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R Gaeta

Publications and source records attributed to R Gaeta.

10 recordsLinked to original sources

Derivation and cross-validation of pharmacokinetic parameters for computer-controlled infusion of lidocaine in pain therapy.

BACKGROUND: Lidocaine administered intravenously is efficacious in treating neuropathic pain at doses that do not cause sedation or other side effects. Using a computer-controlled infusion pump (CCIP), it is possible to maintain the plasma lidocaine concentration to allow drug equilibration between the plasma and the site of the drug effect. Pharmacokinetic parameters were derived for CCIP administration of lidocaine in patients with chronic pain. METHODS: Thirteen patients (mean age 45 yr, mean weight 66 kg) were studied. Eight subjects received a computer-controlled infusion, targeting four increasing lidocaine concentrations (1-7 micrograms.ml-1) for 30 min each, based on published kinetic parameters in which venous samples were obtained infrequently after bolus administration. From the observations in these eight patients, new lidocaine pharmacokinetic parameters were estimated. These were prospectively tested in five additional patients. From the complete data set (13 patients), final structural parameters were estimated using a pooled analysis approach. The interindividual variability was determined with a mixed-effects model, with the structural model parameters fixed at the values obtained from the pooled analysis. Internal cross-validation was used to estimate the residual error in the final pharmacokinetic model. RESULTS: The lidocaine administration based on the published parameters consistently produced higher concentrations than desired, resulting in acute lidocaine toxicity in most of the first eight patients. The highest measured plasma concentration was 15.3 micrograms.ml-1. The pharmacokinetic parameters estimated from these eight patients differed from the initial estimates and included a central volume one-sixth of the initial estimate. In the subsequent prospective test in five subjects, the new parameters resulted in concentrations evenly distributed around the target concentration. None of the second group of subjects had evidence of acute lidocaine toxicity. The final parameters ( +/- population variability expressed as %CV) were estimated as follows: V1 0.101 +/- 53% 1.kg-1, V2 0.452 +/- 33% 1.kg-1, Cl1 0.0215 +/- 25% 1.kg-1.min-1, and Cl2 0.0589 +/- 35% 1.kg-1.min-1. The median error measured by internal cross-validation was +1.9%, and the median absolute error was 14%. CONCLUSIONS: Pharmacokinetic parameters for lidocaine were derived and administration was prospectively tested via computer-controlled infusion pumps for patients with chronic neuropathic pain. The estimated parameters performed well when tested prospectively. A second estimation step further refined the parameters and improved performance, as measured using internal cross-validation.

Adult

Cytogenetic study of workers exposed to methyl-parathion.

When compared with non-exposed controls, a group of pesticide plant workers chronically exposed to methyl-parathion did not show an increased frequency of chromosome aberrations in lymphocyte cultures. Although methyl-parathion increased chromosome aberrations in cases of intoxication, a chronic exposure to small doses in the work place did not seem to produce the same effect.

Adult

Superior transseptal approach for surgical removal of left atrial myxoma.

Eight patients (4 men, 4 women), mean age 51 years, referred to our Institution for left atrial myxoma underwent removal of the tumor through a superior transseptal approach. All patients in sinus rhythm with normal conduction time. The myxomas were localized in the fossa ovalis (3 cases), interatrial septum (2 cases), left appendage (2 cases), and mitral annulus (1 case). One patient died in hospital after emergency operation for low-output syndrome complicated by septic shock. All other patients had an uneventful postoperative course. Atrial arrhythmias did not represent a major postoperative complication. Transient PR interval elongation was occasionally seen. Electrophysiological studies showed normal sinus node function. At 6 months following operation, patients were evaluated with transesophageal echocardiography. There was no tumor recurrence. There were no episodes of arrhythmia in 24-hour electrocardiographic monitoring, and all patients were in NYHA Class I. We believe that the superior transseptal approach gives optimal exposure of the left atrial cavity, overcoming all difficulties related to a small left atrium which is an usual pattern in left atrial myxomas.

Adult