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Biomedical subjects

D Robertson

Publications and source records attributed to D Robertson.

At least 433 records · Page 24Linked to original sources

Inhibition of wool growth in merino sheep following administration of mouse epidermal growth factor and a derivative.

The present study investigates the effects of dosage and different modes of delivery of mouse epidermal growth factor (EGF) on the production of breaks in the fleece and on wool growth in Merino wethers. Subcutaneous infusions of EGF of greater than or equal to 0 . 25 mg kg-0.75 for 7-28 h resulted in a dose-dependent total or partial inhibition of wool production 2-4 weeks later. A complete break appeared in the fleece that was shed. Lower doses had lesser inhibitory effects on wool growth: the fleece was not shed but bore a zone of weakness, termed an incomplete break. Inclusion of the glucocorticoid analogue dexamethasone in the infusate did not alter the action of EGF on the fleece. Although a higher plane of nutrition increased the rate of fibre production, it did not alter the extent of inhibition of wool growth by EGF. Infusion of a peptide from EGF, which lacked eight of the C-terminal amino acids (EGF1-45), was as effective as the parent molecule in inhibiting wool growth. EGF administered as a single subcutaneous injection was less reliable as a method for producing breaks in the fleece. Of seven wethers that received EGF at a dose level between 0 . 27 and 0 . 32 mg kg-0.75, only three shed their fleeces. The remainder either developed incomplete breaks in the wool or were not affected. Administration of EGF at a dose level of 0 . 56 mg kg-0.75 via a rumen tube to one sheep had no discernible inhibitory effect on wool growth.

Animals↗

Clinical correlates of sway in old age--sensory modalities.

Sway has been measured by Wright's Ataxiameter in 151 frail elderly and five young subjects, and compared with various sensory modalities. There is a close relationship between increased sway and impaired vibration sense in the legs. No correlations emerged with proprioception but this may reflect the imprecision of the test. That neither vision nor vestibular deprivation correlated with sway confirms the place of these senses as secondary in the maintenance of posture. Vestibular impairment was found in only 6% of the elderly subjects, by tilt test--and these were the very old. There was a limited relationship between falls in the past year and both sway and proprioception.

Accidents↗

Combination H1 and H2 receptor antagonist therapy in diabetic autonomic neuropathy.

Autonomic neuropathy occurs frequently in diabetic patients but is seldom effectively treated. In our patient, a 34-year-old man with poorly controlled type 1 diabetes and autonomic neuropathy manifested by postural hypotension and diarrhea, treatment with diphenhydramine and cimetidine (H1 and H2 histamine antagonists, respectively) markedly improved the hypotension and diarrhea and led to better blood glucose control.

Adult↗

Outcome of hospital admission of the very elderly.

Hospital utilization by persons aged 85 or older before the development of a specialized geriatric service in a Canadian city is described. Admissions to surgical units slightly outnumbered those to medical units and were more likely to be elective admissions or interhospital transfers. Three fourths of the medical admissions were classified as "emergent," and half of the admissions came through the emergency department. Although a number of patients, particularly older women, came from extended care facilities, most patients had been living in the community before admission. The mean length of stay was 18.8 days and the in-hospital mortality rate was 13 per cent. The majority of patients were discharged to the community, and this placement appeared stable, in that less than 10 per cent of those discharged to the community entered an extended care facility within the one-year follow-up period.

Aged↗

Skeletal deformities in the elderly and their effect on postural sway.

In a group of 151 elderly men and women (age range, 65-85+), postural sway was studied in relation to various physical attributes and skeletal deformities that might be contributory factors. Weight, loss of height (span-height), scoliosis, grip strength, and the knee angle, measured laterally with the subject erect, all proved to be correlated with postural sway. Kyphosis was related to loss of muscle power and other general indications of frailty. Scoliosis appeared to be related to joint disease in the pelvis and lower limbs.

Aged↗

Overproduction of dihydrofolate reductase and gene amplification in methotrexate-resistant Chinese hamster ovary cells.

Stable isolates of Chinese hamster ovary cells that are highly resistant to methotrexate have been selected in a multistep selection process. Quantitative immunoprecipitations have indicated that these isolates synthesize dihydrofolate reductase at an elevated rate over its synthesis in sensitive cells. Restriction enzyme and Southern blot analyses with a murine reductase cDNA probe indicate that the highly resistant isolates contain amplifications of the dihydrofolate reductase gene number. Depending upon the parenteral line used to select these resistant cells, they overproduce either a wild-type enzyme or a structurally altered enzyme. Karyotype analysis shows that some of these isolates contain chromosomes with homogeneously staining regions whereas others do not contain such chromosomes.

Animals↗

Exacerbation of vasotonic angina pectoris by propranolol.

Using a double-blind protocol, we investigated the use of propranolol in patients with coronary artery spasm as assessed by subjective and objective variables. Both low-dose (40 mg every 6 hours) and high-dose (160 mg every 6 hours) propranolol were administered. At both doses, the duration of angina attacks was significantly prolonged but the frequency was not. We conclude that propranolol at doses up to 160 mg every 6 hours as single therapy is frequently detrimental in angina pectoris due to coronary artery spasm and should not be used as the sole treatment of this disorder.

Aged↗

Thallium-201 uptake in variant angina: probable demonstration of myocardial reactive hyperemia in man.

Myocardial thallium scintigraphy was performed in four subjects with variant angina and in one subject with isolated, fixed coronary obstruction. Three subjects with variant angina had short episodes of ischemic ST-segment elevation that lasted 20--100 seconds. Thallium scintigrams demonstrated excess uptake in regions judged to be ischemic by angiographic and electrocardiographic criteria. Two subjects, one with variant angina and the other with a fixed coronary lesion, had prolonged episodes of ischemia that lasted 390--900 seconds. Both had reduced thallium uptake in the ischemic regions. We conclude that myocardial reactive hyperemia is the cause of excess thallium uptake in patients with variant angina who have short episodes of myocardial ischemia.

Adult↗

Evidence that alpha-methylepinephrine is an antihypertensive metabolite of alpha-methyldopa.

Several medullary cardiovascular relay nuclei contain high concentrations of epinephrine and phenylethanolamine-N-methyl transferase (PNMT), the enzyme which catalyzes the conversion of norepinephrine to epinephrine. Since alpha-methylnorepinephrine, a metabolite of alpha-methyldopa, has been shown to be a substrate for adrenal PNMT, we postulated that alpha-methylnorepinephrine would also be a substrate for central PNMT, resulting in the synthesis of alpha-methylepinephrine. Therefore, alpha-methylepinephrine could be an active metabolite of alpha-methyldopa. We have investigated this hypothesis. 1) The centrally-active PNMT inhibitor SKF-64139 attenuated the hypotensive response to alpha-methyldopa in spontaneously hypertensive rats at doses that had little effect on the hypotensive response to clonidine. 2) In radioligand binding studies, alpha-methylepinephrine was as potent as norepinephrine in competing for alpha 2-receptors, more potent than epinephrine, norepinephrine, or alpha-methylnorepinephrine in competing for beta-receptors, and less potent than epinephrine, norepinephrine, or alpha-methylnorepinephrine in competing for alpha 1-receptors. 3) Intracerebroventricular administration of methylepinephrine (1-40 micrograms) to Sprague-Dawley rats elicited profound hypotension and bradycardia. alpha-Methylepinephrine was more potent than epinephrine in lowering blood pressure. We conclude that alpha-methylepinephrine is a centrally active depressor agent and could therefore be an active metabolite of alpha-methyldopa.

Animals↗

Surgical experience with retrogastric and retropancreatic pheochromocytomas.

From 1972 to 1981 at Vanderbilt University Hospital there were seven patients with midline retrogastric or retropancreatic pheochromocytomas. Each of these tumors arose between the aorta and the inferior vena cava. This report details the difficulties in localization before and at operation in the smaller tumors in these sites. Our experience suggests that small midline pheochromocytomas in these sites may be readily missed by computerized tomographic scan, aortography, or surgical search at laparotomy unless subtraction arteriograms are used and the Kocher maneuver is employed at operation routinely.

Adolescent↗

Differential competition by L-alpha-methyldopa metabolites for adrenergic receptors in rat forebrain.

The capacity of a series of intraneuronal metabolites of L-alpha-methyldopa to compete for alpha-1 ([3H]prazosin, alpha-2([3H]clonidine and beta ([3H]dihydroalprenolol) receptor binding in rat forebrain was studied. Each metabolite studied had a unique order of activity at each receptor. These data show that (-)-erythro-alpha-methylnorepinephrine and (-)-erythro-alpha-methylepinephrine compete with high affinity for alpha-2 receptors, thereby supporting the suggestion that alpha-2 receptors mediate hypotensive effects of L-alpha-methyldopa . Furthermore, these metabolites of L-alpha-methyldopa competed with high potency for beta-1 receptors in forebrain and (-)-erythro-alpha-methylepinephrine was more potent than (-)-epinephrine, (-)-norepinephrine and (-)-erythro-alpha-methylnorepinephrine in competing for beta-2 receptors on human lymphocytes. These data suggest that beta receptor stimulation may be important in determining the net effects of L-alpha-methyldopa. L-alpha-Methyldopa metabolites were much less potent than (-)-epinephrine and (-)-norepinephrine in competition for alpha-1 receptors. (+/-)-alpha-Methyldopamine was less potent than other l-alpha-methyldopa metabolites at all three receptors, suggesting that it is unlikely to be an important hypotensive metabolite of L-alpha-methyldopa.

Animals↗

Clinical experience with malignant pheochromocytomas.

In a 30 year period at Vanderbilt University Hospital, the affiliated Nashville General Hospital and the Nashville Veterans Administration Hospital, 64 patients with pheochromocytoma have been observed. In eight of these, the tumor proved to be malignant. Retrospective review of biologic characteristics of pheochromocytomas in this series included clinical, diagnostic imaging, chemical and histopathologic data. Aside from presence of distant metastases, none of these features had predictive value in indicating the biologic malignant nature of the primary tumor. One patient has been cured by radical surgical resection for 16 years. Three others have died with metastatic tumor and three patients are alive with metastatic tumor.

Adolescent↗

Airway response to sublingual nitroglycerin in acute asthma.

To test the efficacy of sublingual nitroglycerin as a bronchodilator, we studied ten patients with acute asthma. After a baseline spirogram, each patient was given 1.2 mg of sublingual nitroglycerin, and subsequent spirograms were obtained a five-minute intervals for 15 minutes. Each patient was then given three subsequent doses of epinephrine (0.5 mg) subcutaneously at 15-minute intervals. Spirograms were obtained 15 minutes after each epinephrine dose. Forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) did not change significantly following sublingual nitroglycerin, but both FEV1 and FVC improved significantly after epinephrine administration. Three patients experienced transient but severe hypotension after receiving sublingual nitroglycerin. The results suggest that sublingual nitroglycerin is not adequate initial therapy for asthmatic attacks and that the administration of sublingual nitroglycerin in acute asthma may be dangerous.

Acute Disease↗