[Safety in the switching traditional cyclosporin to microemulsion cyclosporin in stable renal transplant patients: cooperative study]. / Seguridad en la conversión de ciclosporina tradicional a ciclosporina como microemulsión en trasplante renal estable: estudio cooperativo.

In an open clinical trial we assessed the tolerance and safety of the 1:1 conversion of traditional cyclosporine A (CyA) to a new cyclosporine formulation based on a microemulsion technology (CyN) in 18 patients with stable renal allografts. 56% patients were female. Median patient age was 40.9 +/- 3.2 years (range 18 to 65). Renal transplantation was performed in 24.1 +/- 4.6 months (range 6 to 67 months), prior to the beginning of the study, and 67% of the transplants were from cadaveric donor. The most frequent underlying renal disease was glomerulonephritis (44.4%). None of the patients entering the study were withdrawn prematurely. After 2 weeks of observation for graft function stability, the study was divided in two phases: I: during 4 weeks the patients received CyA traditional at fixed doses (Mean dose administered 3.056 +/- 0.25 mg/Kg/d) and II: during the consecutive 6 weeks with conversion to CyN, with doses adjustment as required (Mean dose 2.887 +/- 0.21 mg/Kg/d). Clinical events, adverse reactions and laboratory parameters were evaluated. Levels of 100-200 ng/ml measured by monoclonal specific fluorescence polarization immunoassay were considered appropriate. There were no significant changes in physical examination and laboratory parameters between phases. The incidence of adverse reactions reported in phase I was only gingival hypertrophy (5%) which persisted in phase II, qualified as probably related to the cyclosporine, and in phase II tremor in 17%, qualified as definitively related. Both drugs were well tolerated and there was no report of acute rejection during the study. We conclude that the tolerance and safety of the 1:1 conversion of CyA to CyN were confirmed by our results, and considering the improved pharmacokinetic properties of the second, the microemulsion presentation will be used preferentially as immunosuppressive drug in the treatment of stable kidney transplant patients.

Prazosin and propranolol in preoperative management of pheochromocytoma.

Combined use of prazosin and propranolol was effective in preoperative management of three patients with norepinephrine(NE)-secreting pheochromocytoma (PHEO). On admission, all were symptomatic and had moderate to severe hypertension despite treatment with diuretics, propranolol, and sympatholytics. Optimal symptomatic and blood pressure (BP) control was achieved with 6 to 10 mg/day prazosin and 120 to 480 mg/day propranolol every 6 hr in equally divided doses. With this therapy, BP and hematocrit were reduced to levels similar to those found in the postoperative period. The daily urinary excretion of catecholamines and their metabolites was not modified during therapy with prazosin and propranolol. There was a drop in supine systolic (40 to 64 mm Hg) and diastolic (32 to 52 mm Hg) BP in all patients 1 to 2 hr after the first dose of prazosin (1-mg tablet); in two subjects this was accompanied by a larger orthostatic fall (74 and 92 mm Hg systolic; 65 and 78 mm Hg diastolic BP). The high incidence of first-dose effect suggests that a single oral dose of 1 mg of prazosin could aid in the diagnosis of PHEO. The effectiveness of prazosin in controlling the hypertension induced by NE-secreting PHEO suggests that, in man, pressure responses to augmented levels of NE are mediated solely through alpha 1-receptors.

Cerebrospinal fluid and plasma dopamine-beta-hydroxylase activity in human hypertension.

Cerebrospinal fluid (CSF) and plasma dopamine-beta-hydroxylase (DBH) activity was measured in 22 normotensive (NT), 31 essential hypertensive (EH), and 11 renal hypertensive (RH) patients. Although no differences were observed in their plasma DBH, the mean CSF-DBH activity and specific activity of EH were significantly lower than those of NT and RH patients. Very low CSF-DBH (less than 0.15 units/ml of CFS or less than 0.5 units/mg of CSF protein) was found only in EH (26% of EH). Of the 31 EH patients, 19(60%) had CSF-DHB activities lower than 0.5 units/ml, whereas only 5 of 22 NT (23%) and no RH fell within this range. Nevertheless, 20% of EH, 55% of NT, and 40% of RH patients had CSF-DBH activities above the mean value for NT (less than 0.9 units/ml). NT subjects with very low plasma DBH (less than 50 units/ml) had CSF-DBH activities that fell within normal range. With the exception of these subjects, the specific activity of CSF-DBH was always lower than that of the plasma enzyme. The concentration of albumin, alpha 1, beta, and gamma globulins was measured in plasma and CSF obtained from the last five NT, four EH, and two RH patients. A positive linear relationship was obtained when the log of the plasma/CSF concentration ratio for these proteins was plotted against their molecular weight. Similar slopes and intercepts were obtained for these patients, suggesting that no major differences seem to exist in their blood-brain-barrier permeability to proteins. The results suggest that measurements of CSF-DBH could be of help in the differential diagnosis of human hypertension and in the neurochemical characterization of EH. If CSF-DBH reflects central noradrenergic activity, its reduction might indicate the existence of a central catecholaminergic defect in a subgroup of EH patients.