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Biomedical subjects

M J Lewis

Publications and source records attributed to M J Lewis.

At least 271 records · Page 15Linked to original sources
PubMed1982

Pharmacokinetic studies of various preparations of glyceryl trinitrate.

1 The pharmacokinetics and pharmacodynamics of five pharmaceutical preparations of glyceryl trinitrate (GTN) have been studied in six healthy volunteers. 2 Peak plasma GTN levels of 1.4 +/- 0.1 ng/ml were achieved at 3 min after sublingual administration (0.5 mg); 2.8 +/- 0.6 ng/ml and 2.5 +/- 0.3 ng/ml at 2 h and 4 h after Nitrocontin (6.4 mg) and Sustac (6.4 mg) respectively; 2.7 +/- 0.1 ng/ml and 2.5 +/- 0.2 ng/ml at 30 min after the cream (23 mg) and ointment (35 mg) respectively. 3 The mean times to reach half peak plasma GTN levels were 4.2 +/- 0.7 min after sublingual GTN, 6.5 +/- 0.9 h after Nitrocontin, 4.1 +/- 0.7 h after Sustac, 46.1 +/- 10.2 min after the ointment and 50.2 +/- 39.2 min after the cream. 4 Plasma nitrate (NO3) levels were undetectable after sublingual administration; peak NO3 levels were 0.48 +/- 0.03 microgram/ml at 4 h after Nitrocontin, 0.45 +/- 0.02 microgram/ml at 6 h after Sustac, 0.68 +/- 0.04 microgram/ml at 6 h (end of study) after the ointment and 0.63 microgram/ml at 4 h after the cream. 5 Plasma nitrite (NO2) was undetectable after sublingual GTN and peak NO2 levels were 0.48 +/- 0.04 microgram/ml at 2 h after Nitrocontin, 0.48 +/- 0.02 microgram/ml at 2 h after Sustac, 0.69 +/- 0.02 microgram/ml at 1 h after the ointment and 0.64 +/- 0.02 microgram/ml at 1 h after the cream. 6 Blood pressure (BP) declined throughout the 11 min of the study after sublingual GTN but did not change significantly after Nitrocontin or Sustac. After the ointment and the cream BP fell to the lowest level 30-60 min after administration and remained low throughout the 6 h of the study. 7 Heart rate (HR) increased to a maximum 5 min after sublingual administration with no significant increase after Nitrocontin or Sustac. After the ointment and the cream HR increased gradually to a maximum 30-60 min after administration remaining high throughout the rest of the study.

Adult↗
PubMed1981

Factors influencing the establishment and spread of R-plasmids in an experimental model of urinary tract infection.

An experimental model simulating infection of the urinary tract was used to investigate factors influencing the transfer of plasmid-mediated drug resistance in the human bladder in the absence of antibiotic therapy. When a small number of cells carrying plasmid-mediated drug resistance was added to an established population of sensitive cells, it was found that varying the physical conditions of the bladder model had no significant effect on the spread of the plasmid and, under all conditions used, exponential spread of the plasmid through the originally sensitive population occurred. When the initial donor cells were killed shortly after addition to the model, exponential transfer of resistance amongst the established sensitive population still occurred. Thus, even in the absence of antibiotic therapy, only a small number of initial transfer events was required for a fully resistant population to be developed. This was true of both actively multiplying and early stationary phase cultures. An initially greater proportion of resistant cells, or the use of an antimicrobial agent to which some of the cells are resistant, would ensure that this process occurred more rapidly.

Bacteriological Techniques↗
PubMed1981

Age-related decline in brain stimulation reward: rejuvenation by amphetamine.

A decline in a brain stimulation reward responding occurred in rats 15-20 months of age. These animals had platinum bipolar electrodes implanted in the lateral hypothalamus-medial forebrain bundle area of the brain at 6 months and were vigorous and reliable responders after implantation. The decline in behavior was demonstrated by a decrease in rate of lever-presses, increase in impedance to the stimulating current and failure to complete reward threshold determination procedures. Priming, increased current, food deprivation, and reshaping were generally ineffective individually or in combination. A single low dose (0.25-0.30 mg/kg) of d-amphetamine 5 to 30 minutes prior to session reinstated BSR behavior in the aged rats; although threshold and impedance were higher than 6-8 month values and priming and reshaping were required in some cases. Rate of response was unchanged. Unexpectedly, all rats showed improved performances in at least two subsequent sessions without further amphetamine. These data are discussed from the perspective of brain neurochemistry and possibility that such manipulation had a rejuvenating effect on declining neurotransmitter systems, particularly dopamine.

Aging↗
PubMed1981

Acute effects of acebutolol on cardiovascular function in man.

1 The acute cardiovascular effects of acebutolol were measured at constant paced heart rate in thirteen patients investigated for possible coronary artery disease, six of whom showed significant coronary stenosis with regional myocardial dysfunction, seven of whom proved normal. Acebutolol 0.75 mg/kg i.v. was given to three patients with coronary artery disease and three normals, and 1 mg/kg i.v. to the other patients.2 Measurements were made of cardiac output, left ventricular and arterial pressures, and left ventricular angiography. Isovolumic and ejection phase parameters of left ventricular function, and systemic vascular resistance were derived. Plasma levels of acebutolol were measured. 3 The acute effects of acebutolol were a slight fall in cardiac output, LV dp/dt and dP/dt/P. There was no change in LV or arterial pressures, no consistent change in LVEDP or EDV, and no consistent change in ejection fraction or mean VCF. These changes imply a small negative inotropic effect, more marked at the higher dose. 4 The effects of acebutolol differed in patients with ischaemic heart disease compared with normals in that LVEDP and EDV increased, mean VCF decreased and cardiac output was lowered more. 5 These data are consistent with myocardial and vascular effects of beta-adrenoceptor blockade more marked at the higher dose and more marked in patients with ischaemic heart disease.

Acebutolol↗
PubMed1981

The effects of propranolol and acebutolol on the overnight plasma levels of anterior pituitary and related hormones.

1 The effects of single evening doses of the beta-adrenoceptor blocking agents propranolol (80 mg orally) and acebutolol (200 mg orally) on plasma levels throughout the night of prolactin, growth hormone, luteinising hormone, follicle stimulating hormone, cortisol and testosterone have been studied in seven healthy male volunteers. 2 Three way analysis of variance showed that acebutolol significantly reduced circulating levels of prolactin and follicle stimulating hormone, but did not alter the levels of the other hormones studied. 3 Propranolol significantly reduced follicle stimulating hormone and testosterone, and significantly increased circulating levels of cortisol, but caused no change in the other hormones studied. 4 Prolactin, luteinising hormone, testosterone and cortisol showed a significant variation with time indicating the existence of a diurnal rhythm in the pattern of their secretion. 5 There was a significant inter-subject variability in all the hormones studied. 6 There was a significant between-subject variation in response to both propranolol and acebutolol. 7 Different subjects showed significant variations with respect to time in prolactin, growth hormone and cortisol levels. 8 Neither propranolol nor acebutolol significantly altered the time course of secretion of any of the hormones studied. 9 Possible relationships of these beta-adrenoceptor blocker-induced changes in anterior pituitary and related hormones to the antihypertensive mechanism of acebutolol and propranolol are discussed.

Acebutolol↗
PubMed1981

The effect of chronic propranolol treatment on overnight plasma levels of anterior pituitary and related hormones.

1 Treatment of eight healthy males with propranolol (80 mg twice daily) for 6 weeks resulted in a significant reduction in overnight plasma levels of prolactin and LH. 2 Plasma testosterone levels were elevated whilst GH and cortisol were unchanged by such treatment. 3 Measurement of overnight hormone levels 48 h after discontinuing treatment showed no evidence of a 'rebound' phenomenon. 4 Cortisol, GH, prolactin, and testosterone plasma levels all showed time dependent changes: propranolol treatment significantly altered the time course of cortisol but not of the other hormones. 5 The effects of chronic propranolol treatment are discussed in terms of a probable direct central action of the drug. In addition the lowered plasma prolactin levels may directly contribute to the hypotensive action of propranolol.

Adult↗
PubMed1981

Adrenergic hypersensitivity after beta-blocker withdrawal.

We investigated the possibility of a rebound increase in sympathetic response after stopping beta-blocker treatment by measuring heart rate under conditions of increased sympathetic drive, as provided by standing with vasodilatation, or the Valsalva manoeuvure. Significant rebound increases in heart rate were observed after stopping propranolol given for one or more weeks but not when given for only four days. The amplitude of the rebound heart rate relative to the control heart rate off beta-blockers was similar after propranolol, atenolol, oxprenolol, or acebutolol, and in hyperthyroid subjects.

Adrenergic beta-Antagonists↗
PubMed1980

Myocardial stiffness during hypoxic and reoxygenation contracture.

Isolated rat papillary muscle preparations were used to study hypoxic contracture, and cat papillary muscle preparations with ouabain to study reoxygenation contracture. Electronic analysis of the response to rapid small sinusoidal perturbations gave a continuous measurement of the elastic and viscous components of total stiffness. Increased resting force during hypoxic contracture was characterised by an increase in resting elastic and viscous stiffness relative to the control stiffness-active force relationships. During reoxygenation contracture the stiffness-force relationships followed those of active force development. The linear active force-elastic stiffness relationship (dt/dl=kT+c) was also reversibly altered during hypoxic contracture, predominantly by an increase in intercept c. These data imply that hypoxic contracture unlike reoxygenation contracture is not due solely to a rise in intracellular calcium, but is associated with a component of stiffness not participating an active force development, for example rigor.

Animals↗
PubMed1980

The effects of bromocriptine in methyldopa treated hypertension.

1. The effects of treatment with the dopaminergic agonist bromocriptine were studied in nine patients with essential hypertension receiving methyldopa as sole therapy. 2. In Phase 1 of the study, the addition of bromocriptine on a single-blind basis caused a significant fall in lying and standing blood pressures. Plasma prolactin fell significantly but there was no significant change in the other biochemical parameters measured. All patients volunteered that they felt a sense of well-being after starting bromocriptine treatment. 3. In Phase 2 of the study the substitution of placebo for bromocriptine in a randomized double-blind trial significantly increased lying and standing blood pressures and plasma prolactin. No consistent or significant changes were observed in methyldopa-induced side-effects following the substitution of placebo for bromocriptine. 4. In Phase 3 of the study, a gradual increase in blood pressure was observed in all patients over a few months after stopping bromocriptine therapy. 5. The significance of these findings in relation to the role played by plasma prolactin and central dopaminergic activity in blood pressure regulation is discussed.

Adult↗
PubMed1980

Electron microscopic evidence of flagella and pili on Legionella pneumophila.

Twenty-one strains of Legionella pneumophila, representing the six known serotypes of the organism, cultured on various bacteriological media and in the yolk sacs of fertile hens' eggs were examined by negative stain electron microscopy for flagella and pili. These appendages were usually observed after cultivation on media capable of inducing an early profuse growth of the organisms.

Culture Media↗
PubMed1979

Determinants of hypoxic contracture in isolated heart muscle preparations.

Further studies on hypoxic contracture are described, using resting and contracting isolated muscle preparations from several species. The effect of temperature, pH, substrate, calcium concentration, osmolality and inotropic interventions was explored. The 'protective' effect of acidosis was not contingent on its negative inotropic influence. No evidence was adduced that hypoxic contracture can be modulated other than by altering energy supply or demand. The study does not discriminate between rigor and rised cytosolic calcium as mechanisms causing hypoxic contracture, but demonstrates that hypoxic contracture is not directly dependent on the availability of intracellular calcium.

Animals↗