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Biomedical subjects

J T Watson

Publications and source records attributed to J T Watson.

At least 127 records · Page 7Linked to original sources
PubMed1980

Nuclear magnetic resonance and computed tomography: comparison of normal human body images.

Normal human body images of the thorax and abdomen were obtained using nuclear magnetic resonance (NMR) and computed tomography. Correlation of the images allowed precise anatomic identification of organs and structures. Differences between the images appear to be significant. NMR has potential as a methodology for assessing and imaging nuclear composition. Certain clinical implications from this technique are discussed.

Humans↗
PubMed1980

Axial lengths and refractive errors in kittens reared with an optically induced anisometropia.

An anisometropia was simulated in kittens during the critical period of development by securing a high-powered negative lens in front of one eye. Refractive error measurements obtained with an objective infrared optometer indicated that the deprived eyes of the anisometropic kittens were significantly more myopic than the normal eyes. A-scan ultrasonography showed that these differences in refractive error were correlated with an increase in the axial dimensions of the deprived eyes. The results of this experiment demonstrate that form deprivation associated with a habitually defocused retinal image produces an experimental myopia which is similar in nature to the refractive error changes produced by lid fusion and corneal opacification.

Age Factors↗
PubMed1978

Effects of caffeine on plasma renin activity, catecholamines and blood pressure.

Using a double-blind, randomized, cross-over protocol, we studied the effect of a single dose of oral caffeine on plasma renin activity, catecholamines and cardiovascular control in nine healthy, young, non-coffee drinkers maintained in sodium balance throughout the study period. Caffeine (250 mg) or placebo was administered in a methylxanthine-free beverage to overnight-fasted supine subjects who had had no coffee, tea or cola in the previous three weeks. Caffeine increased plasma renin activity by 57 per cent, plasma norepinephrine by 75 per cent and plasma epinephrine by 207 per cent. Urinary normetanephrine and metanephrine were increased 52 per cent and 100 per cent respectively. Mean blood pressure rose 14/10 mm Hg one hour after caffeine ingestion. There was a slight fall and then a rise in heart rate. Plasma caffeine levels were usually maximal one hour after ingestion but there was considerable individual variation. A 20 per cent increase in respiratory rate correlated well with plasma caffeine levels. Under the conditions of study caffeine was a potent stimulator of plasma renin activity and adrenomedullary secretion. Whether habitual ingestion has similar effects remains to be determined.

Administration, Oral↗
PubMed1978

A selective and sensitive assay for urinary metanephrine and normetanephrine using gas chromatography mass spectrometry with selected ion monitoring.

Vapor phase methodology for quantitative analysis of urine for metanephrine and normetanephrine as the pentafluoropropionyl derivative is described. The use of selected ion monitoring provided sufficient sensitivity and selectivity that milliliter aliquots of urine required only a simple scheme of sample processing; preliminary purification consisted of percolation through a column of XAD-2 followed by solvent extraction. The sample extracts were converted to the pentafluoropropionyl derivatives and analyzed by gas chromatography mass spectrometry with selected ion monitoring. Quantitative analysis was based on alpha[2H2]-beta-[2H1]metanephrine and alpha-[2H2]-beta-[2H1]normetanephrine which were added to the urine sample at the outset. The calibration plots for metanephrine and normetanephrine were linear from 10 ng ml-1 to 2000 ng ml-1 of urine permitting the detection of metanephrine and normetanephrine levels throughout the normal range and well into the subnormal range. Examples of application of the methodology to clinical investigation are described. The overall reproducibility of the sample processing methodology and instrumentation was assessed by replicate analyses of the same urine sample over a period of several weeks; the coefficient of variation was +/- 2.5% (n = 8).

Chromatography, Gas↗
PubMed1978

Gentisuric acid: metabolic formation in animals and identification as a metabolite of aspirin in man.

Gentisuric acid was synthesized from gentisic acid and glycine ethyl ester. NMR, mass spectrometric and elemental analysis confirmed the product as GU, and physicochemical characteristics were determined. A TLC-densitometric technique was developed to estimate GU and other metabolites of aspirin. Conjugation of gentisic acid with glycine to form GU was catalyzed by a mitochondrial fraction of rat and beef liver. GU was also formed by the rat liver microsomal hydroxylation of salicyluric acid, and phenobarbital pretreatment increased this formation. A random survey showed GU in 76% of SA-positive urines from aspirin-treated patients. Identity of GU in urine from two aspirin-treated patients was confirmed by TLC and mass spectrometric analysis, and hydrolysis of the compound from one patient yielded glycine and gentisic acid. Urine from controls or post-aspirin treatment patients did not show GU by TLC analysis. These results demonstrate for the first time the metabolic formation of GU in animals and its occurrence as a metabolite of aspirin in man.

Acyltransferases↗
PubMed1978

Relation between plasma concentration of indomethacin and its effect on prostaglandin synthesis and platelet aggregation in man.

The dose and plasma levels of indomethacin correlated with inhibition of prostaglandin synthesis as measured both by urinary excretion of the major metabolite of prostaglandin E2 (PGE-M) and by the release of prostaglandin E2 from thrombin-stimulated platelets. Considerable intersubject variability was observed in the suppression of PGE-M excretion. In some patients 37.5 mg indomethacin daily, usually considered subtherapeutic, caused suppression. Maximal suppression (greater than 90%) occurred in some after a daily dose of 75 mg, whereas 150 mg was required to achieve this level of inhibition in others. Suppression of the excretion of PGE-M by 60% occurred when the end of the dosage interval plasma levels of indomethacin were in the range 0.05 to 0.3 microgram/ml, which implies that a somewhat higher average steady-state concentration during the dosage interval was required to achieve this effect. A similar degree of inhibition of the release of PGE2 on thrombin-stimulated platelets was associated with the same range of plasma levels. Upon discontinuation of the drug, the levels of indomethacin in plasma decreased exponentially; inhibition of the release of PGE2 from platelets by indomethacin declined linearly with time and in parallel with the logarithm of the diminishing plasma levels.

Adult↗
PubMed1977

Prostaglandin-mediated hypercalcemia in the VX2 carcinoma-bearing rabbit.

Prostaglandin biosynthesis and metabolism were studied in the VX2 carcinoma-bearing rabbit, an animal model of prostaglandin-mediated hypercalcemia. All the identification and quantification of the prostaglandins were done by gas chromatography-mass spectrometry. The tumor incubated in vitro converted exogeneous arachidonic acid principally to PGE2. Biosynthesis from endogenous precursor lipids yields mainly PGE2 and PGF2alpha. The 100,000 x g supernatant fluid of the tumor did not contain any metabolizing enzymes. Significant hypercalcemia developed between the first and second week after tumor implantation. The levels of the major plasma metabolite of PGE2, 15-keto-13,14-dihydro-PGE2, became elevated at one week, had risen 25-fold by the end of the second week, and at the fourth week were elevated to 256 times the pre-incubation levels. The concentration of 15-keto-13,14-dihydro-PGF2alpha in plasma rose in parallell but to a lesser degree. 7alpha-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid, the major urinary metabolite of the E prostaglandins, was elevated two weeks after tumor implantation and rose until the fifth week. Indomethacin treatment lowered both serum calcium and the plasma level of 15-keto-13,14-dihydro-PGE2.

Animals↗
PubMed1976

Effect of hypertonic mannitol and intraaortic counterpulsation on regional myocardial blood flow and ventricular performance in dogs during myocardial ischemia.

Studies were performed to determine if intervention with hypertonic mannitol and intraaortic balloon counterpulsation increases regional myocardial blood flow during acute myocardial ischemia. Anesthetized dogs on right heart bypass were studied. Heart rate was kept constant by atrial pacing. Myocardial ischemia was provided by ligating the proximal left anterior descending coronary artery for 12 minute periods. Infusion of hypertonic mannitol begun immediately after ligation increased coronary blood flow to the ischemic area by 36 +/- 9.0% (standard error) (P less than 0.01) and to the nonischemic left ventricle by 21 +/- 8.8% (P less than 0.05) as compared with flow in the same regions during the control coronary ligation. Intraaortic balloon counterpulsation begun immediately after ligation increased regional coronary flow to the ischemic region by 20 +/- 8.4% (P less than 0.05) but did not significantly alter flow to the nonischemic left ventricle as compared with levels during the control ligation. Combined intraaortic counterpulsation and hypertonic mannitol increased coronary flow to the ischemic region by 46 +/- 13% (P less than 0.02) and to the nonischemic left ventricle by 59 +/- 22% (P less than 0.05) as compared with flow during occlusion of the left anterior descending artery with mannitol alone. The data demonstrate that both hypertonic mannitol and intraaortic counterpulsation increase left ventricular ischemic regional flow and that combined hypertonic mannitol and intraaortic balloon counterpulsation provide a greater increase in regional coronary blood flow to both the ischemic and nonischemic regions of the left ventricle than mannitol alone.

Acute Disease↗
PubMed1976

Determination of 15-keto-13,14-dihydro-metabolites of PGE2 and PGF2alpha in plasma using high performance liquid chromatography and gas chromatography-mass spectrometry.

A method is described for the measurement of 15-keto-13,14-dihydrometabolites of PGE2 and PGF2alpha in peripheral human plasma. This involves purification by high performance liquid chromatography followed by determination of levels by combined gas chromatography-mass spectrometry using tetradeuterated analogs of the metabolites as internal standards. The levels of these metabolites in plasma are considered to be a more reasonable index of the entry of PGE2 and PGF2alpha into peripheral blood than are the levels of the corresponding primary prostaglandins. The endogenous levels of 15-keto-13, 14-dihydro-PGE2 and 15-keto-13,14-dihydro-PGF2alpha found in peripheral plasma are 33 +/- 10 pg/ml (SD; n=6) and 40 +/- 16 pg/ml (SD; n=6), respectively.

Chromatography, Gas↗
PubMed1976

Similarities in coronary flow between external counterpulsation and intra-aortic balloon pumping.

The ability of external counterpulsation (Cardiassist) and intra-aortic balloon pumping (AVCO) to influence collateral coronary blood flow in ischemic myocardium was measured in anesthetized dogs. Cardiac output and heart rate (atrial pacing) were held constant on right-heart bypass. Both external counterpulsation and balloon pumping augmented peak diastolic pressure (30 mmHg and 38 mmHg, respectively), while mean aortic pressure, peak left-ventricular pressure, left-ventricular end-diastolic pressure, maximum left-ventricular dp/dt, hematocrit, and osmolality remained unchanged. Regional coronary blood flow was measured using 9-mum radioactive microspheres. External counterpulsation and balloon pumping begun immediately following ligation of the left-anterior descending coronary artery significantly increased collateral coronary blood flow 29 +/- 7.5% (SE, P is less than .01) and 20 +/- 8% (P is less than .05), respectively, to ischemic myocardium. This redistribution of collateral coronary blood flow produced by both methods of counterpulsation was primarily to the subepicardial region of the ischemic myocardium. The mechanism responsible for the measured increases in collateral coronary blood flow appears most likely to be an increased pressure gradient produced by diastolic augmentation.

Animals↗
PubMed1976

Influence of dobutamine on regional myocardial blood flow and ventricular performance during acute and chronic myocardial ischemia in dogs.

The data from this study document that dobutamine is a powerful inotropic agent in anesthetized dogs with acute myocardial ischemia and in awake, unsedated ones with chronic myocardial infarction. Dobutamine significantly increases heart rate at relatively small doses in anesthetized dogs with acute myocardial ischemia but considerably larger amounts of dobutamine are required to significantly increase heart rate in awake, unsedated dogs with myocardial infarction. Dobutamine also significantly increases regional myocardial blood flow to all areas of the heart at 20mug/kg/min in both anesthetized dogs with acute myocardial ischemia and awake, unsedated ones with myocardial infarction. However, in anesthetized dogs 20mug/kg/min of dobutamine significantly increases epicardial ST-segment elevation during acute myocardial ischemia. Propranolol prevents the inotropic and chronotropic effects of dobutamine in both anesthetized and awake, unsedated dogs. This study suggests that during experimental acute myocardial ischemia dobutamine given at doses that significantly increase heart rate and contractility may increase the extent of myocardial damage. The data also suggest that this agent should be of value in the setting of severe myocardial depression without associated severe coronary artery disease to increase cardiac contractility at doses that do not markedly alter heart rate. The hemodynamic and coronary blood flow effects of dobutamine in patients with and without severe coronary artery disease should be evaluated.

Acute Disease↗
PubMed1976

Effect of hypertonic mannitol and isoproterenol on regional coronary flow following right ventriculotomy.

We studied the changes which occurred in regional coronary blood flow after right ventriculotomy and the subsequent effects of hypertonic mannitol or isoproterenol infusion. Regional coronary flows were measured with radioactive microspheres (9 micron) in open-chest anesthetized dogs. Either hypertonic mannitol (25%) was infused at 3.2 ml/min or 7.6 ml/min for 30 minutes, or normal saline at 7.6 ml/min for 30 minutes followed by isoproterenol at 0.05-0.10 mug/kg/min. In the mannitol treated animals right ventricular, left artrial and aortic pressures, heart rate, and cardiac output did not change significantly following vertical ventriculotomy, whereas in the saline-isoproterenol treated animals aortic pressures fell significantly. Coronary flow to the peri-incisional area fell from 41 to 24 ml/min-100 g (P less than 0.05) following ventriculotomy, increased by 34% (P less than 0.05) when osmolality rose after mannitol by 37 mOsm, but was unchanged with isoproterenol. The data indicate that a vertical ventriculotomy reduces flow to adjacent myocardium and that subsequent infusion of hypertonic mannitol at moderate rates significantly increases coronary flow to this region.

Animals↗
PubMed1976

The influence of combined intra-aortic balloon counterpulsation and hyperosomotic mannitol on regional myocardial blood flow in ischemic myocardium in the dog.

We investigated the combined effectiveness of intra-aortic balloon counterpulsation and hyperosmotic mannitol (25%) on regional myocardial blood flow during acute coronary insufficiency. Cardiac output and paced heart rate were held constant in chloralose-anesthetized dogs during right heart bypass. Acute coronary insufficiency was produced by ligation of the proximal left anterior descending coronary artery (LAD). Regional myocardial blood flow was measured using radioactive microspheres. Left ventricular end-diastolic pressure, mean aortic pressure, maximum left ventricular dp/dt, and hematocrit were unchanged by combined mannitol infusion and balloon pumping. Studies of combined treatment with balloon pumping and mannitol immediately after the second of two 13-minute consecutive reversible ligations of the LAD demonstrated that (1) collateral coronary blood flow increased 46% (P less than 0.02) in ischemic myocardium compared with mannitol infusion along during the first LAD ligation, and (2) collateral coronary blood flow increased 27% (P less than 0.05) in ischemic myocardium compared with balloon pumping along during the first LAD ligation. Studies in which combined treatment was delayed until 20 minutes after LAD ligation demonstrated that collateral coronary blood flow was elevated by 33% (P les than 0.05) in ischemic myocardium compared to control studies in which balloon pumping alone had no effect. The results suggest that the increase in collateral coronary blood flow was in part a result of an increased transmural pressure gradient produced by balloon diastolic augmentation and the ability of mannitol to reduce coronary vascular resistance in ischemic myocardium.

Animals↗