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Biomedical subjects

A Tarantino

Publications and source records attributed to A Tarantino.

At least 19 recordsLinked to original sources
PubMed1992

Advantages of cyclosporine as sole immunosuppressive agent in children with transplanted kidneys.

A prospective study of intentional stopping of steroids 6 months after transplantation was done with 29 pediatric renal transplant recipients with a mean age of 10.4 +/- 3.4 years. Immunosuppression consisted of cyclosporine and methylprednisolone. We stopped giving MP to 24 children: to twenty after six months, four after 11-20 months. "Crude graft survival" was 97% during a mean follow-up of 36.7 +/- 15 months. The rejection rate was 48% during the first 6 months and 29% in the period after stopping MP. At present, 20/24 children (83%) have remained on CsA alone (18 patients) or CsA and azathioprine (2 patients) during a mean follow-up of 30 +/- 17 months. CsA nephrotoxicity occurred in 20.6% of patients, gum hypertrophy in 45%, hypertrichosis in 24%, and neurological symptoms in two patients (6.8%). Linear growth significantly improved after stopping MP: mean catch-up growth for prepuberal children 1.38 height standard deviation score (HSDS) and for pubertal children 1.6 HSDS. Bone age did not increase more rapidly than chronologic age. Weight/height index (W/HI) also improved. There was also a significant reduction in the use of antihypertensive drugs. Calculated glomerular filtration rate was decreased, though not significantly, after stopping MP. Thus, when graft survival is good, stopping corticosteroids corrects the major handicap of children with irreversible uremia--the poor linear growth--and improves the W/HI and control of arterial pressure. Longer follow-up periods are necessary to exclude significant worsening of renal function and an increased incidence of chronic rejection after stopping the steroid.

Adolescent↗
PubMed1992

Renal transplant recipients and chronic liver disease: statistical evaluation of predisposing factors.

278 azathioprine and methylprednisolone (AZA)-treated and 406 ciclosporin (CS) treated patients with a kidney graft functioning for more than 1 year were investigated for the presence of chronic liver disease (CLD), defined as an increase in transaminases of 1.5 times the upper normal limits for a period of at least 12 months. The prevalence of CLD was 36 and 27% in the two groups, respectively. The univariate analysis showed that male sex, alcohol abuse and HBsAg positivity correlated with CLD onset in the AZA group while blood transfusions, length of dialysis treatment, pretransplantation CLD, HBsAg positivity and ferritin levels over 800 ng/ml correlated with CLD onset in CS. The multivariate analysis identified male sex and HBsAg positivity in the AZA group and age over 18 years, high ferritin levels and HBsAg positivity in the CS group as risk factors predictive of CLD onset. Liver failure represented the 4th cause of death in the AZA group but 1 of the 2 most important causes of death in CS in the long term. However, these drawbacks were overcome by the overall low mortality rate in CS. Therefore, renal transplantation should not be refused to patients positive for HBsAg and/or with preexisting liver disease.

Adult↗
PubMed1991

The impact of azathioprine and cyclosporine on long-term function in kidney transplantation.

To assess the impact of cyclosporine on long-term kidney function in transplant patients, we retrospectively analyzed 273 patients on azathioprine and 308 on CsA with graft functioning at 1 year. To balance the length of follow-ups, the observation of patients was cut at 5 years. Actual graft survival rate at 5 years was similar in Aza and CsA (88% vs. 90%). Multivariate analysis in Aza pts showed that proteinuria (P = 0.006) and hypertension at 1 year (P = 0.002) increased the probability of irreversible graft failure by 2.47 and 2.85, respectively. In CsA patients, proteinuria (P = 0.007) and plasma creatinine higher than 2.5 mg/dl (P = 0.006) increased the probability of graft failure by 5.12 and 6.48, respectively. In both Aza and CsA patients with a follow-up of at least 5 years, plasma creatinine levels were significantly worse at 5 years vs. 1 year (P = 0.004). The slopes of plasma creatinine values plotted vs time were not different between the two groups. Chronic graft dysfunction (CGD) was defined as a stable increase of plasma creatinine of at least 50% above stable values at 1 year. The probability of remaining without CGD at 5 years was 75% for CsA and 80% for Aza patients (P = N.S.). Multivariate analysis of factors influencing the development of CGD showed that hypertension (P = 0.003) and proteinuria at 1 year (P = 0.081) increased the probability of developing CGD by 2.19 and 1.76, respectively, in Aza, while in CsA patients proteinuria only (P = 0.063) increased the probability of developing CGD by 2.29. Graft survival at 5 years after development of CGD was 34% in Aza and 53% in CsA-treated patients. These data confirm that in the long-term CsA does not cause a higher prevalence of CGD and show that, in the presence of CGD, CsA has a superior protective effect than Aza.

Adult↗
PubMed1991

A randomized prospective trial comparing cyclosporine monotherapy with triple-drug therapy in renal transplantation.

In a prospective trial 151 recipients of renal transplants were randomly assigned to treatment with CsA alone (74 patients) and to low dose of AZA, prednisolone, and CsA (77 patients). At two years, graft survival was 84% for the monotherapy and 90% for the triple therapy. This difference was not statistically significant. The number of rejection episodes was similar in the two groups, but the severity of rejection was significantly worse among the patients on monotherapy. More kidneys were lost because of rejection (6 versus 3), and a higher number of methylprednisolone pulses was used for treating rejection (5.2 +/- 2.3 versus 4.3 +/- 2.9; P = 0.0077). CsA nephrotoxicity episodes were more frequent among patients on monotherapy (23 versus 7; P less than 0.02). Infectious episodes were equally distributed between the two groups. Creatinine clearance was poorer in the monotherapy-treated patients at the third month (42 +/- 16 ml/min versus 48 +/- 15 ml/min; P = 0.02), but no differences were observed between the two groups since the sixth month after transplantation. Many patients on monotherapy required changes in maintenance therapy. In fact, one patient was switched to conventional immunosuppression because of Cremophor-induced anaphylaxis. Another patient who developed Kaposi's sarcoma 4 months after surgery was switched to steroids alone. Excluding 5 patients who lost their grafts a few days after transplantation, only 30 of 74 patients (40%) could be kept without steroids. We conclude that both the therapeutic protocols can give good results in renal allotransplantation; however, monotherapy could create some problems in keeping the balance between drug toxicity and significant immunosuppression. On the contrary, triple therapy is easier to handle, especially in the early posttransplant period when the differential diagnosis between acute rejection and CsA-related nephrotoxicity can be difficult even for a skilled clinician.

Adult↗
PubMed1988

Inhibition of rat colon motility by stimulation of atypical beta-adrenoceptors with new gut-specific agents.

The new putative beta-adrenergic agonists SR 58306A, 2-[(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl)amino]-1-phenylethanol hydrochloride and SR 58339A, 2-[(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl)amino]-1- (3-chlorphenyl) ethanol hydrochloride, were studied in vitro in comparison with reference compounds. SR 58306A and SR 58339A, unlike isoprenaline and the beta2 selective adrenergic agonists salbutamol and ritodrine, potently inhibited rat colon spontaneous contractions (EC50 5.9 and 1.1 x 10(-7) M) without increasing guinea-pig atrium frequency or relaxing guinea-pig trachea. The nonselective beta-adrenergic antagonists alprenolol, pindolol and propranolol competitively antagonized the action of SR 58306A on the colon, which was not prevented by either of the selective antagonists atenolol (beta 1) and ICI 118551 (beta 2). In the same preparation only alprenolol competitively antagonized isoprenaline; antagonism by either pindolol or propranolol was not competitive. These results suggest that in the rat colon isoprenaline interacts with different beta-receptor subclasses, whereas our new gut-specific compounds such as SR 58306A inhibit colonic motility by selectively stimulating atypical beta-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1988

The Milan clinical trial with cyclosporine in cadaveric renal transplantation. A three-year follow-up.

Between February and November 1983, 108 recipients of cadaveric renal transplants entered a randomized multicenter trial and were treated either with cyclosporine (CsA) and prednisone (n = 55) or with conventional treatment based on azathioprine (Aza) and glucocorticoids (n = 53). The graft survival probability at 3 years was 76% for CsA patients and 48% for Aza patients (P less than 0.001). The cumulative number of acute rejections was significantly lower in the CsA group (32 vs. 104, P less than 0.001). Incidence of early posttransplant anuria was similar in both groups and did not affect renal function after three years. Nephrotoxicity in CsA patients, when present, was handled by reducing the dose of CsA, but in 12/55 patients a change to conventional therapy was thought to be necessary. However, in this group of 12, one patient lost the allograft because of irreversible rejection and one patient died 14 months later because of an infection. Mean creatinine clearance after three years was significantly lower in the CsA patients (54.7 +/- 2.6 ml/min) than in Aza patients, (67.2 +/- 4.9 ml/min, P less than 0.05). Considering only patients with grafts functioning after three years and still on the original randomized therapy, the mean creatinine clearance was similarly and significantly decreased from 1 to 3 years in both groups. There were no significant differences in occurrence of severe infections. Side effects such as hypertension, hypertrichosis, tremor and gum hyperplasia were more frequent in CsA patients.

Acute Kidney Injury↗
PubMed1988

A randomized trial comparing triple-drug and double-drug therapy in renal transplantation.

A controlled trial was carried out in 86 cadaveric and 14 living haploidentical renal transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (Aza) and steroids with those of higher doses of CsA plus steroids. Patients were followed for 12-26 months after transplantation. The actuarial 2-year patient and graft survival rate was 100% for living-donor transplants. In cadaver renal transplants the 2-year patient survival rate was 100% for patients assigned to the triple regimen and 93% for those allocated to the double regimen. The actuarial 2-year cadaver graft survival rates were 86% and 90.6%, respectively. There were significantly more patients who had severe infections (P less than 0.05), particularly interstitial pneumonia (P less than 0.005), in the double-therapy group. On the other hand, there were more patients who rejected and more patients with severe rejections; more pulses of steroids were also required for patients on the triple regimen, although these differences were not significant. The mean trough blood levels of cyclosporine at the various times were about half as high in patients on triple therapy. There were no differences between the two groups in creatinine clearance at any time. A control renal biopsy, taken from patients with stable renal function after 6-12 months, showed only mild abnormalities. The lesions were semiquantitatively assessed. There was a higher score for interstitial infiltrate in patients on triple therapy (P less than 0.05). On the other hand, the incidence and the mean score of interstitial fibrosis were greater in patients on double therapy, although these differences were not significant. Thus, although similar results were obtained with both regimens, at the doses we used double therapy seems to have more powerful immunosuppressive effects and may prevent rejection, either acute or chronic, better. However, it might expose the patient to a greater risk of infection and of cyclosporine-related nephrotoxicity than triple therapy.

Acute Kidney Injury↗
PubMed1987

Renal lesions in ciclosporin A-treated kidney transplant patients.

Ninety renal biopsies (RB) in 73 out of 152 ciclosporin A (CsA)-treated allograft patients were studied by light and electron microscopy; they were grouped according to the clinical setting: (1) prolonged posttransplant anuria (9 RB), (2) early graft function deterioration (14 RB), (3) late graft function deterioration (15 RB) and (4) control biopsies (52 RB) at least 6 months after Tx. Glomerular, tubular abnormalities, interstitial cellular infiltrate and fibrosis, peritubular capillary mononuclear cell congestion (PCC), vascular changes and erythrocyte extravasation were evaluated and the following morphologic patterns were identified alone or in combination: acute (AR) and acute on chronic rejection (ACR), toxic tubulopathy (TT), interstitial stripe fibrosis (ISF), CsA-associated arteriolopathy (CsAA). AR was observed in 95% of RB in group 1 and 2, and in 26% in group 3, never in group 4; PCC and TT were only observed concomitantly with AR; ACR was found in 26% of group 3; ISF in 53% of group 3, sometimes linked to CsAA and, of moderate entity, in 70% of group 4. CsAA was noted in 10% of all RB, mainly in group 3 (26%), although in some RB of group 2 (13%) as well.

Adolescent↗
PubMed1986

Cutaneous lesions in 67 cyclosporin-treated renal transplant recipients.

Sixty-seven out of 100 kidney transplant recipients treated with cyclosporin and methylprednisolone were evaluated for the presence of dermatological manifestations. Only 2 patients had no dermatological lesions; 80% had iatrogenic lesions, 38% infectious, 13% miscellaneous, 3% cancerous lesions, while 28% had cutaneous manifestations related to previous uremic state. Most of the lesions concerned the pilosebaceous unit: hypertrichosis (60%), epidermal cysts (28%), pilar keratosis (21%), acne (15%), folliculitis (12%) and sebaceous hyperplasia (10%). Among infectious manifestations, viral lesions were the most frequent and were very severe in the first month after transplantation. Two patients developed a squamous-cell epithelioma and a probable cutaneous lymphoma, respectively.

Adolescent↗
PubMed1985

Relative affinities of the quaternary narcotic antagonist, N-methyl levallorphan (SR 58002), for different types of opioid receptors.

The relative affinities for different subtypes of opioid receptors (mu, kappa and delta) of the peripheral narcotic antagonist N-methyl levallorphan (SR 58002) have been studied in two in vitro smooth muscle systems (guinea-pig ileum and rabbit vas deferens) and by binding studies (guinea-pig brain and cerebellum membranes) using selective tritiated ligands. All the evidence obtained indicates that SR 58002 is a pure antagonist with relative affinity for mu receptors vs kappa and delta superior to that of the parent tertiary compound, levallorphan.

Animals↗