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Biomedical subjects

W J Louis

Publications and source records attributed to W J Louis.

At least 145 records · Page 8Linked to original sources
PubMed1986

The influence of age and sex on cardiac, renal and caudal artery catecholamine content in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats.

Noradrenaline (NA), adrenaline (A) and dopamine (DA) levels were measured in the heart, kidney and caudal artery of male and female SHR and WKY rats aged 6, 14 and 28 weeks, and the influence of strain, sex and age on catecholamine content determined. Levels of A were elevated in all three regions of SHR compared to WKY rats, independent of age and sex. This may represent increased A accumulation in sympathetic nerves resulting from the increased sympatho-adrenomedullary hyper-reactivity of the SHR strain. DA levels were also elevated in the heart and kidney of SHR rats, independent of sex and age. Na levels were lower in the heart of SHR rats, but this appeared to be partly a consequence of cardiac hypertrophy and partly due to strain difference between older male but not female rats. Thus a simple association between decreased cardiac NA levels and hypertension appeared unlikely. It is emphasised that further genetic studies of F2 backcross rats would be required to establish an etiological association between these differences in catecholamine levels and differences in blood pressure between the SHR and WKY strains.

Age Factors↗
PubMed1986

Positive chronotropic responses to cardiac alpha 1-adrenoreceptor activation in the pithed rat.

Adrenaline (0.1-10 micrograms/kg), noradrenaline (0.1-10 micrograms/kg) and phenylephrine (1-100 micrograms/kg) acted on both cardiac alpha 1- and beta-adrenoreceptors to induce positive chronotropic responses in the pithed rat. When beta-adrenoreceptors were blocked by propranolol (1 mg/kg), the residual chronotropic responses were due to activation of alpha 1-adrenoreceptors since they were significantly reduced by prazosin (10-100 micrograms/kg). Methoxamine (10-300 micrograms/kg) acted solely on cardiac alpha 1-adrenoreceptors to induce positive chronotropic responses which were abolished by prazosin (10-100 micrograms/kg) alone, as has been demonstrated previously for amidephrine. The rank order of potency for eliciting the positive chronotropic response to alpha 1-adrenoreceptor activation was adrenaline greater than noradrenaline greater than phenylephrine greater than methoxamine. The positive chronotropic responses to adrenaline (3-10 micrograms/kg), noradrenaline (3-10 micrograms/kg) and phenylephrine (30-100 micrograms/kg) produced by activating alpha 1-adrenoreceptors had a slower time course than did the chronotropic responses produced by activation of beta-adrenoreceptors.

Adrenergic alpha-Agonists↗
PubMed1986

Short-term myocardial uptake of lidocaine and mexiletine in patients with ischemic heart disease.

Determination of short-term myocardial drug uptake and subsequent redistribution was performed in 27 patients with ischemic heart disease for the antiarrhythmic agents lidocaine and mexiletine, using frequent simultaneous measurements of drug concentration in aortic and coronary sinus blood, combined with measurement of coronary sinus blood flow after intravenous bolus injection of the drug. Maximal myocardial drug content per unit resting coronary sinus blood flow (MDC:F) was significantly greater in patients in whom coronary sinus pacing at 100 beat/min was performed during the initial period of drug uptake. Maximal myocardial drug content occurred after 2.4 +/- 0.2 (SEM) for lidocaine and after 5.5 +/- 0.6 min for mexiletine (p less than .001), and pacing did not affect time to maximum myocardial drug content. In nonpaced, but not paced, patients maximal MDC:F was greater in the lidocaine group than that in the mexiletine group. The subsequent efflux of lidocaine from the myocardium was more rapid that that of mexiletine in both paced and nonpaced groups.

Adult↗
PubMed1985

Double blind comparative study of omeprazole 10 mg and 30 mg daily for healing duodenal ulcers.

Healing of duodenal ulcers was assessed in 66 patients who received omeprazole either 10 mg or 30 mg daily for four weeks in a double blind study. Healing was rapid in both groups. At two weeks the ulcers in 15 of the 30 patients taking 10 mg daily had healed compared with 28 of the 36 (78%) taking 30 mg daily (p less than 0.03). At four weeks the respective proportions had risen to 83% (25/30) and 94% (33/35) (p greater than 0.05). In non-smokers the proportion of ulcers healed did not differ significantly with the two doses, although there was a trend for less healing at two weeks with 10 mg daily; in smokers significantly fewer ulcers (p less than 0.05) were healed with 10 mg than 30 mg daily at two weeks (7/16 (44%) v 17/21 (81%] and at four weeks (12/16 (75%) v all 21 (100%]. Adverse reactions were few and transient and were considered unlikely to be due to omeprazole.

Adult↗
PubMed1985

Omeprazole: a study of its inhibition of gastric pH and oral pharmacokinetics after morning or evening dosage.

Pharmacodynamic and pharmacokinetic studies of omeprazole, a new gastric antisecretory agent, were undertaken in 8 healthy subjects. The drug was administered orally as an encapsulated enteric-coated granulate (40 mg daily at 9 am or 9 pm for 5 days), and its effect on the integrated 24-h gastric pH was determined, together with its apparent bioavailability. The pretreatment 24-h median pH was 1.9 (interquartile range 1.4-2.9). After 5 days of treatment, the median pH had risen to 5.0 (3.7-6.0) (p less than 0.01) with morning dosage and 4.5 (3.0-5.6) (p less than 0.01) with evening dosage. This corresponded to a greater than 99% reduction in 24-h median hydrogen ion activity, with morning dosage having a greater effect (from 9 am to 8 pm) (p less than 0.01) than evening dosage. The relative bioavailability of omeprazole increased twofold from day 1 to day 5 of treatment with morning dosage (p less than 0.02) and threefold with evening dosage (p less than 0.02), suggesting that increased absorption of this acid-labile drug occurs with increasing inhibition of acid secretion. We conclude that this formulation of omeprazole presently being used in clinical trials is a highly potent antisecretory agent in humans, although its optimal effect may not be observed for several days.

Adult↗
PubMed1985

The measurement of central noradrenergic activity in spontaneously hypertensive rats: a comparison of free 3,4-dihydroxyphenylethyleneglycol levels with FLA-63 induced noradrenaline depletion.

Noradrenergic activity was measured in the brainstem, hypothalamus and thoracic spinal cord of male and female spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 6 and 28-36 weeks of age. Two techniques were used, measurement of a major noradrenaline (NA) metabolite, free 3,4-dihydroxyphenylethyleneglycol (DHPG), and measurement of the rate of decline in brain NA levels following dopamine-beta-hydroxylase (DBH) inhibition by FLA-63. There was a good correlation between the changes with age in NA turnover measured by the two techniques. NA levels and NA turnover measured by both techniques fell with age in brainstem and thoracic spinal cord in both SHR and WKY rats. In both strains these falls in turnover were associated with increases in blood pressure. However, the increase in blood pressure in the SHR was greater than in the WKY, even though NA turnover fell to a similar extent in both strains. These data show a difference in the pattern of change in NA levels and turnover in the brainstem and thoracic spinal cord compared to other brain regions and may therefore be related to the development of higher levels of blood pressure in older rats in both strains. They do not offer a simple explanation for the much higher blood pressures seen at all ages in the SHR.

Animals↗
PubMed1985

Cardiac alpha-adrenoceptors involving positive chronotropic responses.

Phenylephrine, adrenaline, and noradrenaline have been shown to act on both alpha- and beta-adrenoceptors to produce an increase in heart rate in the pithed rat and rat isolated atria. Abolition of these responses requires blockade of both types of adrenoceptors. The rank order of alpha-adrenoceptor agonists to produce positive chronotropic responses was adrenaline greater than noradrenaline greater than phenylephrine greater than methoxamine. In the case of methoxamine, positive chronotropic responses were largely due to the activation of alpha 1-adrenoceptors. The positive chronotropic responses to activation of alpha 1-adrenoceptors developed more slowly than did the response to beta-adrenoceptor activation in the pithed rat. The fact that blockade of one receptor type enhanced the positive chronotropic responses to activation of the other receptor type suggests that there may be an interaction between the cardiac alpha 1- and beta-adrenoceptors mediating positive chronotropic responses. In the rat isolated atria, the calcium antagonists verapamil (10 nmol/L) and nifedipine (10 nmol/L) also inhibited the alpha 1-adrenoceptor-mediated positive chronotropic effect of phenylephrine to the same extent as prazosin (10 nmol/L). Prazosin was not a calcium antagonist, as shown by its failure to block the contracture of the depolarized rat isolated aortic strips. Neither verapamil nor nifedipine were alpha 1-adrenoceptor antagonists at these concentrations.

Animals↗
PubMed1984

High-performance liquid chromatographic determination of platinum (II) in plasma ultrafiltrate and urine: comparison with a flameless atomic absorption spectrometric method.

A technically simple, rapid and sensitive high performance liquid chromatographic assay for cis-dichlorodiammineplatinum (II) in human plasma ultrafiltrate and urine is described. The drug was chelated by exchange with diethyldithiocarbamate and extracted into chloroform. Nickel (II) was used as an internal standard which allows correction for the matrix effects observed with previous chromatographic and spectrometric methods. Chromatography was performed on a mu-Bondapak CN column and the eluent measured spectrophotometrically at 254 nm. Precision and reproducibility were both excellent and the detection limit was less than 50 ng/ml using only 1 ml of biological fluid.

Chromatography, High Pressure Liquid↗
PubMed1984

Combined gas chromatographic-mass spectrometric procedure for the measurement of captopril and sulfur-conjugated metabolites of captopril in plasma and urine.

A gas chromatographic-mass spectrometric method is described for the simultaneous measurement of the novel anti-hypertensive drug captopril, and the following metabolites: captopril disulfide dimer, S-methyl captopril, and S-methyl captopril sulfone. With this method all derivatives can be chromatographed using conventional gas chromatography of hexafluoroisopropyl esters in one temperature-programmed run and these can then be quantitated using selected-ion monitoring techniques. Using urine or plasma, captopril, S-methyl captopril and the disulfide dimer of captopril in concentrations as low as 1 ng/ml, 10 ng/ml and 25 ng/ml, respectively can be detected. The reproducibility of the method is satisfactory both within-assay and inter-assay. This technique has demonstrated that the pattern of urinary excretion of these compounds in both man and rat was similar. Excretion of unchanged captopril, S-methyl captopril and the disulfide dimer over 6 h in man given captopril (50 or 100 mg) chronically was 18.3%, 0.97% and 3.06%, respectively. Corresponding excretion of these three compounds in the rat following a single 10 mg/kg dose was 18.3%, 2.69% and 1.8%, respectively. A possible sulfone oxidation product of S-methyl captopril was not detected in the urine of either man or rat.

Animals↗
PubMed1984

Methicillin-resistant Staphylococcus aureus in an Australian teaching hospital.

A survey was undertaken of all isolations of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) at a large Australian teaching hospital over a 12 month period. All methicillin-resistant isolations obtained from the Casualty and Outpatient clinics were from staff members or patients with recent hospital contact. Twenty per cent of all methicillin-resistant isolations from in-patients were from specimens taken within 2 days of the patient's admission. Each of these patients had had hospital contact within the previous 4 months and it is assumed that the majority of them reintroduced the organism into the hospital. Such patients may provide an important means by which infection control procedures are bypassed. Patients who were relatively more likely to become infected or colonized with methicillin-resistant than with methicillin-sensitive strains included the elderly and those with postoperative wound infections (especially after orthopaedic or vascular surgery), spinal injuries, peripheral vascular disease, chronic skin ulcers or chronic diseases of the respiratory or urinary tracts. Eleven per cent of MRSA wound isolates and 15 per cent of sputum isolates were associated with serious infections requiring specific treatment, emphasizing the ability of these strains to produce serious illness. A small proportion of staff and asymptomatic patients were found to harbour MRSA and the importance of these individuals in facilitating cross-infection requires further investigation.

Adult↗
PubMed1984

Failure of psychosocial stress to induce chronic hypertension in the rat.

The effect of psychosocial stress produced by aggregation in a special cage designed by Henry was investigated in three separate experiments using Wistar-Kyoto (WKY), Sprague-Dawley (SD) and F1 hybrids of the Japanese spontaneously hypertensive and Wistar-Kyoto (SHR-WKY F1) rats. Each aggregated group displayed typical 'stressed' behavioural disturbances. Adrenal hypertrophy, elevation of plasma renin activity and gastric erosions were noted in male aggregated SD rats; while adrenal enlargement, elevation of plasma noradrenaline and gastric erosions were found in male aggregated SHR-WKY F1 rats. Sustained hypertension, however, did not develop in any strain nor in any subgroup within each strain. Gastric erosions were also noted in isolated SD and SHR-SKY F1 rats suggesting that long term isolation of rats also induces stress. Isolated rats also remained normotensive throughout. Reduced haematocrit was found in both aggregated and isolated male SHR-WKY F1 rats suggesting increased plasma volume. We conclude that neither stress due to psychosocial disturbances nor that due to isolation produces chronic hypertension in the three strains of rat studied.

Adrenal Glands↗
PubMed1984

Pharmacology of combined alpha-beta-blockade. I.

Several compounds of the chemical class arylethanolamines have been shown to possess combined alpha- or vasodilator and beta-adrenoceptor blocking properties. The first drug was labetalol (AH5158)[5-(1-hydroxy-2)1-methyl-3-phenylpropyl(amino)-ethyl (salicylamide)]. Others include medroxalol, bucindolol and YM-09538, which differ from labetalol either by the nature of the substitution on the primary benzene ring and/or on the terminal nitrogen. All of these drugs are non-selective beta-blockers, except for bucindolol whose selectivity has not been carefully defined. The rationale for the development of this group of drugs was the knowledge that blockade of one adrenoceptor subtype causes reflex stimulation of the other, i.e. vasoconstriction after nonspecific beta-blockade and tachycardia after alpha-blockade. Since both of these compensatory responses act to prevent a fall in blood pressure, a relatively weak blockade of both receptor types should act synergistically to produce a lowering of blood pressure with minimal physiological disturbance. Haemodynamic studies have confirmed that the additional alpha-blocking properties of labetalol produce a pattern of haemodynamic changes unlike that of propranolol and other simple beta-adrenoceptor blocking agents. Peripheral vascular resistance, which falls acutely during the initial administration of the drug, tends to fall further during prolonged administration and the pulse rate tends to remain only slightly lower than pretreatment levels. In addition, at normal dose levels cardiac output is maintained by a compensatory increase in stroke volume. Thus, blood pressure is lowered largely by a reduction in vascular resistance, and although the heart rate falls significantly during exercise, the cardiac output is maintained by an increase in stroke volume. This pattern of events is different to that seen with beta-blocking agents which consistently reduce cardiac output during exercise. Currently labetalol is the only member of this group of drugs which is in established clinical use. Its antihypertensive efficacy has been confirmed in many studies and it has been shown to be effective in the management of both hypertensive emergencies and in the long term management of severe hypertension. It is particularly valuable in allowing a reduction in the number of drugs required for adequate blood pressure control. The early theoretical prediction that postural hypotension would occur with high doses is now acknowledged to be labetalol's major dose-limiting side effect. Most of the available pharmacokinetic data on labetalol were derived from studies which utilised a fluorimetric assay.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1984

Age related changes of catecholamines and their metabolites in central nervous system regions of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats.

Adrenaline (A), dopamine (DA), noradrenaline (NA) the NA metabolite 3,4-dihydroxyphenylethylene-glycol (DHPG) and the DA metabolite 3,4 dihydroxyphenylacetic acid (DOPAC) were assayed in brain regions of male and female WKY and SHR at 6, 14, 28 and 36-40 weeks. Age related differences in catecholamine levels between the two strains were only seen with NA measurements. DOPAC levels were elevated in the striatum of SHR compared to WKY rats at all ages studied which might reflect the known hyperactivity of SHR strain. In the SHR NA but not DHPG levels in several regions, DA and DOPAC levels in midbrain and DA levels in lower brainstem were elevated at 6 weeks of age. These changes may represent a generalized alteration in central catecholamine metabolism in SHR during the early development of hypertension or merely reflect strain differences. It is emphasised that further genetic studies of F2 backcross rats are required to establish an aetiological association between these differences in catechol levels and differences in blood pressure between SHR and WKY rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

The involvement of central alpha adrenoceptors in the antihypertensive actions of methyldopa and clonidine in the rat.

The antihypertensive effects of methyldopa and clonidine result from agonist activity at alpha adrenoceptor sites within the brain. Methyldopa is converted enzymatically to alpha-methylnoradrenaline in noradrenergic neurones in rat brain and replaces the natural transmitter, noradrenaline. Radioligand receptor studies show that alpha-methylnoradrenaline differs from noradrenaline in being much more selective (70 times) for the alpha 2 subclass of adrenoceptors than noradrenaline and it is likely that the antihypertensive action of methyldopa results from selective activation of alpha 2 adrenoceptors by alpha-methylnoradrenaline in the nucleus tractus solitarius and the anterior hypothalamus. Radioligand studies also show that clonidine is a selective alpha 2 adrenoceptor agonist although it probably interacts with alpha 1 adrenoceptors at higher concentrations. With regard to a withdrawal syndrome after cessation of clonidine treatment, the cardiovascular and behavioural components can now be characterised in a rat model. The components include increases in basal blood pressure and heart rate, as well as increases in cardiovascular reactivity and also increases in rapid eye movement (REM) sleep, body shakes and tremor which is reminiscent of an opiate withdrawal syndrome. Increased central noradrenergic activity is involved in this syndrome and alpha 1 and alpha 2 adrenoceptors mediate opposing effects on the REM sleep rebound component.

Animals↗