Biomedical subjects

G Harrison

Publications and source records attributed to G Harrison.

At least 55 records · Page 3Linked to original sources

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↗

PubMed1998

The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties.

Cytogenetics is considered one of the most valuable prognostic determinants in acute myeloid leukemia (AML). However, many studies on which this assertion is based were limited by relatively small sample sizes or varying treatment approach, leading to conflicting data regarding the prognostic implications of specific cytogenetic abnormalities. The Medical Research Council (MRC) AML 10 trial, which included children and adults up to 55 years of age, not only affords the opportunity to determine the independent prognostic significance of pretreatment cytogenetics in the context of large patient groups receiving comparable therapy, but also to address their impact on the outcome of subsequent transplantation procedures performed in first complete remission (CR). On the basis of response to induction treatment, relapse risk, and overall survival, three prognostic groups could be defined by cytogenetic abnormalities detected at presentation in comparison with the outcome of patients with normal karyotype. AML associated with t(8;21), t(15;17) or inv(16) predicted a relatively favorable outcome. Whereas in patients lacking these favorable changes, the presence of a complex karyotype, -5, del(5q), -7, or abnormalities of 3q defined a group with relatively poor prognosis. The remaining group of patients including those with 11q23 abnormalities, +8, +21, +22, del(9q), del(7q) or other miscellaneous structural or numerical defects not encompassed by the favorable or adverse risk groups were found to have an intermediate prognosis. The presence of additional cytogenetic abnormalities did not modify the outcome of patients with favorable cytogenetics. Subgroup analysis demonstrated that the three cytogenetically defined prognostic groups retained their predictive value in the context of secondary as well as de novo AML, within the pediatric age group and furthermore were found to be a key determinant of outcome from autologous or allogeneic bone marrow transplantation (BMT) in first CR. This study highlights the importance of diagnostic cytogenetics as an independent prognostic factor in AML, providing the framework for a stratified treatment approach of this disease, which has been adopted in the current MRC AML 12 trial.

Acute Disease↗

PubMed1998

Perceived ethnicity and the risk of compulsory admission.

Black-Caribbean patients are more often admitted compulsorily to psychiatric wards than patients from other ethnic groups. We tested the hypothesis that perceived ethnicity of a patient had no independent effect on the risk of compulsory admission. For all consecutive admissions over a 6-month period to acute psychiatric wards in Nottingham, medical officers responsible for the decision to admit completed a questionnaire recording clinical details of the patients and reasons for admission. The results showed that 43.2% of Black-Caribbean patients and 18.8% of White patients were admitted compulsorily (unadjusted odds ratio 3.29, 95% CI 1.71-6.33). Perceived ethnicity (Black-Caribbean) was significantly associated with being young, receiving a diagnosis of psychosis, and being perceived to be at a risk of violent acting out. A forced entry logistic regression model was used to adjust for hypothesised confounding variables such as age, sex, diagnosis, risk, socio-economic status and level of social support. A diagnosis of psychosis, risk of committing violence and being Black-Caribbean had independent effects on the risk of being compulsorily detained. The odds ratio for compulsory detention of Black-Caribbean patients was 2.16 (95% CI 1.03-4.52) after adjusting for the hypothesised confounding variables.

Adolescent↗

PubMed1998

Quantos somos? The second national population census of Mozambique.

"Between 1 and 15 of August [1997], Mozambique had its second country-wide population census. This briefing will outline how the census ran--an operation of considerable scale in an extremely poor and war-damaged country--and will also raise some broader questions which relate the census to Mozambique's contemporary politics."

Africa↗

PubMed1998

Adjunctive use of inhaled nitric oxide during implantation of a left ventricular assist device.

BACKGROUND: The aim of this study was to evaluate the efficacy of inhaled nitric oxide in the prevention and reversal of pulmonary hypertension during and after left ventricular assist device implantation. METHODS: Inhaled nitric oxide (20 ppm) was administered to seven consecutive patients undergoing implantation of a left ventricular assist device at the time of implantation and for the first 24 hours after operation. RESULTS: Withdrawal of inhaled nitric oxide at 24 hours after operation was associated with a significant rise in both the transpulmonary gradient (from 8+/-1 to 14+/-2 mm Hg, p < 0.01) and in pulmonary vascular resistance (from 110+/-19 to 196+/-32 dynes x sec x cm[-5], p < 0.01). In two patients, the rise in pulmonary vascular resistance resulted in a critical fall in left ventricular assist device flow and hemodynamic deterioration, necessitating urgent reinstitution of inhaled nitric oxide. CONCLUSION: The administration of inhaled nitric oxide at the time of left ventricular assist device implantation prevents rises in pulmonary vascular resistance that in some patients result in critical reductions in left ventricular assist device flow. We suggest that inhaled nitric oxide is a useful adjunctive treatment that should be routinely available at the time of left ventricular assist device implantation.

Administration, Inhalation↗

PubMed1997

Structural and functional characterisation of two proteolytic fragments of the bacterial protein toxin, pneumolysin.

Proteolytic cleavage of the bacterial protein toxin pneumolysin with protease K creates two fragments of 37 and 15 kDa. This paper describes the purification of these two fragments and their subsequent physical and biological characterisation. The larger fragment is directly involved in the cytolytic mechanism of this pore-forming protein, via membrane binding and self-association. The smaller fragment lacks ordered structure or discernible activity.

Bacterial Proteins↗

PubMed1997

Annexin V-mediated calcium flux across membranes is dependent on the lipid composition: implications for cartilage mineralization.

Annexin V is a major component of matrix vesicles and has a role in mediating the influx of Ca2+ into these vesicles, thus promoting the initiation of hypertrophic cartilage matrix mineralization. However, the mechanisms and factors regulating annexin V-mediated Ca2+ influx into these vesicles are not well understood. Since the lipid composition of matrix vesicles differs from that of the plasma membrane of chondrocytes and is rich in phosphatidylserine, we asked whether the lipid composition may regulate annexin V function. We prepared liposomes containing different concentrations of phosphatidylserine and determined how the lipid composition affected (a) the interactions between annexin V and liposomes and (b) annexin V-mediated Ca2+ influx into the liposomes. We found that annexin V was able to bind to every liposome tested. However, we observed the most prominent increases in tryptophan 187 emission intensity, a measure of the degree of interactions between annexin V and lipid bilayers, only with liposomes containing a high concentration of phosphatidylserine. In addition, a significant fraction of annexin V associated with phosphatidylserine-rich liposomes was not extractable by EDTA treatment but required a detergent, indicating that annexin V inserts into bilayers of these liposomes. Chemical cross-linking analysis revealed that matrix vesicles and phosphatidylserine-rich liposomes induced the formation of the annexin V hexamer. Interestingly, a significant Ca2+ influx in the presence of annexin V occurred only in liposomes containing a high phosphatidylserine content. Moreover, annexin V-mediated Ca2+ influx into these liposomes was inhibited (i) by anti-annexin V antibodies and (ii) by treatment with zinc and cadmium, indicating the essential role of the protein in Ca2+ influx. The results of this study indicate that phosphatidylserine-rich bilayers induce the formation of a hexameric annexin V, possibly leading to a Ca2+-dependent insertion of annexin V into the bilayer and establishment of annexin V-mediated Ca2+ influx into matrix vesicles or liposomes. The phosphatidylserine-rich membrane of matrix vesicles in vivo may thus offer an ideal specialized environment in which the biological function of annexin V is optimized, leading to rapid Ca2+ influx, intralumenal crystal growth, and cartilage matrix mineralization.

Animals↗

PubMed1997

Increased incidence of psychotic disorders in migrants from the Caribbean to the United Kingdom.

BACKGROUND: Several studies have replicated the finding of increased incidence of schizophrenia and related psychoses in first and second generation migrants from the Caribbean. The finding has remained consistent in studies employing different methods, but concern has been expressed about indirect methods of calculating the population at risk. This study aims to overcome these short-comings. METHOD: A further prospective study was undertaken in Nottingham assembling an inception cohort of psychotic patients (N = 168) presenting from a defined catchment area. The 1991 census, which includes codings for self-ascribed ethnic origin, was used to calculate the denominator, employing correction factors for potential under-enumeration. Case-ascertainment was based upon all service contacts and subjects had in-depth assessments including the SCAN. Collateral history was obtained from informants. RESULTS: Subjects born in the Caribbean, or who had one or both parents born in the Caribbean, had a greatly elevated risk (incidence ratios above 7) for all psychotic disorders and for ICD-10 (DCR)-defined F20 Schizophrenia. CONCLUSIONS: The size of the increase and the methodological safeguards employed support the validity of this now highly replicated finding. A personal or family history of migration from the Caribbean is a major risk factor for psychosis; the consistency of this finding justifies a systematic evaluation of potential aetiological factors. Any hypothesis derived from the evidence so far must explain: increased incidence in first and second generation migrants; increased risk for all psychoses (including affective psychoses); and an effect specifically associated with a migration history from the Caribbean to Northern Europe.

Adolescent↗

PubMed1997

Continuing (maintenance) therapy in lymphoblastic leukaemia: lessons from MRC UKALL X. Medical Research Council Working Party in Childhood Leukaemia.

The relationship between the prescribed dose of drugs during continuing (maintenance) therapy, the degree of marrow suppression caused, and subsequent event-free survival was examined in a cohort of 740 children with lymphoblastic leukaemia treated on MRC UKALL X. Girls, younger children, and patients who had received intensification treatment, were prescribed lower doses of mercaptopurine, became neutropenic more readily, and had more interruptions of treatment. Children who had one or more episodes of neutropenia with a count of <0.5 x 10(9)/l had a better prognosis than those who never became neutropenic. We conclude that early intensification treatment influences the probability of neutropenia during continuing treatment and that patients exhibiting myelosuppression during this phase of treatment have a better chance of prolonged remission.

Adolescent↗

PubMed1997

Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA. MRC Adult Leukaemia Working Party.

Cytogenetic classification of 350 adults with acute lymphoblastic leukaemia on MRC UKALL XA trial showed the following statistically significant associations: t(9;22) (11%) increased with increasing age and leucocyte counts (WBC) and most had a C/pre-B immunophenotype. t(4;11) (3%) was associated with higher WBCs, increasing age and null immunophenotype. Other abnormalities of 11q (abn11q) (4%) were associated with male sex and T-cell ALL. High hyperdiploidy (7%) and abn9p (5%) decreased with increasing WBC. High hyperdiploid patients were younger and tended to have C/pre-B ALL. Triploidy/tetraploidy (3%) decreased and pseudodiploidy (11%) increased with increasing WBC. Cytogenetic classification was prognostically important (chi-square for heterogeneity of classification = 53.56; P < 0.0001) and added significance to age, sex and WBC. A poor prognosis for patients classed as t(9;22) (13% disease-free survival at 3 years), as t(4;11) 24% at 3 years) and hypodiploid (11% at 3 years), and good prognosis for abn12p (4% of subjects) and high hyperdiploidy (74% and 59% at 3 years respectively) were statistically significant, but the 54% 3-year disease-free survival for patients with t(1;19) was not. The prognosis of patients classed as t(9;22) was independent of other single variables. Abn12p, abnormalities of 11q (including t(4;11) cases) and hypodiploidy added prognostic significance to all other variables combined.

Adolescent↗

PubMed1997

Characterization and genomic organization of Ty1-copia group retrotransposons in rye (Secale cereale).

The genomic organisation of the Ty1-copia retrotransposons in rye (Secale cereale) has been studied. We have used the polymerase chain reaction (PCR) to amplify sequences from a conserved domain of the reverse transcriptase gene of the Ty1-copia retrotransposons in this species. Sequence analysis of 26 of these PCR products shows them to be a highly heterogeneous population, a feature that is common in plants. Slot blot analysis shows that there are about 100,000 individual Ty1-copia retrotransposons in rye. In situ hybridization of a heterogeneous probe, representing the whole population of rye Ty1-copia retrotransposon sequences, to chromosome spreads of triticale (xTriticosecale), a rye-wheat hybrid, shows that these sequences are present throughout all the rye chromosomes but absent from the centromeric regions and, in particular, from the terminal heterochromatin. Southern analysis of oat, barley, wheat, and rye, using as a probe R9, one of the rye sequences that is closely similar to the BARE-1 element of barley, shows that close relatives of this retrotransposon subgroup are present in all these species in high copy number. Northern analysis on RNAs from seedlings shows that the BARE-1 subgroup is transcribed in all these cereal plants but in variable amounts: high in barley, moderate in wheat and rye, and extremely low in oat.

Amino Acid Sequence↗

PubMed1997

The Nottingham Acute Bed Study: alternatives to acute psychiatric care.

BACKGROUND: Although modern psychiatric services seek alternatives to hospitalisation wherever appropriate, the national trend toward higher bed occupancies on acute psychiatric wards has refocused attention on community-based alternatives and methods of assessing reed for acute care. METHOD: We surveyed key decision makers in a community-oriented district service with a low acute psychiatric bed to population ratio, in order to examine alternatives to hospitalisation in a cohort of consecutive admissions over a six-month period. RESULTS: Alternatives to acute ward hospitalisation were identified for 29% of admissions, and for 42% of those with an admission duration of more than 60 days. Residential options were chosen more often than intensive community support. Simulated bed day savings were considerable. CONCLUSIONS: In a community-oriented service, key decision-makers could identify further alternatives to acute ward hospitalisation, although relatively few non-residential, community support options were chosen. Although this methodology has limitations, data based upon keyworker judgements probably have greater local 'ownership', and the option appraisal process itself may challenge stereotyped patterns of resource use.

Acute Disease↗

PubMed1997

The predictive validity of a diagnosis of schizophrenia. A report from the International Study of Schizophrenia (ISoS) coordinated by the World Health Organization and the Department of Psychiatry, University of Nottingham.

BACKGROUND: Outcome is important in the validation of psychiatric diagnosis, as most disorders lack clinicopathological correlates. We describe the predictive validity of four definitions of schizophrenia (DSM-III-R, ICD-10, ICD-9 and CATEGO S+), in a representative cohort of patients selected during their first episode of psychosis. METHOD: Each definition of schizophrenia was applied to 99 patients. Their respective ability to predict 13-year outcome (Global Assessment of Functioning scales) was assessed. RESULTS: DSM-III-R and ICD-10 diagnoses of schizophrenia have high predictive validity for long-term outcome, and both provide relatively stable diagnoses. ICD-9 is reasonably good at predicting disability, but not symptoms, and CATEGO S+ showed no predictive validity. Adding six-month duration criteria to ICD-10, ICD-9 and CATEGO S+ improved their predictive validity, and removing the six-month duration criterion from DSM-III-R commensurately reduced predictive validity. CONCLUSIONS: Modern diagnostic systems (DSM-III-R and ICD-10) have high predictive validity, and are superior to ICD-9. The six-month duration criterion of DSM-III-R schizophrenia accounts for its predictive validity and stability over 13 years, but restricts its use in first-episode studies. The one-month duration criterion of ICD-10 is less restrictive, without major compromises in predictive validity or stability.

Adolescent↗