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Biomedical subjects

D Robertson

Publications and source records attributed to D Robertson.

At least 325 records · Page 18Linked to original sources
PubMed1988

Analysis of 1071 gift procedures--the case for a flexible approach to treatment.

An analysis of the outcome of first gamete intrafallopian transfers for 1071 women indicates that for those aged 40 years or more all the oocytes had to be transferred to obtain a 19.2% pregnancy rate. In this age-group pregnancy rate and multiple pregnancy rate were significantly lower than those for younger women. Success rate, but not multiple pregnancy rate, was significantly higher in the group of women from whom 11 or more oocytes were recovered and transferred after ovulation induction than when only 1-4 oocytes were recovered and transferred. The findings suggest that the number of oocytes transferred should depend on clinical circumstances.

Abortion, Spontaneous↗
PubMed1988

Smoking and mechanisms of cardiovascular control.

In humans short-term administration of nicotine, whether by smoking or intravenous injection, will typically raise blood pressure by 5 to 10 mm Hg and heart rate by 10 to 25 bpm. Smoking causes reduced myocardial contractility and left ventricular function in patients with angina pectoris or heart failure. Nicotine's mechanism of action is more complex than the classic concept of nicotinic ganglionic stimulation can account for. Nicotine exerts a potent pressor effect in the ventral lateral medulla (C-1 area). Little current data are available documenting the efficacy of centrally acting antihypertensive agents and converting-enzyme inhibitors with regard to preventing nicotine's acute cardiovascular effects.

Animals↗
PubMed1988

Depletion of brainstem epinephrine stores by alpha-methyldopa: possible relation to attenuated sympathetic outflow.

The antihypertensive effect of alpha-methyldopa (MD) is believed to be critically dependent on its ability to deplete endogenous catecholamines or cause the synthesis of false neurotransmitters. We used liquid chromatography with electrochemical detection (LCEC) and negative chemical ionization gas chromatography-mass spectrometry (GC-MS) for quantitation of catecholamines and MD metabolites in rat. MD intraperitoneally (100 mg/kg q12 hr X 12 days), significantly increased alpha-methylnorepinephrine (MNE) in brain (1.02 +/- 0.33 micrograms/g), heart (1.67 +/- 0.57 micrograms/g) and adrenal glands (114.93 +/- 50.47 micrograms/g) Endogenous norepinephrine (NE), epinephrine (E) and dopamine (DA) were reduced. ME levels were 2.19 +/- 0.44 micrograms/g (n = 6) in the adrenal gland but only 99 +/- 26 pg/g (n = 3) in the brainstem. MD-induced endogenous brainstem NE depletion was more than compensated by MNE production, but brainstem E depletion was not compensated for by a stoichiometric production of brainstem ME. We conclude (1) although ME is a metabolite of MD, it is present in extremely low concentrations in brainstem and (2) central epinephrine-containing neurons are depleted of neurotransmitter by MD therapy. If this selective epinephrine depletion occurs in the bulbospinal tract neurons responsible for maintaining sympathetic tone, then this effect could contribute to the antihypertensive effect of MD.

Adrenal Glands↗
PubMed1988

Neuropeptide Y is a vasoconstrictor of human coronary arteries.

Neuropeptide Y (NPY) is a 36-amino-acid polypeptide which coexists with catecholamines in many adrenergic and noradrenergic neurons. It has been demonstrated to exert pressor effects in the perfused guinea pig heart and to constrict large cerebral and coronary blood vessels in animal studies. To determine if NPY might be a human coronary vasoconstrictor, the authors studied its effect on postmortem human coronary arteries. Proximal epicardial coronary rings were studied in a superfusion apparatus in Krebs-Ringer bicarbonate buffer (37 degrees C, pH 7.4) presaturated with 95% O2-5% CO2. Concentration-response curves were obtained using NPY in 0.1% bovine serum albumin in buffer and the responses were compared to those obtained in the presence of alpha 1, beta, and cyclooxygenase antagonists. A dose-related constrictor effect was obtained with NPY, which was significantly more potent than noradrenaline, constriction often being seen at 10(-12) M concentration. A vasorelaxant effect was seen in nonatherosclerotic vessels at higher concentrations. The vasoconstriction produced by noradrenaline was potentiated by subthreshold concentrations of NPY. The vasoconstrictor effect of NPY was not inhibited by prazosin (10(-6) M), and the vasodilatory effect was not inhibited by propranolol (10(-5) M). Indomethacin (3 X 10(-6) M) did not alter either vasoconstriction or vasorelaxation. The authors conclude that NPY is a potent constrictor of the human coronary artery at concentrations that may be achievable in vivo; it may thus be a contributor to sympathetic enhancement of coronary artery tone.

Coronary Vessels↗
PubMed1988

Purinergic receptors in the brainstem mediate hypotension and bradycardia.

Adenosine acts at many sites to modulate neuronal activity. The purpose of this study was to investigate a possible role for adenosine as a neuromodulator of brainstem cardiovascular control. Microinjections of adenosine (0-2.3 nmol) were made stereotaxically into various brainstem sites. Injection of adenosine into the nucleus tractus solitarii (NTS) produced dose-related decreases in heart rate and systolic and diastolic blood pressures. Maximal changes occurred 90 seconds after injection. Injection into the area postrema also produced decreased heart rate and systolic and diastolic blood pressures. No significant effect occurred following injection into the C1 area. Adenosine 5'-triphosphate and its analogue, beta, gamma-methylene adenosine 5'-triphosphate also produced dose-related and potent vasodepressor and bradycardia effects in the NTS. Injection of 1,3-dipropyl-8-p-sulfophenylxanthine (0.92 nmol), a potent adenosine receptor antagonist, produced no effect itself, but abolished for 45 minutes the actions of further injections of adenosine and adenosine 5'-triphosphate (but not L-glutamate) in both the NTS and area postrema. Thus, NTS and area postrema injections of adenosine decrease blood pressure and heart rate in anesthetized normotensive rats through adenosine receptors located in these areas. These findings support a role for endogenous adenosine as a central modulator in cardiovascular control.

Adenosine↗
PubMed1988

A comparison of nucleoside transport and metabolism in hypertensive and normotensive rats.

In a previous study, we discovered that spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) are dissimilar with respect to the depressor potency differentiated between intravenously and intra-arterially infused adenosine. To test the hypothesis that this dissimilarity may reflect a difference between the two strains in adenosine transport or metabolism, we compared the kinetics of nucleoside transport (i.e., [3H]uridine uptake) in erythrocytes and the pulmonary disposition of [3H]adenosine in SHR versus WKY. [3H]Uridine uptake in rat erythrocytes was linear for 4 minutes and inhibitable with dipyridamole. Kinetic analysis (i.e., Hofstee plots) of initial uptake velocity indicated no difference between the two strains with respect to apparent Km (196 +/- 40 vs 230 +/- 29 microM in WKY and SHR, respectively) and maximum velocity (7.5 +/- 0.4 vs 8.3 +/- 0.5 pmol/2 min/12% Hct in WKY and SHR, respectively). Approximately 50% of [3H]adenosine infused into the pulmonary artery of perfused rat lung was transported into the lung, and 85% of this material was incorporated into the nucleotide pool. Radioactivity in the lung perfusate consisted initially of equal amounts of adenosine and inosine; however, within 60 seconds after administration of [3H]adenosine most of the effluent radioactivity was inosine. No differences were detected in adenosine uptake, intracellular metabolism, or extracellular metabolism in lung from SHR versus WKY. Our data indicate that any difference between SHR and WKY with respect to the biological response to adenosine cannot be attributed to differences in adenosine disposition and, therefore, must be due to pharmacodynamic differences between the strains.

Adenosine↗
PubMed1988

A simple liquid-chromatographic method applied to determine caffeine in plasma and tissues.

In this simple, reliable assay for quantifying caffeine in plasma and tissues, methylxanthines are first partly purified from plasma and acid extracts of tissue by passage through solid-phase columns. The ease of this extraction method permits a relatively large number of samples to be processed daily. Quantification is by reversed-phase high-pressure liquid chromatography (mobile phase: acetic acid/acetonitrile/water, 2/6/92 by vol). Caffeine is eluted in 20 min. The reliability of this method allows its automation. This method has been adapted to measure caffeine in brain and kidney extracts and in as little as 10 microL of plasma. After 10 days of oral administration of caffeine (1 g/L, in drinking water) to six rats, the mean (+/- SEM) concentrations of caffeine in plasma, brain, and kidney were 18.6 +/- 6.0 micrograms/mL, 16.2 +/- 1.5 micrograms/g, and 18.9 +/- 2.0 micrograms/g, respectively. Correlations were linear between concentrations of caffeine in plasma and brain (r = 0.86) and between concentrations in plasma and kidney (r = 0.91). This method should be useful in studying the effects and mechanisms of actions of methylxanthines.

Animals↗
PubMed1987

Endogenous restoration of noradrenaline by precursor therapy in dopamine-beta-hydroxylase deficiency.

DL-dihydroxyphenylserine was given by mouth in a single-blind, placebo-controlled trial to two patients with orthostatic hypotension due to dopamine-beta-hydroxylase deficiency, in the hope of providing noradrenaline by endogenous decarboxylation. Dose-dependent increases in blood pressure were obtained over the range 150-600 mg. After 600 mg mean arterial pressure rose 33 and 19 mm Hg and these rises were tightly correlated with an increase in plasma noradrenaline (r = 0.995, p less than 0.001 and r = 0.88, p less than 0.05). Urinary noradrenaline increased from undetectable levels to 338 and 511 micrograms/24 h. Standing time (a correlate of functional capacity) also increased significantly in both patients. No side-effects were noted.

Adult↗
PubMed1987

The potent pressor effect of phenylpropanolamine in patients with autonomic impairment.

We determined the pressor effect of phenylpropanolamine hydrochloride, a widely used sympathomimetic agent, in 14 patients with autonomic failure and orthostatic hypotension. Blood pressure was monitored every five minutes in the sitting position with an automated device. Oral administration of 25 mg of phenylpropanolamine hydrochloride in nine patients produced significant increases in systolic (32 mm Hg), diastolic (15 mm Hg), and mean (21 mm Hg) blood pressures. The pressor effect appeared within the first 60 minutes and was still present at 105 minutes. There was no change in heart rate. Blood pressure was also significantly raised by administration of 12.5 mg of oral phenylpropanolamine hydrochloride in five additional patients. We conclude that administration of 25 mg of phenylpropanolamine hydrochloride elicits a potent pressor response in patients with orthostatic hypotension and that significant hypertension may result.

Aged↗
PubMed1987

A single bone marrow-derived stromal cell type supports the in vitro growth of early lymphoid and myeloid cells.

A clonal cell line (ALC) derived from murine bone marrow stroma is capable of supporting the continuous, in vitro growth of early lymphoid and myeloid cell populations. The growth-promoting effects of ALC are in part mediated through M-CSF and a pre-B cell growth factor, both of which accumulate in ALC-culture supernatant. To analyze the lymphoid growth factor produced by ALC cells, we derived a pre-B cell indicator line that is dependent on ALC-growth-conditioned medium. Using a combination of biological and biochemical analyses, we have established that the pre-B cell growth factor produced by ALC cells is distinct from IL-1, IL-2, IL-3, and IL-4 (BSF-1), suggesting that the early stages of B-cell development are regulated by a unique stroma-derived growth factor.

Animals↗