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Biomedical subjects

G Harrison

Publications and source records attributed to G Harrison.

At least 55 records · Page 3Linked to original sources
PubMed2000

Comparison of allogeneic transplant versus chemotherapy for relapsed childhood acute lymphoblastic leukaemia in the MRC UKALL R1 trial. MRC Childhood Leukaemia Working Party.

BACKGROUND: Although reinduction rates are good for children with relapsed acute lymphoblastic leukaemia there is no consensus on whether bone marrow transplantation (BMT) is the most effective treatment to prolong second remission. PATIENTS AND METHODS: Analyses comparing the outcome of related donor allogeneic BMT (related allograft) with chemotherapy are unreliable because of selection biases. To avoid these biases, the MRC UKALL R1 trial was analysed by HLA-matched donor availability. RESULTS: No significant difference in outcome was found between the donor and no donor groups. The donor group had a non-significant eight-year event-free survival (EFS) advantage of 8%, (95% confidence interval -9%-24%) over the no donor group. Patients with a first remission less than two years appeared to benefit most from having a donor, although the effect was only marginally significantly different from patients with longer first remission. Analysis by treatment received gave similar results, with BMT patients having a 5% (P = 0.8) eight-year EFS advantage over patients who received chemotherapy. CONCLUSIONS: Related allograft was not found to be significantly better than chemotherapy, but there was the possibility of a moderate EFS benefit with related allograft. especially in patients with a short first remission.

Adolescent↗
PubMed2000

Ethnic disadvantage and schizophrenia.

OBJECTIVE: To review and interpret epidemiologic research on ethnic disadvantage and schizophrenia. METHOD: A search of the research literature was conducted. RESULTS: Seventeen population-based studies were reported in the United Kingdom and the Netherlands from 1967 to 1997. The studies report high incidence rates for immigrants whose position in society is disadvantaged, than majority-group native-born, with a range of relative incidence from 1.7 to 13.2. It is proposed that the developmental task for formulating the life plan challenges the young adult's executive function abilities, which may be weaker in individuals vulnerable to schizophrenia. Formulating the life plan may be made more difficult by the position in society of disadvantaged ethnic minorities, raising the risk for schizophrenia. CONCLUSION: Further research on executive function, and the developmental challenge of formulating the life plan, might provide insights into the etiology of schizophrenia, as well as suggest avenues for prevention.

Adult↗
PubMed2000

Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980-1997. Medical Research Council Childhood Leukaemia Working Party.

Results of three consecutive completed UK trials (1980-1997) for childhood lymphoblastic leukaemia are presented. National accrual has progressively increased so that over 90% of all the country's ALL cases were treated on the latest trial reported, UKALLXI. From 1980 to 1990, event-free and overall survival progressively improved, following adoption of an American therapy template and use of two post-remission intensification modules. Since 1990 despite demonstration of the benefit of a third intensification module overall event-free survival (EFS) has not improved further. Survival remains high due to a good retrieval rate especially for those relapsing off treatment after receipt of two intensification pulses. Possible reasons for the plateau in event-free survival (including type and dose of induction steroid, dropping of induction anthracycline, type and dose of asparaginase, gaps early in therapy following intensification, and overall lack of compliance in maintenance) are being explored in the latest protocol ALL '97. Cranial irradiation had been successfully replaced by a long course of intrathecal methotrexate injections for the majority of patients. Age (<1 year >10 years) sex (male) and white count >50 x 10(9)/l plus slow initial bone marrow clearance were consistently the most important independent prognostic indicators during this time period. Rome/NCI criteria accurately predict standard and high-risk groups for B cell lineage, but not consistently for T cell disease. This international collaborative venture might help us to define those truly at highest risk, and how we can optimise therapy for specific subgroups including T-ALL and those with unfavourable cytogenetics.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the medical research council UKALLR1 study.

We have examined the toxicity and overall outcome of the Medical Research Council UKALL R1 protocol for 256 patients with relapsed childhood acute lymphoblastic leukaemia (ALL). Second remission was achieved in over 95% of patients. Two patients died during induction and seven patients died of resistant disease. The overall actuarial event-free survival (EFS) at 5 years for all patients experiencing a first relapse was 46% (95% CI 40-52). Duration of first remission, site of relapse, age at diagnosis and sex emerged as factors of prognostic significance. Five-year EFS was only 7% for children relapsing in the bone marrow within 2 years of diagnosis, but was 77% for those relapsing without bone marrow involvement > 2.5 years from diagnosis. All analyses in this report are by treatment received. For those receiving chemotherapy alone, the 5-year EFS was 48%; for autologous bone marrow transplantation (BMT), the 5-year EFS was 47%; for unrelated donor BMT, it was 52%; and for related donor BMT, the 5-year EFS was 45%. The groups, however, were not comparable with respect to risk factor profile, and therefore direct comparison of EFS is misleading. Adjustment for time to transplant and prognostic factors was used to reduce the effects of biases between treatment groups, but did not suggest benefit for any particular treatment. There was failure of our planned randomization scheme in this trial with only 9% of those eligible being randomized, which highlights the difficulties in running randomized trials especially in patients who have relapsed from a previous trial. The optimal treatment for relapsed ALL therefore remains uncertain. Alternative approaches are clearly needed for those with early bone marrow relapse if outcome is to improve.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Three-year outcome of first-episode psychoses in an established community psychiatric service.

BACKGROUND: Changes in service provision, secular trends in substance misuse and changing social structures might affect outcome in psychosis. AIMS: To assess the three-year outcome of an inception cohort of first-episode psychoses treated in a modern, community-oriented service; to compare outcomes with an earlier cohort treated in hospital-based care; and to examine the predictive validity of ICD-10 diagnostic criteria. METHOD: Three-year follow-up (1995-1997) of an inception cohort of first-episode psychoses and comparison with two-year follow-up (1980-1982) of the Determinants of Outcome of Severe Mental Disorders (DOSMED) Nottingham cohort. RESULTS: On most outcome measures, non-affective psychoses had a worse outcome than affective psychoses. Affective psychoses had better outcome than previously reported. Substance-related psychoses had very poor occupational outcome. Similar proportions of the current and DOSMED cohort were in remission but the former were rated as having greater disability. CONCLUSIONS: In a modern community service, 30-60% of patients with first-episode psychoses experience a good three-year outcome. The ICD-10 criteria have good predictive validity.

Activities of Daily Living↗
PubMed2000

Assessing effectiveness of treatment of depression in primary care. Partially randomised preference trial.

BACKGROUND: There is a mismatch between the wish of a patient with depression to have counselling and the prescription of antidepressants by the doctor. AIMS: To determine whether counselling is as effective as antidepressants for depression in primary care and whether allowing patients to choose their treatment affects their response. METHOD: A partially randomised preference trial, with patients randomised to either antidepressants or counselling or given their choice of either treatment. The treatment and follow-up were identical in the randomised and patient preference arms. RESULTS: There were 103 randomised and 220 preference patients in the trial. We found: no differences in the baseline characteristics of the randomised and preference groups; that the two treatments were equally effective at 8 weeks, both for the randomised group and when the randomised and patient preference groups for a particular treatment were combined; and that expressing a preference for either treatment conferred no additional benefit on outcome. CONCLUSIONS: These data challenge several assumptions about the most appropriate treatment for depression in a primary care setting.

Adolescent↗
PubMed2000

Regulatory roles of zinc in matrix vesicle-mediated mineralization of growth plate cartilage.

Zinc (Zn2+) has long been known to play important roles in mineralization and ossification of skeletal tissues, but the mechanisms of Zn2+ action are not well understood. In this study we investigated the effects of Zn2+ on mineralization in a cell culture system in which terminal differentiation and mineralization of hypertrophic growth plate chondrocytes was induced by retinoic acid (RA) treatment. Addition of Zn2+ to RA-treated cultures decreased mineralization in a dose-dependent manner without affecting alkaline phosphatase (APase) activity. Characterization of matrix vesicles (MVs), particles that initiate the mineralization process, revealed that vesicles isolated from RA-treated and RA/Zn2+-treated cultures showed similar APase activity, but vesicles from RA/Zn2+-treated cultures contained significantly less Ca2+ and Pi. MVs isolated from RA-treated cultures were able to take up Ca2+ and mineralize in vitro, whereas vesicles isolated from RA/Zn2+-treated cultures were not able to do so. Detergent treatment, which ruptures the MV membrane and exposes preformed intravesicular Ca2+-Pi-phospholipid complexes, did not restore the Ca2+ uptake abilities of MVs isolated from RA/Zn2+-treated cultures, suggesting that vesicles from RA/Zn2+-treated cultures did not contain functional Ca2+-Pi-phospholipid complexes. Zn2+ treatment did not affect the content of annexins II, V, and VI in MVs or the Ca2+-dependent, EDTA-reversible binding of these molecules to the membrane surface. However, Zn2+ treatment did affect the EDTA-nonreversible binding of these molecules to the MV membrane, suggesting that Zn2+ interferes with the assembly of annexins in the MV membrane. In addition, Zn2+ inhibited annexin II-, V-, and VI-mediated Ca2+ influx into liposomes. In conclusion, Zn2+ inhibits the mineralizing competence of intravesicular Ca2+-Pi-phospholipid complexes and function of annexin channels, thereby controlling Ca2+ influx into MVs, the formation of the first crystal phase inside the vesicles and initiation of mineralization.

Animals↗
PubMed1999

Utility of cytokeratin 7 and 20 subset analysis as an aid in the identification of primary site of origin of malignancy in cytologic specimens.

This study was undertaken to assess the utility of combined cytokeratin (CK) 7/20 immunoprofile determination in malignant cytologic cell blocks as an aid to the identification of tumor primary site of origin. Fifty-one cases in which CK 7/20 immunocytochemistry was performed as part of the initial workup were retrieved. Their contribution to the final cytologic diagnosis of tumor primary site of origin was analyzed. CK reactivity patterns were 7+/20- (n = 34), 7-/20+ (n = 9), 7-/20- (n = 7), and 7+/20+ (n = 1). The CK 7+/CK 20- immunophenotype was the most common one obtained, and due to its wide expression in a number of common carcinomas, the least informative. The second most common immunophenotype was CK 7-/20+, which is associated with colorectal origin, and as such was very useful when obtained. The CK immunoprofile was more useful in the setting of a prior carcinoma, being a major diagnostic determinant in 13 cases (55%) from group 1 (those with a prior history of malignancy), compared to 8 cases (29%) from group 2 (those with no prior history of malignancy). In the setting of prior carcinoma, the CK immunoprofile is most useful when carcinomas under consideration have different expected immunoprofiles (e.g., CK 7+/CK20- carcinomas, including lung, breast, ovary, endometrium, and others, vs. CK 7-/CK 20+ carcinomas, primarily colorectal). When similar immunoprofiles are obtained, their usefulness is greater if they are immunoprofiles other than the most common 7+/20- pattern. Similarly, in newly diagnosed carcinomas, the CK immunoprofile either helps to narrow the differential diagnosis or points to a specific diagnosis.

Biomarkers↗
PubMed1999

Markers of inappropriate placement in acute psychiatric inpatient care: a five hospital study.

BACKGROUND: Previous researchers in the UK have measured the prevalence of the 'inappropriateness' of acute adult psychiatric inpatient placements by eliciting the judgements of health professionals. We extended the methodology by identifying inpatient sub-groups with stable characteristics that were associated with elevated risk of inappropriate placement, and by calculating the level of that risk. METHODS: A 1-day census was taken in five hospitals. Using a structured instrument, consultant psychiatrists recorded judgements on current placements, recommended alternative placements and stated why alternatives had not been used. Judgements were obtained for 100% of the 261 inpatients. Risk ratios and adjusted odds ratios were calculated to identify sub-groups that were at high risk. RESULTS: Eighty-eight inpatients were inappropriately placed, a point prevalence of 34% (95% CI 28-40%). Consultants recorded that services outside hospital, if available, could have supported most of these inpatients as an alternative to at least part of their hospital stay. Diagnostic rather than socio-demographic or administrative characteristics, in particular primary diagnoses of substance-related disorder, personality disorder, anxiety/stress, and schizophrenia with co-morbid substance misuse, were the strongest markers of elevated risk. CONCLUSIONS: The point prevalence of inappropriate placement within the British mental health-care system is considerable. Diagnostic categories are reasonable pragmatic markers. Further research should aim to identify a strong marker of risk within the numerically large sub-group of schizophrenia without substance misuse.

Adolescent↗
PubMed1999

Outcome for children with relapsed acute myeloid leukaemia following initial therapy in the Medical Research Council (MRC) AML 10 trial. MRC Childhood Leukaemia Working Party.

Between May 1988 and March 1995, 359 children with acute myeloid leukaemia (AML) were treated in the MRC AML 10 trial. Three risk groups were identified based on cytogenetics and response to treatment. One hundred and twenty-five children relapsed--103 in the bone marrow only, 12 in the bone marrow combined with other sites, and six had isolated extramedullary relapses (site was not known in four cases). Eighty-seven children received further combination chemotherapy, one all-trans retinoic acid for acute promyelocytic leukaemia, and one a matched unrelated donor allograft in relapse, and 61 achieved a second remission. One patient with no details on reinduction therapy also achieved second remission. Treatment in second remission varied--44 children received a BMT (22 autografts, 12 matched unrelated donor allografts, 10 family donor allografts), and 17 were treated with chemotherapy alone. The overall survival rate for all children (treated and untreated) was 24% at 3 years, with a disease-free survival of 44% for those achieving a second remission. Length of first remission was the most important factor affecting response rates--children with a first remission of less than 1 year fared poorly (second remission rate 36%, 3 year survival 11%), whereas those with longer first remissions had a higher response rate (second remission rate 75%, 3 year survival 49%, P < 0.0001).

Acute Disease↗
PubMed1999

Use of standardized flow cytometric determinants of multidrug resistance to analyse response to remission induction chemotherapy in patients with acute myeloblastic leukaemia.

We have used a combination of flow cytometric assays to define multidrug resistance (MDR) positive and negative blasts in cryopreserved samples from 47 MRC trial patients with acute myeloblastic leukaemia (AML). Our primary test is a standardized assay for daunorubicin accumulation. Confirmatory assays for MDR comprised the cyclosporin modulation assay for rhodamine-123 uptake as a measure of functional P-glycoprotein and the measurement of lung resistance protein and multidrug resistance associated protein (with LRP-56 and MRPr1 respectively). 57% of samples had both low accumulation and at least one positive confirmatory test. 32% were MDR negative in all four assays. 15% of patients had primary chemo-resistant disease. Resistant disease rates were 22% for confirmed MDR-positive patients and 0% for confirmed MDR-negative patients (P=0.07). Complete remission was achieved in 74% of patients, with rates of 63% in confirmed MDR-positive patients and 93% in confirmed MDR-negative patients (P=0.06). The use of a standardized method for daunorubicin uptake, combined with the use of confirmatory tests, should reduce the uncertainty that is currently characteristic of MDR evaluation in leukaemia. In comparison with daunorubicin uptake, p-gp expression, measured using MRK-16 antibody, was more closely associated with remission rates (P =0.01). This suggests an additional role for p-glycoprotein in mediating drug resistance beyond that of a drug efflux pump.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Phase II trial of radical surgery for locally advanced pelvic neoplasia.

BACKGROUND: Reported operative mortality and survival rates following total pelvic exenteration (TPE) for recurrent pelvic neoplasia are now as good as those for many primary treatments. The currently accepted primary treatments for these tumours are, however, still either radiotherapy alone or radiotherapy and chemotherapy. The primary aim of this study was to evaluate the safety and tolerability of TPE and secondarily to ascertain survival after TPE. METHODS: This was a phase II study of 50 patients with locally advanced pelvic tumours who underwent TPE. RESULTS: Thirty-two patients (64 per cent) underwent TPE for recurrent carcinoma of the cervix, seven (14 per cent) for rectal cancer, three (6 per cent) for vulval carcinoma, three (6 per cent) for vaginal carcinoma, two (4 per cent) for prostate cancer and three (6 per cent) for other tumours. The 30-day mortality rate was 8 per cent with an in-hospital mortality rate of 16 per cent. The crude morbidity rate was 62 per cent, with 23 patients (46 per cent) having grade III or IV toxicity. A complete response was achieved in 63 per cent and a partial response in 37 per cent of patients. The overall median survival time was 86 weeks; it was 111 weeks in patients in whom a complete response was achieved. CONCLUSION: The survival and operative mortality rates that are now attainable with TPE are comparable to those achieved with chemoradiotherapy in advanced pelvic neoplasia. TPE should no longer be reserved for salvage therapy and should perhaps be compared with chemoradiotherapy as first-line treatment in a phase III randomized trial in patients with these tumours.

Adult↗
PubMed1999

Improved outcome of acute myeloid leukaemia in Down's syndrome.

OBJECTIVE: To review the clinical features, treatment, and outcome of children in the UK with Down's syndrome and acute myeloid leukaemia (AML). DESIGN: A retrospective study of 59 children with Down's syndrome and AML presenting between 1987 and 1995. Data were obtained from hospital case notes, trial records, and by questionnaire. RESULTS: The patients were unusually young (median age, 23 months) with a predominance of megakaryoblastic AML. Two of the seven infants who presented with abnormal myelopoesis aged 2 months or younger achieved complete spontaneous remission. Most of the older children with AML (32 of 52) were treated on recognised intensive protocols but 13 received individualised treatment and seven symptomatic treatment alone. Only four received a bone marrow transplant (BMT) in first remission. For the 45 older children who received chemotherapy the overall survival was 55% (median follow up 4.5 years). Patients on individualised protocols had a similar overall survival and toxic death rate but marginally higher relapse rate than those on standard (intensive) protocols. Children with Down's syndrome treated on the national AML 10 trial had a similar overall survival (70% v 59%) at five years to children of comparable age without Down's syndrome: their improved relapse risk (12% v 38%) offset the slight increase in deaths as a result of treatment toxicity (19% v 11%). CONCLUSION: Neonates with Down's syndrome and abnormal myelopoesis may achieve spontaneous remission, and older children with Down's syndrome and AML can be treated successfully with intensive chemotherapy, without BMT.

Acute Disease↗
PubMed1999

Prevalence of substance misuse in first-episode psychosis.

BACKGROUND: Reports suggest a high prevalence of substance misuse in psychotic disorders but few studies examine comorbidity at onset of psychosis. AIMS: To identify the prevalence and pattern of substance use and misuse in first-episode psychosis, and relationships with diagnosis, mode of presentation and demographic variables. METHOD: Consensus diagnoses for 168 subjects presenting with first-episode psychosis were made using ICD-10 diagnostic criteria. Information on substance use and misuse was obtained from multiple sources. We examined associations between substance misuse, diagnosis and demographic factors. RESULTS: Criteria for drug use, drug misuse or alcohol misuse were met by 37% of the sample. One-year prevalence rates were 19.5% (drug misuse) and 11.7% (alcohol misuse). Thirteen subjects (8.4%) received a primary diagnosis of substance-related psychotic disorder; a significant increase compared with an earlier cohort from the same catchment area. Drug misuse was associated with younger age of onset of psychosis, male gender and non-African-Caribbean ethnicity. CONCLUSIONS: This study confirms high rates of substance misuse at onset of psychosis. There is evidence for an increase in diagnosis of substance-related psychotic disorders over time. Those most at risk of substance misuse are young males.

Adolescent↗
PubMed1999

Evaluating the Health of the Nation Outcome Scales. Reliability and validity in a three-year follow-up of first-onset psychosis.

BACKGROUND: The HoNOS has been developed as a routine measure of outcomes in mental health. AIMS: To explore the validity and interrater reliability of HoNOS in a first-onset psychosis follow-up study. METHOD: Between 1992 and 1994 we ascertained a cohort of all persons with first-onset psychosis. We re-assessed these people at 3 years (n = 166) with several outcome scales, including HoNOS. Patients' keyworkers also completed the HoNOS. We estimated concurrent validity by calculating correlations between HoNOS and other scales, and interrater reliability. RESULTS: Researcher HoNOS correlated highly with other scales (0.46 < p < 0.86; P < 0.001). Keyworker HoNOS correlations were lower (0.41 < p < 0.51; P < 0.05), but still significant for all scores except the HoNOS-social subscale (0.12 < p < 0.28). Agreements between researcher and keyworker HoNOS were modest (0.47 < ICC < 0.85). CONCLUSIONS: In this research cohort HoNOS correlates well with established outcome scales. Keyworker ratings show similar, but weaker, relationships; its use in routine settings may require further training for calibration of severity.

Adult↗
PubMed1999

Outcome of psychosis in people of African-Caribbean family origin. Population-based first-episode study.

BACKGROUND: An increased incidence of psychotic disorders has repeatedly been reported among African-Caribbeans in the UK. AIMS: To test whether the increased incidence of psychotic disorders in first- and second-generation African-Caribbeans in the UK could be caused by a relative excess of affective-related psychoses with good prognosis. METHOD: Thirty-three patients of African-Caribbean family origin identified in a population-based study of first-episode psychoses were compared with the remaining cases. Three-year outcomes and patterns of course were compared. RESULTS: There was a trend for better outcomes in African-Caribbean patients for symptoms and social disability, but patterns of course were similar (odds ratio = 0.9 (0.50 to 2.00)) [corrected]. Pattern of course improved after adjustment for confounding by gender, social class, age, diagnosis and duration of untreated illness (odds ratio = 0.59 (0.21 to 1.66)) [corrected]. Diagnostic profiles were similar, with no evidence of greater diagnostic instability in the African-Caribbean group. CONCLUSION: Pattern of course of psychosis did not differ significantly by ethnic family background. An excess of good-prognosis affective psychoses is an unlikely explanation for increased rates of psychosis in African-Caribbeans.

Adolescent↗
PubMed1999

Diagnostic stability of first-episode psychosis. Comparison of ICD-10 and DSM-III-R systems.

BACKGROUND: The temporal stability of a diagnosis is one measure of its predictive validity. AIMS: To measure diagnostic stability in first-episode psychosis using ICD-10 and DSM-III-R. METHOD: Between 1992 and 1994 we ascertained a cohort of persons with first-episode psychosis (n = 168), assigning to each a consensus diagnosis. At three-year follow-up, longitudinal consensus diagnoses, blind to onset diagnoses, were made. Stability was measured by the positive predictive values (PPVs) of onset diagnoses. For onset schizophrenia, we also calculated sensitivity, specificity and concordance (kappa). RESULTS: First-episode ICD-10 and DSM-III-R schizophrenia had a PPV of over 80% at three years. Over one-third of cases with ICD-10 F20 schizophrenia at three years had non-schizophrenia diagnoses at onset. Manic psychoses showed the highest PPV (91%). For onset schizophrenia, both systems had high specificity (ICD-10: 89; DSM-III-R: 93%), but low sensitivity (ICD-10: 64%; DSM-III-R: 51%) and moderate concordance (ICD-10: 0.54; DSM-III-R: 0.46). CONCLUSIONS: Bipolar disorders and schizophrenia showed the highest stability. DSM-III-R schizophrenia did not have greater stability than ICD-10 schizophrenia.

Adolescent↗