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Biomedical subjects

M Hann

Publications and source records attributed to M Hann.

At least 19 recordsLinked to original sources
PubMed2005

Dynamics of bone marrow changes in patients with chronic idiopathic myelofibrosis following allogeneic stem cell transplantation.

Scant knowledge exists about the dynamics of fibro-osteosclerotic bone marrow (BM) lesions and regeneration of hematopoiesis following allogeneic peripheral stem cell transplantation (SCT) in chronic idiopathic myelofibrosis. Therefore, an immunohistochemical and morphometric study was performed on BM biopsies in 20 patients before and at standardized intervals (days 30 through 384) following SCT. In responding patients, a total regression of the pretransplant increased fibrosis was completed in the posttransplant period after about six months, while the extent of osteosclerosis did not change significantly during observation time. The quantity of CD61+ megakaryocytes including precursors was strikingly variable after SCT and, by using planimetric methods, atypical microforms exhibiting a dysplastic aspect could be demonstrated. These anomalies may be responsible for posttransplant thrombocytopenia. CD34+ progenitor cells were increased before transplantation, however, their number declined rapidly to normal values in responding patients. Nucleated erythroid precursors revealed a decreased amount before and after SCT accounting for anemia. Large clusters of this cell lineage indicated an initial hematopoietic reconstitution comparable with the expansion of the neutrophil granulopoiesis. Proliferative activity and apoptosis showed an increase until one year after SCT that implied a still regenerating hematopoiesis in keeping with an enhanced cell turnover.

Adolescent↗
PubMed2004

Prescribing patterns in high-need Health Authority populations: how does an ethnically mixed composition affect volume and cost?

BACKGROUND: Prescribing is the most common therapeutic intervention in primary care, and there is substantial variation in prescribing practice across England. We investigate broad patterns of prescribing across Health Authorities in England, concentrating on ethnically diverse populations. METHODS: Initially we examined the association between a number of prescribing indicators from the Prescribing Support Unit Prescribing Toolkit and 'Needs Profiles'. We then considered whether the observed patterns of prescribing were appropriate, that is, could be largely explained by variations in the prevalence of a medical condition for which the corresponding group of drugs would be prescribed. RESULTS: The volume and cost of prescribing was generally lower in more ethnically diverse Health Authority populations when compared with more elderly or deprived populations. There was a significant negative association between ethnic composition and net-ingredient-cost per patient of cardiovascular drugs, but this disappeared upon adjusting for mortality from coronary heart disease. CONCLUSIONS: The volume and cost of prescribing was generally lower in more ethnically diverse Health Authority populations relative to other high-need population profiles. Further work on this subject matter is merited, particularly if individual level data is available.

Age Factors↗
PubMed2002

Quality assessment for three common conditions in primary care: validity and reliability of review criteria developed by expert panels for angina, asthma and type 2 diabetes.

OBJECTIVES: To field test the reliability, validity, and acceptability of review criteria for angina, asthma, and type 2 diabetes which had been developed by expert panels using a systematic process to combine evidence with expert opinion. DESIGN: Statistical analysis of data derived from a clinical audit, and postal questionnaire and semi-structured interviews with general practitioners and practice nurses in a representative sample of general practices in England. SETTING: 60 general practices in England. MAIN OUTCOME MEASURES: Clinical audit results for angina, asthma, and type 2 diabetes. General practitioner and practice nurse validity ratings from the postal questionnaire. RESULTS: 54%, 59%, and 70% of relevant criteria rated valid by the expert panels for angina, asthma, and type 2 diabetes, respectively, were found to be usable, valid, reliable, and acceptable for assessing quality of care. General practitioners and practice nurses agreed with panellists that these criteria were valid but not that they should always be recorded in the medical record. CONCLUSION: Quality measures derived using expert panels need field testing before they can be considered valid, reliable, and acceptable for use in quality assessment. These findings provide additional evidence that the RAND panel method develops valid and reliable review criteria for assessing clinical quality of care.

Angina, Unstable↗
PubMed2001

Identifying predictors of high quality care in English general practice: observational study.

OBJECTIVES: To assess variation in the quality of care in general practice and identify factors associated with high quality care. DESIGN: Observational study. SETTING: Stratified random sample of 60 general practices in six areas of England. OUTCOME MEASURES: Quality of management of chronic disease (angina, asthma in adults, and type 2 diabetes) and preventive care (rates of uptake for immunisation and cervical smear), access to care, continuity of care, and interpersonal care (general practice assessment survey). Multiple logistic regression with multilevel modelling was used to relate each of the outcome variables to practice size, routine booking interval for consultations, socioeconomic deprivation, and team climate. RESULTS: Quality of clinical care varied substantially, and access to care, continuity of care, and interpersonal care varied moderately. Scores for asthma, diabetes, and angina were 67%, 21%, and 17% higher in practices with 10 minute booking intervals for consultations compared with practices with five minute booking intervals. Diabetes care was better in larger practices and in practices where staff reported better team climate. Access to care was better in small practices. Preventive care was worse in practices located in socioeconomically deprived areas. Scores for satisfaction, continuity of care, and access to care were higher in practices where staff reported better team climate. CONCLUSIONS: Longer consultation times are essential for providing high quality clinical care. Good teamworking is a key part of providing high quality care across a range of areas and may need specific support if quality of care is to be improved. Additional support is needed to provide preventive care to deprived populations. No single type of practice has a monopoly on high quality care: different types of practice may have different strengths.

Chronic Disease↗
PubMed2001

General practitioner services in primary care groups in England: is there inequity between service availability and population need?

This study examined the coverage of minor surgery, child health surveillance and chronic disease management for asthma and diabetes in relation to population need and key organisational features of general practice in the 481 primary care groups (PCGs) in England. PCG-level summary scores were developed to estimate the relative availability of all four services and their relative importance in discriminating between high and low levels of service provision. The coverage of services was widespread and, in such circumstances, there was no systematic evidence of poorer service availability for PCGs with higher population need (the 'inverse care' law). Rather this relation was localised, being most predominant for PCGs covering London and its suburbs. In these PCGs, there was no association between indicators of lack of capacity, such as single-handed practice, and levels of service provision.

Asthma↗
PubMed2001

Methodological issues in the development of a national database for primary care groups and trusts.

At the National Primary Care Research and Development Centre (NPCRDC) we have constructed a national database for all primary care groups (PCGs) in England. At its core, the database links information about population socio-economic and demographic characteristics to generic health status and to the organisation, resourcing and activities of general practice. In this paper we describe and discuss the problems with linking these data, and with defining the boundaries and the local populations of PCGs, given that they have been established on the basis of administrative expediency rather than geographical coherence. We then consider the implications of these difficulties for needs assessment in primary care groups.

Database Management Systems↗
PubMed2000

Novel three-dimensional capillary electrophoresis system for complex and trace analysis.

A novel triple column capillary electrophoresis system is described. Design specifications facilitate method development and analyses by providing on-line, selective, pre-concentration and clean-up of both high (ml) and low (microl) volumes of specific analytes in two dimensions and separation via an additional third dimension. The system described additionally provides four distinct detection capabilities via both contactless conductivity and UV. The addition of a third dimension to the previously reported "coupled-column" systems, and further modifications made, has allowed for optimal identification, separation, and quantitation of micro-components in complex mixtures. The ability to perform both capillary zone electrophoretic and isotachophoretic separations on-line and in any combination enhances the scope for rapid analytical method development and analysis of complex or trace sample components.

Conductometry↗
PubMed2000

Symptom attribution and the recognition of psychiatric morbidity.

OBJECTIVE: Patients' interpretation of ambiguous physical symptoms may influence illness presentation in primary care. The present study sought to investigate the influence of symptom attribution style on the recognition of psychiatric morbidity by general practitioners (GPs). METHODS: Patients consulting GPs completed assessments of attribution style and General Health Questionnaires (GHQs), while GPs provided independent ratings of psychiatric distress. Analysis examined the relationship between patient demographic variables, attribution style (using the Symptom Interpretation Questionnaire [SIQ]), and GP and GHQ assessments of patients' mental health. RESULTS: The results indicate that severity of disorder and patient age were reliable predictors of recognition: normalizing and psychological attributions were additional predictors in some analyses, but their effects were inconsistent. CONCLUSIONS: The results provide some support for the role of symptom attribution in the recognition of psychiatric morbidity, but suggest that the predictive value of such attributions may be relatively modest. The SIQ may not be the optimum instrument for the measurement of attributions.

Adolescent↗
PubMed1999

Chemoinformatics--a new name for an old problem?

Library chemistry and high-throughput screening require greater use of chemoinformatics to increase their effectiveness. Recent advances in chemoinformatics include new molecular descriptors and pharmacophore techniques, statistical tools and their applications. Visualisation methods and hardware development are also opening new opportunities. The advent of a chemically aware web language and cross-platform working is ensuring that chemoinformatics methods are becoming available to all chemists in a more appropriate manner. Much time will continue to be wasted with incompatible file types without internationally agreed standards.

Chemical Phenomena↗
PubMed1999

The effect of panel membership and feedback on ratings in a two-round Delphi survey: results of a randomized controlled trial.

BACKGROUND: Past observational studies of the RAND/UCLA Appropriateness Method have shown that the composition of panels affects the ratings that are obtained. Panels of mixed physicians make different judgments from panels of single specialty physicians, and physicians who use a procedure are more likely to rate it more highly than those who do not. OBJECTIVES: To determine the effect of using physicians and health care managers within a panel designed to assess quality indicators for primary care and to test the effect of different types of feedback within the panel process. METHOD: A two-round postal Delphi survey of health care managers and family physicians rated 240 potential indicators of quality of primary care in the United Kingdom to determine their face validity. Following round one, equal numbers of managers and physicians were randomly allocated to receive either collective (whole sample) or group-only (own professional group only) feedback, thus, creating four subgroups of two single-specialty panels and two mixed panels. RESULTS: Overall, managers rated the indicators significantly higher than physicians. Second-round scores were moderated by the type of feedback received with those receiving collective feedback influenced by the other professional group. CONCLUSIONS: This paper provides further experimental evidence that consensus panel judgments are influenced both by panel composition and by the type of feedback which is given to participants during the panel process. Careful attention must be given to the methods used to conduct consensus panel studies, and methods need to be described in detail when such studies are reported.

Attitude of Health Personnel↗
PubMed1996

[Charge selectivity of peritoneal transport in CAPD patients under stable states and during peritonitis].

To investigate charge selectivity of peritoneal transport in CAPD, dialysate/plasma concentration ratios (D/P) were calculated for creatinine (Cr) and 3 amino acids with almost the same molecular weight but quite different charges: glutamic acid (Glu: negatively charged), glutamine (Gln: near neutrally charged) and lysine (Lys: positively charged). The study population consisted of 23 stable patients and 11 patients with peritonitis on CAPD. In the stable patients, the samples of dialysate were taken at 2 and 4 hours and blood samples were obtained at 4 hours after the infusion of 2 liters of 2.27 or 2.5% glucose CAPD dialysate; the samples of patients with peritonitis were obtained at 4.1 +/- 1.1 hours of dwell time. In stable patients, D/P of Glu was much lower than the values for Gln, Lys and Cr at both 2 and 4 hours (p < 0.01), and D/P of Lys was significantly lower than that of Gln (p < 0.01). There was no significant difference in D/P between Gln and Cr. In patients with peritonitis, D/P of Glu was also significantly lower than the values for Gln and Cr (p < 0.05 and p < 0.01), however, no significant differences were found between D/P of Lys and the values of Glu and Gln. Ratios of both [D/P Glu]/[D/P Lys] and [D/P Glu]/[D/P Gln] were much higher in peritonitis patients than in stable patients. In conclusion, peritoneal transport in stable CAPD patients shows charge selectivity, and the order of molecular charge for transperitoneal mobility among small solutes is neutral > positive > negative. The selectivity, however, is decreased or lost during peritonitis.

Adult↗
PubMed1994

Inhibition of human platelet aggregation by GR91669, a prototype fibrinogen receptor antagonist.

In order to produce more potent and specific fibrinogen receptor (GpIIb/IIIa) antagonists, the Arg-Gly of a chemical series based upon Arg-Gly-Asp was replaced by alkyl chains of varying lengths. The most potent in this series, GR91669, inhibited aggregation of human gel-filtered platelets (GFP) in vitro induced by ADP or the thromboxane A2 mimetic, U46619, with IC50 values of 200nM and 500nM respectively and was selected for further studies. Its inhibitory effects on GFP were reversed by addition of excess fibrinogen. The compound also inhibited ADP- or U46619-induced platelet aggregation in human whole blood (IC50 values of 700nM in both cases). 125I-Fibrinogen binding to ADP-stimulated platelets was inhibited by GR91669 with an IC50 (65nM) similar to that against platelet aggregation. GR91669 (1mM) did not inhibit U46619-induced platelet shape change or 14C-5HT secretion from platelets stimulated by collagen, U46619 or thrombin. Therefore GR91669 inhibits aggregation but has no significant effect on stimulus-response events, a profile consistent with fibrinogen receptor blockade. In addition, GR91669 (1mM), unlike echistatin or Gly-Arg-Gly-Asp-Ser, did not disrupt vitronectin recptor-dependent attachment of cultured HUVECS in vitro and similarly did not inhibit Mac-1 dependent adhesion of human granulocytes. Thus, of the integrins tested, GR91669 appears to be specific for GpIIb/IIIa. Following intravenous administration to marmosets of 1 or 10 mg/kg GR91669, ADP (10 microM)-induced platelet aggregation ex vivo was abolished for 15 and 60 minutes respectively. Greater than 50% inhibition was maintained for 30 minutes and 2 hours respectively. GR91669, therefore appears to be a potent, specific fibrinogen receptor antagonist in vitro and which is also active in vivo.

Amino Acid Sequence↗
PubMed1994

Respiratory responses to CO2 rebreathing in lung transplant recipients.

To evaluate the respiratory responses after lung transplantation, we studied the hypercarbic ventilatory response in 20 patients with severe obstructive pulmonary disease and compared it with that of 10 normal subjects. Eleven patients underwent bilateral lung transplantation and 9 patients had single-lung transplantation. All patients had preoperative hypercapnia (51.3 +/- 9.7 mm Hg) and blunted slopes of CO2 rebreathing curves for minute ventilation (0.39 +/- 0.20 L.min-1.mm Hg-1) and inspiratory occlusion pressure (0.35 +/- 0.30 s-1). The hypercapnia and blunted ventilatory responses persisted at the initial postoperative test (5.8 +/- 2.0 days) despite improved pulmonary function (preoperative forced expiratory volume in 1 second [FEV1], 0.57 +/- 0.16 L; initial postoperative FEV1, 1.83 +/- 0.65 L; p < 0.001). By the 15th to 30th postoperative day (21.3 +/- 6.0 days), compared with preoperative and initial postoperative values, end-tidal CO2 had normalized (40.6 +/- 6.9 versus 51.3 +/- 9.7 and 49.6 +/- 10.3 mm Hg; p < 0.005) and was coupled with enhanced ventilatory responses for the rebreathing curve for minute ventilation (1.26 +/- 0.7 versus 0.39 +/- 0.20 and 0.32 +/- 0.32 L.min-1.mm Hg-1; p < 0.005) and the inspiratory occlusion pressure curve (0.98 +/- 7.4 versus 0.35 +/- 0.30 and 0.41 +/- 0.29 s-1; p < 0.005). These respiratory responses developed without a change in postoperative pulmonary function (initial postoperative FEV1, 1.83 +/- 0.65 L versus last postoperative FEV1, 1.96 +/- 0.66 L; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Improved potency and specificity of Arg-Gly-Asp (RGD) containing peptides as fibrinogen receptor blocking drugs.

A range of cyclic RGD based peptides have been developed to mimic the conformation of RGD within fibrinogen. These peptides, as well as echistatin (IC50 = 0.05 microM) and GRGDS (IC50 = 25 microM) fully inhibited adenosine diphosphate (ADP) (10 microM)-induced platelet aggregation of human gel-filtered platelets (GFP). RGDF was the most potent linear peptide in inhibiting ADP-induced aggregation (IC50 = 8 microM) but cyclisation, using a 6,5 bicyclic coupling group to produce GR83895, led to an approximately 10-fold increase in potency (IC50 = 0.9 microM). In GFP, ADP-induced 125I-fibrinogen binding was inhibited (> 80%) by echistatin, GRGDS or GR83895 at concentrations (IC50 values 0.05 microM, 25 microM and 1.4 microM respectively) similar to those needed to inhibit aggregation. All three compounds also completely inhibited ADP- and U46619-induced aggregation in both platelet rich plasma (PRP) and whole blood. In contrast to platelet aggregation, U-46619-induced 14C-5HT secretion in PRP was not inhibited by GR83895 or echistatin, indicating that agonist-induced signal transduction is not affected by either agent, a profile consistent with that predicted for a specific fibrinogen receptor blocking drug. To test specificity of action, echistatin, GR83895 and GRGDS were also examined for their ability to detach cultured human umbilical vein endothelial cells attached to plastic through a vitronectin receptor dependent process. GR83895 only caused detachment at concentrations 100-fold greater than those required to inhibit platelet aggregation, in contrast to GRGDS and echistatin which caused cell detachment at concentrations similar to those inhibiting aggregation. In summary, cyclisation of RGD-containing peptides has led to both improved potency and specificity of action. Such specificity of action may prove to be an important consideration for the successful development of a fibrinogen receptor blocking drug as an anti-thrombotic drug.

Amino Acid Sequence↗
PubMed1987

[Induction of brain tumors with methylnitrosourea. Comparative study of 2 strains of rats].

For clarifying the question with respect to the different incidence in various animal strains of the formation of cerebral tumours 10 BD II and Wistar rats were given methyl-nitrosourea (a weekly amount of 5 mg per kg of life-weight over a period of 35 weeks). After an average of 398 and 367 days half the number of animals in each group showed cerebral tumours. These primarily seem to be isomorphous gliomas which then show an increase in malignity.

Animals↗