Biomedical subjects
Publications and source records attributed to L Whitley.
Defining the values at stake as we move into managed care is an awesome--yet necessary--endeavor. To help sort things out, the Society for Health and Human Values brought together health care ethicists and medical humanists to discuss how human values are being incorporated into health care reform. Here's an excerpt from that conversation.
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We compared parameters of maximal expiratory flow with other tests used in the detection of small airways obstruction (SAD) in a canine model of bronchiolitis obliterans. Bronchiolitis was produced by instilling a 1% solution of nitric acid into the airways of 8 dogs (Group N). In 5 control dogs, a normal saline solution was instilled (Group C). Plethysmographic lung volumes, oscillatory airway resistance (RL), and tests for SAD were examined after bronchiolitis was produced. To evaluate peripheral airway function, the single-breath nitrogen washout curve was used to obtain the slope of phase III and to estimate the lung volume at which a terminal increase in N2 concentration was observed (closing capacity). Maximal expiratory flow-volume curves while the dogs breathed air and 80:20 helium:oxygen (HeO2) were performed to obtain the air flow rate at 50% vital capacity (V50), the corresponding HeO2 flow rate (delta Vmax), and the lung volume at which air and HeO2 flow rates were equal (Viso). After injury, the histologic aspects of the lung in Group N showed acute and chronic inflammation of the small airways. The RL did not change in Group N, despite a relative increase in peripheral airway resistance, which when measured increased about 4 times. Compared with Group C, significant increases in closing capacity and Viso and significant decreases in V50 were observed in Group N. Although predicted to decrease in SAD, delta Vmax did not change. We conclude that delta Vmax is relatively insensitive to SAD. Possible mechanisms resulting in reduced V50 but maintained delta Vmax in this model were further examined in terms of the concepts outlined by the wave-speed theory of flow limitation.
This preliminary clinical study describes the pharmacokinetic characteristics of flunarizine (FLN) following single and multiple dosing in epileptic patients receiving comedication. Three groups [phenytoin (PHT) only, carbamazepine (CBZ) only, and PHT plus CBZ] of four patients each were studied. Large interindividual differences, but no statistically significant differences in pharmacokinetic parameters, were observed between the three groups. Following a single dose, mean values (and ranges) for apparent clearance, volume distribution, and elimination half-life (t1/2) were 0.504 L/h/kg (0.086-1.119), 12,431 L (1,959-20,920), and 308 h (61-506), respectively. FLN had no effect on PHT or CBZ steady-state levels but PHT or CBZ appeared to induce the metabolic disposition of FLN. The effect of dose on FLN kinetics could not be evaluated in this preliminary study.
ADD 94057, a metabolite of fluzinamide, manufactured by the A. H. Robins Company, blocks chemically- and electrically-induced seizures in animals. The primary objective of this open add-on study was to evaluate patient tolerability of ADD 94057 at ascending target plasma concentrations. Nine subjects with medically refractory seizures were receiving phenytoin (PHT, 3), carbamazepine (CBZ, 3), or both (3). A pharmacokinetic profile after a single oral 400-mg dose of ADD 94057 was used to calculate ADD 94057 dosages. After a 4-week baseline period, patients were treated for 4 weeks with weekly ADD 94057 dosage escalations. Two patients completed the study at their assigned highest dosage level; the other patients finished the study at lower dosages. The patients receiving PHT (but not CBZ) tolerated higher plasma concentrations of ADD 94057 than did patients receiving CBZ, alone or in combination with PHT. Adverse experiences included headache, ataxia, blurred vision, diplopia, dizziness, lightheadedness, and mild confusion. Eight of nine patients had reductions in seizure frequency from baseline.
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