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Biomedical subjects

M J Morris

Publications and source records attributed to M J Morris.

At least 91 records · Page 5Linked to original sources

Enalapril and atenolol in essential hypertension: attenuation of hypotensive effects in combination.

In 16 patients with essential hypertension the effects of enalapril 20 mg once daily were compared with those of atenolol 50 mg once daily, with the two drugs in combination and with placebo using a double-blind cross-over design with allocation of treatment order by randomised Latin squares. For each patient there were four treatment phases, each of four weeks duration, which together comprised a 2 x 2 factorial experiment. All blood pressure parameters were reduced in the three active treatment phases compared to placebo (p less than 0.001). Supine blood pressures (group means) were 171/97 (placebo), 147/85 (enalapril), 154/84 (atenolol) and 144/78 (enalapril plus atenolol) (S.E.M. +/- 2/+/- 1-ANOVA), and standing blood pressures were 170/105 (placebo), 146/92 (enalapril), 154/92 (atenolol) and 147/86 (enalapril plus atenolol) (S.E.M. +/- 3/+/- 1). In the combination phase there was an additional hypotensive response but the potential fully additive effects of the two agents were attenuated by 30-50%. The mechanism of the attenuated hypotensive effect of the combined agents has not been determined. Plasma atrial natriuretic peptide (ANP) concentration was doubled in the presence of atenolol (P less than 0.01) suggesting that ANP may contribute to the hypotensive effect of the beta-blocker.

Aldosterone↗

Inhibition of vasodepressor neurons in the caudal ventrolateral medulla of the rabbit increases both arterial pressure and the release of neuropeptide Y-like immunoreactivity from the spinal cord.

The role of bulbospinal neuropeptide Y (NPY)-containing neurons of the rostral ventrolateral medulla in the rabbit in mediating the increase in blood pressure that occurs during inhibition of cells in the caudal ventrolateral medulla was investigated in urethane-anaesthetized rabbits. In the present experiments bilateral injections of the GABA agonist, muscimol, into the caudal ventrolateral medulla elicited a slowly-developing rise in arterial pressure that was maximal 15 min after the injection. Accompanying this increase in arterial pressure was an increase in the release of NPY-like immunoreactivity (NPY-LI) into the spinal subarachnoid space. This pattern of response is similar to that seen after direct chemical stimulation of the NPY-containing cells of the rostral ventrolateral medulla. Taken together, these findings suggest that tonically active neurons in the caudal ventrolateral medulla exert their effects by inhibiting sympathoexcitatory NPY-containing neurons whose cell bodies are situated in the rostral ventrolateral medulla.

Animals↗

Plasma atrial natriuretic peptide is increased during atrial pacing in conscious rabbits.

The effect of increases in heart rate on plasma atrial natriuretic peptide (ANP) concentrations was investigated in conscious rabbits. Plasma ANP concentrations were significantly increased following abrupt increases in heart rate produced by atrial pacing at 400 beats/min. Pacing at 300 beats/min resulted in smaller increases in plasma ANP concentration. Stepwise increases in heart rate produced by atrial pacing at 250, 300, 350 and 400 beats/min resulted in increases in plasma ANP concentrations at 400 beats/min only. The increase in plasma ANP concentration during atrial pacing correlated significantly with the increase in heart rate achieved.

Animals↗

Microinjection of kainic acid into the rostral ventrolateral medulla causes hypertension and release of neuropeptide Y-like immunoreactivity from rabbit spinal cord.

Microinjections of kainic acid were made into the pressor area of the rostral ventrolateral medulla oblongata of anaesthetized rabbits, in the region of the C1 adrenaline-containing neurons. Over the 65 min following the microinjection, there was a significant increase in blood pressure, as well as an increase in the release of neuropeptide Y-like immunoreactivity into the spinal subarachnoid space. These data provide evidence for a functional bulbospinal neuropeptide Y-containing projection which may be responsible for mediating the pressor effects of stimulation of the rostral ventrolateral medulla.

Animals↗

Treatment of hypertension with enalapril and hydrochlorothiazide or enalapril and atenolol: contrasts in hypotensive interactions.

To determine the nature of the resultant effect on blood pressure when angiotensin converting enzyme (ACE) inhibitors are combined with other hypotensive agents in the treatment of uncomplicated essential hypertension, two randomized, double-blind, crossover trials were conducted. In each trial there were four treatment phases, each 4 weeks in duration, comprising a 2 X 2 factorial experiment. Twenty-one patients completed the first study in which the effects of enalapril (10 mg twice daily) were compared with hydrochlorothiazide (25 mg twice daily), with the two drugs in combination and with placebo. All blood pressure parameters were reduced in the three active treatment phases compared with placebo (P less than 0.001). Enalapril and hydrochlorothiazide were equally effective and in combination their hypotensive effects were fully additive. Sixteen patients completed the second study which compared the effects of enalapril (20 mg daily), atenolol (50 mg daily), the two drugs in combination and placebo. All blood pressure parameters were again reduced in all phases compared with placebo (P less than 0.001). Enalapril and atenolol were also equally effective, but in combination their hypotensive effects were less than fully additive, with attenuation of the potential additive response by 30-50%. These results indicate that a diuretic-ACE inhibitor combination can be expected to have a greater hypotensive effect than a beta-blocker-ACE inhibitor combination. Both hydrochlorothiazide and atenolol increased plasma atrial natriuretic peptide (ANP) concentrations (P less than 0.01), suggesting that ANP could contribute to the hypotensive effects of these two drug classes.

Angiotensin II↗

Role of renal nerve activity, plasma catecholamines and plasma vasopressin in cardiovascular responses to intracisternal neurotoxins in the rabbit.

We have examined the acute (0-3 h) effect of intracisternally administered 5,7-dihydroxytryptamine (DHT) and 6-hydroxydopamine (6-OHDA) on blood pressure, heart rate, renal nerve activity, plasma adrenaline, plasma noradrenaline and plasma vasopressin in conscious rabbits. The increase in blood pressure seen following 5,7-DHT treatment was associated with increases in adrenaline and vasopressin levels and renal nerve activity throughout the response. The increase in blood pressure which followed 6-OHDA administration was associated with an increase in renal nerve activity alone. These findings indicate that the rise in blood pressure elicited by these drugs involves an increase in sympathetic nerve activity. The absence of a rise in vasopressin levels during the response to 6-OHDA suggests that the rise in blood pressure seen in these animals is due entirely to a bulbospinal sympathoexcitatory pathway.

5,6-Dihydroxytryptamine↗

Increases in plasma neuropeptide Y concentrations during sympathetic activation in man.

Neuropeptide Y (NPY) coexists with noradrenaline in postganglionic sympathetic neurons. In order to test the hypothesis that NPY may be released along with catecholamines by activation of the sympathoadrenal system we measured plasma NPY-like immunoreactivity (NPY-LI) concentrations during cold pressor test, head up tilt and bicycle exercise in healthy volunteers. All 3 manoeuvres resulted in elevation of blood pressure, heart rate and plasma noradrenaline and adrenaline concentrations. These were accompanied by increases in plasma NPY-LI concentrations on cold pressor test and exercise, but not with head up tilt. The increases in both NPY-LI and catecholamines were greatest with exercise. These findings suggest that NPY is released at the same time as noradrenaline when sympathetic noradrenergic nerves are activated.

Adult↗

Plasma neuropeptide y levels rise in patients undergoing exercise tests for the investigation of chest pain.

Neuropeptide Y (NPY) is colocalised with noradrenaline in post-ganglionic sympathetic neurons. In order to examine the possibility that activation of the sympathetic nervous system might cause release of NPY into the plasma NPY levels were measured in 16 patients undergoing exercise tests for investigation of chest pain. Plasma NPY concentrations rose in 14 out of the 16 patients, and the mean level of plasma NPY increased from 335 (s.e.m. = 37) to 455 (s.e.m. = 41) pg/ml. Plasma noradrenaline and adrenaline levels increased four- and two-fold respectively. The increase in NPY correlated with the increase in noradrenaline, suggesting that NPY may be released with noradrenaline when sympathetic noradrenergic nerves are activated.

Adult↗

Effects of enalapril and hydrochlorothiazide on blood pressure, renin-angiotensin system, and atrial natriuretic factor in essential hypertension: a double blind factorial cross-over study.

The hypotensive and hormonal effects of the angiotensin converting enzyme (ACE) inhibitor enalapril (10 mg twice daily) were compared with those of hydrochlorothiazide (25 mg twice daily), with the two drugs in combination and with placebo in 21 patients with essential hypertension. For each patient there were four randomised double-blind treatment phases, each of four weeks' duration, which comprised a 2 X 2 factorial experiment. All blood pressure parameters were reduced in the three active treatment phases compared to placebo (p less than 0.001). Supine mean blood pressures were 119 mmHg (placebo), 113 mmHg (hydrochlorothiazide), 108 mmHg (enalapril), and 98 mmHg (hydrochlorothiazide plus enalapril) (SEM 3 mmHg, ANOVA). Enalapril and hydrochlorothiazide were equally effective and well tolerated and their hypotensive effects were additive. Enalapril increased plasma renin activity (PRA), reduced plasma angiotensin II (AII) and aldosterone concentrations, and reduced ACE activity, whereas hydrochlorothiazide increased PRA, plasma AII, and aldosterone concentrations without altering ACE activity. With combination treatment the effects of enalapril on PRA and plasma AII concentrations were potentiated whereas those on plasma aldosterone concentration and ACE activity were additive. Atrial natriuretic factor plasma concentration in the placebo phase was 92 pg/ml and increased to 145 pg/ml in the hydrochlorothiazide phase (p less than 0.001, SEM 13 pg/ml), but there was no significant change in either the enalapril or combination phases.

Aged↗

Specific increase in renal alpha 1-adrenergic receptors following unilateral renal denervation.

The effect of unilateral surgical renal denervation on adrenergic receptors in rat kidney was investigated. Denervation was performed by mechanically stripping the nerves from the renal artery and then painting with phenol. This procedure resulted in a decrease in norepinephrine content to less than 10% of the contralateral kidney. The concentrations of alpha 1-, alpha 2-, beta 1- and beta 2-adrenergic receptors were measured in both kidneys of rats 1 week following left renal denervation. Alpha 1-receptor concentrations increased in the denervated left kidneys relative to the intact right kidneys. Alpha 2-, beta 1- and beta 2-receptor concentrations were not different between left and right kidneys. These results indicate that the different classes of adrenergic receptor in the kidney are differentially regulated by agonist stimulation.

Animals↗

Embryonic hypothalamic tissue transplanted to the IVth ventricle of newborn Brattleboro rats.

The hypothalamic region, dissected from normal rat embryos, was transplanted into the IVth ventricle of newborn mutant Brattleboro rats. Water intake and urine osmolality were measured in both the recipient animals and unoperated littermate controls during a 7-week period following weaning. No differences were found between operated and unoperated animals. Ten weeks after transplantation, host animals were fixation perfused and the brains prepared for either catecholamine fluorescence or vasopressin immunohistochemistry. Well-developed grafts were found in the IVth ventricle of the hosts. They received innervation from the host locus coeruleus and contained many neurons with vasopressin-like immunoreactivity. Vasopressin-containing fibers were found running from the grafts into the host medulla.

Animals↗

The late adverse effect of splenectomy on patient survival following cadaveric renal transplantation.

Kidney and patient survival of 351 consecutive patients undergoing first cadaveric renal transplants since 1968 were reviewed to determine the effects of splenectomy on outcome. Special emphasis was given to analysis of 106 splenectomized and 102 nonsplenectomized patients treated since 1975. During the first two years after transplant, kidney survival was better in the splenectomized patients, with no adverse effect on patient survival. However, after the first two years, patient survival became significantly worse in splenectomized patients (35.5% vs. 60.5% at 84 months). Of the deaths, infection was the cause in 26.7% of nonsplenectomized patients compared with 50% of splenectomized patients (P less than 0.07). Of patients alive at one year posttransplant, death rates were not different in patients splenectomized before 1975 or after 1975. Timing of splenectomy (prior vs. concurrent) had no effect on outcome. The adverse effect of splenectomy on mortality appeared to be more pronounced in younger (less than or equal to 45 year-old) than in older (greater than 45 year-old) patients. Splenectomy should not be performed routinely in preparation for a cadaveric transplant because of an unacceptably high late mortality that is primarily from sepsis.

Adult↗

The influence of hair-removal methods on wound infections.

The influence of preoperative shaving v clipping on wound infection rate was studied in 1,013 patients undergoing elective operations at a single hospital. Patients were prospectively randomized to be either shaved or clipped the night before or the morning of operation. The AM clipper method was associated with significantly fewer infections than were the other methods, both at discharge and at 30-day follow-up. The greatest benefit was in the group with clean wounds. For each 1,000 patients treated, a savings of approximately $270,000 could be realized if the AM clipper method replaced shaving for preoperative hair removal. Preoperative shaving is deleterious, and the practice should be abandoned.

Hair Removal↗

Plasma and skeletal muscle amino acids following severe burn injury in patients and experimental animals.

This study describes and analyzes sequential changes in plasma and skeletal muscle free amino acids following severe burn injury. Plasma free amino acids were determined in children (n = 9) with burns averaging 60% total body surface area and were compared with laboratory beagles (n = 44) which received a flame burn totaling 30% of their body surface area. In addition, needle biopsy specimens were obtained from the semitendonosus muscle in the animals to determine free intracellular amino acids. In both patients and animals the amount of total free amino acids in plasma fell following burn, suggesting relative protein deficiency. This drop was primarily due to a 47% drop in nonessential amino acids. However, plasma phenylalanine was consistently higher than normal following burn, and was strongly associated with death and weight loss in both animals and patients, especially when analyzed as a ratio with tyrosine. This finding suggested excessive catabolism, hepatic dysfunction, or both. Plasma levels of several amino acids correlated significantly with weight loss. Alterations in muscle free amino acids generally were similar to plasma amino acids. Exceptions were muscle alanine and glycine which strongly correlated with weight loss. However, the determination of muscle free amino acid profiles did not yield clinically useful information not available from plasma profiles. Plasma levels of liver enzymes suggested progressive hepatic dysfunction. These studies show that the laboratory beagle is a good model for studying the metabolic alterations of amino acids that accompany burn injury, since they mimic humans in many parameters which appear to be most useful with respect to clinical evaluation.

Amino Acids↗

Abnormalities in lung function following clinical recovery from Mycoplasma pneumoniae pneumonia.

Pulmonary function was studied in 15 patients who had clinically and radiologically recovered from proven Mycoplasma pneumoniae pneumonia, 21 weeks (mean) previously. Ten patients were tested again 43 weeks (mean) later. Lung volumes and measurements of airways resistance were generally normal. Transfer factor and diffusion constant were initially reduced in the smokers and significantly improved between the two studies, being normal at the second testing. It is suggested smokers take longer to recover from mycoplasma pneumonia although all cases had returned to normal a year after the illness.

Adolescent↗

Formaldehyde asthma: challenge exposure levels and fate after five years.

Because of current concern regarding possible adverse health effects of formaldehyde, we have reinvestigated two renal dialysis unit nurses shown to have formaldehyde asthma by inhalation provocation tests in 1973 and 1975, respectively. Their original tests were repeated and the formaldehyde levels generated (previously unknown) were measured. One nurse had not worked with formaldehyde since 1976 and had had no further symptoms. Her 1981 test (15-minute exposure to 6 parts per million [ppm] formaldehyde) provoked no asthmatic response. The other nurse had continued to work with formaldehyde, though under much improved conditions, and mild intermittent attacks of asthma had continued. Her test (five-minute exposure to 3 ppm formaldehyde) provoked a late asthmatic reaction similar to that observed in 1975. We conclude that in sensitized subjects specific late asthmatic reactions may be provoked by brief exposures to formaldehyde at about the current Occupational Safety and Health Administration standard (3 ppm); and that while asthmatic responsiveness may persist with continuing low levels of intermittent exposure, it may be lost following complete cessation of exposure.

Adult↗