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Biomedical subjects

A D Morris

Publications and source records attributed to A D Morris.

At least 73 records · Page 4Linked to original sources
PubMed1998

Association of road-traffic accidents with benzodiazepine use.

BACKGROUND: Psychomotor studies suggest that commonly prescribed psychoactive drugs impair driving skills. We have examined the association between the use of psychoactive drugs and road-traffic accidents. METHODS: We used dispensed prescribing as a measure of exposure in a within-person case-crossover study of drivers aged 18 years and over, resident in Tayside, UK, who experienced a first road-traffic accident between Aug 1, 1992, and June 30, 1995, and had used a psychoactive drug (tricyclic antidepressant, benzodiazepine, selective serotonin-reuptake inhibitor, or other psychoactive drug [mainly major tranquillisers]) between Aug 1, 1992, and the date of the accident. For each driver, the risks of having a road-traffic accident while exposed and not exposed to a drug were compared. FINDINGS: 19386 drivers were involved in a first road-traffic accident during the study period. 1731 were users of any study drug. On the day of the accident, 189 individuals were taking tricyclic antidepressants (within-patient exposure odds ratio for an accident 0.93 [95% CI 0.72-1.21]), 84 selective serotonin-reuptake inhibitors (0.85 [0.55-1.33]), 235 benzodiazepines (1.62 [1.24-2.12]), and 47 other psychoactive drugs (0.88 [0.62-1.25]). The risk associated with benzodiazepine use decreased with increasing driver's age and was greater when the breath test for alcohol was positive. A dose-response relation was evident with benzodiazepines. The increased risk with benzodiazepines was significant for long-half-life drugs, used as anxiolytics, and for short-half-life hypnotics (all zopiclone). INTERPRETATION: Users of anxiolytic benzodiazepines and zopiclone were at increased risk of experiencing a road-traffic accident. Users of anxiolytic benzodiazepines and zopiclone should be advised not to drive.

Accidents, Traffic↗
PubMed1998

Which drugs benefit diabetic patients for secondary prevention of myocardial infarction? DARTS/MEMO Collaboration.

UNLABELLED: Diabetic patients have increased mortality following myocardial infarction. We review the evidence for benefit in diabetic patients, of the major drug groups used as secondary prevention. Beta blockers: meta-analyses suggest a reduction in mortality of 35% with beta blockers. Diabetic patients should receive beta blockers post myocardial infarction. In many patients, the benefits of beta blockers will outweigh relative contraindications. Aspirin: meta-analyses of antiplatelet therapy in high-risk subjects have shown substantial benefits. Aspirin should be prescribed for secondary prevention. Lipid lowering with statins: subgroup analyses of the major secondary prevention trials show substantial benefits across a wide range of baseline cholesterol and LDL levels. These drugs should be prescribed as secondary prevention to patients with diabetes whose total cholesterol is > 4.0 mmol(-1). Angiotensin converting enzyme inhibitors (ACEIs): the few subgroup analyses that exist from ACEI trials suggest that diabetic and non-diabetic patients derive similar benefits. Diabetic subjects who have systolic dysfunction after myocardial infarction should receive ACEIs. Treatment combination: data exist to suggest that most of these drugs produce benefit independently. CONCLUSION: diabetic patients benefit from secondary prevention with drug treatment as much as, or more than, non-diabetic patients.

Adrenergic beta-Antagonists↗
PubMed1998

A study of the reproducibility of three different normalisation methods in intramuscular dual fine wire electromyography of the shoulder.

The purpose of this study was to determine the most appropriate method of normalisation for dual fine wire electromyography of shoulder muscles. Five healthy subjects were studied, with one muscle investigated in each subject (2 supraspinatus, 2 infraspinatus, 1 subscapularis). Three dual fine wire electrodes were inserted 1 cm apart around the recognised insertion points. Each subject performed five types of cyclic exercise on an isokinetic muscle dynamometer with an isometric maximal voluntary contraction (MVC) being performed before and after the exercise protocol. The EMG signal was normalised using each of the MVC voltage, the peak voltage and the whole-cycle mean voltage. There was a considerable difference (5-143%) between the MVC signals pre- and post-protocol, although no systematic trend was demonstrable. The overall mean between electrode variation in the normalised signal measured at the peak of the cycle ranged from 48-71% when normalised to pre-protocol MVC, but only 4-13% when normalised to the peak voltage and 9-17% using the whole-cycle mean voltage. However the pattern of activation within the movement cycle, which was preserved by normalisation using the peak or mean signal, was consistent between different electrode positions. It was concluded that the EMG signal depended on electrode position even when near the recognised insertion point, and that the MVC signal is highly variable in magnitude between electrodes and between pre- and post-protocol measurements.

Adult↗
PubMed1998

Systemic nitric oxide synthase inhibition increases insulin sensitivity in man.

1. Recent evidence shows that skeletal muscle blood flow is an important determinant of insulin sensitivity and that insulin-mediated vasodilatation is nitric oxide dependent. These results have given rise to the hypothesis that endothelial nitric oxide inhibition may decrease insulin sensitivity in humans. 2. We examined this hypothesis directly by evaluating the effects of systemic nitric oxide synthase inhibition with NG-monomethyl L-arginine (3 mg h-1 kg-1) on whole-body glucose uptake (euglycaemic hyperinsulinaemic clamp) and calf blood flow (bilateral calf venous occlusion plethysmography) in 16 healthy male subjects in a randomized, double-blind, placebo-controlled, crossover study. 3. NG-Monomethyl L-arginine infusion was associated with a pressor effect (119/61 +/- 2/2 compared with 114/58 +/- 2/2 mmHg for placebo; P < 0.001), and a negative chronotropic response (57 +/- 2 compared with 62 +/- 2 beats/min for placebo; P < 0.001). The glucose infusion rate was significantly increased after infusion of NG-monomethyl L-arginine (8.9 +/- 0.9 compared with 7.9 +/- 0.8 mg min-1 kg-1 for placebo; P = 0.002). Whole-body glucose uptake increased during the clamp, with values of 9.4 +/- 0.7 and 10.9 +/- 0.8 mg min-1 kg-1 for placebo and NG-monomethyl L-arginine respectively (P = 0.036; 95% confidence interval 0.2,2.8). NG-Monomethyl L-arginine was associated with increased calf blood flow by comparison with placebo (P < 0.05, area under curve). 4. These data show for the first time that systemic inhibition of nitric oxide synthesis increases rather than decreases whole-body glucose uptake. We suggest that the higher skeletal muscle blood flow seen after NG-monomethyl L-arginine may explain the observed increase in whole-body glucose uptake.

Adult↗
PubMed1998

How reproducible is bilateral forearm plethysmography?

AIMS: In studies using strain-gauge forearm plethysmography to measure changes in forearm blood flow (FBF) during intra-arterial infusions of vasoactive substances, measurements are often made in both arms simultaneously and the change in ratio of the infused and control arms used to express responses. However, the reproducibility of bilateral plethysmography in this setting has not been addressed in published studies. The unilateral technique remains in use, and forearm vascular resistance (FVR), an alternative method of expressing responses, is used by some investigators. We have assessed: (a) the intra-subject variability of bilateral FBF measurements (FBF ratios) at rest, after unilateral forearm exercise, and during intra-arterial infusions of vasoconstrictor substances; (b) whether bilateral plethysmography is more reproducible than unilateral plethysmography; and (c) the reproducibility of FVR (unilateral and bilateral). METHODS: Study 1 Nine healthy subjects attended 3 study days, 1 week apart. FBF was measured at rest and after 2 min of standardized unilateral forearm exercise; between-day intra-subject variability was expressed as coefficients of variation (CV) calculated using two-way analysis of variance (ANOVA). Study 2 Five healthy subjects attended 2 study days when FBF was measured during incremental infusions of noradrenaline (15, 30, 150, 300 pmol min[-1]) and angiotensin II (1, 5, 10, 50 pmol min[-1]); for each individual subject at each dose intra-subject variability was assessed using the difference between responses (percentage change from baseline) on days 1 and 2. RESULTS: Study 1 At rest, intra-subject variability (CV) of baseline FBF ratios was 19% compared with 31% (left) and 39% (right) for unilateral FBF measurements. After ipsilateral exercise, unilateral FBF measurements were more reproducible (32 vs 17%) than FBF ratios; by 20 min after exercise, the previous pattern had been re-established (19 vs 27%). Intra-subject variability (CV) of baseline FVR ratio and post-exercise FVR was 14%. Study 2 Inter-quartile ranges of the differences between responses on days 1 and 2 (FBF ratios vs FBF) were: angiotensin II 14 vs 18%; noradrenaline 16 vs 27%. CONCLUSIONS: FBF ratios are more reproducible than unilateral FBF measurements at rest (CV 19% vs 39%) and for measuring responses to intra-arterial infusions of vasoconstrictor substances. FVR may have a small reproducibility advantage. Non-experimental stimuli can cause significant and misleading changes in measured responses if unilateral measurements are used; it is therefore recommended that responses to intra-arterial infusions should be measured using bilateral forearm plethysmography with the results expressed as FBF ratios.

Angiotensin II↗
PubMed1998

Lacidipine: effects on vascular pressor responses throughout the dosage interval in normotensive subjects.

AIMS: To assess the duration and consistency of the pharmacological activity of the dihydropyridine calcium antagonist drug, lacidipine. METHODS: Eight healthy normotensive young males participated in a double-blind randomised crossover comparison of single and multiple doses (for 2 weeks) of lacidipine and placebo. The calcium antagonist effects were quantified at 2, 6 and 24 h post dose by the extent of the attenuation of the pressor responses to the intravenous administration of the vasoconstrictors angiotensin II and noradrenaline. RESULTS: After 2 weeks of treatment, lacidipine consistently and significantly attenuated the pressor responses to both agents at 2 h post dose. At 6 and 24 h post dose there was a significant and progressive decline in the effectiveness of lacidipine in attenuating the pressor responses and for the response to angiotensin II there was no statistically significant effect at either 6 or 24 h post dose. CONCLUSIONS: These results indicate that there is an obvious 'peak' in the pharmacological activity of lacidipine at about 2 h post dose and that this activity is not fully and consistently maintained throughout 24 h.

Adult↗
PubMed1998

Hyperosmolar nonketotic coma precipitated by lithium-induced nephrogenic diabetes insipidus.

A 45-year-old man, with a 10-year history of manic depression treated with lithium, was admitted with hyperosmolar, nonketotic coma. He gave a five-year history of polyuria and polydipsia, during which time urinalysis had been negative for glucose. After recovery from hyperglycaemia, he remained polyuric despite normal blood glucose concentrations; water deprivation testing indicated nephrogenic diabetes insipidus, likely to be lithium-induced. We hypothesize that when this man developed type 2 diabetes, chronic polyuria due to nephrogenic diabetes insipidus was sufficient to precipitate hyperosmolar dehydration.

Antimanic Agents↗
PubMed1998

Dietary sodium restriction impairs insulin sensitivity in noninsulin-dependent diabetes mellitus.

Dietary sodium restriction has a variety of effects on metabolism, including activation of the renin-angiotensin system. Angiotensin II has complex metabolic and cardiovascular effects, and these may be relevant to the effects of both nonpharmacological and pharmacological interventions in noninsulin-dependent diabetes mellitus (NIDDM). We have assessed the effect of dietary sodium restriction on insulin sensitivity and endogenous glucose production in eight normotensive patients with diet-controlled NIDDM who underwent hyperinsulinemic clamp studies in a randomized, double-blind, placebo-controlled cross-over protocol after two 4-day periods on sodium replete (160 mmol/day) and sodium deplete (40 mmol/day) diets. Mean +/- SD 24-h urinary sodium was 197 +/- 76.0 mmol (replete) and 67 +/- 19.5 mmol (deplete), P = 0.03. Insulin sensitivity was 42.0 +/- 11.3 mumol/kg.min (replete) and 37.0 +/- 11.6 mumol/kg.min (deplete), P = 0.04 (a reduction of 12%). Blood pressure was 130 +/- 21/78 +/- 11 mmHg (replete) and 128 +/- 12/73 +/- 10 mmHg (deplete). Dietary sodium restriction may result in a decrease in peripheral insulin sensitivity in normotensive patients with NIDDM, possibly via an elevation in prevailing angiotensin II concentrations.

Aged↗
PubMed1998

Diabetes and lower-limb amputations in the community. A retrospective cohort study. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland/Medicines Monitoring Unit.

OBJECTIVE: There are few U.K. data on the incidence rates of amputation in diabetic subjects compared with the nondiabetic population. RESEARCH DESIGN AND METHODS: We performed a historical cohort study of first lower-extremity amputations based in Tayside, Scotland (population 364,880) from 1 January 1993 to 31 December 1994. The Diabetes Audit and Research in Tayside Scotland (DARTS) database was used to identify a prevalence cohort of 7,079 diabetic patients on 1 January 1993. We estimated age-specific and standardized incidence rates of lower-limb amputations in the diabetic and nondiabetic cohorts. Results were compared with a previous study that evaluated lower-extremity amputations in diabetic patients in Tayside in 1980-1982. RESULTS: There were 221 subjects who underwent a total of 258 nontraumatic amputations. Of the 221 subjects, 60 (27%) patients were diabetic (93% NIDDM), and 63% were first amputations. The median duration of diabetes was 6 years (range: newly diagnosed to 41 years). Nonhealing ulceration (31%) and gangrene (29%) were the two main indications for amputation in the diabetic subjects. Of the 161 nondiabetic subjects, 140 (80%) underwent first amputations. The adjusted incidences in the diabetic and nondiabetic groups were 248 and 20 per 100,000 person-years, respectively. Tayside patients with diabetes thus had a 12.3-fold risk of an amputation compared with nondiabetic residents (95% CI 8.6-17.5). The estimated proportion of diabetic patients in the population rose from 0.81% in 1980-1982 to 1.94% in 1993-1994, whereas the absolute rate of amputation in diabetic subjects was unchanged from that in 1980-1982. CONCLUSIONS: These population-based U.K. amputation data are similar to amputation rates in the U.S. Amputation rates appear to have decreased significantly since 1980-1982. The impact of diabetes education and prevention programs that target the processes leading to amputation can now be evaluated.

Adolescent↗
PubMed1997

Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus. The DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland. Medicines Monitoring Unit.

BACKGROUND: Intensive insulin treatment effectively delays the onset and slows the progression of microvascular complications in insulin-dependent diabetes mellitus (IDDM). Variable adherence to insulin treatment is thought to contribute to poor glycaemic control, diabetic ketoacidosis, and brittle diabetes in adolescents and young adults with IDDM. We assessed the association between the prescribed insulin dose and the amount dispensed from all community pharmacies with the Diabetes Audit and Research in Tayside Scotland (DARTS) database. METHODS: We studied 89 patients, mean age 16 (SD 7) years, diabetes duration 8 (4) years, and glycosylated haemoglobin (HbA1c) 8.4 (1.9)%, who attended a teaching hospital paediatric or young-adult diabetes clinic in 1993 and 1994. The medically recommended insulin dose and cumulative volume of insulin prescriptions supplied were used to calculate the days of maximum possible insulin coverage per annum, expressed as the adherence index. Associations between glycaemic control (HbA1c), episodes of diabetic ketoacidosis, and all hospital admissions for acute complications and the adherence index were modelled. FINDINGS: Insulin was prescribed at 48 (19) IU/day and mean insulin collected from pharmacies was 58 (25) IU/day, 25 (28%) of the 89 patients obtained less insulin than their prescribed dose (mean deficit 115 (68; range 9-246] insulin days/annum). There was a significant inverse association between HbA1c and the adherence index (R2 = 0.39; p < 0.001). In the top quartile (HbA1c > 10%), 14 (64%) of individuals had an adherence index suggestive of a missed dose of insulin (mean deficit 55 insulin days/annum). There were 36 admissions for complications related to diabetes. The adherence index was inversely related to hospital admissions for diabetic ketoacidosis (p < 0.001) and all hospital admissions related to acute diabetes complications (p = 0.008). The deterioration in glycaemic control observed in patients aged 10-20 years was associated with a significant reduction (p = 0.01) in the adherence index. INTERPRETATION: We found direct evidence of poor compliance with insulin therapy in young patients with IDDM. We suggest that poor adherence to insulin treatment is the major factor that contributes to long-term poor glycaemic control and diabetic ketoacidosis in this age group.

Adolescent↗
PubMed1997

The diabetes audit and research in Tayside Scotland (DARTS) study: electronic record linkage to create a diabetes register. DARTS/MEMO Collaboration.

OBJECTIVES: To identify all patients with diabetes in a community using electronic record linkage of multiple data sources and to compare this method of case ascertainment with registers of diabetic patients derived from primary care. DESIGN: Electronic capture-recapture linkage of records included data on all patients attending hospital diabetes clinics, all encashed prescriptions for diabetes related drugs and monitoring equipment, all patients discharged from hospital, patients attending a mobile unit for eye screening, and results for glycated haemoglobin and plasma glucose concentrations from the regional biochemistry database. Diabetes registers from primary care were from a random sample of eight Tayside general practices. A detailed manual study of relevant records for the 35,144 patients registered with these eight general practices allowed for validation of the case ascertainment. SETTING: Tayside region of Scotland, population 391,274 on 1 January 1996. MAIN OUTCOME MEASURES: Prevalence of diabetes; population of patients identified by different data sources; sensitivity and positive predictive value of ascertainment methods. RESULTS: Electronic record linkage identified 7596 diabetic patients, giving a prevalence of known diabetes of 1.94% (0.21% insulin dependent diabetes, 1.73% non-insulin dependent): 63% of patients had attended hospital diabetes clinics, 68% had encashed diabetes related prescriptions, 72% had attended the mobile eye screening unit, and 48% had biochemical results diagnostic of diabetes. A further 701 patients had isolated hyperglycaemia (plasma glucose > 11.1 mmol/l) but were not considered diabetic by general practitioners. Validation against the eight general practices (636 diabetic patients) showed electronic linkage to have a sensitivity of 0.96 and a positive predictive value of 0.95 for ascertainment of known diabetes. General practice lists had a sensitivity of 0.91 and a positive predictive value of 0.98. CONCLUSIONS: Electronic record linkage was more sensitive than general practice registers in identifying diabetic subjects and identified an additional 0.18% of the population with a history of hyperglycaemia who might warrant screening for undiagnosed diabetes.

Diabetes Mellitus↗
PubMed1997

Angiotensin-converting enzyme gene polymorphism and cardiovascular disease.

1. The crucial role played by the renin-angiotensin-aldosterone system in the cardiovascular system and the immense therapeutic potential of angiotensin-converting enzyme inhibitors and, more recently, angiotensin II receptor blocking agents, in both heart failure and post-myocardial infarction is becoming increasingly evident. Polymorphisms within the genes controlling this enzyme system are candidates for the elucidation of the pathogenesis of cardiovascular disease and this link is both intriguing and provocative. Recently, an association between a polymorphism of the angiotensin-converting enzyme gene and phenotypic expression of cardiovascular disease, namely myocardial infarction, was reported. Since then, several small case-controlled studies have confirmed an association with manifestations of ischaemic heart disease or various other cardiac end-points. However, in a large prospective study the angiotensin-converting enzyme gene conferred no appreciable risk. 2. Our aim was to review the evidence that links polymorphisms of the angiotensin-converting enzyme gene with cardiovascular disease. We searched the Medline database (1990-1997) using the key words myocardial infarction, ischaemic heart disease, angiotensin-converting enzyme and polymorphisms and performed a search of the reference citation of relevant articles. We selected clinical studies on cardiovascular disease related to the angiotensin-converting enzyme genotype. 3. Taken together, the available evidence supports the notion that the DD-angiotensin-converting enzyme genotype adversely influences specific cardiovascular diseases but appears to do so in specific geographical areas and in particular patient subgroups. It is not yet known whether it does this through an interaction with other genes or by as yet unexplained biochemical mechanisms. 4. We should regard the current data with the angiotensin-converting enzyme genotype as an intriguing clue in the pathogenesis of cardiovascular disease. However, the main factor against this potential benefit is that the impact of the DD genotype appears to be small and its clinical manifestations rather heterogeneous.

Cardiovascular Diseases↗
PubMed1997

Specific insulin assays, insulin sensitivity and blood pressure.

Serum insulin concentrations have been used as markers of insulin resistance in population studies examining the relationship between insulin resistance and blood pressure, but the relationship is variable among studies. We hypothesized that differences in cross-reactivity of insulin assays with proinsulin and its split/des-amino products might account for the variation. We therefore examined fasting and post-glucose load serum insulin concentrations (determined by both specific and conventional assays), insulin sensitivity (measured by the euglycaemic clamp technique), and blood pressure, in a group of 56 diabetic (NIDDM) and non-diabetic subjects. Insulin concentrations as measured by the two methods were highly correlated (r = 0.97, p < 0.0001), and the relationships among serum insulin concentrations, insulin sensitivity and blood pressure were independent of assay method; for example, in non-diabetic subjects the univariate correlation between log10AUC insulin and insulin sensitivity index was similar with both methods [r = -0.81 vs. r = -0.82, p < 0.0001 (specific vs. conventional assay)]. Discrepancies between studies in the relationship between serum insulin concentrations and blood pressure are unlikely to be due to cross-reactivity of conventional insulin assays with proinsulin-like molecules.

Adult↗
PubMed1997

Eriochrome Black T, structurally related to suramin, inhibits angiogenesis and tumor growth in vivo.

The polyanionic species suramin is a potential anti-cancer agent of narrow therapeutic index. Among other pharmacological characteristics, suramin is an inhibitor of angiogenesis. We have targeted its angiostatic properties as part of a program to discover less toxic analogs. From screening a series of commercially available compounds, structurally related to suramin and containing a sulfonic acid substituted naphthylamine moiety, we discovered a new lead, Eriochrome Black T (EBT). EBT is a novel inhibitor of angiogenesis, more potent and less toxic than suramin in the chick chorioallantoic membrane assay. EBT was more active than suramin in inhibiting endothelial cell proliferation in primary culture and in inhibiting proliferation of three tumor cell lines, A431, L1210 and M5076 (IC50 10-100 microM). Cell cycle studies on the A431 line showed that both EBT and suramin caused an accumulation of cells in the S phase, EBT being 10-fold more potent. We suggest that this cell cycle perturbation is linked to inhibition of topoisomerase II catalytic activity. EBT was found to be a moderate but significant inhibitor of matrix metalloproteinases (10 microM range), more efficient than suramin. In a s.c. M5076 sarcoma model in mice, EBT had similar efficacy to suramin both by the i.p. or s.c. route and was moreover better tolerated. Combined pharmacological results show that EBT compared favorably with suramin in all assays, and that in ovo and in vivo, EBT is an analog of suramin with diminished toxicity.

Animals↗