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Biomedical subjects

D Robertson

Publications and source records attributed to D Robertson.

At least 415 records · Page 23Linked to original sources
PubMed1983

Variability of noise-induced damage in the guinea pig cochlea: electrophysiological and morphological correlates after strictly controlled exposures.

Anaesthetized guinea pigs were exposed to loud tones (1 h, 10 kHz, 112-118 dB SPL) with continuous control of the sound pressure at the tympanic membrane. N1 electrocochleograms were used to measure functional damage immediately and 21 days after the exposure. Damage to the organ of Corti was assessed by scanning electron microscopy and light and transmission electron microscopy. Principal findings were: (1) Functional impairment after 21 days showed large inter-animal variation which was not the result of changes in the effective damaging energy. (2) Structural damage to the stereocilia was also variable and did not always correlate with functional impairment, although when N1 thresholds were elevated damage to the stereocilia was always present. (3) Unknown factors within the cochlea must be responsible for variations in individual susceptibility to permanent noise-induced hearing loss.

Animals↗
PubMed1983

Alpha-adrenergic blockade in vasotonic angina: lack of efficacy of specific alpha 1-receptor blockade with prazosin.

To clarify the possible role of the alpha 1-adrenergic receptor in angina due to coronary artery spasm, a double-blind, randomized, placebo-controlled trial of the specific alpha 1-antagonist, prazosin, was performed. Six patients with vasotonic angina were studied, with efficacy measured by continuous electrocardiographic recording and the tabulation of chest pain and nitroglycerin usage. Despite plasma prazosin levels adequate to produce a six-fold shift in the response to phenylephrine, there was no significant difference in the number of ischemic episodes while taking prazosin (9.8 +/- 6.3 episodes/24 h) compared with placebo (10.5 +/- 6.9). There was also no difference in the length of ischemic episodes, which averaged 231 +/- 35 seconds with placebo and 231 +/- 33 with prazosin. Chest pain and nitroglycerin usage were not altered by prazosin. These data suggest that coronary artery spasm is not primarily caused by an effect on or an abnormality of the coronary vascular alpha 1-receptor.

Adrenergic alpha-Antagonists↗
PubMed1983

Phospholipid synthesis in the squid giant axon: enzymes of phosphatidylinositol metabolism.

We examined the properties of several enzymes of phospholipid metabolism in axoplasm extruded from squid giant axons. The following synthetic enzymes, CDP-diglyceride: inositol transferase (EC 2.7.8.11), ATP:diglyceride phosphotransferase, diglyceride kinase (EC 2.7.2.-), and phosphatidylinositol kinase (EC 2.7.1.67), were all present in axoplasm. Phospholipid exchange proteins, which catalyzed the transfer of phosphatidylinositol and phosphatidylcholine between membrane preparations and unilamellar lipid vesicles, were also found. However, we did not find conditions under which the synthesis of CDP-diglyceride, phosphatidylserine, and phosphatidylinositol-4,5-diphosphate could be measured. Subcellular fractionation by differential centrifugation showed that the axoplasmic inositol transferase and phosphatidylinositol kinase activities were largely "microsomal," while the diglyceride kinase and exchange protein activities were primarily "cytosolic."

1-Phosphatidylinositol 4-Kinase↗
PubMed1983

Respite admissions and the disabled elderly.

A retrospective descriptive study of the elderly patients served by a respite admission program in a teaching hospital is described. Data were collected by health record review and interviews with the program social worker. In the three years covered by the study there were 28 patients, with a mean age of 80.5 years. Fifty-seven per cent were male, 68 per cent, married, 29 per cent, widowed, and 3 per cent, single. When first admitted they were all living in their own homes or the home of a child. Seventy-nine per cent of the patients had moderate or severe dementia, with or without physical disability. Family members were the main caregivers and home care services provided support in 54 per cent of cases. Ninety-three per cent of the patients attended the geriatric day hospital. The patients received respite admissions for a mean of 10.8 months. At the end of the study more than a third of the patients were still living at home and half had entered long-term care facilities. By means of respite admissions supplemented by day hospital attendance it has been possible to maintain in the community disabled elderly patients who might otherwise have required immediate institutionalization. The need for more respite care and in-home services is discussed and a role for long-term care facilities as major providers of respite care suggested.

Aftercare↗
PubMed1983

Effect of alcohol on the integrity of the intestinal epithelium.

The absorption of macromolecules from the small intestine of rats was studied in terms of the amount of peroxidase activity that appeared in thoracic duct lymph after a 10 mg dose of horseradish peroxidase had been injected directly into the lumen of the duodenum. When the horseradish peroxidase was injected as a solution in saline no peroxidase activity was detected in the lymph. When ethyl alcohol was included in the dose at final concentrations of 12.5-16% the flow rate of the lymph increased markedly for an hour or so and during this time peroxidase activity was detected in the lymph. An electronmicroscope study of the duodenal epithelium that had been exposed to alcoholic solutions of horseradish peroxidase showed that the enzyme had penetrated between the enterocytes. It was concluded that the presence in the intestine of substantial amounts of alcohol temporarily destabilises the intercellular junctions of the epithelium and thus promotes the absorption of materials which are normally excluded.

Animals↗
PubMed1983

Dynamic regulation of leukocyte beta adrenergic receptor-agonist interactions by physiological changes in circulating catecholamines.

beta-Adrenergic receptors on human mononuclear leukocytes were assessed using [125I]iodohydroxybenzylpindolol binding. Subjects were studied supine and after being ambulatory, a maneuver that increases plasma catecholamines approximately two-fold. beta-Receptor affinity for agonists, measured by the competition of [125I]iodohydroxybenzylpindolol binding by (-)isoproterenol was significantly reduced with ambulation and this reduction was associated with a reduction in the proportion of beta-receptors binding agonist with a high affinity from a mean (+/- SEM) of 42 +/- 5 to 24 +/- 2% (P less than 0.01). In a parallel series, beta-adrenergic-stimulated adenylate cyclase activity was also reduced with postural change from 4.6 +/- 1.1 to 2.4 +/- 0.6 pmol [32P]cAMP/min per mg protein (P less than 0.05) after ambulation. Similar reductions in the proportion of receptors binding agonist with a high affinity were seen after infusion of norepinephrine. We conclude that the maneuver of ambulation reduces leukocyte beta-receptor responsiveness and affinity for agonists, probably by the effect of increased plasma catecholamines mediating an uncoupling of the beta-receptor-adenylate cyclase complex.

Adenylyl Cyclases↗
PubMed1983

Acute reduction in human platelet alpha 2-adrenoreceptor affinity for agonist by endogenous and exogenous catecholamines.

The binding characteristics of l-epinephrine to intact human platelets were assessed under conditions of physiological and pharmacological variations in plasma catecholamine concentration. In competition with the alpha 2-adrenoreceptor antagonist yohimbine, mean platelet receptor affinity for l-epinephrine was decreased 3.4-fold after 2 h of upright posture and exercise. This change in agonist affinity correlated significantly with the increases in plasma epinephrine and norepinephrine that were stimulated by upright posture and exercise. Supine subjects infused with l-norepinephrine or l-epinephrine for 2 h also averaged a 3.3- and 2.7-fold decrease in platelet alpha 2-adrenoreceptor affinity for agonist with no change in receptor number or antagonist affinity. The alpha 2-adrenoreceptor agonist affinity changes were specific for alpha-agonists since they were blocked by phentolamine, and incubation with 10(-5) M isoproterenol produced no change in alpha 2-adrenoreceptor affinity for l-epinephrine. In vitro exposure of intact human platelets to 10(-6) to 10(-10) M l-epinephrine for 2 h produced a concentration-related decrease in alpha 2-adrenoreceptor affinity for agonist. In all three paradigms, average slope factors approached 1.0 as affinity decreased, which is consistent with a heterogeneous receptor population that becomes more homogeneous after agonist exposure. Incubation of platelet-rich plasma with 10(-6) to 10(-8) M l-epinephrine resulted in a dose- and time-related loss of aggregatory response to l-epinephrine; this demonstrates that agonist affinity changes are correlated with changes in receptor sensitivity. These observations demonstrate that physiological variations in plasma catecholamines acutely modulate the intact human platelet alpha 2-adrenoreceptor's affinity for agonist, and can thereby alter the sensitivity of platelets to alpha 2-adrenergic agonist.

Adrenergic alpha-Agonists↗
PubMed1983

Influence of alpha-methyldopa treatment on adrenergic receptor binding in rat forebrain.

We studied the influence of 6 days treatment with alpha-methyldopa (50 mg/kg s.c.) twice daily on radioligand binding to alpha 1 [3H)prazosin), alpha 2 [3H)clonidine) and beta[3H)dihydroalprenolol (DHA] receptors in rat forebrain. A 27% rise (p less than 0.05) in the Bmax for (3H)prazosin without change in Kd was found. Following alpha-methyldopa, the Kd for (3H)clonidine was increased from 1.78 +/- 19 to 3.03 +/- nM and Bmax fell from 197 +/- 20 to 167 +/- 19 fmoles/mg protein (p less than 0.05). These findings suggest that chronic alpha-methyldopa therapy induces changes in alpha 1 and alpha 2 receptors which may modify the antihypertensive effect of alpha-methyldopa.

Animals↗
PubMed1983

The health consequences of caffeine.

Acutely administered caffeine modestly increases blood pressure, plasma catecholamine levels, plasma renin activity, serum free fatty acid levels, urine production, and gastric acid secretion. It alters the electroencephalographic spectrum, mood, and sleep patterns of normal volunteers. Chronic caffeine consumption has no effect on blood pressure, plasma catecholamine levels, plasma renin activity, serum cholesterol concentration, blood glucose levels, or urine production. Caffeine does not appear to be useful for increasing the motility of hypomotile sperm in artificial insemination or in the therapy of minimal brain dysfunction, cancer, or Parkinson's syndrome, but it may be effective as a topical treatment of atopic dermatitis and as systemic therapy for neonatal apnea. Caffeine does not seem to be associated with myocardial infarction; lower urinary tract, renal, or pancreatic cancer; teratogenicity; or fibrocystic breast disease. The role of caffeine in the production of cardiac arrhythmias or gastric or duodenal ulcers remains uncertain.

Brain↗
PubMed1983

Central and peripheral cardiovascular effects of alpha-methylepinephrine.

We compared peripheral and central cardiovascular effects of (+/-)-alpha-methylepinephrine (alpha-ME) and (+/-)-alpha-methylnorepinephrine (alpha-MNE), two putative active metabolites of alpha-methyldopa to those of (-)-epinephrine in urethane-anesthetized normotensive rats. Intravenous administration of 1 microgram doses of alpha-ME (4.3 nmol) lowered blood pressure whereas alpha-MNE (4.5 nmol) and (-)-epinephrine (3.0 nmol) raised blood pressure. Heart rate responses to each were opposite to the blood pressure response, consistent with reflex buffering. When administered into the cerebral ventricle (5-20 micrograms) (15-90 nmol) and nucleus of the solitary tract (0.3-10 nmol), each catecholamine caused marked reductions in both blood pressure and heart rate. alpha-ME was more potent than alpha-MNE and the endogenous catecholamine, (-)-epinephrine, in its central depressor effect. The greater potency of alpha-ME relative to alpha-MNE and (-)-epinephrine suggests that it could contribute to antihypertensive actions of alpha-methyldopa.

Animals↗
PubMed1982

Caffeine down-regulates beta adrenoreceptors in rat forebrain.

We studied the influence of caffeine treatment (50 mg/kg for 3 doses) on catecholamine utilization and adrenergic receptor binding in female rats. Caffeine enhanced the reduction in forebrain norepinephrine levels following alpha-methyl-p-tyrosine without altering the reduction in dopamine levels. Caffeine reduced the apparent number of beta receptors in forebrain as measured by the Bmax for [3H]dihydroalprenolol binding. No changes in alpha1 or alpha2 receptor binding, as measured with [3H]prazosin and [3H]clonidine, respectively, were noted. These data show that caffeine selectively increases the rate of norepinephrine utilization in rat forebrain and that this is associated with a small, but significant, reduction in beta receptor density in this brain area.

Animals↗
PubMed1982

Geriatric assessment unit in a teaching hospital.

A geriatric assessment unit has been in operation in a Canadian teaching hospital since October 1979. In the first 15 months of operation there were 203 admissions involving 153 persons aged 65 years or older, many of whom were impaired both physically and mentally. In many cases these patients could be discharged back to the community following assessment and rehabilitation. Only a few had to be placed immediately in extended care facilities. The mean stay in the unit was less than 3 weeks. There was a mortality of 3% among patients in the unit. For older persons who present with complex health problems a geriatric assessment unit provides an environment for comprehensive assessment, treatment and rehabilitation. A thorough assessment at, or preferably before, the point at which their health breaks down enables older people to return to and remain in the community and helps to prevent them from being admitted to an institution while they are still able to function with reasonable independence.

Aged↗
PubMed1982

Effects of acoustic trauma on stereocilia structure and spiral ganglion cell tuning properties in the guinea pig cochlea.

Guinea pigs were exposed to loud pure tones from 107 to 129dB SPL for 1 h. After varying recovery periods N1 electrocochleograms and single spiral ganglion cell recordings were obtained. The exposed cochleas were examined by scanning electron microscopy. The relationships between N1 thresholds, single neuron tuning curves and hair cell damage are described.

Action Potentials↗