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Biomedical subjects

D D Miller

Publications and source records attributed to D D Miller.

At least 271 records · Page 15Linked to original sources

Comparative sensitivity of exercise, cold pressor and ergonovine testing in provoking attacks of variant angina in patients with active disease.

Exercise, ergonovine and the cold pressor test have been used to provoke variant angina attacks. The sensitivity of these three tests was compared in 34 hospitalized patients with well documented, active variant angina who had recently undergone coronary arteriography. The three tests were usually performed on three consecutive days, and 28 of the 34 had the three tests within 1 week. Angina was provoked by ergonovine in all 34 patients, by exercise in 17 and by cold pressor test in only five (p less than 0.005). ST elevation developed during the ergonovine test in 32 (94%), during exercise in 10 (29%) and during the cold pressor test in only three (9%). With ergonovine, one patient had only ST depression and one had no ECG changes. During the cold pressor test two patients had pseudonormalization of abnormally negative T waves and 29 had no ECG changes. Exercise induced T-wave pseudonormalization in four patients, ST depression in nine others and no ECG changes in 11. ST elevation was more frequent with ergonovine than with either of the other tests (p less than 0.0001). ST elevation or T-wave pseudonormalization occurred more often with exercise than with cold (p less than 0.05), but both occurred less often than with ergonovine (p less than 0.0001). We conclude that the sensitivity of the ergonovine test is very high in patients with active variant angina and that exercise will provoke angina with ST elevation in about 30% of these cases. In contrast, the sensitivity of the cold pressor test is too low to be of much clinical value in the diagnosis of variant angina.

Adult↗

Factors influencing the long-term prognosis of treated patients with variant angina.

To determine the prognosis of variant angina and the factors influencing it, 169 consecutive patients hospitalized in our coronary unit were followed for a mean of 15.3 months (range 1 to 68). Survival at 1, 2, and 3 years was 95%, 90%, and 87%, respectively; survival without myocardial infarction was 80%, 78%, and 75%. Twenty of the 22 myocardial infarctions and eight of the 14 deaths occurred within the first 3 months. Mantel-Haenszel log-rank analysis demonstrated that coronary disease, ventricular function, and the degree of disease activity were significant interdependent variables that influenced both survival and survival without infarction. At 1, 2, and 3 years, survival for patients with multivessel disease was 81%, 76%, and 66%; for patients with one-vessel disease, 97%, 92%, and 92%; and for patients without stenoses greater than or equal to 70%, 98% at each year (p = .0003). Survival without infarction at 1 year was 88% in patients with no stenoses greater than or equal to 70% and 82% in patients with single-vessel disease; it did not change thereafter in either group, but was 62%, 58%, and 50% at 1, 2, and 3 years in patients with multivessel disease (p = .001). Treatment did not influence survival in any subgroup (only 14 patients died overall) or survival without infarction in patients with multivessel disease. However, in patients without multivessel disease, treatment with nifedipine, diltiazem, and verapamil improved survival without infarction compared to treatment with perhexiline maleate or long-acting nitrates alone (92% vs 67% at 1, 2, and 3 years; p less than .005). Thus in addition to preventing angina, nifedipine, diltiazem, and verapamil appear to reduce complications in patients with variant angina without multivessel disease.

Adult↗

Cimetidine's effect on steady-state serum nortriptyline concentrations.

A cimetidine-nortriptyline interaction in a 52-year-old black male is reported. After concomitant administration of cimetidine and nortriptyline for two weeks, steady-state nortriptyline concentrations fell 42 percent when cimetidine was discontinued. Later, during rechallenge with cimetidine, serum nortriptyline concentrations increased significantly, but subsequently fell again when cimetidine was discontinued. The possible clinical consequences of this interaction are discussed.

Cimetidine↗

Symptomatic coronary artery spasm following radiotherapy for Hodgkin's disease.

Four years after mediastinal radiation for Hodgkin's lymphoma, a 32-year-old man developed angina at rest and with varying levels of physical activity. At coronary arteriography, 40 percent to 50 percent stenoses were seen in the left coronary artery; ergonovine induced severe coronary spasm. Treatment with diltiazem eliminated all anginal attacks.

Adult↗

Binocular neurons and binocular function in monkeys and children.

Electrophysiologic studies have shown that binocular neurons of the striate cortex of monkeys are irreversibly lost when the visual axes of the eyes are optically dissociated during the first weeks of life. The present study was a behavioral investigation of monkeys reared with optical dissociation. After brief periods of experimental strabismus, the monkeys showed poor binocular summation performance and were unable to see random dot stereograms even after two years of post-treatment normal binocular vision. These monkeys' performance on the stereopsis task was virtually identical to the stereoperformance of clinically diagnosed stereoblind children.

Adolescent↗

Investigation of the effects of phospholipase C on human platelets: evidence that aggregation induced by phospholipase C is independent of prostaglandin generation, released ADP and is modulated by cyclic AMP.

Effects and the mechanism of action of phospholipase C (PLC), from Clostridium perfringens, on washed human platelets were examined to better understand the role of PLC in platelet function. PLC caused aggregation and secretion of [14C]-5HT, without concomitant loss of cytoplasmic, LDH, in a concentration dependent manner. P-nitrophenylphosphorylcholine, a substrate for PLC, blocked these responses in a concentration dependent manner. In other experiments hirudin, alpha-1-antitrypsin and soybean trypsin inhibitor did not inhibit PLC-induced activation of human platelets. PLC-induced aggregation and [14C]-5HT secretion was not inhibited by aspirin, a known inhibitor of prostaglandin biosynthesis. PLC-induced aggregation was selectively inhibited by analogs of 7,8-dihydroxybenzazepine and 7,8-methylenedioxybenzazepine in a concentration dependent manner. These two agents had no effect on arachidonic acid-induced aggregation. PLC-induced aggregation was not inhibited by apyrase, an enzyme which hydrolyzes ADP. In other experiments, PLC-treated platelets did not exhibit any platelet activating factor-like activity. Prostaglandin E1 and trifluoperazine showed concentration dependent inhibitor effects on PLC-mediated aggregation and secretion of [14C]-5HT. These findings indicate that: a) PLC is capable of inducing aggregation and specific secretion of [14C]-5HT without causing lysis of platelets; b) mechanism of PLC-induced activation of platelets is independent of prostaglandin generation or action, released ADP, and PAF; and c) cyclic AMP plays a modulatory role in PLC-mediated secretion and aggregation of human platelets.

Adenosine Diphosphate↗

Bronchoselective actions of a new series of trimetoquinol analogues.

In selected beta 1- (guinea pig atrial) and beta 2- (guinea pig trachea and lung parenchyma) adrenoceptor systems, we have examined the interaction of isoproterenol (ISO), trimetoquinol (TMQ), erythro- and threo-diastereoisomers of 1-(3,4,5-trimethoxy-alpha-methylbenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (alpha-methylTMQ), alpha-dimethylTMQ, N-methylTMQ and N-[2-methyl-2-(3,4,5-trimethoxyphenyl)propyl]dopamine (open chain dimethylTMQ analogue). The rank order of potency for agonists in trachea was threo-alpha-methylTMQ greater than (+/-)-TMQ greater than ISO greater than erythro-alpha-methylTMQ greater than N-methylTMQ greater than alpha-dimethylTMQ. Only N-methylTMQ gave an intrinsic activity similar to ISO, whereas the alpha-methylated TMQ analogues were partial agonists in this beta 2-system. In atria, the rank order of beta 1-potency was ISO greater than (+/-)-TMQ greater than threo-alpha-methylTMQ greater than N-methylTMQ = erythro-alpha-methylTMQ. Maximal chronotropic effects of all compounds, with the exception of threo-alpha-methylTMQ, were similar to ISO in this preparation. Both alpha-dimethylTMQ and open chain dimethylTMQ analogues were inactive as agonists in this beta 1-system. The ratio of beta 2 : beta 1 selectivity (trachea vs. atria), relative to ISO for threo-alpha-methylTMQ, erythro-alpha-methylTMQ, TMQ and N-methylTMQ was 106.5, 27, 7 and 5.8, respectively. Whereas the rank order of potency for selected compounds in lung parenchyma was ISO greater than threo-alpha-methylTMQ = TMQ greater than erythro-alpha-methylTMQ, the comparative beta 2-selectivity (lung parenchyma vs. atria) relative to ISO, for erythro-alpha-methylTMQ, threo-alpha-methylTMQ and TMQ was 2.5, 1.9 and 0.24, respectively. It is concluded that lipophilic substitutions on the alpha-carbon of the 1-(3,4,5-trimethoxybenzyl)-substituent of TMQ can generate compounds which are potent bronchoselective adrenoceptor agonists. Threo-alpha-methylTMQ and erythro-alpha-methylTMQ were more beta 2-selective than (+/-)-TMQ.

Animals↗

Biological effects of substituting enriched 54Fe for natural iron in rats.

The effect of feeding an enriched stable isotope of iron, 54Fe, to rats was examined. Weanling rats were fed semisynthetic diets in which 54Fe was substituted for all added natural iron for a period of 21 days. Growth; feed conversion; total liver, spleen, and femur iron; and hemoglobin concentrations; hematocrit; RBC and WBC volume; FEP concentration; kidney and heart aconitase activities; erythrocyte and liver catalase activities; liver microsomal oxidase activity; and pathological lesions did not differ between control and 54Fe enriched animals. Based on the biochemical and histological parameters examined in the study an isotope effect of 54Fe was not observed.

Animals↗

In vitro estimation of iron availability in meals containing soy products.

Effects on relative nonheme iron availability of soy protein products incorporated into meals were evaluated. An in vitro method was used to estimate nonheme iron availability. Incorporation of soy isolate into a semisynthetic meal reduced estimated iron availability (dialyzable iron) compared to an egg white control, but this effect was reversed by baking the soy isolate. Ascorbic acid was not as effective in increasing estimated iron availability in soy-containing meals as in an egg white control meal. When 34 individual soy products were substituted for egg white in semisynthetic meal, iron availability range from 3.23 to 0.00% dialyzable iron. Iron availability appears to be inversely related to the protein content of the soy products. Soy isolates, as a group, had lower relative iron availability than the group of soy flours evaluated. The amount of soy product protein incorporated into a standard meal was negatively correlated with relative iron availability. The majority of meals containing soy products had lower estimated iron availabilities than meals that did not contain soy.

Ascorbic Acid↗

Vancomycin pharmacokinetics in normal and morbidly obese subjects.

In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight [TBW], 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW. The mean terminal half-life and volume of distribution values were significantly different between the two groups. Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981). There results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients. This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 micrograms/ml in the two groups (23.4 +/- 1.5 mg/kg per day for normal weight subjects and 24.0 +/- 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects). Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations. In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively). To avoid high transient peak concentrations which would occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals. The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.

Adult↗

Clinical characteristics associated with sudden death in patients with variant angina.

After hospital discharge, 114 patients with variant angina were followed for a mean period of 26 months. Six died suddenly and 13 others were resuscitated from sudden cardiac death. The extent of coronary disease and the prevalence of left ventricular dysfunction in these 19 "sudden death" patients were similar to those in the patients who did not experience sudden death ("survivors"). During spontaneous episodes of ST elevation recorded in hospital, 56 of the 114 patients had serious arrhythmias: ventricular fibrillation in two, ventricular tachycardia in 28, ventricular couplets or bigeminy in 17, second- or third-degree atrioventricular block in six and asystole in three. Patients with and those without these arrhythmias during attacks were similar with respect to extent of coronary disease, left ventricular function and most other clinical variables. The maximal ST elevation, however, was higher in the arrhythmia group (7.5 +/- 5.7 vs 3.3 +/- 2.3 mm, p less than 0.01). Serious arrhythmias were detected in 16 of the 19 sudden death patients, compared with 36 of the 86 survivors (p less than 0.01). Sudden death occurred during follow-up in 15 of the 36 patients (42%) with ventricular fibrillation, ventricular tachycardia, high-degree atrioventricular block or asystole during attacks, compared with only four of 69 (6%) without these arrhythmias (p less than 0.001). We conclude that variant angina patients with serious arrhythmias during spontaneous attacks differ from other variant angina patient only in the degree of ischemia during attacks, as reflected by maximal ST elevation, but are at a much higher risk for sudden death.

Adult↗

Conformational requirements of alpha 2-adrenergic receptors.

The conformationally restrained trans-extended and cis-folded isomers of 2-(3,4-dihydroxyphenyl)cyclobutylamine were used to establish the conformational requirements of presynaptic alpha 2-adrenergic receptors in the field-stimulated guinea pig ileum. The trans-extended isomer produced a concentration-dependent inhibition of the twitch response with an EC50 of 34 microM. The cis-folded analogue failed to produce a significant inhibition of the twitch response at concentrations up to 1 mM. These results suggest that the presynaptic alpha 2-adrenergic receptor prefers phenethylamines in the trans-extended conformation over the cis-folded conformation. The conformational requirements of alpha 1- and alpha 2-adrenergic receptors appear to be similar.

Animals↗

Erythema nodosum and blastomycosis.

Two patients with blastomycosis and erythema nodosum are described. In one patient, the underlying blastomycosis resolved after wedge resection of the pulmonary infiltrate, but without chemotherapy. In the second patient, the underlying disseminated blastomycosis required amphotericin B therapy. Blastomycosis should be included in the differential diagnosis of erythema nodosum.

Aged↗