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The population pharmacokinetics of infliximab were characterized in patients with active ankylosing spondylitis (n = 274). Serum infliximab concentration data, from a 2-year period, were analyzed using NONMEM. A 2-compartment linear pharmacokinetic model was chosen to describe the pharmacokinetic characteristics of infliximab in serum. Population estimates (typical value +/- standard error) were obtained from the final covariate model: clearance (CL: 0.273 +/- 0.007 L/day), volume of distribution in the central compartment (V(1): 3.06 +/- 0.057 L), intercompartment clearance (Q: 1.72 +/- 0.48 L/day), and volume of distribution in the peripheral compartment (V(2): 2.94 +/- 0.17 L). Interindividual variability for CL and V(1) was 34.1% and 17.5%, respectively. White blood cell count at baseline and the antibody-to-infliximab status were significant covariates to CL; body surface area and sex were significant covariates to V(1). The CL for patients with a positive antibody-to-infliximab status was estimated to be 41.9% to 76.7% higher than for the remaining patients. Other covariates (baseline disease activity and the concomitant medication use of prednisolone, omeprazole, nonsteroidal anti-inflammatory drugs, or analgesics) did not affect infliximab pharmacokinetics. The development of antibodies to infliximab was associated with accelerated infliximab clearance and may represent a potential underlying mechanism for an inadequate response, or loss of response, to infliximab treatment. [ABSTRACT FROM AUTHOR]

Several studies suggest different effects of atrial (AAI) and ventricular single chamber pacing (VVI) for sick sinus syndrome with respect to the suppression of atrial tachycardias and to the prognosis. With this aspect in mind, we studied 222 patients with sick sinus syndrome. 110 of whom had been supplied with AAI systems, and 112 with VVI systems, in the period from January 1978 to December 1986. The mean observation period was 53 ± 28 months. The cumulative 5-year survival rate was not significantly different in the two groups. After subgroups with comparable underlying diseases had been differentiated, patients with coronary heart disease showed a significantly higher survival rate (P < 0.05) under AAI pacing, and the same was shown for patients with no underlying heart disease (P < 0.02). The incidence of chronic atrial fibrillation was 6% in the AAI group and 19% in the VVI group. Patients with preexisting atrial tachyarrhythmias showed the lowest incidence of chronic atrial fibrillation under AAI pacing. Under VVI pacing this incidence was a function of the basic rate of the pacemaker systems. In conclusion, the pacing mode seems to have a prognostic importance in spite of all methodological difficulties. A suppressive effect of AAI pacing on atrial dysrhythmias can also be assumed. [ABSTRACT FROM AUTHOR]

ANP was determined in 13 patients with DDD pacemakers due to total AV block, at rest and during bicycle ergomeny under both pacing modes, DDD and VVI (70/min]. Under DDD pacing, the mean ANP level (normal range 5-95 pg/ml) at rest was 36 ± 18 pg/mL (mean ± SD) and increased significantly by the/actor of 3.5 fo I 27 pg/mL during exercise (p < 0.01). By just changing the pacing mode to WI, the ANP levels rose to 73 ± 28 pg/mL (p <0.01) at rest (= 203% of DDD resting level] and to 216 ± 184 pg/mL (= 170% of DDD peak level) during exercise P < 0.01). These results show that under AV synchronous pacing, the ANP levels we generally lower. A possible explanation for this increased release of ANP during asynchronous WI pacing is the acute increase of the atrial wall tension which occurs when the atria contacts during the systole against closed AV valves. [ABSTRACT FROM AUTHOR]

In 20 volunteers (mean age 35.5 y) and 12 pacemaker patients (mean age 68.7 y), central venous oxygen saturation (SO2) was monitored continuously by means of an optical sensor integrated in an external transvenous pacing lead placed in the right ventricular cavity. From the SO2 signal recorded at rest and during various modalities of exercise, an algorithm for controlling pacing rote of an external pacing system was developed. An open loop system was used in the volunteers, allowing the comparison of the computed pacing rate with the individual intrinsic heart rate. There was an excellent correlation between the two frequencies as far as the dynamic characteristics and the steady state relationship were concerned. In five pacemaker patients who were stimulated via the external lead, a closed loop control of pacing rate was used. In one patient with a DDD pacemaker implanted for third degree AV-block, the rate response of the 502 driven pacemaker was well in accordance with the rate attained with the implanted atrial triggered system. With both pacing modes, exercise capacity as determined on a symptom limited treadmill test was identical. In four patients (3 AV block III, 1 bradyarrhythmia) an improvement in exercise tolerance up to 65 percent could be demonstrated with the rate responsive pacing mode. In all patients, it could be shown that an autoregulating pacemaker system with SO2 is an open possibility. [ABSTRACT FROM AUTHOR]