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Biomedical subjects

H McIntyre

Publications and source records attributed to H McIntyre.

At least 19 recordsLinked to original sources

Optimal evaluation of digital electroencephalograms.

Currently available digital EEG equipment provides considerably greater opportunities for clinical data analysis than is generally appreciated especially when appropriate software is used. Data from 7 different laboratories that had been obtained for routine diagnostic evaluations on 7 different EEG instruments and stored on compact disks were investigated. Since the instruments do not filter the data at input, ultra slow activity down to 0.01 Hz is currently being recorded but the attenuation factor is instrument dependent. Nevertheless, relevant clinical information is potentially available in these data and needs to be explored. Several examples in regard to epilepsy are presented. Determination of seizure onset may depend on the frequencies that are examined. The use of appropriate filter settings and viewing windows for the clinical question to be answered is stressed. Differentiation between simple and complex spike wave discharges, as well as spread of spikes, can readily be achieved by expanding the time base to 1 or 2 seconds and placing a cursor on the peak of the negative spike. Latencies in the millisecond range can then become apparent. EEGs co-registered with MEG should be evaluated with the same software in order to allow an adequate assessment of the similarities and differences between electrical and magnetic activity. An example of a comparison of EEG, planar gradiometers and magnetometers for an averaged spike is shown.

Brain Diseases↗

An overview of the pharmacology and clinical efficacy of indapamide sustained release.

The relationship between blood pressure (BP) and cardiovascular risk is clearly established; hypertension increases the rate of cardiovascular. High systolic blood pressure (SBP) may be the main parameter involved in cardiovascular morbidity and mortality. The benefit of lowering BP, particularly with diuretics has been proven in many outcome studies. Indapamide, a thiazide-type diuretic, was available for many years at a dosage of 2.5 mg in an immediate release formulation. A new sustained release (SR) formulation has been developed in order to allow the same antihypertensive efficacy with a better acceptability profile. This paper reviews the pharmacology of indapamide 1.5 mg SR from the bench to the bedside. Indapamide has a dual mechanism of action: diuretic effect at the level of the distal tubule in the kidney and a direct vascular effect, both of which contribute to the antihypertensive efficacy of the drug. The SR formulation contains a hydrophilic matrix, which delivers a smoother pharmacokinetic profile. This avoids unnecessary plasma peak concentrations, which may be associated with side effects. Indapamide SR has now been extensively used in hypertensive patients, including those at increased risk, for example elderly or diabetic patients. It has been shown to decrease BP, particularly SBP, with 24-h efficacy, allowing a once-daily dosage. Studies have demonstrated BP lowering to be at least as effective as all major therapeutic classes including the more recent antihypertensive drugs. Beyond BP decrease, indapamide SR has also been shown to protect against hypertensive target-organ damage in the heart and the kidney and to have a favorable metabolic profile. A broad evidence-base has accumulated to support the benefit of indapamide 1.5 mg SR in hypertensive patients, alone or as part of combination therapy, as recommended by the majority of guidelines.

Albuminuria↗

The role of losartan in cost-effective hypertension control.

Despite recent guidelines emphasising the need for aggressive treatment in patients with elevated blood pressure, the control of hypertension in Europe and the USA is poor, imposing a considerable burden in terms of patient morbidity and mortality, and associated healthcare costs. A major factor contributing to the suboptimal control of hypertension is the failure of patients to adhere to their prescribed therapy. Drug side-effects are an important cause of non-compliance and prescribing a well-tolerated agent that promotes good compliance is therefore the key to the cost-effective management of hypertension. Several studies have demonstrated that patients are more likely to remain on therapy with the angiotensin II antagonist losartan than other antihypertensives. Although the acquisition costs of new antihypertensives such as losartan are greater than for older drugs, such costs represent only a small proportion of the total cost of prescribing antihypertensive therapy. When accessory costs are also considered, the total cost of care with newer antihypertensives is comparable with those for diuretics. The costs involved if therapy has to be switched due to unacceptable side-effects also need to be taken into account when assessing relative cost effectiveness. Furthermore, savings may accrue from the non-haemodynamic benefits of losartan, such as improved cognitive function and renal protection. Further studies will increase awareness of the true cost effectiveness of antihypertensive drugs.

Antihypertensive Agents↗

Intracellular sodium and contractile function in hypertrophied human and guinea-pig myocardium.

We tested the hypothesis that in left ventricular myocardial hypertrophy (LVH) the positive staircase effect is impaired and is related to a raised intracellular [Na+] ([Na+]i). Human myocardial specimens were obtained from patients undergoing mitral and aortic valve surgery, the latter group had LVH. LVH was induced in guinea-pigs by ascending aortic constriction. The extent of hypertrophy was quantified by measuring myocyte cross-section area, echocardiographic mass (in humans) and heart-to-body weight ratio (in guinea-pigs). The response to increasing stimulation frequency was expressed as the ratio of tension generated at 1.6 and 0.8 Hz (T1.6/0.8); ratios greater and less than 1.0 equate with positive and negative force/frequency relationships respectively. [Na+]i was measured using ion-selective microelectrodes. In human and guinea-pig myocardium T1.6/0.8 values decreased and [Na+]i increased with hypertrophy. For guinea-pig myocardium T1.6/0.8 decreased from 1.39 +/- 0.05 to 1.02 +/- 0.05 and [Na+]i increased from 7.3 +/- 1.4 to 12.1 +/- 1.3 mM in LVH. There was a close relationship between the reduction of T1.6/0.8 and increase of [Na+]i which was also observed when the [Na+]i was increased with strophanthidin in normal myocardium. The recovery of a raised [Na+]i after an acute acidosis was slowed in hypertrophied myocardium and stabilised at a higher level, suggesting that the membrane mechanisms that regulate [Na+]i are reset.

Acidosis↗

Quantitative genetics and the persistence of environmental effects in clonally propagated organisms.

Phenotype is often viewed as a product of genes and the environment in which these genes are expressed. However, numerous studies have shown that environment can cause lasting changes in phenotype that can be passed from one generation to the next, much as genes are transmitted. In clonally propagated organisms, persistence of environmental effects has been observed in a range of plant and animal species, but has rarely been the object of study. We measured the persistence and magnitude of environmental effects on phenotype over three clonal generations in the arctic sedge Eriophorum vaginatum. We found that the environment in which tillers developed had large effects on their later performance (parental effects) and that these effects were in part independent of the size of tillers. The magnitude and persistence of environmental effects did not differ between environmental treatments or among genotypes. However, after 52 weeks of growth and two rounds of clonal propagation, grandparental treatment effects were not significant. We describe methods that can be used in quantitative genetics studies of clonal organisms to reduce bias in estimates of genotypic and environmental variance and argue that the persistence of environmental effects in clonal plant material has ecological and evolutionary consequences similar to those described for maternal environmental effects in sexual organisms.

Environment↗

Abnormal action potential conduction in isolated human hypertrophied left ventricular myocardium.

INTRODUCTION: Cardiac hypertrophy is associated with an increased incidence of arrhythmias that result from altered action potential configuration or propagation velocity. These variables were measured in isolated preparations of human left ventricular myocardium and correlated with the degree of hypertrophy. METHODS AND RESULTS: Cardiac mass was estimated by echocardiography and cell diameter was measured from fixed isolated specimens; the two variables correlated significantly. Action potential duration was measured under field stimulation but was independent of the degree of hypertrophy; however, the duration was longer in septal preparations (405 +/- 12 msec, 37 degrees C, 1-Hz stimulation) than in papillary muscles (342 +/- 11 msec). Conduction velocity decreased progressively as cell diameter increased both in septal and papillary muscle preparations. Cable analysis showed that the variation of conduction velocity could be accounted for adequately by an increase of the intracellular resistivity of the preparations. CONCLUSION: The data suggest that conduction defects occur in a progressive manner in human hypertrophy, which would provide an important substrate for dysrhythmias in human left ventricular hypertrophy and could result from a decrease of electrical coupling between adjacent myocardial cells.

Action Potentials↗

Endotoxemia, complement, and white blood cell activation in cardiac surgery: a randomized trial of laxatives and pulsatile perfusion.

Endotoxin activates complement and white blood cells and all are implicated in the pathologic effects of cardiopulmonary bypass (CPB). We investigated if reduction in intestinal bacterial load with a laxative and/or pulsatile perfusion to improve bowel circulation during CPB reduced endotoxemia and complement and white blood cell activation. Sixty patients were randomized to four groups in a 2 x 2 factorial structure: group 1 (no laxative, nonpulsatile perfusion); group 2 (laxative, nonpulsatile perfusion); group 3 (no laxative, pulsatile perfusion); and group 4 (laxative, pulsatile perfusion). Plasma concentrations of endotoxin, C3a and C5a, and granulocyte elastase (GE) were measured before anesthesia, skin incision, and heparin administration; during CPB (1, 30, 60, 90, and 120 minutes and after protamine administration); and after CPB at 3, 6, 12, 24, and 48 hours and 7 days. In all groups there was a small increase in the concentration of endotoxin (overall from 6 ng/L before CPB to 11 ng/L at 90 to 120 minutes; p < 0.001) and significant increases in C3a, C5a, and GE levels but no significant differences among the groups. Endotoxin levels did not correlate with activation of complement or white blood cells. There was a weak correlation between duration of CPB and levels of C3a (r = 0.14; p < 0.03) and GE (r = 0.25; p = 0.001) but not endotoxin or C5a. There was a general correlation between levels of C3a and GE but not in individual patients. In conclusion, CPB results in statistically significant increases in endotoxin, C3a, C5a, and GE during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Surgical Procedures↗

Primary gastric lymphoma in Auckland, New Zealand.

The case-notes of 30 patients presenting with primary gastric lymphoma in the Auckland area during 1969-87 have been reviewed. The mean age of the study group was 62 years, and 16 were female and 14 were male. There were 22 European, one Maori and seven Polynesian patients. The most common presenting symptom was abdominal pain and five patients presented acutely with gastrointestinal haemorrhage. The lesions occurred more frequently in the distal stomach and half were polypoid and half were ulcerating. They tended to be of substantial size at presentation, with seven being greater than 10 cm in diameter. Nine lesions were confined to the stomach, 12 involved the surrounding lymph nodes and eight were invading adjacent organs. Twenty-three patients underwent partial or total gastrectomy. Four of these received postoperative radiotherapy, and adjuvant chemotherapy was administered to 13. Chemotherapy, or combination chemo- and radiotherapy were used as the primary treatment in seven patients. Following surgical treatment, 18 patients remained alive and well. Five of the seven patients treated nonsurgically were dead of disease at the time of study and the other two remained alive with persisting disease. The following factors were found to affect prognosis adversely: weight loss of greater than 5 kg, tumour invasion of adjacent organs, and non-surgical primary treatment. Involvement of the lymph nodes draining the stomach did not appear to worsen the outlook, and there was little correlation between lesion size and prognosis.

Adult↗

Neuropsychological and behavioral abnormalities in an adolescent with frontal lobe seizures.

A 13-year-old girl had a reversible frontal syndrome secondary to partial complex seizures. She developed sudden and dramatic behavioral changes including sexual disinhibition, loss of concern for personal hygiene, physical and verbal aggression, and pressured and tangential speech. Although the basic neurologic examination was normal, neuropsychological testing revealed selective impairment on tasks sensitive to frontal dysfunction with relatively normal performance on other tests. This case demonstrates that a frontal syndrome can be caused by partial complex seizures and that behavior comparable to that observed in adults with frontal dysfunction may occur in young adolescents.

Adolescent↗

Hypersexuality or altered sexual preference following brain injury.

Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the presenting or dominant feature of brain injury.

Adult↗

The neurologic complications of cardiovascular disease.

Many cardiac disorders masquerade as neurologic problems. Differential diagnosis is discussed, as well as common neurologic presentations of cardiovascular disease, particularly stroke syndromes arising from emboli, the multitude of disorders that results in loss of consciousness, and neurologic symptoms and signs caused by cardiac drugs.

Arrhythmias, Cardiac↗

Opiate mediation of amenorrhoea in hyperprolactinaemia and in weight-loss related amenorrhoea.

Endogenous opiates are involved in the control of pituitary gonadotrophin and PRL secretion, and possibly of food intake. Both hyperprolactinaemia and weight loss (especially in anorexia nervosa) are frequently associated with amenorrhoea and an absence of gonadotrophin pulsatility. Since it has been suggested that increased endogenous opiate tone may operate in both conditions, we infused high-doses of naloxone into twelve patients with amenorrhoea of whom five had hyperprolactinaemia and seven had weight-loss related amenorrhoea. Eleven of the twelve patients had low levels of oestradiol (less than 50 pmol/l). Naloxone induced a marked rise in both LH and FSH levels in all of the five hyperprolactinaemic patients. In contrast, the patients with weight-loss amenorrhoea responded to naloxone with only a small or no rise in gonadotrophins. There was no consistent change in PRL in either group of patients. It is concluded that in hyperprolactinaemia, but not weight-loss amenorrhoea, there is an important endogenous opiate-mediated tonic inhibition of secretion of hypothalamic gonadotrophin releasing hormone.

Adolescent↗

Effects of trimethoprim and sulphonamide preparations on the pituitary-thyroid axis of rodents.

The effects on pituitary-thyroid function of the commonly prescribed anti-bacterial preparations co-trimoxazole and co-trifamole, and their component drugs, have been studied in the rat and compared to the changes caused by propylthiouracil. Co-trimoxazole and co-trifamole, in doses 20-fold in excess of a pharmacological dose administered for 10 days, produced marked changes in hormone levels consistent with blocking of hyperplastic goitre formation, were also demonstrated. Propylthiouracil produced less marked changes of thyroid hormone levels but higher levels of thyroid-stimulating hormone. Pharmacological doses of co-trimoxazole and co-trifamole and sulphamoxole, the sulphonamide component of co-trifamole, caused significant changes in thyroid hormone levels consistent with anti-thyroidal activity. In contrast, there was no evidence that trimethoprim, which is common to both preparations, or sulphamethoxazole, the sulphonamide component of co-trimoxazole, had an anti-thyroidal action, indeed, serum thyroxine levels were significantly increased at pharmacological dosage. We have concluded that the new commonly prescribed combination preparations retain the goitrogenic properties of the earlier sulphonamides.

Animals↗