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Biomedical subjects

A D Morris

Publications and source records attributed to A D Morris.

At least 91 records · Page 5Linked to original sources
PubMed1997

The euglycaemic hyperinsulinaemic clamp: an evaluation of current methodology.

1. The recognition of the role of insulin resistance in disease states and the recent development of new drugs that modify insulin-dependent metabolism has led to increased use of the euglycaemic hyperinsulinaemic clamp to measure in vivo insulin sensitivity, but several key aspects of the technique are poorly documented in the literature. 2. We have evaluated the reproducibility and intersubject variation of measurements of insulin sensitivity in groups of insulin-sensitive and insulin-resistant subjects and assessed the effects of hand warning on haemodynamic and metabolic responses. 3. Subjects participated in one of two protocols: (i) 18 healthy male volunteers and 18 patients with hypertension and glucose intolerance were clamped on two occasions, 1 week apart with measurements of insulin sensitivity (M) derived after 120 and 180 min of hyperinsulinaemia; and (ii) six healthy volunteers were clamped on one occasion with simultaneous sampling of antecubital and 'arterialized' (dorsal hand) venous blood for comparison of plasma glucose concentrations and oxygen saturation and a further six volunteers were clamped on two occasions with and without the use of hand warming. 4. Measurements of M derived after 120 min (M120) and 180 min (M180) of hyperinsulinaemia were reproducible: the coefficients of repeatability (mg/kg per min) of M120 and M180 were 1.0 and 0.9 for volunteers and 1.0 and 1.0 for the patient group, respectively. The intersubject variation in insulin stimulus was high: coefficients of variation for M180 were 22% for volunteers compared with 38% for the patient group. In volunteers compared with the patient group, hand warming significantly increased venous oxygen saturations (95 +/- 2 vs 79 +/- 18%, respectively) and glucose concentrations (5.2 +/- 0.2 vs 4.5 +/- 0.4 mmol/L, respectively) and measurements of M were significantly higher using arterialized compared with antecubital venous blood. However, local hand warming was associated with systemic vasodilatation: blood pressure decreased (e.g. 6 mmHg diastolic; P < 0.05) with a compensatory increase in heart rate (8 b.p.m.). 5. In conclusion, clamps of 120 and 180 min duration yielded measurements of M that were reproducible. The technique is much more robust when used in the context of a crossover design because of the significant (20-40%) intersubject variation in M, even among apparently homogeneous male volunteers. Hand warming effectively arterializes venous blood and gives significantly higher M values, but induces systemic vasodilation, which may confound measurements of M.

Adult↗
PubMed1997

ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside, Scotland. Medicines Monitoring Unit.

OBJECTIVE: To evaluate the association between the use of ACE inhibitors and hospital admission for severe hypoglycemia and to explore the effects of potential confounding variables on this relationship. RESEARCH DESIGN AND METHODS: The association between the use of ACE inhibitors and the incidence of hypoglycemia is controversial. A recent study reported that 14% of all hospital admissions for hypoglycemia might be attributable to ACE inhibitors. We performed a nested case-control study, using a cohort of 6,649 diabetic patients taking insulin or oral antidiabetic drugs, on the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. From 1 January 1993 to 30 April 1994, we identified 64 patients who had been admitted to Tayside hospitals with hypoglycemia and selected 440 control patients from the same cohort. RESULTS: Hypoglycemia was associated with the use of ACE inhibitors (odds ratio [OR] 3.2, 95% CI 1.2-8.3, P = 0.023), whereas use of beta-blockers and calcium antagonists was not associated with an increased risk of hospitalization for hypoglycemia with ORs of 0.9 (95% CI 0.3-3.3) and 1.7 (95% CI 0.2-2.1), respectively. There were significant differences between case and control patients in type of diabetes treatment, diabetes duration, place of routine diabetes care, and congestive cardiac failure. These differences did not confound the relationship between ACE inhibitors and hypoglycemia (adjusted OR 4.3, 95% CI 1.2-16.0). CONCLUSIONS: The results show that the association between ACE inhibitor therapy and hospital admission for severe hypoglycemia is not explained by these confounding factors. Although ACE inhibitors have distinct advantages over other antihypertensive drugs in diabetes, the risk of hypoglycemia should be considered.

Adolescent↗
PubMed1997

No association between non-steroidal anti-inflammatory drugs and acute appendicitis in a case-control study.

BACKGROUND: A recent case-control study reported an association between non-steroidal anti-inflammatory drug (NSAID) use and acute appendicitis. This association was investigated in a case-control study of patients, aged 30 years and over, admitted as an emergency to hospitals in Tayside between 1989 and 1992, who had appendicectomy for acute appendicitis. METHODS: A record-linkage database containing records of dispensed prescriptions and hospital admissions was used. A total of 223 patients were identified. The medical records of 161 were checked, of which 138 were valid cases, and information on white cell count and NSAID exposure was recorded. Community and hospital controls were generated. RESULTS: Some 9.0 per cent of patients were prescribed NSAIDs within 90 days of hospitalization, compared with 7.6 per cent of community controls and 11.5 per cent of hospital controls. The odds ratio was 1.21 (95 per cent confidence interval 0.73-2.01) and 0.75 (0.43-1.32) respectively. There was no significant difference in white cell count between exposed and non-exposed cases. No increased risk of appendicectomy was associated with aspirin use: odds ratio 1.67 (0.52-5.30) and 0.37 (0.12-1.13) using community and hospital controls respectively. CONCLUSION: Appendicectomy for acute appendicitis is not associated with increased prior use of NSAIDs.

Adult↗
PubMed1996

Potential confounding effect of hand-warming on the measurement of insulin sensitivity.

1. Hand-warming is employed during metabolic studies to "arterialize' venous blood, but also has systemic haemodynamic effects. Study 1 aimed to determine if hand-warming affects the value for whole-body insulin sensitivity derived from the hyperinsulinaemic euglycaemic clamp technique. Study 2 was designed to assess the effect of hand-warming on contralateral forearm blood flow. 2. In study 1, eight healthy male subjects attended for four modified euglycaemic clamp studies, during which the right hand was placed in a heated-air hand box (55 degrees C), and the glucose infusion rate was adjusted according to blood samples from a cannula in either an ipsilateral dorsal hand vein or a contralateral antecubital vein with the box switched either on or off. In study 2, five healthy subjects attended two study days when the effect of 2 h of hand-warming (or control) on contralateral forewarm blood flow was measured. 3. Study 1; when clamps were performed according to samples taken from the contralateral antecubital vein, insulin sensitivity values were significantly lower during box-on versus box-off clamps (mean +/- SD 10.2 +/- 3.0 versus 13.0 +/- 3.8 mg min-1 kg-1, P < 0.05, 95% confidence interval -0.2, -5.3). When clamps were performed according to samples taken from the ipsilateral hand, there was no difference in insulin sensitivity during box-on versus box-off clamps (9.2 +/- 2.1 versus 9.0 +/- 1.7 mg min-1 kg-1, P not significant, 95% confidence interval -0.5, +0.9). There was a mean increase in heart rate of 6 beats/min in the box-on conditions (P < 0.05, analysis of variance). Study 2; forearm blood flow in the contralateral arm during hand-warming was significantly higher than in the control condition (P < 0.05, analysis of variance), although heart rate was similar on both study days. 4. Hand-warming had a detectable effect on insulin sensitivity when clamps were performed according to samples withdrawn from the contralateral arm, but no measurable effect when clamps were performed in the conventional manner. In addition, hand-warming increased heart rate during hyperinsulinaemia and contralateral FBF under basal conditions. These findings raise concern about unwanted (potentially confounding) systemic haemodynamic effects of hand-warming on the measurement of insulin sensitivity and insulin-mediated vasodilation.

Blood Glucose↗
PubMed1996

Development of a fluorescence polarization immunoassay for lorazepam quantification.

Lorazepam concentrations have been quantified in biological fluids using gas chromatography and high-performance liquid chromatography (HPLC). However, these methods are too time consuming and labor intensive for most nonresearch laboratories to offer. A fluorescence polarization immunoassay (FPIA) method for quantification of lorazepam was developed and validated using a reverse-phase HPLC method as the reference method. The FPIA method involves a single liquid-liquid extraction of 100 microliters of either serum or plasma, then direct analysis using the TDxFLx (Abbott Diagnostics, North Chicago, IL). FPIA calibrations were linear between 50 and 800 ng/ml using five calibrators prepared in human serum. Within-run precision (n = 10) for three serum controls (75, 300, and 600 ng/ml) resulted in coefficients of variation (CVs) of 5.7%, 5.4%, and 4.2%, respectively. Between-day precision studies for the three serum controls were 7.0%, 8.9% and 4.9%, respectively (n = 5). The analytical recovery of the three serum controls was 104.9%, 97.3% and 98.3%, respectively. There was an excellent linear correlation between the FPIA and HPLC determinations of 43 patient specimens (r = 0.990, slope = 0.961, intercept = 16.3). No interferences were found from many commonly prescribed nonbenzodiazepine drugs; however, other benzodiazepines that were tested will cross-react with this procedure and give inaccurate results. Therefore, this method should not be used in patients who are receiving other benzodiazepines in addition to lorazepam. The FPIA method described herein can be adapted to reliably measure lorazepam concentrations in serum or plasma.

Anti-Anxiety Agents↗
PubMed1995

The effects of rilmenidine and atenolol on mental stress, dynamic exercise and autonomic function in mild to moderate hypertension.

1. The effects of 4 week treatment with rilmenidine or atenolol on tests of mental stress, dynamic exercise, autonomic function and psychometric tests were evaluated in a randomized, double-blind, placebo-controlled, cross-over study. 2. After a 4 week placebo run-in, 12 patients with essential hypertension (blood pressure [BP] 160/95 +/- 15/7 mmHg) received rilmenidine 1-2 mg day-1, and atenolol 50-100 mg day-1, each for 4 weeks, with a 4 week placebo wash-out between drug treatments. 3. Both agents produced a comparable reduction in supine and erect BP. During the mental arithmetic test, BP and heart rate (HR) responses were similar for rilmenidine and atenolol. 4. During bicycle exercise, the increase in HR was significantly greater after rilmenidine (+50 vs 41 beats min-1, P = 0.04). During recovery, the areas under the curve for diastolic BP (46,450 vs 51,400 mmHg s, P = 0.02) and HR (49,445 vs 63,597 beats min-1 s, P = 0.001) were significantly less with atenolol than rilmenidine. 5. Neither rilmenidine nor atenolol affected mental performance as judged by arithmetic and psychomotor tests. Physiological responses to autonomic function tests (deep breathing, facial immersion, isometric handgrip and cold pressor) were preserved with both drugs. The standing to lying ratio was higher on atenolol (P = 0.01) and Valsalva ratio was higher on rilmenidine (P = 0.03). 6. In conclusion, rilmenidine and atenolol exerted comparable antihypertensive effects both at rest and during mental and dynamic stress. Atenolol attenuated HR responses to dynamic exercise and the Valsalva manoeuvre; rilmenidine did not interfere with the physiological responses of BP and HR during autonomic function tests.

Adrenergic beta-Antagonists↗
PubMed1995

Ultrasonic evaluation of movement of the diaphragm after acute cerebral infarction.

Respiratory dysfunction is an important complication of acute stroke but its mechanisms are poorly understood. Previous indirect assessments suggest that paralysis of the diaphragm occurs contralateral to the cerebral lesion. Diaphragmatic excursion was studied with real time ultrasound during quiet and deep breathing in 50 patients within 72 hours of acute stroke and 40 controls. During quiet breathing, hemidiaphragmatic movements were not significantly different between right hemispheric stroke, left hemispheric stroke, and controls. During deep inspiration, there was a significant bilateral reduction in hemi-diaphragmatic excursion in patients with stroke, for both right hemispheric stroke and left hemispheric stroke when compared with controls (both P < 0.001). Thus isolated hemidiaphragmatic paresis does not occur but maximal excursion of the diaphragm is reduced bilaterally in patients with acute stroke. This is a likely contributor to the respiratory dysfunction after acute stroke.

Acute Disease↗
PubMed1995

A comparison of the effects of methotrexate and misonidazole on the germinal cells of the subependymal plate of the rat.

The cytotoxic effects of the drugs methotrexate (MTX) and misonidazole have been assessed in the rat brain by quantifying changes in the constituent cell populations of a glial cell progenitor layer, the subependymal plate (SEP). Three distinct cell types can be identified in the SEP on the basis of their nuclear morphology: cells with small dark (SD), small light (SL) or large light (LL) nuclei. The cells with SD nuclei may present pluripotential glial cell precursors. A reduction in the total nuclear density of the SEP, after the local ventricular administration of MTX, could be accounted for largely by a loss of cells with SD nuclei; to approximately 45% of control values 2 days after MTX followed by a full recovery in numbers by day 5. A further decline in the number of cells with SD nuclei occurred at 12 weeks after MTX administration. The pattern of changes in the cellularity of the SEP, after misonidazole administration, were similar to those observed after MTX treatment, although the magnitude of the response was reduced. It was concluded that both drugs, but MTX in particular, could have a potential additive effect on glial progenitor cells when used in combination with other forms of cancer therapy including radiation.

Animals↗
PubMed1995

A pilot study of streptokinase for acute cerebral infarction.

We evaluated intravenous streptokinase in the treatment of cerebral infarction. Following neurological assessment and cerebral computed tomography (CT), patients aged 40-80 years with symptoms of anterior circulation acute ischaemic stroke were given 1.5 M units streptokinase or saline placebo in a double-blind randomized study. Twenty patients (10 streptokinase, 10 placebo), 11 males, 9 females, aged 57-79 years, were treated out of 512 consecutive admissions to the acute stroke unit over a 2-year period. Initial CT was normal in 11 (6 placebo, 5 streptokinase) and showed early signs of cerebral infarction in nine (4 placebo, 5 streptokinase). Median times from symptom onset to treatment were 5.2 h (placebo) and 5.8 h (streptokinase). Streptokinase treatment was associated with symptomatic hypotension in one patient. Repeat CT at 72 h demonstrated intracerebral haematoma in two patients and haemorrhagic infarction in one patient in the streptokinase group; the two cases of haematoma formation were associated with neurological deterioration and death. One patient in the placebo group had evidence of haemorrhagic infarction at 72 h. There were three deaths in each treatment group, all within the first 14 days. Patients with acute stroke can be evaluated with CT and treated with streptokinase within 6 h, but the opportunity for treatment is currently limited to few patients. Streptokinase treatment is not without risk, but potential clinical benefit justifies ongoing multicentre randomized trials.

Acute Disease↗
PubMed1995

The epidemic that never was: yellow fever in Hawaii.

The Kingdom of Hawaii suffered a disastrous series of epidemics starting from the first contact with Captain Cook's crew and continuing to the present. Despite the huge volume of shipping to and through Hawaii, one plague failed to appear. Yellow Jack (yellow fever) engendered more fear in sailors of the 19th century than any other disease. By 1910 the details of transmission were well-known and Hawaii met all the requirements for an epidemic. On October 30, 1910, the first case of shipboard yellow fever arrived at Honolulu but quarantine averted the threat. On October 28, 1911, a Hawaiian man, employed as a quarantine guard, was reported to have yellow fever and efforts were initiated to control a possible epidemic. This was the only occurrence of yellow fever in Hawaii.

Communicable Disease Control↗
PubMed1995

Comparative effects of rilmenidine and atenolol on tests of autonomic function and mental and dynamic exercise in patients with essential hypertension.

The aim of the present study was to compare the effects of rilmenidine (1-2 mg/day) and atenolol (50-100 mg/day) on tests of mental arithmetic, bicycle exercise, and autonomic function. Twelve male patients with mild-to-moderate hypertension (blood pressure, 160/95 +/- 15/7 mm Hg; age range, 32 to 60 years) completed a randomized, double-blind, crossover study. Both drugs were well tolerated and, after 4 weeks of monotherapy, were associated with significant reductions in supine and erect BP. Hemodynamic responses to mental arithmetic were similar for both drugs, and neither agent affected mental performance as judged by psychomotor testing. The increase in heart rate during bicycle exercise was significantly greater with rilmenidine (50 vs. 41 beats/min, p = 0.04), and during the postexercise recovery phase, areas under the curve for diastolic blood pressure and heart rate were smaller after atenolol than after rilmenidine: 46,450 versus 51,400 mm Hg.s (p = 0.02) and 49,445 versus 63,597 beats/min.s (p = 0.001), respectively. In conclusion, rilmenidine and atenolol exert comparable antihypertensive effects both at rest and during mental and dynamic exercise. Although atenolol blunted the heart rate responses to dynamic exercise and the Valsalva maneuver, rilmenidine showed no interference with physiological hemodynamic responses of blood pressure and heart rate during tests of sympathetic and parasympathetic function.

Adult↗
PubMed1994

Pressor and subpressor doses of angiotensin II increase insulin sensitivity in NIDDM. Dissociation of metabolic and blood pressure effects.

There is evidence that the renin-angiotensin system may be involved in the metabolic as well as the cardiovascular features of diabetes and that pressor doses of angiotensin II (ANG II) increase insulin sensitivity in parallel with blood pressure (BP) in healthy subjects, but the effects of ANG II on insulin sensitivity have not been previously reported in patients with non-insulin-dependent diabetes mellitus (NIDDM). In a randomized, double-blind, placebo-controlled, crossover study, 11 patients with NIDDM attended 3 study days to evaluate the effects of a 3-h infusion of subpressor and pressor doses of ANG II on whole body insulin sensitivity using the euglycemic hyperinsulinemic clamp. BP and heart rate were recorded, and blood samples were collected for serum insulin, C-peptide, potassium, catecholamines, plasma renin activity, and plasma ANG II concentrations. Plasma levels of ANG II (means +/- SD) were 9 +/- 4, 29 +/- 9, and 168 +/- 47 pmol/ml after placebo, low dose infusion, and high dose infusion, respectively. The higher dose of ANG II was associated with significant increases in BP (e.g., 18 mmHg systolic BP at 150 min) and plasma aldosterone. Whole body insulin sensitivity was 23.8 +/- 12.7 mumol glucose.kg-1.min-1 after placebo and 30.6 +/- 12.7 and 27.2 +/- 13.3 following low and high dose ANG II infusions, respectively (P < 0.05, analysis of variance). In summary, acute infusion of ANG II, with or without an increase in BP, increases insulin sensitivity in normotensive patients with NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗