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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 127 records · Page 7Linked to original sources
PubMed1997

Evaluating the options for developing databases to support research-based medicine at the NHS Centre for Reviews and Dissemination.

The paper presents the results of a questionnaire survey and user interface review group experiments to determine the value and ease of use of the Database of Abstracts of Reviews of Effectiveness (DARE) and the NHS Economic Evaluations Database (NEED). The results are interpreted with other recent studies of the use of electronic databases, including the NHS Research Register User Requirements Specification. The study found that most frequent users of the DARE database tend to use the CD-ROM version. Librarians were found to have the greatest awareness of the databases, with relatively low levels of use by operational NHS Staff. Untrained users found the online databases difficult to access and had erroneous perceptions of the database content which were only realised when queries returned unexpected answers. Experienced users of online information systems tended to want more sophisticated search facilities than inexperienced users. Nearly all users in the review groups wanted to access the databases in conjunction with other information sources, such as the Cochrane Library, Medline and the ACP Journal Club, highlighting the need for cross organisational strategies for the dissemination of research-based information.

CD-ROM↗
PubMed1997

Inhalation induction with sevoflurane: a double-blind comparison with propofol.

We conducted a randomized, double-blind comparison of 8% sevoflurane and propofol as induction agents for day-case cystoscopy in 102 patients. All patients received an i.v. cannula and breathed oxygen 5 litre min-1. Anaesthesia was induced with propofol i.v. or inhalation of 8% sevoflurane and 10% Intralipid (as a placebo) i.v., delivered by a blinded observer. Anaesthesia was maintained in all patients with 2% sevoflurane via a face mask. Induction of anaesthesia with sevoflurane was significantly slower compared with propofol (mean 84 (SD 24) s vs 57 (11) s), but was associated with a lower incidence of apnoea (16% vs 65%) and a shorter time to establish spontaneous ventilation (94 (34) s vs 126 (79) s). Induction complications were uncommon in each group but the transition to maintenance was smoother with sevoflurane and was associated with less hypotension compared with propofol. Emergence from anaesthesia induced with sevoflurane occurred significantly earlier compared with propofol (5.2 (2.2) min vs 7.0 (3.2) min) and anaesthetic induction was also significantly cheaper with sevoflurane. According to a postoperative questionnaire, the majority of patients found both anaesthetic techniques acceptable. Nevertheless, significnatly more patients (14%) rated induction with sevoflurane as unpleasant compared with propofol (0) and significantly more patients (24%) would not choose sevoflurane induction compared with propofol (6%). This phenomenon may have been related to the particular patient population studied, however. Inhalation induction with 8% sevoflurane would appear to offer several objective advantages compared with induction with propofol in day-case patients, although a significant minority may dislike this technique.

Adult↗
PubMed1997

Educational progress, behaviour, and motor skills at 10 years in early treated congenital hypothyroidism.

AIM: To assess educational attainments, behaviour, and motor skills at 10 years of age in a group of children with congenital hypothyroidism identified by neonatal screening. SUBJECTS: 59 children with congenital hypothyroidism born in 1978-81, 31 cases with pretreatment thyroxine (T4) values of 40 nmol/l or below (group I) and 28 less severe cases with T4 values over 40 nmol/l (group II), together with 59 classroom control children matched for age, sex, social class, and main language spoken at home. METHODS: The Neale analysis of reading ability; the child health and education study written test of mathematics; Rutter behaviour questionnaires for parents and teachers; the Oseretsky test of motor proficiency (short form). RESULTS: On all measures the congenital hypothyroidism children in group I had less satisfactory scores for educational attainments, behaviour, and motor skills than those in group II and controls. For reading the differences were small and did not reach statistical significance, but the deficits in mathematics and total motor skills were statistically significant (p < 0.01). There were more striking and statistically significant differences in behaviour scores, particularly with respect to attentional difficulties. Although less striking, these were also apparent in the group II children with mild hypothyroidism. CONCLUSIONS: At the age of 10 years severe congenital hypothyroidism is associated with some mild impairment in educational and motor attainments. Behaviour problems are also common, even in some children with less severe congenital hypothyroidism.

Child↗
PubMed1997

Sequence variation at the phenylalanine hydroxylase gene in the British Isles.

Using mutation and haplotype analysis, we have examined the phenylalanine hydroxylase gene in the phenylketonuria populations of four geographical areas of the British Isles: the west of Scotland, southern Wales, and southwestern and southeastern England. The enormous genetic diversity of this locus within the British Isles is demonstrated in the large number of different mutations characterized and in the variety of genetic backgrounds on which individual mutations are found. Allele frequencies of the more common mutations exhibited significant nonrandom distribution in a north/south differentiation. Differences between the west of Scotland and southwestern England may be related to different events in the recent and past histories of their respective populations. Similarities between southern Wales and southeastern England are likely to reflect the heterogeneity that is seen in and around two large capital cities. Finally, comparison with more recently colonized areas of the world corroborates the genealogical origin by range expansion of several mutations.

Alleles↗
PubMed1997

Expression of growth factor receptors is not a prognostic indicator in young patients with colorectal cancer.

Growth factor receptor expression has been shown to be of prognostic significance in certain cancers, but its relevance in young patients with colorectal cancer is unknown. The aim of this study, therefore, is to determine the prognostic relevance of growth factor receptor expression [c-erbB-2, epidermal growth factor receptor (EGFR) and transforming growth factor beta receptor (TGF beta R)] in such patients. Ninety-two patients were evaluated. They were staged using the Jass staging system and the presence of metastases. The expression of EGFR and TGF beta R and the protein production of c-erbB-2 were detected using standard immunohistochemical techniques. The expression of EGFR and TGF beta R and the presence of the c-erbB-2 protein product were not identified as independent prognostic factors for survival. Furthermore, their expression did not correlate with established prognostic indicators such as Jass staging, the presence of extramural vascular invasion and the degree of tumour differentiation.

Biomarkers, Tumor↗
PubMed1996

Environment of infants during sleep and risk of the sudden infant death syndrome: results of 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy. Confidential Enquiry into Stillbirths and Deaths Regional Coordinators and Researchers.

OBJECTIVE: To investigate the role of sleeping arrangements as risk factors for the sudden infant death syndrome after a national risk reduction campaign. DESIGN: Two year population based case-control study. Parental interviews were conducted for each infant who died and for four controls matched for age and date of interview. SETTING: Three regions in England with a total population of 17 million people. SUBJECTS: 195 babies who died and 780 matched controls. RESULTS: Prone and side sleeping positions both carried increased risks of death compared with supine when adjusted for maternal age, parity, gestation, birth weight, exposure to smoke, and other relevant factors in the sleeping environment (multivariate odds ratio = 9.00 (95% confidence interval 2.84 to 28.47) and 1.84 (1.02 to 3.31), respectively). The higher incidence of side rather than prone sleeping led to a higher population attributable risk (side 18.4%, prone 14.2%). More of the infants who died were found with bed covers over their heads (21.58; 6.21 to 74.99). The use of a dummy had an apparent protective effect (0.38; 0.21 to 0.70). Bed sharing for the whole night was a significant risk factor for infants whose mothers smoked (9.25; 2.31 to 34.02). No protective effect of breast feeding could be identified on multivariate analysis. CONCLUSIONS: This study confirms the importance of certain risk factors for the sudden infant death syndrome and identifies others-for example, covers over the head, side sleeping position-which may be amenable to change by educating and informing parents and health care professionals.

Bedding and Linens↗
PubMed1996

Smoking and the sudden infant death syndrome: results from 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy. Confidential Enquiry into Stillbirths and Deaths Regional Coordinators and Researchers.

OBJECTIVE: To investigate the effects of exposure to tobacco smoke and of parental consumption of alcohol and illegal drugs as risk factors for the sudden infant death syndrome after a national risk reduction campaign which included advice on prenatal and postnatal avoidance of tobacco smoke. DESIGN: Two year population based case-control study. Parental interviews were conducted for each infant who died and four controls matched for age and date of interview. SETTING: Three regions in England with a total population of 17 million people. SUBJECTS: 195 babies who died and 780 matched controls. RESULTS: More index than control mothers (62.6% v 25.1%) smoked during pregnancy (multivariate odds ratio = 2.10; 95% confidence interval 1.24 to 3.54). Paternal smoking had an additional independent effect when other factors were controlled for (2.50; 1.48 to 4.22). The risk of death rose with increasing postnatal exposure to tobacco smoke, which had an additive effect among those also exposed to maternal smoking during pregnancy (2.93; 1.56 to 5.48). The population attributable risk was over 61%, which implies that the numbers of deaths from the syndrome could be reduced by almost two third if parents did not smoke. Alcohol use was higher among index than control mothers but was strongly correlated with smoking and on multivariate analysis was not found to have any additional independent effect. Illegal drug use was more common among the index parents, and paternal use of illegal drugs remained significant in the multivariate model (4.68; 1.56 to 14.05). CONCLUSIONS: This study confirms the increased risk of the sudden infant death syndrome associated with maternal smoking during pregnancy and shows evidence that household exposure to tobacco smoke has an independent additive effect. Parental drug misuse has an additional small but significant effect.

Alcohol Drinking↗
PubMed1996

Prolonged metabolic correction in adult ornithine transcarbamylase-deficient mice with adenoviral vectors.

A murine model of ornithine transcarbamylase (OTC) deficiency was used in this study to evaluate the efficacy of recombinant adenoviruses for correcting the metabolic defect in liver. Recombinant adenoviruses deleted in E1 and containing a human OTC cDNA expressed little functional OTC enzyme in vivo and had no observable impact on the underlying metabolic abnormalities of the OTC-deficient mouse (i.e. elevated urinary orotate and serum glutamine). E1-deleted vectors were improved through the use of the strong constitutive promoter from cytomegalovirus driving the normal murine homolog of OTC cDNA and the ablation of E2a with a temperature-sensitive mutation. Infusion of this improved vector into the mouse model was associated with a complete normalization of liver OTC enzyme activity that persisted for at least 2 months with complete but transient correction in serum glutamine and urine orotic acid. These studies illustrate the utility of improved adenoviral vectors in the treatment of liver metabolic disease.

Adenoviridae↗
PubMed1996

Crystallisation of the Bacillus subtilis sporulation inhibitor SinR, complexed with its antagonist, SinI.

The transcription factor SinR, a pleiotropic regulator of late growth processes in Bacillus subtilis, has been crystallised as a complex with its antagonist SinI, in a form suitable for structural analysis. The SinI:SinR crystals diffract X-rays generated from a rotating copper anode source to 2.3 A spacing and a complete native dataset has been collected to this resolution limit. The space group of the crystals is P3(1)21 (or its enantiomorph P3(2)21) with cell dimensions a = b = 60.76 A, c = 87.79 A. Assuming that there is a single SinI:SinR heterodimer in the asymmetric unit, the crystals have a Vm of 2.53 A3.Da-1.

Bacillus subtilis↗
PubMed1996

Allelic association between a Ser-9-Gly polymorphism in the dopamine D3 receptor gene and schizophrenia.

We examined a Ser-9-Gly polymorphism in the dopamine D3 receptor gene for allelic association with schizophrenia in 133 patients currently treated with clozapine and 109 controls. Allele 1 (Ser-9) was significantly more frequent in the patients (69%) than in the controls (56%) (P = 0.004). The 1-1 genotype was more common (43% vs 30%) and the 2-2 genotype less common (5% vs 18%) in patients than in controls. When the patient group was subdivided on the basis of clinical response to clozapine, using a 20-point improvement in the global assessment scale as cut-off, genotype 1-1 was found to be more frequent among the non-responders (53% vs 36%, P = 0.04). To place our results in the context of previous studies of this polymorphism and schizophrenia, we performed a meta-analysis of all published data including the present sample. The combined analysis shows evidence for a modest association between genotype 1-1 and schizophrenia (odds ratio 1.25, 95% confidence interval 1.05-1.49, P = 0.01). These results suggest that the Ser-9 allele, or a nearby polymorphism in linkage disequilibrium, results in a small increase in susceptibility to schizophrenia.

Alleles↗
PubMed1996

Influence of food on the bioavailability and some pharmacokinetic parameters of diprafenone--a novel antiarrhythmic agent.

OBJECTIVE: The present study was done to investigate the effect of food on the bioavailability of diprafenone. METHODS: The most important pharmacokinetic parameters (Cmax, t1/2, AUC) and the relative oral availability of a solid oral preparation of racemic diprafenone were investigated when administered to fasting subjects and 10 min after a standard meal, in an open, randomised, crossover trial. Single oral doses of 100 mg were given on two different occasions, at least 1 week apart. The serum concentrations of diprafenone and its hydroxy-metabolite were determined up to 24 hours after administration by a sensitive, specific HPLC method. Fifteen healthy, male volunteers were enrolled in the trial. Their mean height, weight and age were 183 cm, 80 kg and 22 years, respectively. Fourteen volunteers were found to be rapid hydroxylators and one was a slow hydroxylator of debrisoquine. Only data from the rapid hydroxylators were used in the statistical analysis. RESULTS: Food increased the oral bioavailability of diprafenone by approximately 50%. This effect was similar in rapid and in slow hydroxylators. The only slow hydroxylator in this trial had an AUCzero-last ratio (with food/fasting) of 1.54. These findings suggest that diprafenone should be administered in a constant temporal relationship to food.

Administration, Oral↗
PubMed1996

The influence of smoking cessation and hypertriglyceridaemia on the progression of peripheral arterial disease and the onset of critical ischaemia.

OBJECTIVE: To investigate whether smoking and other cardiovascular risk factors were associated with deterioration of ankle/brachial pressure index or onset of critical ischaemia in patients with mild to moderate intermittent claudication. DESIGN AND SETTING: Longitudinal study in a London teaching hospital. SUBJECTS: 415 consecutive smokers, with symptoms of intermittent claudication and an ankle/brachial pressure index of <0.9, referred for a surgical opinion between April 1985 and December 1990, who were not considered for an immediate surgical procedure. MAIN OUTCOME RESULTS: Reduction in ankle/brachial pressure index of >0.14, onset of critical limb ischaemia. RESULTS: After one year of follow up 183 patients (44%) had stopped smoking (as evaluated by biochemical markers). With longer follow up only 110 patients (27%) had maintained smoking cessation. There were no differences in age, sex, and previous tobacco exposure between stoppers and smokers, but the proportion of diabetics among stoppers (20%) was greater than among those who continued smoking (10%) [p=0.01]. The annual rate of deterioration of ABPI was 21, 16 and 17% respectively in the first, second and third year of follow-up and the onset of critical ischaemia was observed in 52 patients (12.5%) during the period of follow-up. In univariate analyses, continued smoking, diabetes and presence of ischaemic heart disease were not associated with an increased risk of deterioration of ABPI, but hypertriglyceridaemia (> or = 2.2 mmol/l) was, [relative risk 1.7(95% CI 1.21-2.37), p=0.003], and patients having systolic blood pressure in the middle tertile (153-170 mmHg had a reduced risk of deterioration of ABPI, p=0.026. Hypertriglyceridaemia (> or = 2.2mmol/l) was the only independent factor associated with deterioration of ABPI in multivariate analysis [relative risk 1.8(95% CI:1.23-2.59), p=0.003] and also was associated with a relative risk of onset of critical ischaemia of 1.9 [(95% CI: 1.08-2.87), p=0.035], compared with triglyceride levels of <2.2mmol/l. CONCLUSION: For those with mild to moderate claudication, the lack of immediate benefit from cessation of smoking appears to be associated with a gradual return to smoking. Hypertriglyceridaemia was identified as the most important independent factor associated with the progression of peripheral arterial disease and onset of critical ischaemia.

Aged↗
PubMed1996

A phase II study in advanced breast cancer: ZD1694 ('Tomudex') a novel direct and specific thymidylate synthase inhibitor.

ZD1694 ('Tomudex'), a novel, direct and specific thymidylate synthase (TS) inhibitor, was developed in a collaborative research programme between Zeneca Pharmaceuticals and the Institute of Cancer Research (UK) and entered clinical trials in 1991; phase II studies began in 1992, using 3.0 mg m-2 every 3 weeks as a short 15 min infusion. Forty-six patients entered a phase II study of ZD1694 in advanced breast cancer. A total of 74% of patients had received prior systemic therapy (either as adjuvant cytotoxic or hormonal therapy or hormone therapy for advanced disease); 39% had received prior adjuvant cytotoxic chemotherapy. All patients had measurable disease and 50% had liver metastases. In all 43 patients were evaluable for response. Of these patients 26% achieved complete (CR) or partial response (PR) (95% Cl 14-42%). A response rate of 44% was seen in liver metastases. Two patients achieved CR of 265 and 301 days' duration respectively, one in locoregional disease, and one in liver metastases. The most common grade 3/4 adverse events were nausea and vomiting (11%), diarrhoea (11%) and leucopenia (20%). Grade 3/4, self-limited and reversible increases in transaminases were seen in 22% of patients. ZD1694 has useful single agent activity in patients with hormone-refractory advanced breast cancer, comparable with that reported for other anti-metabolites, with acceptable tolerability.

Adult↗