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T B Allison

Publications and source records attributed to T B Allison.

14 recordsLinked to original sources
PubMed1991

Contrary principles.

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Attitude of Health Personnel↗
PubMed1989

Pharmacodynamic modeling of digoxin-induced bradycardia.

Digoxin-induced bradycardia in dogs was used to evaluate several pharmacodynamic models. Digoxin plasma concentrations and response were monitored in beagle dogs administered either 0.05 or 0.025 mg/kg of digoxin iv as an infusion over 5 min. The models investigated were the linking model, the linear model, the effect compartment model, and the inhibitory model. Regression procedures for investigating the effect compartment model were conducted with Emax (the maximal response, where response was the percentage decrease in heart rate) as a variable with an upper bound of 100%, with a constant value of 100%, or alternately with a constant value equal to the maximal observed response. Based on statistical criteria the effect model using Emax as a variable was found to be the best model for describing digoxin-induced bradycardia. For the effect compartment model, CPss(50) (concentration at steady state that will produce 50% of the maximal response) ranged from 3.8-9.8 ng/ml; delta (exponent describing the steepness of the concentration-response relationship) ranged from 0.6-7.1. The implication of these models in understanding concentration-effect relationships are discussed.

Animals↗
PubMed1988

Temperature dependence of phenytoin-protein binding in serum: effects of uremia and hypoalbuminemia.

Phenytoin-protein binding was determined as a function of temperature in uremic patients with normal albumin and in uremic patients with hypoalbuminemia. Free phenytoin levels were determined in ultrafiltrates (MPS-1; Amicon, Lexington, MA, U.S.A.) from serum equilibrated at either 20, 25, 30, 35, or 40 degrees C. Scatchard analyses showed significant differences in phenytoin-protein binding affinity as a function of temperature. Linear regression plots of free phenytoin versus temperature showed the slopes of the uremic and uremic with hypoalbuminemia patients (0.546 and 0.535, respectively) to be 3 times that of patients with normal renal function (0.174). Free phenytoin was analyzed in 150 patients with normal renal function in whom the total phenytoin was in the range of 38.0-80.8 mumol/L. The ultrafiltrate, prepared at 22 +/- 0.5 degrees C, resulted in free phenytoin levels in the range of 3.2-8.3 mumol/L. We have established this as the therapeutic range for the patient population seen at this medical center.

Humans↗
PubMed1987

Effects in mice of testosterone and dihydrotestosterone on platelet aggregation in injured arterioles and ex vivo.

Mice were implanted subcutaneously with placebo pellets, or with pellets containing either testosterone (T) or dihydrotestosterone (DHT). Eight to 19 days later platelet aggregation was produced in pial or mesenteric arterioles by injuring their endothelium with a noxious light/dye stimulus. The onset of platelet aggregation was significantly shortened in the mesenteric arterioles of male mice following implantation of 1.0 mg T or 0.1 mg DHT. However no effect was observed in females, nor did T or DHT alter aggregation in pial arterioles of either sex. Ex vivo studies showed that sodium arachidonate produced greater aggregation of platelets in plasma from testosterone treated males compared with controls. No effect of testosterone was observed ex vivo in platelets from females. These ex vivo results paralleled in vivo data from mesenteric vessels, but not from pial vessels. Moreover DHT failed to influence aggregation ex vivo in either sex. Thus enhanced aggregation observed in vivo in mesenteric arterioles of androgen treated males may not reflect direct action of androgen on the platelet. Rather enhanced aggregation may reflect hormonal action on endothelium or adjacent tissue. In addition to the preceding studies we tested the hypothesis that testosterone's action was due to its conversion to estradiol. This was considered because our data with T and mesenteric vessels resembled that previously reported by us with estradiol. However only minimal elevations in plasma estradiol levels resulted from testosterone treatment.

Animals↗
PubMed1978

Effects on labile metabolites of temporal delay in freezing biopsy samples of dog myocardium in liquid nitrogen.

Sudden hypothermia utilising liquid nitrogen has been used for immediate inhibition of metabolic reactions and preservation of labile compounds in heart muscle. It has been suggested that this rapid transfer of tissue into liquid nitrogen, within 1 to 2 s, is essential for accurate assessment of internal milieu conditions. We tested this hypothesis in normal dogs by measuring phosphocreatin, ATP, glycogen, and lactate concentrations in transmural layers of a core biopsy taken from the posterolateral wall of the left ventricle frozen immediately in liquid nitrogen or held at room temperature for varying times up to 300 s before freezing the tissue. The earliest significant change occurred in phosphocreatine levels after 60 s; only phosphocreatine demonstrated any changes within the first 120 s. These studies indicate that a delay of up to 30 s may be tolerated before freezing tissue without any change occurring in these labile metabolites.

Adenosine Triphosphate↗
PubMed1977

Transmural metabolic gradients in the normal dog left ventricle: effect of right atrial pacing.

The effects of atrial pacing on tissue metabolite levels known to be sensitive to ischemia were examined. Anesthetized dogs were thoracotomized and a pacing electrode was sutured to the right atrium. Pacing at rates of 200 or 250 beats/min (10 animals per group) was performed for 15 min after base-line hemodynamic data had been obtained. At the end of the pacing period, a transmural biopsy was taken, frozen in liquid nitrogen, and sectioned into subepicardial, midmyocardial, and subendocardial layers. ATP, phosphocreatine, lactate, and glycogen were extracted and analyzed. Significant (P less than 0.001) transmural gradients of each of these metabolites existed in the control group. Pacing had no significant (P greater than 0.2) effect on any metabolite from layer to layer at 200 or 250 beats/min. However, indices of heart work (i.e., contractility (dP/dt), stroke work, and stroke volume) demonstrated significant reductions (P less than 0.01) due to pacing, while circumflex artery blood flow increased more than twofold (P less than 0.001) at the highest rate. These data suggest that physiologic autoregulation occurred during pacing and protected the subendocardium from stress-induced ischemic insult.

Adenosine Triphosphate↗
PubMed1976

Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes.

Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.

Adenosine Diphosphate↗
PubMed1976

Reduced high-energy phosphate levels in rat hearts. II. Effects of sodium cyanate.

The effects of increased blood-oxygen affinity, due to carbamylation of hemoglobin in vivo, on aerobic metabolism in the heart were studied in rats. Adult male rats were injected intraperitoneally 3 times weekly for 10 wk with sodium cyanate (60 mg/kg). Significant derangement of blood-oxygen interaction was observed. Oxygen-dissociation curves were left shifted by 13 mmHg (35.1-21.8), and the overall deoxygenation rate (k) was reduced 41% (6.142-3.624; s(-1)); P is less than 0.001 for each parameter. Heart ATP and PCr levels were reduced (ATP: 19.4-16.7; PCr: 15.0-11.0, mum/g dry wt; P is less than 0.001 for each). In addition, glycogen levels fell (161.4-112.9, mum C6/g dry wt; P is less than 0.001). Myocardial lactate levels increased 54% (2.6-4.0, mum/g dry wt; P is less than 0.01) in the cyanate-treated group. These findings strongly suggest a hypoxia-induced activation of glycolysis as a consequence of altered oxidative metabolism in rats treated with sodium cyanate.

Adenosine Triphosphate↗
PubMed1975

Inability of selenium to affect creatine metabolism in rat muscle.

1. Two groups of adult rats were placed in a metal-free environment and pair-fed with selenium-supplemented and Se-deficient diets. 2. After 5 months the animals were killed and skeletal muscle concentrations of creatine, creating phosphate, ATP, protein and Se were determined. 3. Se deficiency was indicated by the low Se content of the skeletal muscle from the deficient animals, but no changes were found in the amounts of the other components. 4. These results suggest that Se may not be involved in creatine metabolism and that Se deficiency may not be concerned independently in the development of nutritional dystrophy, where changes are found in the levels of protein, creatine, creatine phosphate and ATP.

Adenosine Triphosphate↗