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Biomedical subjects

D Robertson

Publications and source records attributed to D Robertson.

At least 451 records · Page 25Linked to original sources

Thromboxane A2 in vasotonic angina pectoris: evidence from direct measurements and inhibitor trials.

Thromboxane A2 (TxA2), an arachidonic acid metabolite causing vasoconstriction and platelet aggregation, is a putative mediator of coronary-artery vasospasm. To determine whether platelet-released TxA2 causes coronary arterial vasospasm, we measured plasma thromboxane B2 (TxB2, the inactive hydration product of TxA2) in the radial-artery and coronary-sinus blood of seven patients and performed therapeutic trials of antiplatelet agents in nine. Although coronary-sinus TxB2 levels rose from the base line approximately fivefold with spontaneous ischemia, samples drawn early in ischemia showed no rise over base-line values. Although a 150 mg dose of aspirin reduced urinary dinor-TxB2 levels by over 75 per cent, it had no effect on the course of the chronic recurrent form of angina pectoris due to vasospasm ("vasotonic angina"). Similarly, indomethacin had no effect on the frequency or duration of ischemia. TxA2 is unlikely to cause vasotonic angina, but it may be released during coronary vasospasm.

Adult↗

alpha-Methylepinephrine, a methyldopa metabolite that binds to alpha-receptors in rat brain.

The presence of phenylethanolamine-N-methyl transferase in those brain-stem nuclei where methyldopa is thought to act suggested to us that methylepinephrine could be an active metabolite of methyldopa. We assessed the potential of methylepinephrine to be an active metabolite by determining its capacity to compete for ligands which bind to alpha-receptors in rat brain. Thus, the abilities of epinephrine, norepinephrine, methyldopa, (+/-)-methylnorepinephrine and (+/-)-methylepinephrine to compete for alpha 1-([3H]WB-4101) and alpha 2-([3H]clonidine) binding sites in rat brain wee compared. Order of potency at each binding site was: [3H]WB-4101 -- (-)epinephrine = (-)-norepinephrine greater than (+/-)-methylnorepinephrine greater than (+/-)-methylepinephrine much greater than (-)-methyldopa; [3H]clonidine -- (-)-epinephrine greater than (+/-)-methylnorepinephrine greater than (-)-norepinephrine greater than (+/-)-methylepinephrine much greater than (-)-methyldopa. Since it can compete with a specific ligand for alpha 2-receptors, methylepinephrine could be a centrally active metabolite of methyldopa.

Animals↗

Inhibition and recovery of growth processes in roots of Pisum sativum L. exposed to 60-Hz electric fields.

Roots of Pisum sativum L. were chronically exposed in aqueous inorganic nutrient medium to 60-Hz electric fields between 140 and 490 V/m (growth medium conductivity approximately 0.08 S/m). The growth rate, meristematic mitotic index, and growth rate recovery of the roots were determined. At 140 V/m there was no perturbation in growth rate or mitotic index. At 430 V/m the growth rate and the mitotic index were reduced. The mitotic index had a maximum depression (approximately 55% of control), which occurred at 4 h. The depression in growth rate was immediate and constant over time. When roots were exposed to an electric field at 430 V/m for 2 days, the growth rate was depressed by about 40%. When the field was terminated, the growth rate steadily increased and was almost normal after 5 days. At 490 V/m root growth rate was almost completely arrested. According to these results, there is a narrow range of induced membrane potentials that span the range from slightly altered to almost completely arrested growth rates.

Electromagnetic Fields↗

The Bezold-Jarisch reflex: possible role in limiting myocardial ischemia.

A patient with a 5-year history of nonexertional episodic chest discomfort terminating in nausea presented with recurrent periods of marked ST elevations. Each observed episode terminated in the triad of bradycardia, hypotension, and nausea. ST elevation normalized almost immediately when this triad supervened. It is hypothesized that this represented activation of the Bezold-Jarisch reflex. Resolution may have been due to reflexly mediated parasympathetic coronary vasodilation. An episode of ST elevation occurred 24 h after admission which did not result in activation of the Bezold-Jarisch reflex. Following this latter episode, Q waves and enzymatic evidence of myocardial infarction were documented.

Angina Pectoris↗

Relationship of 60-Hz electric-field parameters to the inhibition of growth of Pisum sativum roots.

Roots of Pisum sativum were chronically exposed to 60-Hz electric fields ranging from 215--430 V/m and current densities from 1.5--2.7 mA/cm2. Adjustments of the exposure medium's conductivity (0.035--0.14 mho/m) allowed for distinction between a field or a current induced perturbation in root growth rates. Inhibition of root growth rates was directly related to the magnitude of the applied field and not the current density. The results are consistent with the postulate that the applied field acts upon the cell membrane and perturbs its function.

Cell Division↗

Pitfalls in the diagnosis of extraadrenal pheochromocytoma.

Precise localization of pheochromocytomas is an essential part of their preoperative management. As a significant number of these tumors may be extraadrenal multiple, or hypovascular, they may not be detected by computerized body tomography (CBT) or arteriography without film subtraction. In seven patients with extraadrenal pheochromocytomas, all tumors were demonstrated by arteriography. In two cases, subtraction films revealed tumors that had not been visualized on the non-subtraction films. CBT, performed in four patients, demonstrated a mass in two but failed to visualized tumors in the other two.

Adolescent↗

Postprandial alterations in cardiovascular hemodynamics in autonomic dysfunction states.

The effect of food ingestion of supine blood pressure was assessed during 25 studies in 10 subjects with autonomic dysfunction. Profound decreases in both systolic and diastolic pressure occurred. The mean (+/- standard error of the mean) maximal reduction in systolic blood pressure for the entire group was 49 +/- 6 mm Hg (range 22 to 98). The response also occurred in hypertensive subject after surgical sympathectomy and during alpha adrenergic blockade and hence appears to be a general phenomenon when sympathetic vasoconstrictor function is impaired. The depressor effect of food ingestion was enhanced by propranolol, attenuated by indomethacin and unaffected by diphenhydramine and cimetidine. The phenomenon is thus not explained by histamine release, and can only partly be accounted for by release of arachidonic acid metabolites. Evidence that insulin may play a role in the phenomenon is discussed. Manipulation of diet may prove to be an important adjunct in the management of patients with autonomic dysfunction.

Aged↗

The clinical spectrum of autonomic dysfunction.

Classic cases of idiopathic autonomic dysfunction are easily recognized, but certain presentations may not immediately suggest the diagnosis. Among 297 cases in the experience of our institutions, eight have been selected as illustrative of the difficulties which may be encountered. The disorder may present as angina pectoris, Parkinsonism, night blindness, nasal stuffiness, malignant hypertension, postprandial fainting, intracerebral hemorrhage and respiratory arrest. About half of the patients with idiopathic orthostatic hypotension manifest supine hypertension. These subjects are extremely sensitive to pressor and depressor agents; those who have angina pectoris complicating their disease are characteristically worsened by nitroglycerin.

Aged↗

(alpha S)-erythro-alpha-methylepinephrine: preparation and stereoselective binding to adrenergic receptors in rat forebrain.

The enantiomers of a number of catecholamines, including (alpha S)- and (alpha R)-erythro-alpha-methylepinephrine, were evaluated for their capacity to compete for binding sites in rat forebrain homogenates with [3H]prazosin, a ligand which selectively binds to adrenergic receptors of the alpha 1 subtype. (alpha R)-erythro-alpha-Methylepinephrine is devoid of apparent biological activity, but the activity of the alpha S isomer is substantial. The latter is less active than the endogeneous catecholamines, (R)-norepinephrine and (R)-epinephrine, but the stereospecific competition for [3H]prazosin binding sites by the catecholamine isomers with the beta R configuration is additional evidence that (alpha S)-erythro-alpha-methylepinephrine may be a biologically active metabolite of L-alpha-methyl-3,4-dihydroxyphenylalanine.

Animals↗

The aging game: a new teaching method in geriatric medicine.

The aging game, a simple yet effective educational method for teaching gerontology and geriatric medicine, is described. Groups of up to 20 students participate. A series of 100 cards bearing statements about old age, some of which are true and some of which are false, are distributed among them. By exchanging cards and by gradual grouping of the students, the participants endeavor to secure a hand in which all the statements are true. The game ends with all cards being reviewed by the teacher and the participants together. The aging game has been used with physicians, medical students, nurses, therapists, social workers and mixed groups of health professionals. A modified version has been used in pre-retirement education and public education on aging.

Geriatrics↗

Primary auditory neurons: nonlinear responses altered without changes in sharp tuning.

Two-tone suppression as well as distortion product responses in mammalian auditory neurons were altered by exposure to short, high intensity tones in the frequency region of the suppressing or primary tones. These changes occurred without significant alteration of the single neurons' tuning curves. The findings support the notion that two-tone suppression and distortion product responses are a function of the integrity of cochlear regions remote from the final transduction site.

Acoustic Stimulation↗

Tolerance to the humoral and hemodynamic effects of caffeine in man.

Acute caffeine in subjects who do not normally ingest methylxanthines leads to increases in blood pressure, heart rate, plasma epinephrine, plasma norepinephrine, plasma renin activity, and urinary catecholamines. Using a double-blind design, the effects of chronic caffeine administration on these same variables were assessed. Near complete tolerance, in terms of both humoral and hemodynamic variables, developed over the first 1-4 d of caffeine. No long-term effects of caffeine on blood pressure, heart rate, plasma renin activity, plasma catecholamines, or urinary catecholamines could be demonstrated. Discontinuation of caffeine ingestion after 7 d of administration did not result in a detectable withdrawal phenomenon relating to any of the variables assessed.

Adult↗

Regulation of human leukocyte beta receptors by endogenous catecholamines: relationship of leukocyte beta receptor density to the cardiac sensitivity to isoproterenol.

High levels of beta receptor agonist have previously been shown to down-regulate beta receptor density on circulating leukocytes in man; however, the factors controlling receptor density under physiological conditions have not previously been defined. To determine whether beta receptor density is normally down-regulated by circulating, physiological levels of catecholamines we have examined the relationship between receptor density and catecholamine levels. Urinary epinephrine and norepinephrine were significantly reciprocally correlated to lymphocyte receptor density. A similar relationship existed between beta receptor density and supine plasma epinephrine, norepinephrine, upright epinephrine, and norepinephrine levels. Change in sodium intake from 10 to 400 meq/d caused a 52% increase in lymphocyte and a 48% increase in polymorphonuclear beta receptor density. The changes in receptor density were accompanied by an increase in the sensitivity to isoproterenol measured as a fall in the dose of isoproterenol required to raise the heart rate by 25 beats per minute. Beta receptor density on both lymphocyte and polymorphonuclear cells was significantly correlated to the cardiac sensitivity to isoproterenol. Propranolol administration resulted in an increase in the density of beta receptors on lymphocyte and polymorphonuclear cells that correlated with the subject's pretreatment catecholamine levels. These findings, therefore, suggest that physiological levels of catecholamines normally down-regulate beta receptors in man and that blockade of this down-regulation by propranolol allows receptor density to increase.

Adult↗

Follicular development in the neonatal mouse ovary; effect of epidermal growth factor.

The growth of the ovary has been studied in the mouse after administration of epidermal growth factor (EGF). Newborn females injected daily with EGF for the first 5 days of life showed a retardation of ovarian development. The number of follicles in the resting pool (small follicles) was significantly greater than in control animals and there were fewer growing follicles at more advanced stages of development (types 3b and 4). The percentage of mitotic figures in the follicular and surface epithelia of the ovary and the epithelium of the extra-ovarian rete was also significantly reduced after EGF. The results indicate that EGF may inhibit rather than promote the growth of follicles in the neonatal mouse ovary in vivo.

Animals↗

Effects of epidermal growth factor on hair growth in the mouse.

The growth of the first hair coat in male mice was studied during administration of epidermal growth factor (EGF). Injections of 1 or 4 micrograms EGF/g body weight for 14 consecutive days from birth resulted in the development of curved overhairs (monotrichs), caused a retardation in rate of growth in length of hair and a reduction in hair diameter and length of follicle bulb. Growth rate partially recovered after cessation of EGF treatment. However, some of the effects produced by injections of EGF during the formation of the first coat were detected in the second and third generations of hair. Since EGF also retarded rate of body growth, we compared the effect of EGF on hair growth with that of restricting food intake in neonatal mice during the development of the first coat. Hair growth was slowed in underfed animals but the effects were less marked than those found in EGF-treated mice of similar body weights.

Animals↗

Prostaglandin suppression: inability to correct severe idiopathic orthostatic hypotension.

A 70-year-old man with classic severe idiopathic orthostatic hypotension received three different indomethacin dose regimens. Baseline urinary prostaglandin concentrations were modestly elevated. Although indomethacin greatly lowered prostaglandin production, no sustained improvement in blood pressure or symptoms occurred. It is proposed that the interindividual variations in vascular reactivity and circulating prostaglandin levels may account for the beneficial responses to indomethacin of some patients and the modest responses of others.

Aged↗