welfare benefit application form. A 'micro-costing' study was undertaken with assessment of monetary benefits received. RESULTS: The indicative set-up costs of similar welfare rights services are pound 8125 in a GP setting and pound 9307 per annum in a hospital setting at 2002 prices. Total annual unclaimed Disability Living Allowance/Attendance Allowance granted to successful claimants was pound 184,382 in the GP setting (n = 84 from 137) and pound 169,309 in the hospital setting (n = 79 from 131). CONCLUSIONS: Welfare rights advice received during a visit to a GP practice or a hospital out-patient department can substantially reduce the level of unclaimed benefit in arthritic populations including the elderly; with mobility and care difficulties. A welfare rights service integrated within a GP practice or hospital that screens people with arthritis using HAQ scores and encourages those with scores >/=1.5 to see a WRO for help with welfare benefit confers monetary benefits for service users that substantially outweigh set-up costs.

Aged↗
PubMed2003

Population screening for neonatal liver disease: potential for a community-based programme.

OBJECTIVES: To evaluate a community-based screening programme for detecting neonatal liver disease by the quantitation of conjugated bilirubin in blood. SETTINGS AND METHODS: Prospective cohort/observational study using spare plasma from routinely collected liquid neonatal screening specimens from babies born in Birmingham over a two-year period. Babies with a conjugated bilirubin above 18 mumol/l and comprising more than 20% of the total bilirubin were followed up. A total of 27654 neonates were tested in the community, with a further 2425 samples from babies hospitalised at the time of the test. RESULTS: In the community-based series, 84.7% of the specimens received were analysed, the remainder being unusable mainly because of gross haemolysis (8.6%) or insufficient sample (5.8%). In 107 neonates the results were above the cut-off limits (0.46% of the number analysed). Of these, 12 had persistently abnormal results, 11 of whom had confirmed liver disease. The liver diseases detected included neonatal hepatitis (n=6), extra-hepatic biliary atresia (n=2), hypopituitarism (n=1), alpha-1-antitrypsin deficiency (n=1) and Alagille syndrome (n=1). The sensitivity and specificity of the test for babies in the community were 100% and 99.6%, respectively. CONCLUSIONS: Conjugated bilirubin in plasma measured at 6-10 days is a reliable marker for neonatal liver disease, and a population screening programme based on this method has the potential to improve the survival and quality of life of infants born with liver disease. However, testing as part of the neonatal screening programme will prove practical only if the method can be adapted to use dried blood spots.

Bilirubin↗
PubMed2001

Neuroblastomas with chromosome 11q loss and single copy MYCN comprise a biologically distinct group of tumours with adverse prognosis.

Neuroblastoma is a heterogeneous tumour and its effective clinical management is dependent on accurate prognostic evaluation. In approximately 25% of patients amplification of the MYCN oncogene is known to be associated with a poor outcome. In order to identify additional molecular markers with prognostic potential in non-MYCN-amplified neuroblastomas, we looked for a correlation between clinical outcome and loss of heterozygosity (LOH) on four chromosomes that frequently show alteration in neuroblastoma (chromosomes 3, 4, 11 and 14). Chromosome 11q loss (with frequent parallel loss of chromosomes 3p, 4p and/or 14q) was found exclusively in tumours without MYCN amplification and was significantly associated with poor event-free survival. The 2-year event-free survival rate for 11q LOH cases was 30%, compared to 34% for MYCN-amplified cases and 100% for cases without these abnormalities. While 11q LOH was associated predominantly with advanced-stage disease, 2 cases with low-stage disease and 11q LOH both suffered relapses. We conclude that chromosome 11q loss defines a biologically distinct group of tumours without MYCN amplification that appear to have potential for aggressive metastatic growth. Thus this genetic alteration may be an important new prognostic marker in neuroblastoma.

Biomarkers, Tumor↗
PubMed2001

South Asian ethnicity and material deprivation increase the risk of Epstein-Barr virus infection in childhood Hodgkin's disease.

In order to further define the factors associated with the observed variations in the Epstein-Barr virus-positive rate in childhood Hodgkin's disease, we have studied the effect of material deprivation (measured by the Townsend score) and ethnic origin on the frequency of Epstein-Barr virus-positivity in 55 cases of childhood Hodgkin's disease, diagnosed between 1981 and 1999, from a multi-ethnic region of the United Kingdom. Epstein-Barr virus status was determined by immunohistochemistry for the Epstein-Barr virus-encoded latent membrane protein-1. 62% of cases were Epstein-Barr virus-positive. Ethnic group was the strongest predictor of Epstein-Barr virus-positivity, with South Asians having a more than 20-fold risk of being Epstein-Barr virus-positive compared with non-South Asians. An increased risk was still present after adjusting for deprivation. Townsend scores were significantly higher (indicating more deprivation) in the Epstein-Barr virus-positive group, particularly in males. The relative risk of Epstein-Barr virus-positivity showed a gradient with increasing Townsend score; the risk being 7-times higher in the most deprived quartile compared with the least deprived group. Although the association between Townsend score and Epstein-Barr virus-positivity was reduced after adjusting for ethnic group, the risk of Epstein-Barr virus-positivity was still 3-times higher in the most deprived compared with the least deprived quartile. In addition, cases having 2 or more siblings were 5-times as likely to be Epstein-Barr virus-positive as those from smaller families. These results provide the first evidence of a strong association between Epstein-Barr virus-positive Hodgkin's disease and South Asian children from the United Kingdom. In addition, deprivation may increase the likelihood of Epstein-Barr virus-positive disease independently of ethnicity.

Adolescent↗
PubMed2000

Changes in the incidence of childhood autism and other autistic spectrum disorders in preschool children from two areas of the West Midlands, UK.

The incidence of childhood autism and other autistic spectrum disorders (ASDs) in preschool children was determined for two areas of the West Midlands between 1991 and 1996. Children diagnosed before the age of 5 years and residing within the study areas at diagnosis were detected from the records of four child development centres. The incidence rate per 10,000 children per year for the combined areas was 8.3 for all children with ASDs, 3.5 for classical childhood autism (CA), and 4.8 for other ASDs. Rates were similar in both areas, despite differences in social deprivation and proportions of ethnic minorities. While rates for classical CA increased by 18% per year, a much larger increase (55% per year) was seen for 'other ASDs', suggesting that clinicians are becoming increasingly able and/or willing to diagnose ASDs in preschool children.

Autistic Disorder↗
PubMed2000

Factors affecting survival in White and Asian children with acute lymphoblastic leukaemia.

Some studies suggest that Asian children with leukaemia have a worse outcome than Whites. Survival of Asians with ALL treated at the Birmingham Children's Hospital from 1975 to 1994 was the same as that of Whites, despite their greater deprivation and poorer nutrition. For one 5-year period (1980-1984) Asians had significantly poorer survival, even after adjustment for prognostic factors. Poor treatment compliance during that period may have contributed to this difference.

Asia↗
PubMed2000

Clonal diversity of Ig and T-cell receptor gene rearrangements in childhood B-precursor acute lymphoblastic leukaemia.

The majority of paediatric B precursor acute lymphoblastic leukaemias in children are derived from a single transformed haematopoietic cell with complete or partial VDJ recombination within the immunoglobulin heavy chain gene. A high frequency of patients also show rearrangements within TCRdelta and TCRgamma loci and in up to 40% of children there is an excess of immune system gene rearrangements compared with the number of identified alleles of immune system genes, suggesting the presence of multiple leukaemic subclones -clonal diversity. It has been observed by us and other investigators that in individual patients the pattern of immune system gene rearrangements often changes between presentation and relapse. In order to explore the possibility that clonal diversity plays a biological role during disease progression we optimised methods for subclone detection and analysed the prognostic significance of clonal diversity among 75 children with B precursor-ALL. Our results suggest that clonal diversity plays a role in disease progression as patients with oligoclonal disease showed a significantly shorter disease free survival than patients with monoclonal disease. This trend was of particular importance in the 'standard risk' group of ALL where aggressive disease could not be recognised by other means. In addition, generation of independent subclones from an early, non-rearranged tumour progenitor appears to be a common feature among leukaemias with aggressive clinical behaviour. We speculate on the type of genetic factors which may participate both in the generation of subclones and also in wider genomic instability and which are likely to be required for the aggressive clinical phenotype in children with ALL.

Burkitt Lymphoma↗
PubMed2000

Artificial neural networks and survival prediction in ovarian carcinoma.

The standard use of known survival predictors for ovarian cancer in clinical practice are primarily based on disease stage. This does not permit a real individualization of a patient's potential outcome. This study assessed the value of neural networks to refine the prediction of survival based only on information gleaned at primary surgery. The possibility exists that such methods may permit further elucidation of outcome and influence management.

England↗
PubMed1999

Quality of life in alcohol-dependent subjects--a review.

Although alcohol misuse is a major cause of morbidity and mortality and an important health care burden, the Quality of Life (QoL) of alcohol misusing subjects has been little studied to date. For example, only 5 out of 442 accepted abstracts at a recent international QoL conference concerned alcohol-dependent subjects. This paper reviews the ongoing and published work in the area focusing upon QoL characteristics of alcohol-dependent subjects, the link between QoL comorbidity and alcoholism, QoL alcohol dependency and social environment, changes in QoL status as a result of abstinence, minimal or controlled drinking, QoL as a predictor of relapse to heavy drinking and the importance of using a QoL measure when assessing treatment outcomes together with some of the present difficulties with existing measures. The main conclusions from the review were that the QoL of alcohol-dependent subjects is very poor but improved as a result of abstinence, controlled or minimal drinking. The important factors in the QoL of alcohol-dependent subjects are psychiatric comorbidity, social environment and disturbed sleep.

Alcoholism↗
PubMed1998

Neuroblastoma in Europe: differences in the pattern of disease in the UK. SENSE. Study group for the Evaluation of Neuroblastoma Screening in Europe.

BACKGROUND: Neuroblastoma is a major contributor to childhood cancer mortality, but its prognosis varies with age and stage of disease, and some tumours regress spontaneously. Urinary screening programmes or clinical examination may detect the disease before symptoms appear, but the benefit of early diagnosis is uncertain. We examined the incidence, pattern, and presentation of neuroblastoma in four European countries. METHOD: Population-based incidence rates were derived for France, Austria, Germany, and the UK. Age, sex, and stage distribution were analysed by Mantel-Haenszel techniques and Poisson regression. The proportion of incidental diagnoses (cases without symptoms found at routine health checks or during investigation of other disorders) and mortality rates were also compared. FINDINGS: Between 1987 and 1991, 1672 cases of neuroblastoma were diagnosed in children under 15 years old (France, 624; Austria, 69; Germany, 493; UK, 486). Age-standardised annual incidence was significantly lower in the UK (10.1/million) than in France (12.5) and Germany (11.4). In the UK a deficit of low-stage disease in infants was accompanied by an excess of stage IV in older children. The UK had significantly fewer incidental diagnoses (8%) than Austria (27%) and Germany (34%). UK mortality rates were significantly higher than German or French rates. INTERPRETATION: In the UK, neuroblastoma diagnosis is delayed, possibly because of a less rigorous system of health checks for children. Although some overdiagnosis occurs in mainland Europe, our data suggest that in the UK some low-stage cases, undetected in infancy, may later present as advanced disease. This finding has implications for screening programmes and organisation of routine surveillance of infant health in the UK.

Adolescent↗
PubMed1998

Clonal diversity of Ig and T-cell-receptor gene rearrangements identifies a subset of childhood B-precursor acute lymphoblastic leukemia with increased risk of relapse.

Current prognostic indicators such as age, sex, and white blood cell count (WBC) fail to identify all children with more aggressive forms of B-precursor acute lymphoblastic leukemia (ALL), and a proportion of patients without poor prognostic indicators still relapse. Results obtained from an analysis of 65 pediatic B-precursor ALL patients indicated that subclone formation leading to clonal diversity, as detected by Ig and T-cell receptor (TCR) gene rearrangements, may represent a very useful prognostic indicator, independent of age, sex, and WBC. Disease-free survival was significantly shorter in those patients showing clonal diversity at presentation. Furthermore, clonal diversity was detected not only in the majority of high-risk patients who relapsed but was also associated with a high probability of relapse in standard-risk patients. Sixty-five percent (13/20) of standard-risk patients who also showed clonal diversity subsequently relapsed, whereas the percentage of relapses among standard-risk patients without clonal diversity was much lower at 19% (7/36). Continued clonal evolution during disease progression is an important feature of aggressive B-precursor ALL. All 5 patients with clonal diversity who were followed up in our study showed a change in the pattern of clonality between presentation and relapse. This implies an important role for clonal diversity as a mechanism of disease progression through the process of clonal variation and clonal selection.

Adolescent↗
PubMed1998

Population screening for neonatal liver disease: a feasibility study.

BACKGROUND: Extra-hepatic biliary atresia and several other causes of neonatal liver disease carry high mortality and morbidity rates, especially if not treated early in life. Despite professional recommendations, delayed referral of infants with prolonged jaundice continues to be a significant problem. One approach to reducing the age of referral and diagnosis is population screening to detect significant conjugated hyperbilirubinaemia as an index of liver dysfunction. METHODS: To investigate this possibility, and to provide reference data on bilirubin and its conjugated and unconjugated fractions in a normal newborn population, 1157 neonates were anonymously tested (median age 7 days, range 4-28 days) using surplus plasma from routinely collected neonatal screening specimens, using dry slide chemistry. RESULTS: Of 2310 specimens received, 50% were suitable for analysis. The remainder were either haemolysed or insufficient (10% and 40% of the total, respectively). Total bilirubin concentrations ranged from 9 to 428 micromol/l and conjugated bilirubin from 0 to 175 micromol/l, although the latter was rarely increased to more than 30 micromol/l (2.5th-97.5th percentile ranges 15-285 micromol/l and 0-18 micromol/l, respectively). The range of the percentage of conjugated bilirubin was 0-57% (2.5th-97.5th percentile; range 0-20%). CONCLUSION: An increased conjugated bilirubin, expressed as a concentration or as the percentage of the total bilirubin, could be used as a specific marker to screen for liver dysfunction in neonates. This approach has the potential to improve the age of referral and the prognosis of infants with neonatal liver disease.

Bilirubin↗
PubMed1997

The role of carboxy-terminal portion of beta subunit of human chorionic gonadotropin in human immunodeficiency virus infection.

Human chorionic gonadotropin (hCG) and the beta subunit of this dimer glycoprotein hormone (beta hCG) have been reported by us to inhibit HIV replication. In order to identify the active site responsible for the antiviral activity, twelve overlapping peptides spanning across beta hCG were examined for their effect against HIV-caused cell death. Although the NH2-terminus of beta hCG appeared to contribute to activity, the core region was biologically inert. The most potent activity was observed with the fragment representing the carboxy-terminus of beta hCG. The dose response curve to serial dilutions of the peptide, containing amino acid residues 106-145, had a bell-shaped appearance - characteristic of hCG and beta hCG. The peak of activity corresponded to 100 ng/ml - the dose at which two thirds of virus-exposed MT-4 T lymphocytes survived. None of the tested peptides were toxic to MT-4. While the mechanism of action remains unclear, the results suggest that the COOH-terminal portion, unique to beta hCG, confers anti-HIV activity.

Anti-HIV Agents↗