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J Parkes

Publications and source records attributed to J Parkes.

At least 19 recordsLinked to original sources
PubMed2006

Non-invasive markers associated with liver fibrosis in non-alcoholic fatty liver disease.

The diagnosis of fibrosis within liver disease is important for prognosis, stratification for treatment, and monitoring of treatment efficacy. The rising incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) has driven the search for accurate non-invasive tools of liver fibrosis within this condition. With the aid of a systematic review, we explore how the field has evolved from the discovery of simple blood parameters to panel markers of liver fibrosis. We will discuss the biological plausibility, limitations, potential uses, and emerging diagnostic techniques of non-invasive markers in this rapidly expanding field.

Biomarkers↗
PubMed2006

A review of the evidence on the effects and costs of implantable cardioverter defibrillator therapy in different patient groups, and modelling of cost-effectiveness and cost-utility for these groups in a UK context.

OBJECTIVES: To update the systematic review evidence on the effectiveness, health-related quality of life (HRQoL) and cost-effectiveness of implantable cardioverter defibrillators (ICDs); compilation of new data on the service provision in the UK; and on the clinical characteristics, survival, quality of life and costs of ICD patients in the UK, and a new cost-effectiveness model using both international RCT and UK-specific data. DATA SOURCES: Electronic databases searched from November 1999 to March 2003, this was supplemented by a systematic review of research published during 2003-5. Survey data. REVIEW METHODS: Studies were selected and assessed. A survey of ICD centres was carried out. Basic data were obtained from two major implanting centres including 535 patients (approximately 10% of overall UK activity) implanted between 1991 and 2002, and retrieval of fuller data, on patient characteristics, management and resource use, from patient notes for a sample of 426 patients was attempted. A cross-sectional survey collected HRQoL data (using the Nottingham Health Profile, Short Form 36, Hospital Anxiety and Depression questionnaire, EuroQoL 5 Dimensions and disease-specific questions) on a sample of 229 patients. A Markov model combined UK patient data with data from published randomised controlled trials (RCTs) to estimate incremental costs per life-year or quality-adjusted life-year (QALY) gained. RESULTS: None of the economic analyses in the studies found could be directly applied to the UK. The multiple sources of routine data available (including the national ICD database) provide an imperfect picture of the need for and use of ICDs. Implantation rates have been rising to a rate of around 20 per million population. Mean age is increasing and most ICDs are implanted into men aged 45-74 years. There is significant geographical variation. A survey of 41 UK centres provided additional evidence, particularly of variation in level of activity and resourcing. Most detailed data were obtained for 380 patients (89%). The postal survey produced a 73% response rate. Demographic characteristics of these patients were similar to ICD recipients in the UK as a whole and patients included in secondary prevention RCTs. Mean actuarial survival at 1, 3 and 5 years was 92%, 86% and 71%, respectively. Patient age at implantation and functional status significantly affected survival. Levels of most of the HRQoL measures were lower than for a UK general population. There was no evidence of a change with time from implantation. Patients who had suffered ICD shocks had significantly poorer HRQoL. Most patients nevertheless expressed a high level of satisfaction with ICD therapy. Mean initial costs of implantation showed little variation between centres (23,300 pounds versus 22,100 pounds) or between earlier and more recent implants. There appeared to be greater variation between patients presenting along different pathways. Postdischarge costs (tests, medications and follow-up consultations) and costs of additional hospitalisations were also calculated. Using the Markov model it was found that over a 20-year horizon, mean discounted incremental costs were 70,900 pounds (35,000-142,400 pounds). Mean discounted gain was 1.24 years (0.29-2.32) or 0.93 QALYs. Cost-effectiveness was most favourable for men aged over 70 years with a left ventricular ejection fraction (LVEF) below 35%. If the treatment effect were to continue, then the cost per life-year over a lifetime might fall to around 32,000 pounds. Five RCTs of ICDs, a meta-analysis and, a cost-effectiveness analysis of ICDs used in primary prevention, and a meta-analysis of ICDs in patients with non-ischaemic cardiomyopathy have been published recently. These trials provide confirmation of survival benefit of ICDs used in primary prevention in both ischaemic and non-ischaemic cardiomyopathy patients. Costs per QALY ranged from US$34,000 in older trials to controls being both less expensive and more effective (CABG Patch, DINAMIT). More recent trials estimated cost per QALY between $50,300 and $70,200. The inconsistency in evidence for a HRQoL benefit has not been resolved and further work on risk stratification is necessary. CONCLUSIONS: The evidence of short- to medium-term patient benefit from ICDs is strong but cost-effectiveness modelling indicates that the extent of that benefit is probably not sufficient to make the technology cost-effective as used currently in the UK. One reason is the high rates of postimplantation hospitalisation. Better patient targeting and efforts to reduce the need for such hospitalisation may improve cost-effectiveness. Further cost-effectiveness modelling, underpinned by an improved ICD database with reliable long-term follow-up, is required. The absence of a robust measure of the incidence of sudden cardiac death is noted and this may be an area where further organisational changes with improved data collection would help.

Aged↗
PubMed2004

Discharge planning from hospital to home.

BACKGROUND: Discharge planning is a routine feature of health systems in many countries. The aim is to reduce hospital length of stay and unplanned readmission to hospital, and improve the co ordination of services following discharge from hospital thereby bridging the gap between hospital and place of discharge. Sometimes discharge planning is offered as part of an integrated package of care, which may cover both the hospital and community. The focus of this review is discharge planning that occurs while a patient is in hospital; we exclude studies that evaluate discharge planning with follow up care. OBJECTIVES: To determine the effectiveness of planning the discharge of patients moving from hospital. SEARCH STRATEGY: Relevant studies were identified using Medline, Embase, SIGLE database for grey literature, Bioethics database, Health Plan, Psych. Lit, Sociofile, CINAHL, Cochrane Library, Econ Lit, Social Science Citation Index, EPOC register. The review was updated using the EPOC trials register in August 2002. SELECTION CRITERIA STUDY DESIGN: randomised controlled trials (RCTs) that compare discharge planning (the development of an individualised discharge plan) with routine discharge care. PARTICIPANTS: all patients in hospital. INTERVENTION: the development of an individualised discharge plan. DATA COLLECTION AND ANALYSIS: Data analysis and quality assessment was undertaken independently by two reviewers using a data checklist. Studies are grouped according to patient group (elderly medical patients, surgical patients, and those with a mix of conditions), and by outcome. MAIN RESULTS: Three new studies were included in this update. In total we included eleven RCTS: 6 trials recruited patients with a medical condition (2,368 patients), and four recruited patients with a mix of medical and surgical conditions (2,983 patients), one of these four recruited medical and surgical patients as separate groups, and the final trial recruited 97 patients in a psychiatric hospital and from a general hospital. We failed to detect a difference between groups in mortality for elderly patients with a medical condition (OR 1.44 95% CI 0.82 to 2.51), hospital length of stay (weighted mean difference -0.86, 95% CI -1.9 to 0.18), readmission rates (OR 0.91 95% CI 0.67 to 1.23) and being discharged from hospital to home (OR 1.15 95% CI 0.72 to 1.82). This was also the case for trials recruiting patients recovering from surgery and those recruiting patients with a mix of medical and surgical conditions. One trial comparing a structured care pathway for patients recovering from a stroke with multidisciplinary care reported a significant rate of improvement in functional ability and quality of life for the control group (median change in Barthel score between 4 to 12 weeks of 2 points for the treatment group, versus 6 for the control group, p<0.01); (Euroqol scores at 6 months 63 for the treatment group, vs. 72 for the control group, p<0.005). Two trials reported that patients with medical conditions allocated to discharge planning reported increased satisfaction compared with those who received routine discharge. No statistically significant differences were reported for overall health care costs. REVIEWER'S CONCLUSIONS: The impact of discharge planning on readmission rates, hospital length of stay, health outcomes and cost is uncertain. This reflects a lack of power as the degree to which we could pool data was restricted by the different reported measures of outcome. It is possible that even a small reduction in length of stay, or readmission rate, could have an impact on the timeliness of subsequent admissions in a system where there is an shortage of acute hospital beds.

Controlled Clinical Trials as Topic↗
PubMed2004

What influences physiotherapy use by children with cerebral palsy?

AIM: To investigate factors that influence the frequency of physiotherapy currently used by a population of children with moderate to severe cerebral palsy (CP). METHODS: A survey using a postal questionnaire was sent to 212 parents of children with moderate to severe CP. The families were identified from a geographically defined case register of children with CP in Northern Ireland (the Northern Ireland Cerebral Palsy Register). Eighty-five per cent of parents responded. One-third of parent responses regarding their child's use of physiotherapy were validated with their child's physiotherapist and the level of agreement was high. RESULTS: Ninety-four per cent (169/180) of children received conventional physiotherapy from a statutory source during the school term. Of these, 61% (104/169) used 'intense' levels of physiotherapy (defined as at least twice a week). A higher proportion of intense users were children with severe CP compared with moderate CP (69% vs. 47%; P < 0.01); with moderate intellectual impairment (IQ </= 70 > 50) compared with severe (IQ </= 50) or no intellectual impairment (IQ > 70) (81% vs. 64% vs. 39% respectively; P < 0.01) and at schools for physical disability (PD) compared with severe learning disability (SLD) or mainstream (MS) schools (82% vs. 66% vs. none respectively; P < 0.001). After controlling for severity of motor impairment and the presence and severity of intellectual impairment, children with CP at MS schools used on average significantly less physiotherapy compared with children with similar levels of motor impairment at PD schools (P < 0.001). CONCLUSIONS: Children with CP in MS schools use less physiotherapy compared with children with similar levels of disability in special schools. Organizing services around special schools may limit the degree to which children with CP and other disabilities are successfully integrated into MS education.

Adolescent↗
PubMed2003

Evaluation of a prison outreach clinic for the diagnosis and prevention of hepatitis C: implications for the national strategy.

BACKGROUND: Hepatitis C virus (HCV) infection is a major public health problem recognised by the UK National Strategy that proposes that a care pathway for assessment, diagnosis, and treatment be established in all prisons, integrated within managed clinical networks. A prison sentence provides the opportunity to focus on traditionally hard to reach patients. AIMS: To evaluate the prevalence of HCV infection in a UK prison cluster and to assess the effectiveness of a prison outreach service for hepatitis C. SUBJECTS: Male prisoners. METHODS: A nurse specialist led clinic within a cluster of adult prisons was established, offering health education on hepatitis C, advice on harm minimisation, and HCV testing. Infected prisoners were offered access to a care pathway leading to treatment. Outcome measures were uptake of the service, and diagnosis and treatment of hepatitis C. RESULTS: A total of 8.5% of 1618 prisoners accepted testing: 30% had active infection with HCV. Most were ineligible for treatment due to psychiatric illness or did not receive treatment for logistic reasons. Injecting drug use was the major risk factor in all cases. Only 7% of HCV polymerase chain amplification positive inmates received treatment in prison. CONCLUSION: There is a large pool of HCV infected prisoners at risk of complications, constituting a source of infection during their sentence and after discharge. A prison outreach clinic and care pathway was perceived as effective in delivering health education, reducing the burden on prison and hospital services. It provided an opportunity for intervention but had a limited effect in eradicating HCV in prisoners and it remains unclear how this might be achieved.

Adult↗
PubMed2002

Use of physiotherapy and alternatives by children with cerebral palsy: a population study.

OBJECTIVES: To describe the use of physiotherapy services and alternative therapies by a population of children with moderate to severe cerebral palsy (CP). DESIGN: Descriptive cross-sectional survey. SUBJECTS: A total of 212 parents of children aged 4-14 years with moderate to severe CP were identified from the Northern Ireland Cerebral Palsy Register (NICPR) and a random subsample of their paediatric physiotherapists. MAIN MEASURES: A standardized description of motor impairment or assessment form; a postal questionnaire to parents and paediatric physiotherapists (to validate parents' reports of service use). RESPONSE RATES: In total, 85% of parent questionnaires were returned and 100% of paediatric physiotherapists responded. RESULTS: Service use among families was high; on average the families had contact with approximately seven services in a 6-month time interval. The overwhelming majority of children (96%) received physiotherapy during the school term and most (59%) received treatment at least twice a week for 30 min; 43% of children had their physiotherapy discontinued over the summer holidays. Over one-quarter (28%) of families had opted out of the NHS and bought alternatives like conductive education (21%) or private forms of conventional physiotherapy (16%). Children with more severe forms of CP, in special education, particularly at schools for physical disability, were high-intensity users of the physiotherapy service. Despite this, 74% of parents wanted more physiotherapy for their child. CONCLUSIONS AND IMPLICATIONS: The demand for physiotherapy services is likely to continue given the relatively stable prevalence rate of CP, the proportion of children with disabling CP and the level of parent interest in the service. A number of quality aspects and gaps in the service have been identified.

Adolescent↗
PubMed2002

Implantable cardioverter-defibrillators in arrhythmias: a rapid and systematic review of effectiveness.

OBJECTIVE: To review the effectiveness of implantable cardioverter-defibrillators (ICDs) in the management of risk factors for sudden cardiac death. DESIGN: Systematic review of randomised controlled trials identified from searching eight electronic databases, bibliographies of relevant studies, and consulting experts. MAIN OUTCOME MEASURES: Absolute and relative reduction in mortality. RESULTS: Seven trials met the inclusion criteria. These showed changes in absolute risk of total mortality ranging from +1.7% to -22.8% (relative risk reductions -7% to +54%). Estimated benefits from ICD treatment compared with conventional drug treatment at three years were 0.23 to 0.80 additional years of life. CONCLUSIONS: Evidence suggests that ICDs reduce total mortality in particular subgroups of patients at high risk of ventricular arrhythmias. The optimal strategy for identifying the patients who could benefit most is not clearly established. Ongoing trials into the treatment of cardiac failure with ICDs may provide further evidence about subgroups in whom ICDs are most cost effective.

Adult↗
PubMed2001

Teaching critical appraisal skills in health care settings.

BACKGROUND: Critical appraisal is the process of assessing and interpreting evidence by systematically considering its validity, results and relevance to an individual's work. Within the last decade critical appraisal has been added as a topic to many medical school and UK Royal College curricula, and several continuing professional development ventures have been funded to provide further training. OBJECTIVES: To assess the effects of teaching critical appraisal skills to health professionals, on the process of care, patient outcomes and knowledge of health professionals. SEARCH STRATEGY: We searched The Cochrane Library (to Issue 2 2000), MEDLINE (1966 to 1997), EMBASE (1980 to 1997), Eric (1966 to 1997), Cinahl (1982 to 1997), Lisa (1976 to 1997), Sigle (1980 to 1997), Science Citation Index (1981 to 1997), PsycLit (1974 to 1997), the world-wide-web, and reference lists of articles. We also contacted major medical education centres. SELECTION CRITERIA: Randomised trials, controlled clinical trials, controlled before and after studies and interrupted time series analyses of educational interventions teaching critical appraisal to health professionals. The outcomes were: process of care; patient mortality, quality of life, and satisfaction; and health professional knowledge/awareness based upon objective, standardised, validated instruments. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and three reviewers independently assessed study quality. MAIN RESULTS: One USA hospital-based randomised trial was included involving 44 doctors. The outcome assessed was critical appraisal knowledge. Process of care, patient health or attitude/awareness outcomes were not assessed. Critical appraisal teaching was reported to have resulted in a 25% improvement (adjusted figure) in critical appraisal knowledge in the intervention group compared to a 6% improvement in the control group, which was statistically significant (p=0.02). REVIEWER'S CONCLUSIONS: There is evidence that critical appraisal teaching has positive effects on participants' knowledge, but as only one study met the inclusion criteria the validity of drawing general conclusions about the effects of teaching critical appraisal is debatable. There are large gaps in the evidence as to whether teaching critical appraisal impacts on decision-making or patient outcomes. It is also unclear whether the size of benefit seen is large enough to be of practical significance, or whether this varies according to participant background or teaching method. The evidence supporting all outcomes is weakened by the generally poorly designed, executed and reported studies that we found.

Decision Making↗
PubMed2001

Cerebral palsy in Northern Ireland: 1981--93.

This paper describes the method of compilation of the Northern Ireland Cerebral Palsy Register (NICPR) and outlines the epidemiology of cerebral palsy (CP) in Northern Ireland in 1981--93 based on an analysis of 784 cases. Multiple and overlapping sources of notification were used to compile the NICPR. Each case was followed up with a standardised assessment completed at age 5 years and validated by a paediatrician. Over 70% of cases were multiply notified, and paediatricians were the most important source of notification. Cases of CP most likely to be under-ascertained included those very mildly affected, cases who died before the register began (death certificates were searched but found to be unreliable) and cases who moved out of the area before their diagnosis was confirmed. The prevalence of CP for the birth period 1981--93 was 2.24 per 1000 livebirths [95% CI 2.08, 2.40]. There were no statistically significant temporal or geographic variations in the rate of CP. Almost half the cases of CP were of low birthweight (<2500 g), and this proportion increased during 1987--89, but decreased (P < 0.01) more recently (1990--93). The proportion of cases weighing <1000 g trebled from 3% in 1981--83 to 10% in 1990--93 (P < 0.01). The most common CP subtype was bilateral spastic cerebral palsy (55%). Just over a quarter (29%) of cases were unable to walk (with/without aids), and one-fifth (22%) had no useful hand/arm function. Almost half (49%) the cases had at least one other impairment (intellectual, sensory impairment or active seizures) in association with their CP. Prevalence rates and the pattern of disability in populations of people with CP can only be evaluated on the basis of the methods of case definition and ascertainment. We have demonstrated the methods necessary to ensure valid, standard and detailed information on CP for the purposes of surveillance, service planning and research.

Algorithms↗
PubMed2000

Prenatal diagnosis of dominant dystrophic epidermolysis bullosa, by COL7A1 molecular analysis.

We report the first direct molecular prenatal diagnosis, undertaken for the autosomal dominant form of dystrophic epidermolysis bullosa (DDEB). The proband had a moderately severe form of DDEB, with episodic blistering of skin and mucosal involvement. Diagnostic histopathological examination, using electron microscopy to evaluate skin from a fresh blister, demonstrated a zone of cleavage beneath the epidermal-dermal junction, thereby assigning the EB as dystrophic. DNA analysis of COL7A1, the gene encoding type VII collagen, identified a heterozygous transversion (G to A) in the triple helix domain (G2043R). For any subsequent pregnancy, the affected mother and the unaffected father of the proband requested prenatal prediction, which was thereafter carried out in DNA extracted from a chorionic villus sample obtained at 11 weeks of gestation. Restriction enzyme analysis of COL7A1 exons 73 and 74 amplified by PCR, demonstrated the presence of the G2043R mutation, and the pregnancy was subsequently terminated. Molecular analysis of DNA extracted from fetal tissues confirmed the prenatal prediction.

Base Sequence↗
PubMed2000

Discharge planning from hospital to home.

BACKGROUND: Discharge planning is the development of an individualised discharge plan for the patient prior to leaving hospital for home, with the aim of containing costs and improving patient outcomes. It has been suggested that discharge planning can reduce unplanned readmission to hospital. OBJECTIVES: To assess the effects of discharge planning for patients moving from hospital to home. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register, the Cochrane Controlled Trials Register, MEDLINE (1966 to 1996), EMBASE (1980 to 1996), Sigle (1980 to 1996), Bioethics (1985 to 1996), Health Plan (all available years), PsycLit (1974 to 1996), Cinahl (1982 to 1996), EconLit (1969 to 1996), Social Science Citation Index (1992 to 1996), and reference lists of articles. SELECTION CRITERIA: Randomised trials and controlled trials comparing discharge planning with routine discharge for hospital patients. The outcomes were mortality, clinical complications, hospital length of stay, readmissions, discharge destination, general and disease specific health status, functional status, psychological well-being, patient satisfaction, carer satisfaction, carer burden, cost to the health service, patient and family, general practice, and community services. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Eight studies were included involving 4837 patients. Four studies recruited patients with a medical condition; four recruited patients with a mix of medical and surgical conditions, and one of these recruited medical and surgical patients as separate groups. There was a small reduction in hospital length of stay for elderly medical patients allocated to discharge planning (weighted mean difference -1.01, 95% CI -2.06 to 0.05). The effects of discharge planning on readmission rates were mixed. No statistically significant differences were detected for patient health outcomes. Patients with medical conditions allocated to discharge planning reported increased satisfaction compared with those receiving routine discharge. No statistically significant differences were reported for overall health care costs, although one study reported a significant reduction in readmission costs for medical patients allocated to discharge planning. REVIEWER'S CONCLUSIONS: The studies showed mixed results, which may reflect the different study populations and the different ways the intervention was implemented. There is some evidence that discharge planning may lead to reduced hospital length of stay, and in some cases reduced readmission to hospital. There is also some evidence that discharge planning increased patient satisfaction. There was no evidence that discharge planning reduced health care costs; however few studies conducted a formal economic analysis.

Controlled Clinical Trials as Topic↗
PubMed2000

Sudden death during restraint: a study to measure the effect of restraint positions on the rate of recovery from exercise.

A small number of mental health patients have died suddenly following violent behaviour and restraint by staff. The safety of certain restraint positions has been questioned. This study evaluates two control and restraint (C & R) positions commonly used by health service staff. A repeated measures design was used to study rate of recovery from exercise in volunteer staff, measured by pulse oximetry, comparing the restraint positions with a seated (control) position. It was found that the recovery time for pulse rate of subjects restrained in a face-down position was significantly longer than for subjects restrained in a face-up position. No significant findings were made in terms of comparison between the control position and the restraint positions, and no significant changes in oxygen saturation were noted during restraint. It is concluded that restraint position may be a factor in death during restraint, but only where other factors contribute to the overall situation.

Adult↗
PubMed2000

Implantable cardioverter defibrillators: arrhythmias. A rapid and systematic review.

PROPOSED SERVICE: The service proposed is the use of implantable cardioverter defibrillators (ICDs) in the management of risk factors leading to sudden cardiac death (SCD). ICDs are similar in size to a pacemaker and are intended to prevent death due to life-threatening ventricular tachyarrhythmias. EPIDEMIOLOGY AND BACKGROUND: SCD occurs in approximately 100,000 people annually in the UK and is usually due to ventricular tachyarrhythmia. Increasing numbers of people are surviving a first episode of ventricular tachyarrhythmia and are at high risk of further episodes. Standard treatments for those at high risk have been anti-arrhythmic drugs, catheter ablation or surgery and, increasingly, vasodilating beta-blockers. METHODS: Electronic databases were searched for the period 1980-99. In addition, bibliographies of related papers were assessed for relevant studies, and experts were contacted to identify additional published and unpublished references. Studies were included if they were systematic reviews, meta-analyses or randomised controlled trials (RCTs) comparing ICDs with conventional therapy in people at high risk of SCD. NUMBER AND QUALITY OF STUDIES AND DIRECTION OF EVIDENCE: Seven RCTs on effectiveness the majority of which were of good quality, eight cost-effectiveness analyses most of which were older studies and based on non-UK data, and two good-quality literature reviews one of which was a critical appraisal of the literature of effectiveness and cost-effectiveness of ICD therapy, and the other a review of the cost-effectiveness of ICD therapy. These showed changes in absolute risk of total mortality ranging from an increase of 1.7% to a reduction of 22.8% (relative risk reductions of -7% to +54%). SUMMARY OF BENEFITS: Estimated benefits from RCT data are 0.23-0.8 additional years of life with ICD therapy compared with anti-arrhythmic drug therapy. COSTS: Unit cost of ICDs (based on 1999/2000 prices), ranges from pound 12,500 to pound 22,000. Total discounted costs for 3 years range from pound 20,000 to pound 29,000. COST-EFFECTIVENESS: Cost-effectiveness estimates in the literature identified range from $11,000 to $146,000 per life-year saved. Using UK cost data from three hospitals and trial survival data from one RCT, the estimate of cost-effectiveness from this review ranges between pound 20,250 and pound 87,000 per life-year saved. COST-UTILITY: Cost per quality-adjusted life-year is estimated by the authors of this review at pound 21,300 to pound 108,800 (using survival data from one trial and quality-of-life indices derived from clinical opinion). These figures remain speculative until quality-of-life data from ongoing trials are available to inform future UK cost-effectiveness/utility analyses. IMPLICATIONS: If implemented for indications supported by evidence from RCTs, ICDs may cost the NHS in excess of pound 24 million per annum. FUTURE RESEARCH: Future research should include the use of British Pacing and Electrophysiological Group registries to assess the use of different types of ICD and current service provision.

Anti-Arrhythmia Agents↗
PubMed1999

Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells.

The expression of cyclin D1 protein in tumour sections from 81 patients with epithelial ovarian cancer was analysed using immunohistochemistry. The tumours that overexpressed cyclin D1 in more than 10% of neoplastic cells were considered positive. Thus overexpression of cyclin D1 was observed in 72/81 (89%) of the cases examined. Protein was detected in both the nucleus and the cytoplasm in 24/81 (30%) and localized exclusively in the cytoplasm in 48/81 (59%) of the tumours. Cyclin D1 was overexpressed in both borderline and invasive tumours. There was no association between protein overexpression and tumour stage and differentiation. Furthermore, no correlation between cyclin D1 expression and clinical outcome was observed. However, in tumours overexpressing cyclin D1 (n = 72), the proportion displaying exclusively cytoplasmic localization of protein was higher in those with serous compared with non-serous histology (P = 0.004, odds ratio 4.8, 95% confidence interval 1.4-19.1). Western analysis using a monoclonal antibody to cyclin D1 identified a 36 kDa protein in homogenates from seven tumours displaying cytoplasmic only and one tumour demonstrating both nuclear and cytoplasmic immunostaining. Using restriction fragment length polymorphism polymerase chain reaction and PCR-multiplex analysis, amplification of the cyclin D1 gene (CCND1 was detected in 1/29 of the tumours demonstrating overexpression of cyclin D1 protein. We conclude that deregulation of CCND1 expression leading to both cytoplasmic and nuclear protein localization is a frequent event in ovarian cancer and occurs mainly in the absence of gene amplification.

Blotting, Western↗
PubMed1999

Tumor metastasis biopsy as a surrogate marker of response to melanoma immunotherapy.

In patients undergoing immunotherapy for metastatic melanoma, the clinical response in immunotherapeutic trials may be partial or difficult to detect. Tumor metastasis biopsy allows direct characterisation of an anti-tumor immunological response. During a phase I/II trial of granulocyte macrophage colony stimulating factor (GM-CSF) transduced autologous melanoma immunotherapy, the cellular response was examined by immunohistochemical analysis in a limited number of tumor biopsies taken from patients who either responded or progressed. Clinical response was associated with tumor infiltration by CD4+ and CD8+ T-cells, macrophages and differentiated dendritic cells (DC), and expression of HLA-DR by the tumor cells. This tumor infiltration was associated with increased melanoma-specific peripheral blood precursor cytotoxic T-lymphocyte (pCTL) and the ability to obtain tumor-infiltrating lymphocytes in vitro. In contrast, progression or a lack of clinical response was associated with a lack of T-cell and DC infiltration into the tumor tissue in all such biopsies. Macrophages and eosinophils infiltrated these tumors, while T-cells and DC were present at some distance from the tumor. These preliminary data strongly suggest that the location and extent of T-cell and DC infiltration, as well as the expression of HLA-DR by tumor cells are associated with a clinical response in this form of melanoma immunotherapy.

Adult↗
PubMed1999

Prospective evaluation of accuracy, precision, and reproducibility of an at-home hemoglobin A1c sampling kit.

BACKGROUND: The measurement of hemoglobin A1c (HbA1c) is critical to the optimal therapeutic management of diabetes. To be most useful, the HbA1c value should be available at the clinical visit. Recently, a number of at-home sampling kits have been developed that facilitate the timely availability of HbA1c results. This is a report of the accuracy, precision (among-subject), and reproducibility (within-subject) of one such kit, B-D A1c, At-Home-Test, which combines a filter paper technique for spotting capillary blood with an immunoturbidometric assay (a variation of the Cobas Integra Hemoglobin A1c method also referred to as Roche Unimate). METHODS: The B-D A1c At-Home test kit was evaluated in a clinical trial using 1625 dried blood spot samples from 59 subjects diagnosed with type 1 or type 2 diabetes collected in an in-clinic setting. Data for replicate samples were compared against those from the standard Cobas Integra Hemoglobin A1c assay and from the BioRad Variant high-performance liquid chromatography [HPLC] assay. The effects of subjecting the dried spotted blood samples to prolonged elevated temperatures was evaluated in a separate laboratory analysis. RESULTS: The B-D A1c At-Home results, which are highly correlated with the standard Cobas Integra Hemoglobin A1c assay, (r2 = 94.7%), demonstrate excellent within-subject reproducibility for 3- to 10-day-old samples (coefficient of variation = 2.7%), and provide a coefficient of variation for among-subjects that is 3.9%. There were no clinically significant differences (i.e., < 0.3 units) in samples aged 3 to 10 days, between venous or capillary blood samples, or from freezing and thawing or prolonged exposure of B-D A1c At-Home dried blood samples to elevated temperatures before assay. CONCLUSIONS: The B-D A1c At-Home kit combines the accuracy, precision, and reproducibility of a clinical laboratory test with the convenience of at-home sample collection. This product may add to the convenience of both patient and health care provider by making it easier for patients to obtain their HbA1c values and have them available at their visit to the clinician.

Adult↗
PubMed1998

A novel single missense mutation identified along the RH50 gene in a composite heterozygous Rhnull blood donor of the regulator type.

Rare individuals who lack all of the Rh blood group antigens are called Rhnull and may be classified as "regulator" or "amorph" types. The suppression of Rh antigen expression for regulator types may be attributed to mutations of the RH50 gene, which is independent of the RH locus. The RH50 gene encodes a glycoprotein that interacts with the Rh proteins to form a functional complex within the red blood cell membrane. This report describes an RH50 gene mutation for a previously unclassified Rhnull donor. Sequencing cDNA clones from Rh50 mRNA revealed a single base change (G836A) yielding a missense and nonconservative mutation (Gly279Glu) within a predicted hydrophobic domain for this membrane protein. Genomic DNA studies using polymerase chain reaction (PCR) restriction analysis and sequencing showed that the Rhnull propositus was a composite heterozygote for this mutation, carrying two alleles with the A and G at nucleotide 836, respectively. In contrast, cDNA studies showed that only the A836 sequence was present, suggesting that the second allele with G836 was apparently silent (no transcript detected). Family studies showed that the mutant RH50 allele (836A) was inherited maternally, whereas the silent RH50 allele (836G) was from paternal transmission. These findings provide further evidence that rare but diverse genetic alterations may occur along the RH50 gene where the Rhnull syndrome of the regulator type occurs. The single amino acid change (Gly to Glu) provides insight into the critical value of these residues for assembly of the Rh antigen complex within the membrane.

Blood Donors↗