Automating total quality management.
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Computer Graphics↗
Biomedical subjects
P Harris
Publications and source records attributed to P Harris.
Cloning of a putative inhibitory amino acid receptor subunit from the parasitic nematode Haemonchus contortus.
A cDNA, HGl, encoding an inhibitory amino-acid receptor subunit has been cloned from a mixed egg population of the parasitic nematode Haemonchus contortus. The predicted amino-acid sequence of the subunit shows 24% to 32% homology with other vertebrate and invertebrate GABAA and glycine receptor subunits and has all the expected motifs for a member of the ligand-gated ion channel superfamily. When expressed in Xenopus oocytes HGl gives a small response to 1 mM glycine, but not to 1 mM GABA, glutamate, taurine or L-alanine.
Alanine↗
Delayed hemopericardium and cardiac tamponade after unrecognized chest trauma.
Delayed hemopericardium after blunt chest wall trauma in children is rare and difficult to recognize before overt signs of cardiac tamponade. We present a 21-month-old girl who developed a late hemopericardium with cardiac tamponade after initially unrecognized blunt chest wall injury.
Adolescent↗
What constitutes general surgical training? Evidence from the log books of trainees in one district general hospital.
It is accepted wisdom that surgical expertise in the UK is achieved by virtue of long service, and perhaps not enough genuine training. The average age at appointment to consultant posts in general surgery has risen from 37.0 years in 1978 to 38.0 in 1992. This message has reached the politicians who run the Health Service: at the Association of Surgeons in Training Annual General Meeting in September 1991 Mrs Virginia Bottomley said 'A complaint often made to me is that trainees, particularly surgical trainees, in the UK are over-experienced but under-trained'. Training posts acquire a reputation (good or bad) based on word of mouth, pass rate in examinations, and success in placing trainees into higher grades. Little is known about the relationship between training and operative experience. Log books have been introduced as a compulsory requirement for the Clinical Surgery in General and Intercollegiate Specialty Examinations. This report aims to define the operative experience of trainees at a District General Hospital by analysis of data obtained from their log books. This information has been used to calculate trainee workload in terms of intermediate equivalents (IE) and service equivalent value (SEV).
Education, Medical, Graduate↗
Impact of general practitioners' referral letters to an emergency department.
INTRODUCTION: We sought to determine the impact of general practitioner communication on the efficient management of patients who present to the emergency department. Casemix, severity, time of presentation, the quality of the letter and the reception of a telephone call were considered. METHOD: All consecutive patients presenting to the emergency department of Mornington Peninsula Hospital (Frankston) for one month in 1992 were included in this survey. The methodology is summarised in Figure 1. RESULTS: The referral letter made no difference to patients' waiting time and time spent in the department and a non significant difference in communication back to the general practitioner. This was found despite the quality of the referral letter, the time of presentation, and the diagnosis. The general practitioners' telephone call, however, decreased significantly the patient's waiting time. Investigations that were reported in the general practitioners' letters and not repeated by the emergency department resulted in a direct saving of $2604 for the month of the study. High interrater reliability was discovered in the rating of letters by six general practitioners. DISCUSSION: Despite the ability of general practitioners to select appropriate cases for referral, only the telephone call results in a quantifiable benefit for patients who attend their general practitioner. The high inter-rater reliability affirms the use of referral letters as audit tools in general practice. Better practical use could be made of general practitioners' referral communication to the emergency department.
Communication↗
Contribution of direct and indirect recognition pathways to T cell alloreactivity.
T cells from an HLA-DR11/DR12 responder were stimulated in mixed lymphocyte culture with cells carrying the DR1 antigen. After priming, T cells proliferated in response to both DR1-positive-stimulating cells and a peptide derived from a polymorphic region of the HLA-DR beta 1*0101 chain presented by responder's antigen-presenting cells (APC). The dominant epitope recognized by the primed T cells corresponded to residue 21-42 and was presented by the responder's HLA-DR12 antigen. The DR1 peptide-reactive T cells express T cell receptor V beta 3. The results demonstrate that allopeptides derived from the processing and presentation of donor major histocompatibility complex molecules by host-derived APC trigger alloreactivity. The frequency of T cells engaged in the indirect pathway of allorecognition is about 100-fold lower than that of T cells participating in the direct recognition of native HLA-DR antigen. However, indirect allorecognition may play an important role in chronic allograft rejection, a phenomenon that is mediated by the activation of T helper cells and of alloantibody-producing B cells.
Alleles↗
The cell cycle genes cdc22+ and suc22+ of the fission yeast Schizosaccharomyces pombe encode the large and small subunits of ribonucleotide reductase.
The cdc22+ gene of Schizosaccharomyces pombe is required early in the cell cycle, and its transcript varies in concentration in step with the cell cycle, with a peak level at the G1-S boundary. The sequences of the cdc22+ gene and of a multicopy suppressor of cdc22ts mutations, suc22+, have been determined. The cdc22+ open reading frame, which is interrupted in the genome by a single intron very close to its 5' end, encodes a protein of 811 amino acids, which has an amino acid sequence highly similar to that of the large subunit of ribonucleotide reductase from several species. The suc22+ gene contains an uninterrupted open reading frame of 391 amino acids, very similar to the sequence of the small subunit of ribonucleotide reductase. Disruption of either gene is lethal. Upstream of the cdc22+ coding region are seven short sequence elements similar to the recognition sequence for MluI, which are involved in regulating periodic transcription of the gene. Inhibition of DNA synthesis by hydroxyurea results in a several-fold increase in the level of the cdc22+ transcript. In contrast, hydroxyurea does not induce the 1.5 kb transcript of suc22+, but results in the induction of a 1.9 kb mRNA which hybridises to suc22+ DNA.
Amino Acid Sequence↗
The effect of inhibition of leukotriene B4 release on lipopolysaccharide-induced production of neutrophil attractant/activation protein-1 (interleukin-8) by human alveolar macrophages.
Whereas we observed previously that concentrations of the lipoxygenase inhibitor nordihydroguaiaretic acid that inhibited leukotriene B4 release from lipopolysaccharide-stimulated human alveolar macrophages in vitro also inhibited subsequent interleukin-8 release, we hypothesized that leukotriene B4 release was required for the release of interleukin-8. Alveolar macrophages from normal nonsmoking volunteers were adhered to plastic and incubated with varying concentrations (25-250nM) of the 5-lipoxygenase activating protein inhibitor MK-886 prior to stimulation with lipopolysaccharide. MK-886 inhibited leukotriene B4 release in a concentration-dependent manner. The concentration of MK-886 that inhibited release by 50% was 53.3 +/- 23.1nM (mean +/- SD), n = 4. Interleukin-8 concentrations in 24hr supernatants were not inhibited by incubation of the cells with any concentration of MK-886, including those that inhibited leukotriene B4 release by > 95%. Thus, MK-886 is an effective inhibitor of human alveolar macrophage release of leukotriene B4, and the release of leukotriene B4 is not a prerequisite for alveolar macrophage release of interleukin-8.
Humans↗
The nature and extent of aggressive behaviour amongst people with learning difficulties (mental handicap) in a single health district.
This paper describes the method and results of a survey of aggressive behaviour amongst people with learning difficulties. The study was confined to a single health district in the South Western Region of the UK with a general population of about 370,000. At the time of the survey, the Mental Handicap Register for the district recorded 1,362 people as having a learning difficulty. The overall prevalence of aggressive behaviour amongst people with learning difficulties for whom base population data was available was 17.6%. The lowest rate was identified amongst day facilities (9.7%) and the highest in hospitals within the district (38.2%). The prevalence rate amongst those attending schools for children with severe learning difficulties was 12.6%. Proportionately more males than females were reported to present problems of aggressive behaviour. The gender difference appeared to be largely accounted for by the disproportionate number of men identified within day facilities. There was no significant evidence of an association between the person's gender and the presence aggressive behaviour within schools or hospitals. The results indicated that, although physical and verbal aggression were the most frequently reported behaviours, many of the sample were also said to engage in other forms of challenging behaviour, particularly self-injurious, ritualistic, stereotypical and withdrawn behaviour. The risk of a serious or very serious injury to another person was very low; 0.7% or six people with learning difficulties from the district were reported to be currently presenting such a risk. Similarly, only 2% of the base population (n = 18) were reported to be extremely difficult to manage. The implications of the findings are discussed.
Adolescent↗
Post thrombolysis management.
Strategies for the evaluation of the post infarction patient need revision in the light of recent findings from thrombolytic trials, and the availability of more effective methods for detecting myocardial viability. A strategy based on determining the risk of re-occlusion from vessel anatomy at coronary angiography and determining the area of myocardium at risk based on sequential analysis of ST segment elevation is discussed.
Coronary Angiography↗
Survey of Australian emergency physicians' expectations of general practitioner referrals.
This paper reports the first study of Australian emergency physicians which concentrates on their relationship with general practitioners. A self-administered questionnaire was mailed to every known fellow and senior trainee of the Australasian College of Emergency Medicine working in Victoria, Australia. Good response rates were achieved (97% from fellows, 78% from trainees). Referral letters from general practitioners were always read by 99% of respondents. Telephone calls from general practitioners were found to be desirable for imparting details of social history or other qualitative information and for determining the appropriateness of the referral. The list of patients' current medication and the details of any emergency treatment administered by the general practitioner were almost universally considered essential inclusions in all urgent referral letters. Other items of information were considered to be influenced by the particular patient presentation. The majority of respondents (87%) felt that a written management plan had some influence on the patient's management in their emergency department. Eighty nine per cent of respondents stated that they always or usually responded to general practitioners' communications. The outcome for patients attending emergency departments with referral letters warrants study. If a good referral letter is seen to be of value in terms of more accurate diagnosis, quicker patient processing, less investigations and better responses, then general practitioners will be encouraged to write better letters. The results of this study offer a useful definition of inappropriate referral to the emergency department and it may now be possible to investigate any link between poor referral letters and inappropriate referrals.
Australia↗
Redistribution of sufentanil to cerebrospinal fluid and systemic circulation after epidural administration in dogs.
Due to its higher lipid solubility, sufentanil may be less likely than morphine to migrate rostrally in the cerebral spinal fluid (CSF) and cause delayed respiratory depression following epidural administration. However, early respiratory depression has been reported in patients after relatively large doses of epidural sufentanil. This has been attributed to systemic drug uptake. We used a dog model to investigate the pharmacokinetics and rostral spread of epidural sufentanil in CSF. Sampling catheters were placed in the lumbar subarachnoid space, the cisterna magna, and femoral arteries of six mongrel dogs. Samples of cisternal CSF, lumbar CSF, and blood were drawn at 0, 1, 5, 15, 30, 60, 90, 120, and 180 min after lumbar epidural sufentanil injection. We measured sufentanil concentrations by gas chromatography-mass spectrometry and used the least squares method to a fit tri-exponential function to each sufentanil concentration versus time data set. Paired t-test was used to test for statistical significance. After epidural sufentanil, lumbar CSF concentrations were significantly higher than plasma or cisternal CSF sufentanil concentrations at all assessment times. Sufentanil concentrations were significantly higher in cisternal CSF than in plasma at 30 and 60 min after injection. Sufentanil appeared rapidly in lumbar CSF, reaching a maximum concentration (Cmax) of 57 ng/mL at 6.5 min. In cisternal CSF, a Cmax of 1.2 ng/mL was reached at 21 min, and Cmax in plasma was 0.35 ng/mL at 6 min. The area under the concentration-time curve (AUC) of sufentanil in cisternal CSF was approximately six times higher than the plasma AUC (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
T cell recognition of self-human histocompatibility leukocyte antigens (HLA)-DR peptides in context of syngeneic HLA-DR molecules.
It has been suggested that self major histocompatibility complex (MHC) peptides bound to self MHC molecules may be involved in the intrathymic induction of self tolerance. We studied the antigenicity of synthetic peptides derived from the first domain of DR beta 1*0101 chain in a DR beta 1*0101 responder. We found that a peptide corresponding to residues 21-42 of the beta chain could elicit the proliferation of autoreactive T cells. A T cell line (TCL-SUN) and 7 of 9 T cell clones (TCC) derived from TCL-SUN specifically recognized peptide 21-42 in the presence of APCs carrying the DR beta 1*0101 allele. DR beta 1*0101 positive APCs stimulated the TCCs in the absence of peptide, although the magnitude of the response was much lower than in cultures with peptide. This suggests that self DR1 molecules are continuously processed into peptides that are presented by the DR1 molecules on the surface of the cells. The data indicate that some T cells whose TCR binds to self MHC peptides presented by self MHC molecules are not deleted, although their ligand is continuously present. TCCs specific for peptide 21-42 presented in the context of DR1 were also stimulated by cells heterozygous for DR beta 1*0301 and 1601, indicating that some DR peptide-specific autoreactive T cells participate in alloreactivity.
Antibodies, Monoclonal↗
The effects of eosinophil-granule major basic protein on lung-macrophage superoxide anion generation.
The effects of major basic protein (MBP) on superoxide anion release in vitro from normal guinea pig (GP) alveolar macrophages (AM) was determined. Native MBP at 55 micrograms/ml had an immediate effect (reduction) on phorbol myristate acetate (PMA)-induced (p less than 0.01) and spontaneous (p = 0.055) superoxide (O2-) release by GP AMs. A similar effect was not observed from AMs incubated for 24 hours with MBP before assessment of O2- release. However, after AMs were incubated with MBP for 48 hours, again there was a significant reduction observed in both PMA-induced (p = 0.01) and spontaneous (p = 0.002) O2- release compared to that of control cultures. The immediate effect of MBP on AM O2- release was not due to cytotoxicity of MBP for AM. In contrast, the effect observed after 48 hours of culture was due, in part, to a direct toxic effect of the MBP on the AM because the viability of AM cultured for 48 hours with MBP (55 micrograms/ml) was 63.6% +/- 13% compared to the viability of control cultures of AM that was 83.9% +/- 7%; p = 0.03. The effect of MBP on AM O2- release at 48 hours was progressive over concentrations ranging from 2 to 55 micrograms/ml. These data suggest that native MBP can affect adversely PMA-induced and spontaneous release of O2- by GP AMs and that this effect depends only in part on the cytotoxic properties of MBP.
Adolescent↗
Is diabetes always diabetes?
Diabetes is always taken to be a life-long diagnosis. In order to re-examine this question, 75 g glucose tolerance tests (OGTT) were performed twice on 37 previously confirmed diabetic patients (mean duration of diabetes of 4.6 years; range 1-15 years) with normal glycosylated haemoglobin levels on regular review. Weight loss since institution of a healthy diet was 7.6 +/- 4.8 kg (+/- SE). Normal glucose tolerance was found in 27% of patients and impaired glucose tolerance in 21% with no significant change on rechallenge. HbA1 was 6.3 +/- 1.5% (+/- SD) (normal < 7.5%) in patients with normal glucose tolerance compared to 7.0 +/- 0.9% (+/- SD) in those with impaired glucose tolerance, P < 0.05. The response of the OGTT in these patients varied with dietary intake and weight. Such individuals could be regarded as having perfectly controlled diabetes or alternatively to have been cured. The definition of diabetes should be reviewed to allow people to escape the diagnosis where permanent change in dietary habits is established.
Blood Glucose↗
Evaluation of a cosmid contig physical map of human chromosome 16.
A cosmid contig physical map of human chromosome 16 has been developed by repetitive sequence finger-printing of approximately 4000 cosmid clones obtained from a chromosome 16-specific cosmid library. The arrangement of clones in contigs is determined by (1) estimating cosmid length and determining the likelihoods for all possible pairwise clone overlaps, using the fingerprint data, and (2) using an optimization technique to fit contig maps to these estimates. Two important questions concerning this contig map are how much of chromosome 16 is covered and how accurate are the assembled contigs. Both questions can be addressed by hybridization of single-copy sequence probes to gridded arrays of the cosmids. All of the fingerprinted clones have been arrayed on nylon membranes so that any region of interest can be identified by hybridization. The hybridization experiments indicate that approximately 84% of the euchromatic arms of chromosome 16 are covered by contigs and singleton cosmids. Both grid hybridization (26 contigs) and pulsed-field gel electrophoresis experiments (11 contigs) confirmed the assembled contigs, indicating that false positive overlaps occur infrequently in the present map. Furthermore, regional localization of 93 contigs and singleton cosmids to a somatic cell hybrid mapping panel indicates that there is no bias in the coverage of the euchromatic arms.
Chromosome Banding↗