The use of anaerobic threshold in assessment of aerobic capacity was evaluated in 34 normal subjects and 47 patients with various kinds of chronic heart disease. Anaerobic threshold was determined as the oxygen consumption (W02) at which a linear relationship between pulmonary ventilation (yE) and V02 was lost during progressive treadmill exercise. Anaerobic threshold determined in this manner was validated with that determined by blood lactate measurements in eight normal subjects and nine cardiac patients (r = .962, p < .001). Thereafter, anaerobic threshold was determined only by respiratory measurements. In symptom-limited, maximal exercise, anaerobic threshold was reached well before maximal effort and corresponded to 70% of maximal V02 both in normal subjects and cardiac patients. Anaerobic threshold decreased as age progressed in normal subjects (r = -.70, p < .001). Anaerobic threshold in cardiac patients was lower than that in the normal subjects and decreased progressively as New York Heart Association functional classification advanced (normal, 32

Objective-To investigate the alterations in autonomic control of heart rate at high altitude and to test the hypothesis that hypoxaemic stress during exposure to high altitude induces non-linear, periodic heart rate oscillations, simnilar to those seen in heart failure and the sleep apnoea syndrome. Subjects-l1 healthy subjects aged 24-64. Main outcome measures-24 hour ambulatory electrocardiogram records obtained at baseline (1524 m) and at 4700 m. Simultaneous heart rate and respiratory dynamics during 2-5 hours of sleep by fast Fourier transform analysis of beat to beat heart rate and of an electrocardiographically derived respiration signal. Results-All subjects had resting hypoxaemia at high altitude, with an average oxyhaemoglobin saturation of 81% (5%). There was no significant change in mean heart rate, but low frequency (0-01-0.05 Hz) spectral power was increased (P < 0*01) at high altitude. Time series analysis showed a complex range of non-linear sinus rhythm dynamics. Striking low frequency (0-04-0.06 Hz) heart rate oscillations were observed during sleep in eight subjects at high altitude. Analysis of the electrocardiographically derived respiration signal indicated that these heart rate oscillations correlated with low frequency respiratory oscillations. Conclusions-These data suggest (a) that increased low frequency power during high altitude exposure is not simply attributable to increased sympathetic modulation of heart rate, but relates to distinctive cardiopulmonary oscillations at -0 05 Hz and (b) that the emergence of periodic heart rate oscillations at high altitude is consistent with an unstable cardiopulmonary control system that may develop on acute exposure to hypoxaemic stress. (Br HeartJ_ 1995;74:390-396) Keywords: heart rate; respiratory rhythm; high altitude Perturbation of the non-linear physiological mechanisms regulating cardiopulmonary function may result in the emergence of highly periodic behaviour in heart rate and ventilatory dynamics. 13 Perhaps the best described examples of such pathological oscillations are Cheyne-Stokes breathing in heart failure and the obstructive sleep apnoea syndrome. Each of these conditions is associated not only with periodic ventilatory dynamics but also with cyclic alterations in heart rate.46 We hypothesised that hypoxaemic stress during exposure to high altitude would also induce non-linear, periodic heart rate dynamics. Subjects and methodsWe studied 11 healthy subjects (nine men and two women) aged 24 to 64 years. All were physically well trained in long distance running, but they were not accustomed to mountain climbing. Two lived at sea level and nine lived at 1524 m. Twenty four hour ambulatory electrocardiograms were recorded with CardioData Dura-Lite cassette recorders (Model 2011) at low (1524 m) and high (4000-4700 m) altitude.The lower altitude ambulatory electrocardiographic recordings were conducted during a usual work day and overnight sleep at 1524 m. The high altitude recordings were performed during an expedition in...

Patient flow in an appointment-based, outpatient internal medicine clinic involving multiple, sequential providers-registrar, triage nurse, physician, and discharger-was studied using computer simulation. Provider task time distributions were obtained through a time-motion study and then input into the computer program, which simulated the clinic situation well. Time interval and sensitivity analyses yielded insights into staffing levels, appointment times, and clinic dynamics. A bottleneck provider was shown, and patient time in the clinic was related to the time of appointment and was slowed by having too many doctors in the clinic. Subsequent operational changes significantly decreased the average observed patient total time in clinic from 75.4 (SD 34.2) minutes to 57.1 (SD 30.2) minutes (p < .001, t test).

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Pentose phosphate metabolism of human red blood cells may be altered by inherited deficiency in cytoplasmic enzymes like glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADP oxidoreductase, E.C. 1.1.1.49), resulting in increased hemolytic susceptibility.' This deficiency may be due either to a mutation at a structural gene or to an alteration in the rate of synthesis or of destruction of the enzyme. Two electrophoretic variants of glucose-6-phosphate dehydrogenase not accompanied by enzyme deficiency have been demonstrated to differ by a single amino acid substitution, and therefore a mutation at a structural gene has been postulated.2 On the other hand, interaction of stromal NAD(P)ase (NAD(P) glycohydrolase, E.C. 3.2.2.6) with glucose-6-phosphate dehydrogenase has been described as a possible mechanism for regulation of the stability of the enzyme.3' 4 Furthermore, two other cytoplasmic enzymes, glutathione reductase (reduced NAD(P):oxidized glutathione oxidoreductase, E.C. 1.6.4.2) and 6-phosphogluconic dehydrogenase (6-phospho-D-gluconate: NAD(P) oxidoreductase, E.C. 1.1.1.44) can be modified in their activity by incubation of hemolysates in the presence of red cell membranes (stromata), suggesting a more general regulatory function of the membranes on the cytoplasmic enzymes.5 6 These modifications consist of activation of glutathione reductase and, when NADP is added to the incubation mixture, inactivation of 6-phosphogluconic dehydrogenase accompanied by change in electrophoretic pattern.' This last effect of the membranes has now been further investigated because of its specificity in the requirement of the coenzyme and because it was accompanied by a structural change in the enzyme. The present data provide evidence that (1) the stromal factor required to induce this effect on 6-phosphogluconic dehydrogenase is NAD(P)ase and (2) a product of the NAD(P)ase reaction with NADP, P-ADPR, interacts with 6-PGD to cause its molecular alteration. Methods.-Freshly drawn heparinized human blood was used in all our experiments. After the washed red cells had been frozen and thawed, stroma-free hemolysate was prepared by centrifugation as previously described6 and, in addition, was passed through a Millipore filter (pore size, 0.80 1A) and checked with a particle counter (Coulter Counter B) for absence of stromata. In some experiments, stroma-free hemolysate was dialyzed by gel filtration through Sephadex G25 eluted with 0.162 M NaCI, and is referred to as dialyzed hemolysate. Partial purification of 6-PGD was accomplished by gel filtration through Sephadex G200 eluted with 0.05 M Tris-HCl buffer and 0.1 M KCl, pH 7.4. The fractions containing 6-PGD activity collected with a Gilson fraction collector formed a peak preceding hemoglobin and are referred to as purified 6-PGD. The activity of 6-PGD was measured at 370C by the method of Glock and McLean.8 Unless otherwise stated, the data refer to the most common human variant, Pd A, as determined by starch gel electrophoresis.9

Famotidine can cause clinical hepatitis, and drug-induced hepatitis can occur after the administration of two different H2-receptor blockers.

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