Effect of timepidium bromide on the motor activity of the sphincter of Oddi: manometric evaluation of intracholedochal pressure.

The intracholedochal pressure changes induced by timepidium bromide were studied in 12 patients who had undergone surgery because of gall bladder stones and were receiving transient external bile drainage by the Kehr method. Cholangiomanometric examination, carried out under basal conditions and after an intravenous dose of 15 mg timepidium bromide, revealed a statistically significant decrease in mean intracholedochal pressure in all 12 patients. It is concluded that timepidium bromide is likely to exert a direct action on the sphincter of Oddi, decreasing its basal tone and thus causing a decrease in intracholedochal pressure.

Derangement of acid-base balance in uremia and under hemodialysis.

Uremic acidosis is due to impaired excretion of ammonium ions in the presence of unchanged acid production. However, the degree of acidosis is quite variable among uremic patients and pre-dialytic bicarbonate levels are mainly independent of dialytic base supply. These observations strengthen the suggestion that extra-renal mechanisms may play a significant role in controlling acid-base balance in uremic patients. The possible effects of diet, intestine, bone, intermediate metabolism, and the global acid-base balance are discussed. The metabolic and clinical effects of mild uremic acidosis are not well defined. In fact, no long-term clinical study have produced clear evidence for increased protein catabolism in humans. Some data provide evidence for reduced bone mineral content and osteomalacic lesions in uremic patients with severe acidosis. Overall, the impact of the present dialytic techniques on acid-base control is quite small, since no major difference is observed in uremic patients treated with different dialytic schedules. Furthermore, the base supply by dialysis does not seem to represent the main mechanism for acid-base correction by dialysis. In conclusion, at present time, metabolic acidosis of uremic patients is often mild and not accompanied by major symptoms. Probably, more attention needs to be paid to the possible noxious effect of over-correction of acidosis.

Detection of anti-erythropoietin antibodies in haemodialysis patients treated with recombinant human-erythropoietin.

An enzyme-immunoassay was developed to evaluate the presence of anti-erythropoietin antibodies in plasma samples obtained from renal failure patients treated with recombinant human erythropoietin (rh-EPO). The assay was specific and reproducible. Normal donors had no antibodies to EPO, while 67% of treated patients were positive to the assay. While the specificity of anti-EPO IgG antibodies was high, their affinity for the antigen was low. This finding can be explained by the very small differences in the structure of rh-EPO compared to that of natural EPO. The assay described could be useful in evaluating the long-term effects of rh-EPO treatment on the control of anaemia in renal failure patients.

Plasma levels of clonidine following epidural bolus injection in children.

BACKGROUND: The use of clonidine as an adjunct to epidural administration of local anesthetics in children has been reported to substantially improve the duration and quality of postoperative analgesia. The aims of the present study were to determine the pharmacokinetic profile and to investigate the interaction between postoperative sedation and analgesia after epidurally administered clonidine in children. METHODS: Plasma levels of clonidine (0-10 h postop) and assessment of postoperative analgesia and sedation (0-24 h postop) were performed at predetermined intervals following lumbar epidural administration of bupivacaine 2.0 mg/kg and clonidine 2 mg/kg in 8 children undergoing ureteral re-implantation surgery using general anesthesia (age range: 1-9 yr, weight range: 9-41 kg). Plasma levels of clonidine were analyzed by radioimmunoassay, and sedation and analgesia were assessed by previously described scoring systems. RESULTS: The venous plasma pharmacokinetics of clonidine following epidural administration showed a considerable interindividual variation. Cmax and Tmax values of clonidine were found to be within the 0.45-0.77 ng/mL and 48-193 min range, respectively. The time to absorb 95% of the clonidine dose from the epidural space into plasma varied between 36 min and 7.6 h. In 6 of the 8 patients postoperative analgesia substantially outlasted the duration of sedation (> or = 2 h). Sedation could not be detected in any patients at plasma concentrations below 0.3 ng/mL. CONCLUSIONS: The pharmacokinetic profile associated with epidural clonidine administration in children (1-9 y) was similar to that previously reported in adults. The postoperative analgesia seen after administration of epidural bupivacaine-clonidine during general anesthesia in children cannot only be explained by residual postoperative sedation.