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Biomedical subjects

G Harrison

Publications and source records attributed to G Harrison.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1997

Incidence of schizophrenia in Nottingham. A comparison of two cohorts, 1978-80 and 1992-94.

BACKGROUND: Several studies have reported a decline of up to 50% in the incidence of schizophrenia over recent decades. We aimed to measure changes in the incidence and diagnostic patterns of first-episode psychosis by comparing two Nottingham cohorts, identified in two equal periods separated by 14 years. METHOD: Two prospectively ascertained cohorts of first-episode psychotic disorder were identified over the time periods 1978-80 and 1992-94. The earlier cohort was of the World Health Organization Determinants of Outcome of Severe Mental Disorder (DOSMD) ten-country study. The later cohort was obtained using similar methodology. Both groups were diagnosed using ICD-10 diagnostic criteria and age-standardised incidence rates were compared. RESULTS: The standardised incidence rate for all psychotic disorders rose slightly from 2.49 to 2.87 per 10000 population per year, but the F20 classification fell significantly by over a third (1.41 to 0.87 per 10000 per year). The second study group (1992-1994) included a greater diversity of psychotic diagnoses compared with the first, in particular an increased proportion of acute and drug-related psychoses. CONCLUSIONS: Methodological considerations call for caution in interpreting such data, but we conclude that the significant fall in the narrowly defined diagnostic category of schizophrenia reflects a real change in the syndromal presentation of psychotic disorders.

Adolescent↗
PubMed1997

The Ty1-copia group of retrotransposons in plants: genomic organisation, evolution, and use as molecular markers.

The genomic organisation and diversity of the Ty1-copia group retrotransposons has been investigated in several crop plants and their relatives from both dicotyledonous and monocotyledonous families, including potato (Solanum tuberosum), faba beans (Vicia faba), Vicia melanops, Vicia sativa, barley (Hordeum vulgare), rye (Secale cereale), and onion (Allium cepa). Extreme heterogeneity in the sequence of the Ty1-copia retrotransposons from all these plants was revealed following sequence analysis of reverse transcriptase fragments. The estimated copy numbers of the Ty1-copia group retrotransposons for the genomes of S. tuberosum, L. esculentum, A. cepa, S. cereale, and V. faba is highly variable, ranging from a few hundred to approximately a million copies per genome. In situ hybridisation data from metaphase and prophase chromosomes of V. faba, S. cereale, and H. vulgare suggest that retrotransposon sequences are dispersed throughout the euchromatic regions of the genome but are almost undetectable in most heterochromatic regions. In contrast, similar data from metaphase chromosomes of A. cepa suggests that although retrotransposon sequences are dispersed throughout the euchromatic regions of the genome, they are predominantly concentrated in the terminal heterochromatin. These results are discussed in the context of the role played by the Ty1-copia group retrotransposons in the evolution of the plant genome. Lastly, the application of retrotransposon sequences as genetic markers for mapping genomes and for studying genetic biodiversity in plants is presented.

Chromosome Mapping↗
PubMed1996

The Ty1-copia group retrotransposons in Vicia species: copy number, sequence heterogeneity and chromosomal localisation.

We present an in-depth study of the Ty1-copia group of retrotransposons within the plant genus Vicia, which contains species with widely differing genome sizes. We have compared the numbers and sequence heterogeneities of these genetic elements in three diploid Vicia species chosen to represent large (V. faba, 1C = 13.3 pg), medium (V. melanops, 1C = 11.5 pg) and small (V. sativa, 1C = 2.3 pg) genomes within the genus. The copy numbers of the retrotransposons are all high but vary greatly, with V. faba containing approximately 10(6) copies, V. melanops about 1000 copies and V. sativa 5000 copies. The degree of sequence heterogeneity of Ty1-copia group elements correlates with their copy number within each genome, but neither heterogeneity nor copy number are related to the genome size of the host. In situ hybridization to metaphase chromosomes shows that the retrotransposons in V.faba are distributed throughout all chromosomes but are much less abundant in certain heterochromatic regions. These results are discussed in the context of plant retrotransposon evolution.

Amino Acid Sequence↗
PubMed1996

Variability of post-void residual urine volume in the elderly.

Residual urine volume, though clinically important as a diagnostic tool, is reported to be variable and unreliable. Variability was examined among 14 geriatric patients, mean age 77 years. Residual urine was measured by ultrasound at three different times of day on each of two visits separated by 2-4 weeks. Results were examined by analysis of variance. Mean residual urine was 154 ml. Between-patient variability was large [standard deviation (SD) 246 ml]. There was no significant difference between values in men and women, nor between visits. Within-patient variability was large because of a large systematic variation with time of day (SD 128 ml), with greatest volumes in the early morning. The inherent, random variability of the measurement was much smaller than this (SD 44 ml). If the physiological factors causing the temporal variation could be controlled, more reproducible measurements would be possible.

Aged↗