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Biomedical subjects

L Gastaldi

Publications and source records attributed to L Gastaldi.

At least 19 recordsLinked to original sources
PubMed1992

Optimization of sampling time for cyclosporine monitoring in transplant patients.

Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were obtained from 22 patients before their morning dose of CsA and at 2, 4, 6, 8, 10, and 12 hours after the dose on the 7th and on the 21st day after heart transplantation. The plasma samples were assayed by both HPLC and FPIA. The Cmax for CsA was achieved over a period ranging from 2 to 6 hours (mean/median = 4.7/4.0) during the day 7 and the day 21 studies. The mean (+/- SD) half-life was 3.2 (1.0) hours on day 7 and 2.9 (1.1) hours on day 21, (P > 0.05); the mean apparent oral clearance was 276 (117) L/hr on the day 7 and 269 (209) L/hr on day 21, (P > 0.05). When CsA plasma concentration by either FPIA and HPLC was monitored, the drug concentration best correlated with AUC was found to correspond to the plasma samples taken 4 to 8 hours after drug administration. The authors conclude that through blood sampling for therapeutic drug monitoring of CsA is not optimal, and that further studies are necessary to correlate concentration monitoring during the dosing interval with pharmacologic and toxicologic parameters.

Adolescent↗
PubMed1991

Hemodialysis-associated cardiac arrhythmias: a lower risk with bicarbonate?

The role of hemodialysis (HD) as an arrhythmogenic event has recently been emphasized. We studied 18 patients by Holter monitoring, comparing the arrhythmogenic effect of acetate dialysis (AHD) and bicarbonate dialysis (BHD). The frequency of ventricular arrhythmias was 93 +/- 66/h in AHD and 32 +/- 26/h in BHD (p less than 0.005). According to the classification of Lown and Graboys, classes III and IV were more often to be found in AHD than in BHD and no patient on BHD was in class IVB and class V. Five patients affected with ischemic heart disease had more frequent and dangerous ventricular arrhythmias than the others; a significant difference between buffers was recorded in all cases but 1. Intradialytic changes in body weight, hematocrit, osmolarity, ionized calcium and potassium during AHD and BHD were similar. The two methods only differed in the quickness and degree of correction of acidosis, and this was related to a significant difference in intraerythrocytic potassium at the end of the session. The quicker and more regular correction of acidosis with BHD and the consequent difference in ionic flows between the intra- and extracellular spaces, as demonstrated by changes in intraerythrocytic potassium at the end of the session, could account for the seemingly less arrhythmogenic effect of BHD.

Acetates↗
PubMed1991

Immune deficiency in uremia: interleukin-2 production and responsiveness and interleukin-2 receptor expression and release.

We have studied the role of interleukin-2 (IL-2) and its receptors in the impaired in vitro lymphocyte response characteristic of hemodialysis patients treated by means of cuprophane membranes. The proliferative response of T lymphocytes as well as T-cell-dependent B cell proliferation after stimulation with mitogens was significantly reduced in hemodialysis patients. The in vitro production of IL-2 after such stimulation in parallel cultures was found to be similar in patients and in controls. The expression of IL-2 receptor on the lymphocyte cellular membrane in the hemodialysis group was also similar to controls. The in vitro proliferative response of uremic lymphocytes to exogenous IL-2, however, was significantly depressed suggesting a reduced availability of biologically active IL-2 receptor. The release of soluble IL-2 receptor by lectin-stimulated lymphocytes in culture was also significantly lower in the patient group; yet, hemodialysis patients has a strikingly elevated level of plasma soluble IL-2 receptor, and similar high levels were also found in three other groups of end-stage renal disease patients dialyzed by means of cellulose acetate, polysulfone and polyacrylonitrile membranes, as well as in a group of uremic patients on conservative treatment. In the hemodialysis patient group a significant positive correlation between levels of soluble IL-2 receptor and the duration of hemodialysis was found. Since soluble IL-2 receptor has been reported to down-regulate lymphocyte responses, the elevation in plasma levels of soluble IL-2 receptor in hemodialysis patients may be a pathogenetic factor in the progressive development of impaired immunity associated with end-stage renal disease.

Aged↗
PubMed1991

Coronary response to transient increases in transmural pressure.

Previous studies have shown that transient increases in aortic blood pressure obtained by occlusion of the descending thoracic aorta, in anesthetized dogs with beta-blockade and vagal section, did not affect coronary vascular resistance apart from a non-significant increase just after release of the constriction. The present study examined whether this response also occurred in the normally innervated heart. Experiments were carried out in six anesthetized dogs, in which pressure in the aortic root and in the left ventricle, as well as flow in the left circumflex coronary artery, were recorded. Coronary vascular resistance was calculated as the ratio of the difference between aortic pressure and left ventricular pressure to coronary circumflex flow during the slow inflow phase. Before occlusion coronary vascular resistance was significantly lower than during the same period in the previous studies using animals with beta-blockade and vagal section. During the occlusion, in contrast with the previous investigation, the increase in aortic pressure caused a significant increase in coronary vascular resistance 10 seconds after the beginning of the occlusion. Coronary vascular resistance was further increased immediately after release of the occlusion, concomitantly with the decrease in aortic pressure, which fell abruptly below the control level. The increase immediately after the release of the constriction was qualitatively similar, but greater in extent, to that observed in the animals with vagal section and beta-blockade. These differences are assumed to depend on a lower vasomotor tone in the normally innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Measurement of cyclosporine in plasma of cardiac allograft recipients by fluorescence polarization immunoassay.

The Abbott TDx fluorescence polarization immunoassay (FPIA) procedure for measuring cyclosporine A (CsA) was evaluated and compared with the Sandoz polyclonal radioimmunoassay (CsA RIA kit) method. This drug assay was evaluated for precision, calibration, stability, and accuracy. Within-run precision studies utilizing 25 replicate analyses of the three control preparations (containing CsA in the 60-800 ng/ml range) resulted in coefficients of variation (CV) ranging from 1.0 to 9.1%. The CVs of between-run precision determined by assaying the same control drug levels for five consecutive working days ranged from 3.9 to 4.6%. Calibration curve stability was assessed by examining the drift in control values over a 2-week period. Maximum plasma ranged from 82.6 to 108.2%. Four hundred plasma samples were obtained from 30 heart-transplant patients during the first 6 months of CsA therapy and each sample was analyzed simultaneously by TDx and RIA. Linear regression analysis of the results obtained for each patient (x = RIA, y = FPIA) revealed the following mean values: r = 0.87, (CV = 13.7%), slope = 1.47 (CV = 39.2%). Moreover, the concentration of CsA was determined in 35 patient samples both by TDx and high-performance liquid chromatography (HPLC). FPIA results up to 12 times higher than HPLC results have been noted.

Chromatography, High Pressure Liquid↗
PubMed1989

[Coronary vascular resistance during transitory variations in aortic pressure].

The present study was aimed at studying the interaction between elastic properties and myogenic responses of the coronary wall in regulating coronary vascular resistance (CVR) during and after sudden changes in perfusion pressure. Whilst the effects of transient reductions and recoveries of the aortic blood pressure (ABP) were previously considered, in the present study attention was paid to the changes induced in CVR by the reverse procedure, i.e., by transient increases followed by abrupt decreases of ABP. The experiments were performed in 6 anesthetized dogs after section of the vagi nerves and beta-adrenergic receptor blockade. The increase of ABP was obtained by a 10 or 20 s constriction of the descending thoracic aorta. During the experimental maneuver, coronary flow increased without any significant change in CVR. Only in the late part of the 20 s constriction a reduction of CVR was observed as a likely consequence of increased myocardial metabolism. Immediately after the release of the constriction, the fall of ABP below the control was accompanied by a significant reduction of coronary flow without any significant increase in CVR. About 10 s later, a remarkable increase in flow occurred together with a significant fall of CVR, while ABP was recovering towards the control. In each animal the exact timing of these changes was independent of the duration of the constriction. When, about 20-30 s from the end of the constriction, ABP was back to the control, the hyperemia was completely over.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Controlled trial of thymopentin in hemodialysis patients who fail to respond to hepatitis B vaccination.

Uremic patients are at high risk of hepatitis B virus (HBV) infection and, despite the availability and efficacy of hepatitis B vaccine, a high rate of non responders has been reported. Forty uremic patients undergoing maintenance hemodialysis who failed to produce any measurable anti-HBs antibody response after 4 administrations of 5 micrograms of Hevac B Pasteur vaccine were admitted to a randomized controlled clinical trial. Group A (14 patients) received 3 doses of 5 micrograms s.c. each of vaccine at monthly intervals and 12 doses of 50 mg s.c. of thymopentin on alternate days between the first and the second vaccination. Group B (11 patients) received 3 doses of 5 micrograms s.c. each of vaccine at monthly intervals. Group C (15 patients) received 3 doses of 10 micrograms s.c. each of vaccine at monthly intervals. Immunization rates were 86% in group A (on both 1-month and 6-month checks), 36% on the 1-month and 27% on the 6-month check in group B, 53% on the 1-month and 47% on the 6-month check in group C. Anti-HBs antibody titers were similar in group A and C but notably lower in group B. Thymopentin seems as useful therapeutical tool for non responder patients. As it promotes T cell maturation and responsiveness, which are impaired in uremia, it could play a major part in the management of uremic immunodeficiency.

Clinical Trials as Topic↗
PubMed1987

Natural history and treatment of uremia secondary to Fabry's disease: an European experience.

Fabry's disease, a very unusual cause of end-stage renal disease, is actually included in the contraindications to renal transplantation. The few published studies, based on very few patients, report a high rate of life-threatening complications, mostly infectious, following kidney transplant in these patients. We have evaluated retrospectively 12 uremic patients in renal function replacement treatment for Fabry's disease. In transplanted patients (n = 8; whole observation period 241 months), no lethal complication was ever recorded. Fever and acroparesthesias ameliorated. Cardio- and cerebrovascular complications did not progress. Although no increase in serum enzymatic activity was measured, renal transplantation provided an alternative route by excretion of an amount of the metabolic product (ceramide-trihexoside). When undergoing maintenance hemodialysis (whole observation period 291 months), 3 deaths and several cardiac and cerebral complications occurred. Angiokeratomas, fever and pains were unmodified. These data disagree with what has been previously stated. The transplanted patients' survival shifts towards the all-time rate and a satisfying rehabilitation is provided. Fabry's disease should not be considered a high-risk disease; and patients suffering from it should decidedly enter a regular transplantation program.

Adolescent↗
PubMed1985

Immune function and renal transplantation in Fabry's disease.

A deficient leucocyte immunological function could cause the reported high rate of lethal infections following renal transplantation in patients affected by Fabry's disease. We have studied humoral immunity, peripheral lymphocyte subsets, mitogenic lymphocyte response in vitro and granulocyte function in three patients with Fabry's disease. The immunological state appears to be quite similar to that of the uraemic population in general, not showing any specific impairment.

Fabry Disease↗