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Biomedical subjects

J Munro

Publications and source records attributed to J Munro.

At least 19 recordsLinked to original sources
PubMed2003

NHS Direct: consistency of triage outcomes.

OBJECTIVES: To examine the consistency of triage outcomes by nurses using four types of computerised decision support software in NHS Direct. METHODS: 119 scenarios were constructed based on calls to ambulance services that had been assigned the lowest priority category by the emergency medical dispatch systems in use. These scenarios were presented to nurses working in four NHS Direct call centres using different computerised decision support software, including the NHS Clinical Assessment System. RESULTS: The overall level of agreement between the nurses using the four systems was "fair" rather than "moderate" or "good" (kappa=0.375, 95% CI: 0.34 to 0.41). For example, the proportion of calls triaged to accident and emergency departments varied from 22% (26 of 119) to 44% (53 of 119). Between 21% (25 of 119) and 31% (37 of 119) of these low priority ambulance calls were triaged back to the 999 ambulance service. No system had both high sensitivity and specificity for referral to accident and emergency services. CONCLUSIONS: There were large differences in outcome between nurses using different software systems to triage the same calls. If the variation is primarily attributable to the software then standardising on a single system will obviously eliminate this. As the calls were originally made to ambulance services and given the lowest priority, this study also suggests that if, in the future, ambulance services pass such calls to NHS Direct then at least a fifth of these may be passed back unless greater sensitivity in the selection of calls can be achieved.

Adult↗
PubMed2002

Investigation of promoter variants of the histamine 1 and 2 receptors in schizophrenia and clozapine response.

We report the identification of four novel histamine 1 (H1-17-C/T, -974-C/A, -1023-A/G and -1536-G/C) and four novel histamine 2 promoter polymorphisms (H2-294-A/G, -592-A/G, -1018-G/A and -1077-G/A) which we have investigated for involvement in susceptibility to schizophrenia, and in clinical response to clozapine treatment. We identified a weak independent association between variants at the H1-1536-G/C locus and schizophrenia, where an excess of the H1-1536-C allele was observed amongst such patients (P = 0.036). However upon correction for multiple testing this relationship was no longer statistically significant. Similar investigation of the H2 receptor polymorphisms revealed association between genotype at the H2-1018-G/A locus and clinical response to clozapine treatment (P = 0.027), though upon correction for multiple testing this difference was no longer significant. We have concluded that the participation of these variants in the disorder is unlikely, particularly in view of their apparent lack of function and unlikely influence on receptor expression. However their nature alludes to the potential presence of other more important alterations further along these regions, where sequences encoding alternate promoters have recently been identified for each receptor that may yet be found to harbour such polymorphisms.

Antipsychotic Agents↗
PubMed2002

Impact of NHS Direct on other services: the characteristics and origins of its nurses.

OBJECTIVE: To characterise the NHS Direct nurse workforce and estimate the impact of NHS Direct on the staffing of other NHS nursing specialties. METHOD: A postal survey of NHS Direct nurses in all 17 NHS Direct call centres operating in June 2000. RESULTS: The response rate was 74% (682 of 920). In the three months immediately before joining NHS Direct, 20% (134 of 682, 95% confidence intervals 17% to 23%) of respondents had not been working in the NHS. Of the 540 who came from NHS nursing posts, one fifth had come from an accident and emergency department or minor injury unit (110 of 540), and one in seven from practice nursing (75 of 540). One in ten (65 of 681) nurses said that previous illness, injury, or disability had been an important reason for deciding to join NHS Direct. Sixty two per cent (404 of 649) of nurses felt their job satisfaction and work environment had improved since joining NHS Direct. CONCLUSION: The NHS Direct nurse workforce currently constitutes a small proportion (about 0.5%) of all qualified nurses in the NHS, although it recruits relatively experienced and well qualified nurses more heavily from some specialties, such as accident and emergency nursing, than others. However, its overall impact on staffing in any one specialty is likely to be small. NHS Direct has succeeded in providing employment for some nurses who might otherwise be unable to continue in nursing because of disability.

Adult↗
PubMed2001

Human fibroblast replicative senescence can occur in the absence of extensive cell division and short telomeres.

Ectopic expression of telomerase blocks both telomeric attrition and senescence, suggesting that telomeric attrition is a mitotic counting mechanism that culminates in replicative senescence. By holding human fibroblast cultures confluent for up to 12 weeks at a time, we confirmed previous observations and showed that telomeric attrition requires cell division and also, that senescence occurs at a constant average telomere length, not at a constant time point. However, on resuming cell division, these long-term confluent (LTC) cultures completed 15-25 fewer mean population doublings (MPDs) than the controls prior to senescence. These lost divisions were mainly accounted for by slow cell turnover of the LTC cultures and by permanent cell cycle exit of 94% of the LTC cells, which resulted in many cell divisions being unmeasured by the MPD method. In the LTC cultures, p27(KIP1) accumulated and pRb became under-phosphorylated and under-expressed. Also, coincident with permanent cell cycle exit and before 1 MPD was completed, the LTC cultures upregulated the cell cycle inhibitors p21(WAF) and p16(INK4A) but not p14(ARF) and developed other markers of senescence. We then tested the relationship between cell cycle re-entry and the cell cycle-inhibitory proteins following subculture of the LTC cultures. In these cultures, the downregulation of p27(KIP1) and the phosphorylation of pRb preceded the complete resumption of normal proliferation rate, which was accompanied by the down-regulation of p16(INK4A). Our results show that most normal human fibroblasts can accumulate p16(INK4A), p21(WAF) and p27(KIP1) and senesce by cell division-independent mechanism(s). Furthermore, this form of senescence likely requires p16(INK4A) and perhaps p27(KIP1).

3T3 Cells↗
PubMed2001

Polymorphisms in the genes for mGluR types 7 and 8: association studies with schizophrenia.

A dysfunctional glutamatergic system has been implicated in the pathophysiology of schizophrenia. The group III metabotropic glutamate receptor (mGluR) types 7 and 8 presynaptically inhibit glutamate release, thereby modulating glutamatergic transmission in the brain. We conducted association studies to investigate the novel Tyr433Phe (mGluR7) variant and the 2846-C/T (mGluR8) polymorphism in schizophrenia. Both variants, present at high frequencies, failed to demonstrate any significant association with schizophrenia (mGluR7 [Tyr433Phe] allele: P=0.33; genotype: P=0.63; mGluR8 [2846-C/T] allele: P=0.72; genotype: P=0.63).

Adult↗
PubMed2001

The reported use of dietary supplements (sip feeds) in hospitals in Wessex, UK.

AIMS: To assess the prevalence of the use of supplements (sip feeds) in district general, psychiatric and community hospitals in the former Wessex health region. METHOD: Cross sectional study of prevalence and determinants of supplement use in 10 district general hospitals (covering medical, surgical, orthopaedic, and elderly specialities), 4 psychiatric hospitals and 3 community hospitals. RESULTS: Overall 14% of patients were being supplemented although the variation across hospitals and specialities was wide (0%-35%); elderly care patients within district hospitals were most likely to be supplemented (20%; range 12-35%). In 34% of patients there was no documented reason as to why supplements were given. 60% of patients were not weighed on admission; 70% did not have a weight history recorded and 83% did not have a current weight recorded. Documentation regarding supplement use appeared to be recorded in an unsystematic manner. CONCLUSIONS: Many patients were not being weighed on admission and appeared to have no documentation as to why supplements were given. Given the importance of malnutrition in hospital patients a more evidence based, objective approach to assessing nutritional requirements, intake and support may be beneficial.

Age Factors↗
PubMed2001

Applications of pharmacogenetics in psychiatry: personalisation of treatment.

In spite of the lack of epidemiological information, pharmacogenetic research has produced evidence of the relationship between genes and treatment response. Genetic variants of metabolic enzymes are related to toxic reactions; polymorphisms in genes coding for drug-targeted neurotransmitter receptors influence therapeutic efficacy. Also, recent studies have shown that response to antipsychotic drugs can be predicted by looking at the individual's pharmacogenetic profile. In addition to providing the first evidence that treatment response can be predicted by looking at a core of key genes, these studies illustrate the feasibility of individualisation of psychiatric treatment.

Aryl Hydrocarbon Hydroxylases↗
PubMed2000

Systematic screening of the 14-3-3 eta (eta) chain gene for polymorphic variants and case-control analysis in schizophrenia.

The neuronal protein 14-3-3 eta is a candidate gene for schizophrenia because it maps chromosome 22q12, a region implicated in the disease by linkage analysis, and is involved in brain development. We systematically screened this gene for polymorphic variants by comparison of public EST sequence data (five cDNAs and 72 ESTs, 21,155 bp of sequence) in parallel with single-stranded conformational polymorphism analysis, and we compared these methods by using a simple power calculation. Twelve potential polymorphisms were identified from EST sequence comparison, and two of these (a 5'-VNTR and 753G/A) were confirmed by SSCP analysis and sequencing. Three additional infrequent polymorphisms (-408T/G; 177 C/G; and 989 A/G) were found by SSCP only. We next examined these variants for association with schizophrenia. One variant in untranslated region of exon 1 (-408 T/G) was found to occur more frequently in the schizophrenic subjects (8%) than the controls (3%; P = 0.01). After fivefold correction of the P value for multiple testing, marginal association was found. Haplotype analysis of pairs of polymorphisms provided no evidence for association of this gene with schizophrenia in the population studied. Am. J. Med. Genet. (Neuropsychiatr. Genet. ) 96:736-743, 2000.

14-3-3 Proteins↗
PubMed2000

Impact of NHS direct on demand for immediate care: observational study.

OBJECTIVES: To quantify the impact of NHS Direct on the use of accident and emergency, ambulance, and general practitioner cooperative services. DESIGN: Observational study of trends in use of NHS Direct and other immediate care services over 24 months spanning introduction of NHS Direct. SETTING: Three areas in England in first wave of introduction of NHS Direct, and six nearby general practitioner cooperatives as controls. SUBJECTS: All contacts with these immediate care services. MAIN OUTCOME MEASURES: Changes in trends in use after introduction of NHS Direct. RESULTS: NHS Direct received about 68 500 calls from a population of 1.3 million in its first year of operation, of which 72% were out of hours and 22% about a child aged under 5 years. Changes in trends in use of accident and emergency departments and ambulance services after introduction of NHS Direct were small and non-significant. Changes in trends in use of general practitioner cooperatives were also small but significant, from an increase of 2.0% a month before introduction of NHS Direct to -0.8% afterwards (relative change -2. 9% (95% confidence interval -4.2% to -1.5%)). This reduction in trend was significant both for calls handled by telephone advice alone and for those resulting in direct contact with a doctor. In contrast, the six control cooperatives showed no evidence of change in trend; an increase of 0.8% a month before NHS Direct and 0.9% after (relative change 0.1% (-0.9% to 1.1%)). CONCLUSION: In its first year NHS Direct did not reduce the pressure on NHS immediate care services, although it may have restrained increasing demand on one important part-general practitioners' out of hours services.

Emergency Service, Hospital↗
PubMed2000

Association analysis of the 5-HT5A gene in depression, psychosis and antipsychotic response.

The serotonergic system is targeted by both antidepressants and atypical antipsychotic drugs such as clozapine. Genetic variation in the 5-HT5A gene might be involved in susceptibility to depression, the major psychoses or in influencing clinical response to treatment. To examine this hypothesis we genotyped two polymorphisms (-19G/C; 12A/T) in the human 5-HT5A receptor gene in a sample of 269 unrelated schizophrenic patients treated with clozapine, 112 bipolar patients, 75 unipolar patients and 187 controls. After five-fold correction for multiple testing, allelic association was found with the -19G/C polymorphism and bipolar affective disorder, (p = 0.025; OR 0.56), unipolar depression (p = 0.004; OR 0.52) and schizophrenia (p = 0.036; OR 0.67) indicating a potential protective effect of the G19 allele. For the 12A/T polymorphism allelic association was observed with unipolar depression only (p = 0.004). We conclude that allelic variation in the human 5-HT5A receptor gene may be involved in susceptibility to schizophrenia and affective disorders but not in determining response to clozapine.

Alleles↗
PubMed2000

Pharmacogenetic prediction of clozapine response.

We did association studies in multiple candidate genes to find the combination of polymorphisms that give the best predictive value of response to clozapine in schizophrenic patients. A combination of six polymorphisms in neurotransmitter-receptor-related genes resulted in 76.7% success in the prediction of clozapine response (p=0.0001) and a sensitivity of 95% (+/- 0.04) for satisfactory response. These results will form the basis for a simple test to enhance the usefulness of clozapine in psychiatric treatment.

Alleles↗
PubMed2000

No influence of adrenergic receptor polymorphisms on schizophrenia and antipsychotic response.

The adrenergic system plays an important role in psychiatric disorders such as depression and schizophrenia. Antagonism of the adrenergic receptor subtypes alpha1A and alpha2A has been found to have an antipsychotic effect. Genetic mutations in these receptors could be related to the alterations in the adrenergic system observed in psychiatric patients and to failure to respond to drug antagonism. We have studied one polymorphism in the alpha1A-adrenergic receptor (Arg492Cys) and two polymorphisms in the promoter region of the alpha2A-adrenergic receptor (-1291-C/G and -261-G/A) in a sample of clozapine-treated schizophrenic patients and controls. No clear differences were observed between the different groups suggesting that these polymorphisms did not play an important role in the aetiology of the disorder or in determining antipsychotic response.

Amino Acid Substitution↗