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Biomedical subjects

J T Miller

Publications and source records attributed to J T Miller.

At least 37 records · Page 2Linked to original sources

Targeting 5'-deoxy-5'-(methylthio)adenosine phosphorylase by 5'-haloalkyl analogues of 5'-deoxy-5'-(methylthio)adenosine.

A series of 5'-haloalkyl-modified analogues of 5'-deoxy-5'-(methylthio)adenosine (MTA), a nucleoside byproduct of polyamine biosynthesis, has been synthesized: 5'-deoxy-5'-[(2-monofluoroethyl)thio]adenosine (10), 5'-deoxy-5'-[(2-chloroethyl)thio]adenosine (4), 5'-deoxy-5'-[(2-bromoethyl)thio] adenosine (5), and 5'-deoxy-5'-[(3-monofluoropropyl)thio]adenosine (13). On the basis of their abilities to serve as substrates of MTA phosphorylase prepared from mouse liver, several of these analogues were characterized for their growth inhibitory effects in MTA phosphorylase-containing (murine L5178Y and human MOLT-4) and MTA phosphorylase-deficient (murine L1210 and human CCRF-CEM) leukemia cell lines. The MTA phosphorylase-containing tumor cell lines, especially of human origin, were found to be more sensitive to treatment by these analogues. Of the analogue series, 10 was the most potent inhibitor of growth in each of the cell lines tested. The analogues, especially compound 10, displayed a reduced capacity to alter polyamine pools relative to MTA, mechanistically indicating a decreased potential for interactions at sites other than MTA phosphorylase. The results indicate that of the analogues tested, compound 10 displayed the best inhibitor/substrate interaction with MTA phosphorylase, which, in turn, correlated with more potent growth inhibition in tumor cell lines containing MTA phosphorylase. Overall, this supports the concept that MTA phosphorylase plays a role in the activation of such analogues.

Adenosine↗

Current therapy of impending myocardial infarction and acute cholecystitis.

The authors discuss the treatment of severe coronary artery disease and acute cholecystitis using laparoscopic laser in one instance and percutaneous transluminal coronary angioplasty (PTCA) in the other. Their report demonstrates that both can be applied with relative safety in close temporal proximity.

Acute Disease↗

Foreign body retrieval using a simple snare device.

We report three patients who had intravascular catheter fragments removed using an easily made snare device fashioned from a 0.038 inch movable-core J-wire and a multi-purpose catheter. The device is easily manipulated and facilitates safe removal of embolized catheters.

Adult↗

Use of exchange wires in coronary angioplasty.

A 300 cm exchange guide wire was used as the primary wire in 59 consecutive patients referred for percutaneous transluminal coronary angioplasty. The success rate of the angioplasty using this as the only wire was 92% (54 of 59), and we were able to pass the exchange guide wire into the distal vessel in 56 of the 59 patients (95%). We believe the exchange wire technique has a place in the first-line approach to complex coronary angioplasty.

Angioplasty, Balloon↗

Nitroglycerin-induced coronary vasodilatory responses in patients during isometric handgrip exercise.

Intracoronary nitroglycerin is frequently administered during invasive procedures such as coronary angioplasty or thrombolysis which may be associated with pain and sympathetic neural stimulation. Whether sympathetic-mediated reflex vasoconstriction interferes with nitroglycerin-induced augmentation of coronary blood flow is unknown. Therefore, coronary and systemic hemodynamics were measured in 19 patients during isometric handgrip exercise (3 min x 25% maximal effort), during intracoronary nitroglycerin, and during handgrip plus intracoronary nitroglycerin. Nine patients had no significant left anterior descending coronary artery stenosis (group 1) and ten patients had greater than 70% left anterior descending coronary artery stenosis (group 2). Handgrip exercise increased heart rate, mean arterial pressure, and coronary sinus and great vein flow 15% while increasing coronary resistance 10%. Intracoronary nitroglycerin (200 micrograms) reduced mean arterial pressure -4 +/- 6% and increased great cardiac vein flow 35-72%. Anterior left ventricular regional coronary flow responses to intracoronary nitroglycerin were unaffected by sympathetic stimulation for group 1. Group 2 had a greater increase in great vein flow with intracoronary nitroglycerin plus handgrip compared to nitroglycerin alone due to increased mean arterial pressure with no change in the great vein resistance. These data indicate that sympathetic stimulation does not alter the nitroglycerin-induced augmentation of coronary sinus and great vein blood flow in patients with and without significant left anterior descending coronary artery stenosis. In patients undergoing invasive interventions who may have increased circulating catecholamines, mild sympathetic (isometric) stimulation does not appear to interfere with the coronary vasodilatory responses to intracoronary nitroglycerin.

Cardiac Catheterization↗

Effects of beta-adrenergic blockade on nitroglycerin-induced augmentation of regional coronary blood flow in patients.

Although beta-adrenergic blockade may increase coronary vascular resistance in some patients with severe ischemic heart disease, the effects of beta blockade on the nitroglycerin (NTG)-induced augmentation of coronary blood flow have not been elucidated. Therefore, systemic hemodynamic and anterior left ventricular regional coronary blood-flow (thermodilution) data were measured during administration of NTG into the left coronary artery, before and 10 min after intravenous propranolol (0.1 mg/kg) in 22 patients. Six patients (Group 1) had normal left coronary arteries and nine (Group 2) had severe coronary artery disease with at least greater than 70% narrowing of the left anterior descending artery. In seven additional patients (three without and four with greater than 70% left anterior descending coronary artery disease), measurements were obtained with constant-paced heart rates (Group 3). Before beta blockade, NTG (200 mcg) significantly increased anterior regional great-vein flow [for Group 1, 84 +/- 38% (81 +/- 20 to 140 +/- 60 ml/min); Group 2, 39 +/- 41% (61 +/- 26 to 83 +/- 38 ml/min); and Group 3, 87 +/- 55% (75 +/- 36 to 144 +/- 86 ml/min)]. In Groups 1 and 2, beta-adrenergic blockade reduced heart rate 10% (p less than 0.01) but did not affect mean arterial or pulmonary artery pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Left atrial enlargement: an early sign of hypertensive heart disease.

Left atrial abnormality on the electrocardiogram (ECG) has been considered an early sign of hypertensive heart disease. In order to determine if echocardiographic left atrial enlargement is an early sign of hypertensive heart disease, we evaluated 10 normal and 14 hypertensive patients undergoing routine diagnostic cardiac catheterization for echocardiographic left atrial enlargement. All patients had normal coronary arteriography, sinus rhythm, normal left ventricular volumes and function, no valvular disease, and no echocardiographic or ECG left ventricular hypertrophy. No patient met ECG criteria for left atrial abnormality. The mean left atrial dimension was 3.46 +/- 0.3 cm in normal individuals versus 4.04 +/- 0.3 cm in the hypertensive patients (p less than 0.01). The left atrial index was also higher in the hypertensive group, 2.18 +/- 0.45 versus 1.88 +/- 0.10 cm/m2 (p less than 0.05), and the left atrial-to-aortic root dimension ratio was significantly higher in the hypertensive group, 1.36 +/- 0.20 versus 1.17 +/- 0.07 (p less than 0.01). We conclude that echocardiographic left atrial enlargement may be an early sign of hypertensive heart disease in patients with no other discernible cause of left atrial enlargement.

Cardiomegaly↗

Attenuation of nitroglycerin-induced coronary hyperemic blood flow in patients with left anterior descending coronary collaterals.

Although intracoronary nitroglycerin (NTG) is frequently administered to patients having occluded coronary arteries undergoing invasive procedures such as percutaneous transluminal coronary angioplasty or thrombolysis, the extent of NTG-induced augmentation of myocardial blood flow in patients with collaterally filled occluded arteries is incompletely understood. To examine NTG-induced increases in coronary blood flow in patients with occluded left anterior descending coronary arteries (LAD), coronary and systemic hemodynamics were measured during bolus administration of NTG into the left coronary artery in 10 patients with normal LAD (Group 1), 11 patients with greater than 70% and less than 100% narrowing of the LAD (Group 2), and 10 patients who had total occlusion of the LAD with angiographic collateral filling and anterior ventricular wall motion abnormalities (Group 3). NTG increased anterior regional great vein flow (thermodilution) from 72 +/- 19 to 140 +/- 60 ml/min (p less than 0.05), 67 +/- 27 to 108 +/- 66 ml/min (p less than 0.05), and 59 +/- 27 to 74 +/- 36 ml/min (p = NS vs. control, p less than 0.05 vs. peak flow for Group 1) with relative increases from control of 91 +/- 41%, 56 +/- 34%, and 25 +/- 22% for the three groups, respectively. The percent change for Group 3 was significantly lower than both Groups 1 (p less than 0.01) and 2 (p less than 0.05). These data indicate that myocardial hyperemic blood flow responses to intracoronary NTG are markedly attenuated in patients with occluded but collaterally supplied vessels. During invasive procedures in these patients, although significantly attenuated, intracoronary NTG may potentially provide a beneficial effect by augmenting blood flow through collaterals or in adjacent regions.

Coronary Angiography↗

Dose-related effects of intracoronary nitroglycerin on coronary hyperemia in patients with coronary artery disease.

Although intracoronary nitroglycerin (NTG) is frequently required during percutaneous transluminal coronary angioplasty or thrombolysis, the dose-related hemodynamic effects and the extent to which intracoronary NTG--induced coronary hyperemia is limited in patients with coronary artery disease have not been defined. Therefore, we studied 19 patients with coronary artery disease (nine with no or minimal luminal narrowing of the left anterior descending coronary artery [group 1] and 10 with significant left anterior descending coronary stenosis [group 2]; mean arterial pressure and thermodilution coronary sinus and great cardiac vein blood flow were measured during bolus administrations of 50, 200, and 300 micrograms of intracoronary NTG. During the NTG-induced hyperemia, mean arterial pressure decreased 0%, 4% (both p = NS), and 6% (p less than 0.05) after 50, 200, and 300 micrograms doses, respectively. heart rate did not change. Global coronary hyperemia was greatest for 200 micrograms with coronary blood flow increasing (74 +/- 32% in group 1 and 53 +/- 25% for group 2) but was significantly different from 50 micrograms only in group 2 patients. Moreover, the regional coronary blood flow responses were attenuated in group 2 compared to group 1 for 50 micrograms, 18 +/- 13% vs 38 +/- 18%, and for 200 micrograms, 35 +/- 15% vs 72 +/- 34% (both p less than 0.05), with the reduction of regional coronary resistance in group 2 attenuated for all three doses of intracoronary NTG. The 300 micrograms dose did not provide further augmentation of either global or regional coronary blood flow or greater reduction in coronary resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Intrinsic factor, free of R proteins, can be prepared from mouse stomach and used in a ligand assay specific for "true" cobalamin.

A ligand assay specific for cobalamin that uses mouse stomach as the source of intrinsic factor has been developed. When mouse stomach extract incubated with radiocobalamin is fractionated by gel chromatography, the radioactive complex elutes as a single peak with apparent molecular weight of 54,900. Formation of the complex is greater than 98% inhibited by human anti-intrinsic factor antibody. When the equivalent of 10,000 pg/ml of cobinamide is added to serum, the apparent cobalamin concentration detected averages 8.5 pg/ml. Correlation with the Lactobacillus leichmannii microbiologic assay results in the regression equation y = 0.97x + 20. In six patients who had megaloblastic anemia the serum cobalamin by the mouse intrinsic factor ligand assay ranged from 0 to 9 pg/ml. Because the primary source of intrinsic factor is free of R proteins, there is no need for extensive purification of the extract. The assay is sensitive, precise, and accurate, and no more difficult to perform than other conventional ligand assay procedures.

Anemia, Megaloblastic↗

The role of discriminative stimuli in concurrent performances.

Key pecking in pigeons was examined under concurrent and parallel arrangements of two independent and simultaneously available variable-interval schedules. Pecks on the changeover key alternated the schedule of reinforcement for responses on the main key. Under concurrent schedules, discriminative stimuli were paired with the reinforcement schedule arranged in each component and changeover responses also alternated these stimuli. Under parallel schedules, changeover responses alternated the effective reinforcement schedule, but did not change the discriminative stimulus. On concurrent procedures, changeover response rate was inversely related to the difference in reinforcement rate between the two components, whereas on parallel schedules no consistent relationship was found. With both schedules, absolute response and reinforcement rates were positively related, although for a given set of reinforcement frequencies, rates were often higher on the concurrent schedules. On concurrent schedules, relative response rates and relative times were equal to relative reinforcement rates. On parallel schedules these ratios were positively related, but response and time ratios were much smaller than were obtained with comparable concurrent schedules. This inequality was most pronounced when absolute reinforcement frequencies were lowest.

Journal Article↗