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Biomedical subjects

F Pisani

Publications and source records attributed to F Pisani.

At least 73 records · Page 4Linked to original sources
PubMed1997

Lamotrigine plasma concentrations in children and adults: influence of age and associated therapy.

The effects of age and concomitant treatment on plasma lamotrigine (LTG) concentration/dose (C/D) ratios were retrospectively evaluated on 482 consecutive routine LTG determinations from 106 chronically-treated patients with epilepsy (40 children and adolescents aged younger than 16 years, and 66 adults aged 17 to 62 years). A linear dose/level relationship was observed in individual patients but not in the cumulative analysis, which failed to show any correlation between the administered LTG dose and plasma concentrations. In the adult group, there were no correlations between the administered LTG dose and plasma concentrations. Associated antiepileptic therapy affected the LTG concentration/dose ratio, which was significantly higher in the patients receiving valproic acid (3.4 +/- 2.0, n = 23) and significantly lower in those treated with enzyme-inducing antiepileptic drugs (0.6 +/- 0.5, n = 57) than in the patients receiving valproic acid in combination with enzyme-inducing antiepileptic drugs, ethosuximide, vigabatrin, or clobazam (1.9 +/- 1.6, n = 26). The LTG C/D ratios significantly increased with increasing plasma valproic acid concentrations, and significantly decreased with increasing phenytoin concentrations. The effect of enzyme-inducing antiepileptic drugs increased with the number of associated drugs. A clear age effect was demonstrated in the homogeneously treated subgroups, in all of which adults had higher C/D ratios than children.

Adolescent↗
PubMed1997

A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation. Italian Multicentre Study Group for Renal Transplantation (SIMTRe).

Whether it is better to treat renal transplant patients with cyclosporine alone, combined with steroids, or combined with steroids and azathioprine is still unclear. After initial therapy with cyclosporine and steroids, 354 cadaver renal transplant recipients were randomly assigned at the post-transplant day 5 to cyclosporine alone (monotherapy), cyclosporine plus steroids (double therapy), or cyclosporine plus steroids plus azathioprine (triple therapy). Monotherapy patients, after a second acute rejection, were switched to either of the two alternative therapies. According to intention-to-treat (ITT) analysis, the 4-year patient survival was 97% in monotherapy, 91% in double therapy, and 96% in triple therapy; the graft survival including death was 84%, 77%, and 88%, respectively; and the pure graft survival was 87%, 85% and 91%, respectively (P = not significant). Acute rejections were diagnosed in 79 patients in monotherapy, 58 in double therapy, and 59 in triple therapy (P < 0.01). Of the patients on monotherapy, 52% were switched to double or triple therapy. In these patients, the 4-year graft survival including death was 68%, and the pure graft survival was 72%, in comparison with 93% and 94%, respectively, for patients who continued on cyclosporine alone. Patients with renal polycystic disease as a cause of renal failure and with low plasma creatinine at the time of randomization (5 days after transplant) had a higher probability of remaining on monotherapy, wherease those with glomerulonephritis or systemic lupus erythematosus (SLE) and with high plasma creatinine levels at randomization had a higher probability of being switched to double or triple therapy. According to ITT analysis, there were fewer ocular (P < 0.0001), osteomuscular (P < 0.002) and cardiovascular complications (P = 0.05) and fewer patients with hypercholesterolemia (P < 0.0028) in the monotherapy group, with no difference between double and triple therapy. Creatinine clearance at 3 years was lower in monotherapy, but no attrition of renal function was seen over the years in any of the groups. Cyclosporine, however used, provided good results in cadaveric renal transplantation. Triple therapy and monotherapy offered a nonsignificantly better patient and graft survival than double therapy. Patients on monotherapy had a higher risk of acute rejection but had fewer adverse events than those on double or triple therapy. Patients maintained on cyclosporine alone had the best graft survival, whereas those who were assigned to monotherapy and had to add steroids because of multiple rejections had the worst outcome. Therefore, it seems reasonable to limit the choice of monotherapy to patients without immune-mediated renal diseases and with good graft function in the early post-transplant period.

Adolescent↗
PubMed1997

Hepatitis C virus infection in Italian kidney graft recipients. Changing risk factors and hepatitis C virus genotypes.

BACKGROUND/AIMS: The risk for hepatitis C virus infection in kidney transplant recipients has been reduced by the introduction of accurate diagnostic tests. Little is known, however, of the current risk factors and the molecular genetics of hepatitis C virus infection in Italy. METHODS: We studied 101 Italian kidney allograft recipients, transplanted between 1975 and 1995, in Italy or abroad. Sera were assayed for biochemistry, presence of HBsAg, anti-hepatitis C virus antibodies, hepatitis C virus-RNA (by reverse transcription nested PCR) and hepatitis C virus genotyping. RESULTS: HBsAg was found in 4 sera and anti-Hepatitis C Virus antibodies in 33 (33%). The duration of pre-transplant dialysis was longer in anti-hepatitis C virus positive than in anti-hepatitis C virus negative patients (5.9 +/- 4.3 vs 2.8 +/- 1.9 years, p = 0.0004). Anti-hepatitis C virus seropositivity was more frequent among patients grafted before than after 1990 (50% vs 27%, p = 0.04) and varied depending on the country of transplantation (25% in Italy; 56% in other European countries; and 40% in non-European developing countries). Twenty-seven sera were hepatitis C virus-RNA positive, including 5 without anti-hepatitis C virus antibodies. Hepatitis C virus genotype 1b was found in 13 (48%) patients, the remainder being infected with genotypes 1a (6 cases), 2a, 2c, 3a and 4. Genotype 1b was largely predominant among patients grafted in Europe but never found in those transplanted in developing countries. All but one patient without a sustained antibody response were infected by non-1b genotypes. Hepatitis C virus-RNA seropositivity was associated (p = 0.03) with a higher dose of prednisone (p = 0.03) and a lower dose of cyclosporine (p = 0.05) used as immunosuppressants. CONCLUSIONS: Current risk factors for hepatitis C virus infection in Italian kidney graft recipients include the duration of haemodialysis, transplantation in developing countries and the level of post-transplant immunosuppression. The pattern of hepatitis C virus genotypes is changing from predominantly 1b to non-1b genotypes and the latter infection often occurs without a sustained antibody response. Few patients develop clinical liver disease.

Adult↗
PubMed1996

High-dose chemotherapy in adult acute myeloid leukemia: rationale and results.

Preclinical studies and retrospective evaluations of clinical trials of a number of cytotoxic drugs have provided a rationale for the use of high doses of chemotherapy in adults with acute myeloid leukemia (AML). To maximize cure and remission rates at an acceptable cost in toxicity, many schedules and combinations of dose-intensive chemotherapy have been tested in recent years in patients with de novo disease, cytosine arabinoside (Ara-C) being the most extensively evaluated drug. In this article we review the principal results of both randomized and non-controlled studies. Our analysis indicates that high-dose Ara-C (HIDAC) used during induction results is no substantial benefit relative to conventional doses of drug. On the other hand, consolidation with HIDAC is a major advance in the treatment of this disease. In fact, in individuals less than 60 years of age and a favorable or intermediate-risk karyotype, HIDAC-based regimens have resulted in survival estimates comparable to those of autologous or allogeneic bone marrow transplantation. Yet, the role of HIDAC is irrelevant in younger individuals with an unfavorable cytogenetic pattern and detrimental in patients greater than 60 years of age. Since recently new cytotoxic agents have expanded the armamentarium of antileukemic drugs, well conducted randomized trials of dose intensive chemotherapy still need to be performed to optimize schedules and combinations of drugs in patients with AML.

Acute Disease↗
PubMed1996

Effect of enzyme inducing anticonvulsants on ethosuximide pharmacokinetics in epileptic patients.

1. To assess the effect of enzyme inducing anticonvulsants on ethosuximide pharmacokinetics, plasma ethosuximide concentrations after a single oral dose (500 mg) of the drug were compared in 12 healthy control subjects and 10 epileptic patients receiving chronic therapy with phenobarbitone, phenytoin and/or carbamazepine. 2. Compared with controls, epileptic patients showed markedly shorter ethosuximide half-lives (29.0 +/- 7.8 vs 53.7 +/- 14.3 h, means +/- s.d., P < 0.001) and higher apparent oral clearance (CL/F) values (15.3 +/- 3.8 vs 9.2 +/- 1.9 ml kg-1 h-1, P < 0.001). The apparent volume of distribution (V/F) of ethosuximide was slightly lower in the patients than in controls (0.6 +/- 0.1 vs 0.7 +/- 0.1 l kg-1, P < 0.05). 3. These findings provide evidence that ethosuximide elimination is increased by enzyme inducing anticonvulsants, the effect probably being mediated by stimulation of cytochrome CYP3A activity. 4. The enhancement of ethosuximide clearance in patients comedicated with enzyme inducing anticonvulsants is likely to be clinically relevant. Higher ethosuximide dosages will be required to achieve therapeutic drug concentrations in these patients.

Adult↗
PubMed1996

Clinically significant pharmacokinetic drug interactions with carbamazepine. An update.

Carbamazepine is one of the most commonly prescribed antiepileptic drugs and is also used in the treatment of trigeminal neuralgia and psychiatric disorders, particularly bipolar depression. Because of its widespread and long term use, carbamazepine is frequently prescribed in combination with other drugs, leading to the possibility of drug interactions. The most important interactions affecting carbamazepine pharmacokinetics are those resulting in induction or inhibition of its metabolism. Phenytoin, phenobarbital (phenobarbitone) and primidone accelerate the elimination of carbamazepine, probably by stimulating cytochrome P450 (CYP) 3A4, and reduce plasma carbamazepine concentrations to a clinically important extent. Inhibition of carbamazepine metabolism and elevation of plasma carbamazepine to potentially toxic concentrations can be caused by stiripentol, remacemide, acetazolamide, macrolide antibiotics, isoniazid, metronidazole, certain antidepressants, verapamil, diltiazem, cimetidine, danazol and (dextropropoxyphene) propoxyphene. In other cases, toxic symptoms may result from elevated plasma concentrations of the active metabolite carbamazepine-10,11-epoxide, due to the inhibition of epoxide hydrolase by valproic acid (sodium valproate), valpromide, valnoctamide and progabide. Carbamazepine is a potent inducer of CYP3A4 and other oxidative enzyme system in the liver, and it may also increase glucuronyltransferase activity. This results in the acceleration of the metabolism of concurrently prescribed anticonvulsants, particularly valproic acid, clonazepam, ethosuximide, lamotrigine, topiramate, tiagabine and remacemide. The metabolism of many other drugs such as tricyclic antidepressants, antipsychotics, steroid oral contraceptives, glucocorticoids, oral anticoagulants, cyclosporin, theophylline, chemotherapeutic agents and cardiovascular drugs can also be induced, leading to a number of clinically relevant drug interactions. Interactions with carbamazepine can usually be predicted on the basis of the pharmacological properties of the combined drug, particularly with respect to its therapeutic index, site of metabolism and ability to affect specific drug metabolising isoenzymes. Avoidance of unnecessary polypharmacy, selection of alternative agents with lower interaction potential, and careful dosage adjustments based on serum drug concentration monitoring and clinical observation represent the mainstays for the minimisation of risks associated with these interactions.

Analgesics, Non-Narcotic↗
PubMed1995

All-trans retinoic acid and low-dose cytosine arabinoside for the treatment of 'poor prognosis' acute myeloid leukemia.

Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer suitable for aggressive chemotherapy, were treated with daily oral all-trans retinoic acid (45 mg/m2) daily and subcutaneous cytosine arabinoside (20 mg standard dose twice a day, day 1 to 10, every 4 weeks). Seventeen patients were males and 16 females, the median age was 67 (range 39-82 years). Eleven patients were at onset of disease, 15 were refractory to previous conventional therapies, three were in first relapse and three in second relapse and one patient had a secondary AML. Seventeen patients had a bone marrow blast infiltration < 50% and 16 > or = 50%. A total of 16 (48%) patients entered complete remission; the rate of complete remission increased to 88% in those patients (n = 17) with < 50% blast infiltration at the time of entering the study. Seventeen patients (52%) were resistant. The difference in response to therapy, according to bone marrow blast percentage (< or > or = 50%), was statistically significant (P < 0.001). Median duration of complete remission was 34.4 weeks (range 6.4-62.8). Mild to moderate hematologic toxicity was the most common side-effect. In conclusion all-trans retinoic acid and low-dose cytosine arabinoside appears to be an effective regimen for inducing complete remission in 'poor prognosis' acute myeloid leukemia and patients with < 50% bone marrow infiltration are likely to represent the ideal target to receive this combination therapy.

Adult↗
PubMed1995

[Ureteral obstruction in the kidney transplant patient].

Ureteric obstruction is a common complication following kidney transplantation ranging from 2% to 5% after one year and till 9% after five years post-transplantation. It hinders the return to good renal function and in certain cases leads to the organ loss or patient mortality. Technical factors and ureteric ischemia are the most important causes. The authors report their experience with kidney transplantation and 6 cases of ureter obstruction with a global incidence of 5.5%. We discuss the aetiology, the management and the treatment for this complication emphasizing the importance of either color Doppler ultrasound for the diagnosis or percutaneous nephrostomy for the radiological establishment of the blocked level as well as the first choice of treatment. In order to reduce the morbidity and mortality for this complication early and aggressive treatment is advocated.

Adolescent↗
PubMed1994

Single dose pharmacokinetics of carbamazepine-10,11-epoxide in patients on lamotrigine monotherapy.

The pharmacokinetics of a single oral dose of carbamazepine-10,11-epoxide (CBZ-E, 100 mg) were compared in 10 patients on chronic monotherapy with lamotrigine (LTG, 200-300 mg/day) and in 10 drug-free healthy control subjects. CBZ-E pharmacokinetic parameters in LTG-treated patients were found to be similar to those observed in controls (half-life: 7.2 +/- 1.6 vs 6.1 +/- 0.9 h; apparent oral clearance: 110.8 +/- 53.1 vs 120.5 +/- 29.9 ml/h/kg; apparent volume of distribution: 1.08 +/- 0.37 vs 1.04 +/- 0.25 l/kg respectively; means +/- s.d.). These data indicate that, contrary to previous suggestions, LTG has no effect on the metabolic disposition of CBZ-E.

Adult↗
PubMed1994

Effects of the antidepressant drug viloxazine on oxcarbazepine and its hydroxylated metabolites in patients with epilepsy.

The effects of Viloxazine (VLX, 100 mg b.i.d. for 10 days) on the steady-state plasma concentrations of Oxcarbazepine (OXC), its active metabolite 10, 11-dihydro-10-hydroxy-carbazepine (MHD) and the corresponding diol (DHD) were studied in a randomized, double-blind cross-over placebo-controlled trial in 6 epileptic patients stabilized on a fixed dosage of OXC. Administration of VLX resulted in an 11% increase in the plasma concentration of MHD (p = 0.003) associated with a 31% fall in DHD levels (p = 0.0001). Plasma concentrations of unchanged OXC were unaffected by VLX. No changes in seizure frequency nor signs of drug toxicity were observed during the study. Although VLX may inhibit the conversion of MHD to the inactive diol, the interaction is unlikely to be of clinical significance.

Adult↗