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Biomedical subjects

F Pisani

Publications and source records attributed to F Pisani.

At least 55 records · Page 3Linked to original sources
PubMed1998

Hepatic steatosis: a specific sign of hepatitis C reinfection after liver transplantation.

Hepatitis C virus (HCV) infection is one of the major causes leading to orthotopic liver transplantation (OLT) worldwide. Although viral infection persists in almost all patients, the pathology of recurrent HCV infection after OLT is not well characterized. To address this issue, we compared the pathological findings of 28 patients who underwent transplantation for HCV-related cirrhosis (group A, aged 47 +/- 15 years; 23 men, 5 women) with those of 21 patients who underwent transplantation for nonviral indications (group B, aged 45 +/- 21 years; 13 men, 8 women) during the first year after transplantation. Patients from group A were assessed for serum HCV RNA by 5' untranslated region nested polymerase chain reaction before and 1 year after OLT. Patients underwent protocol liver biopsies 3 months and 1 year after transplantation. Group A patients more frequently had histological evidence of hepatic steatosis than group B patients, both at 3 months (P = .003) and 1 year (P = .003) after OLT. Fibrosis and portal inflammation were statistically more frequent in group A 1 year after transplantation. The sensitivity of steatosis in detecting histological disease recurrence was 100% at 3 months and 94% at 1 year; the specificity was 40% and 60%, respectively. Conversely, steatosis was 100% specific in detecting viral recurrence, with a sensitivity of 89%. The 1-year actuarial incidence of abnormal transaminase levels was 52% in group A and 13% in group B (P = .05). No biochemical or histological differences between patients infected with genotype 1b and patients with other HCV genotypes were found. Hepatic steatosis is a specific sign of viral recurrence after liver transplantation and a less specific sign of disease recurrence. HCV-infected liver transplant recipients often develop abnormal transaminase levels and liver fibrosis 1 year after OLT; these features are unrelated to HCV genotypes.

Adult↗
PubMed1998

Immunosuppression without prednisone after liver transplantion is safe and associated with normal early graft function: preliminary results of a randomized study.

Prednisone has been commonly considered the mainstay of immunosuppressive therapy after liver transplantation. Recent data suggest that prednisone withdrawal late after transplant reduces complications without affecting graft function. We report here the preliminary results of an open-label, randomized study aimed at investigating whether prednisone therapy can be completely avoided during the first 3 months after transplantation. Twenty-seven consecutive patients were randomized to receive double (group A: cyclosporine and azathioprine) or triple (group B: prednisone, cyclosporine, and azathioprine) immunosuppressive therapy after liver transplantation. Six patients died within the first 3 weeks in each group and were excluded from the calculations. The present results refer to 10 patients in group A and 11 in group B. The actuarial 1-year survival did not differ between the two groups (90.9% vs 88.8%). There were no differences with respect to infectious complications or episodes of histological acute graft rejections. Only one severe acute rejection occurred in group A and two in group B. During the first month after transplant, liver and kidney functions tended to be better in the group of patients treated without prednisone, although there were no differences in the mean cyclosporine blood levels. These data, though preliminary, indicate that early immunosuppression without the use of prednisone is safe and tends to be associated with improved liver and renal functions compared to conventional triple therapy.

Adult↗
PubMed1998

Spike-induced interference in auditory sensory processing in Landau-Kleffner syndrome.

OBJECTIVES: Landau-Kleffner Syndrome (LKS) is an epileptic syndrome characterised by a deficit in language comprehension and production, paroxysmal epileptiform activity in the posterior temporal leads, and by the inconsistent presence of epileptic fits. Its interest lies in the fact that it stands as a model for the study of interference of epileptiform activity on cognitive function, although the pathophysiology of the decline in language skills that follows its onset has not yet been clarified. METHODS: We have recorded spike-triggered auditory evoked responses in a group of 6 children with LKS, to investigate whether the occurrence of individual EEG paroxysms is able per se to induce a decline in the response of the auditory cortex. RESULTS: Results have indicated that left hemisphere spikes are associated with a greater reduction in amplitude and an increase in latency of the NI, than spikes occurring in the right hemisphere. No stable change in the evoked response has been detected outside of the EEG paroxysm. CONCLUSIONS: We postulate EEG interictal activity is able to induce impairment in processing auditory information and that this may play a role in the pathogenesis of language deficit in LKS.

Auditory Cortex↗
PubMed1998

Frontal lobe epilepsy associated with tuberous sclerosis: electroencephalographic-magnetic resonance image fusioning.

We studied the topographic relationships between cortical and subcortical lesions shown on magnetic resonance images (MRI) and sources of epileptiform activity in a series of nine children with intractable epilepsy and tuberous sclerosis complex. Although video-electroencephalographic (EEG) monitoring was suggestive of a frontal seizure onset, interictal EEG was, in seven of nine cases, in the form of apparently bisynchronous discharges. In all cases, the use of a short time lag estimation procedure based on a nonlinear correlation function between surface recorded EEG signals allowed the detection of a lateralized onset of EEG paroxysmal activity. Furthermore, a computerized method based on a source localization EEG-MRI image fusioning procedure, has revealed a topographic concordance between well-defined frontal cortical lesions shown on MRI and site of onset of paroxysmal discharges. Lennox-like EEG patterns frequently reported in children with tuberous sclerosis complex could be the result of the tendency of frontal tubers to induce secondary bilateral synchrony, with implications in the medical and eventually surgical management of the often drug-resistant associated seizures.

Child↗
PubMed1998

[Diverticulosis of the gallbladder. A case report and review of the literature].

We report a case of diffuse diverticulosis of the gallbladder in a 32 year old patient, who presents epigastric pains and decayed general conditions. With the suspicion of a primitive tumor of the gallbladder, we make a cholecystectomy and the intraoperative histological examination shows a "diffuse diverticulosis of the gallbladder wall"; it displays micro-stones inside diverticulums, too. The patient, after the surgical treatment, has no problem and he gets back to his normal weight. The literature shows the rarity of this disease; its etiopathogenesis is connected with congenital factors. In our opinion, the many terms used (cholecystitis glandularis proliferans, hypertrophic, adenomyomatosis) to define those conditions are not appropriate for our case but rather for the gallbladder's chronic inflammation characterized by the Rokitansky-Ashoff sinuses.

Adult↗
PubMed1998

Advantages of Neoral conversion in renal transplant patients.

BACKGROUND: Sandimmun Neoral is a microemulsion formulation of Sandimmun cyclosporin (Cya) with predictable pharmacokinetics, superior absorption and less dependent upon bile production. Recently Neoral replaced the old Cya in the clinical ground. METHODS: The aim of this study was to assess the effectiveness, safety and advantages of this conversion in 90 adult renal transplant patients with stable renal function transplanted at least 24 months earlier. There were 48 males and 42 females with a mean age of 39 years (range: 18-56). Mean interval from transplant to conversion was 3.6 years (range: 2.7-5.4). Conversion rate was 1:1. Mean Neoral dose at conversion was 3.8 mg/kg/day (range: 2.1-5.7). RESULTS: One month after conversion mean Neoral dose was 3.4 mg/kg/day (range: 2.2-3.9) and at six months was 3.2 mg/kg/day (range: 2.1-4). Serum creatinine and CyA trough levels remained stable. We did not observe rejection episodes or infections. The incidence of side effects due to CyA was slightly increased and there were not differences in terms of arterial pressure values and number of antihypertensive drugs given. CONCLUSIONS: The conclusion is drown that conversion to Neoral is safe and results in rapid attainment of therapeutic trough levels. Six months after conversion the mean Neoral dose was decreased of 0.6 mg/kg/die per patient.

Adolescent↗
PubMed1997

Arrest of replication fork progression at sites of topoisomerase II-mediated DNA cleavage in human leukemia CEM cells incubated with VM-26.

Recent studies have shown that the anticancer drugs VM-26 and mitoxantrone stabilize preferentially the binding of topoisomerase IIalpha to replicating compared to nonreplicating DNA. To further understand the mechanisms by which cleavable complex-forming topoisomerase II inhibitors interfere with DNA replication, we examined the effects of VM-26 on this process in human leukemia CEM cells. Both the inhibition of DNA synthesis and cell survival were directly related to the total amount of drug-stabilized cleavable complexes formed in VM-26-treated cells. DNA chain elongation was also inhibited in a concentration-dependent fashion in these cells, which suggested that VM-26-stabilized cleavable complexes interfered with the movement of DNA replication forks. To test this hypothesis directly, we monitored replication fork progression at a specific site of VM-26-induced DNA cleavage. A topoisomerase II-mediated cleavage site was detected in the first exon of the c-myc gene in VM-26-treated cells. This cleavage site was downstream of a putative replication origin located in the 5' flanking region of the gene. Replication forks, which moved through this region of the c-myc gene in the 5' to 3' direction, were specifically arrested at this site in VM-26-treated cells, but not in untreated or aphidicolin-treated cells. These studies provide the first direct evidence that a VM-26-stabilized topoisomerase II-DNA cleavable complex acts as a replication fork barrier at a specific genomic site in mammalian cells. Furthermore, the data support the hypothesis that the replication fork arrest induced by cleavable complex-forming topoisomerase II inhibitors leads to the generation of irreversible DNA damage and cytotoxicity in proliferating cells.

DNA Damage↗
PubMed1997

In vitro down-regulation of bcl-2 expression by all-trans retinoic acid in AML blasts.

Using flow cytometry, we have investigated the effects of 0.5 microM all-trans-retinoic acid (ATRA) on bcl-2 expression in the blast cells of 25 acute myeloblastic leukemia (AML) patients and the HL-60 cell line after incubation for 6 days. We observed a significant decrease of bcl-2 expression after treatment with ATRA in 12 of 25 AML samples and the HL-60 cells. The mean fluorescence intensity (MFI) ratio for the bcl-2 levels of the ATRA responders (n = 12) was reduced to 7.9 +/- 4.8 following incubation with ATRA compared with 10.9 +/- 6.5 (mean +/- SD) for control samples incubated without ATRA (p = 0.011). There was no significant difference between the baseline bcl-2 MFI ratio in the ATRA responders (11.14 +/- 7, n = 12) and the non responders (14.18 +/- 11.3, n = 13; p = 0.432). The down-regulation of bcl-2 expression by ATRA was not significantly associated with CD34-negative or -positive AML. There was no correlation between AML subtypes and regulation of bcl-2 expression by ATRA. Complete remission and overall survival were not significantly improved in bcl-2 down-regulated cases. Our data confirm that ATRA can down-regulate the bcl-2 expression in AML blasts. Because many chemotherapeutic agents also operate through the activation of programmed cell death and bcl-2 levels are positively associated with resistance to apoptosis, ATRA can be used in combination chemotherapy to increase the chemosensitivity of some patients with AML.

Antineoplastic Agents↗
PubMed1997

Stereoselective pharmacokinetic analysis of valnoctamide in healthy subjects and in patients with epilepsy.

OBJECTIVE: To investigate the pharmacokinetics of the four stereoisomers of valnoctamide, a mild tranquilizer endowed with anticonvulsant properties. METHODS: Racemic valnoctamide, 400 mg, was administered orally to seven healthy subjects and to six patients with epilepsy stabilized with long-term carbamazepine therapy. In the patients with epilepsy, valnoctamide kinetics was also reassessed after 8-day oral dosing at a dosage of 600 mg daily. Plasma samples were assayed by gas chromatography-mass spectrometry with use of a capillary column coated with chiral stationary phase that enabled baseline resolution of the four stereoisomers, designated hereafter as A, B, C, and D (where A and C, together with B and D, represent enantiomeric pairs). RESULTS: In healthy subjects, stereoisomers A, C, and D showed similar kinetics, with an apparent oral clearance (CL/F) of about 4 1/2 L/hr, a half-life (t1/2) of about 10 hours, and an apparent volume of distribution (VSS/F) of about 65 L. However, stereoisomer B showed a much higher clearance (8.7 +/- 0.9 L/hr) and a shorter t1/2 (5.8 hours). For all stereoisomers, CL/F values in patients with epilepsy were about tenfold higher than those found in healthy subjects. Compared with healthy subjects, patients with epilepsy also showed shorter t1/2 values and higher VSS/F values for each of the stereoisomers. After 7-day dosing, CL/F values at steady state were lower than those determined in the same patients after a single dose. CONCLUSIONS: Valnoctamide exhibits enantioselectivity and diastereoselectivity, an observation that may have important practical implications if pharmacodynamic differences between stereoisomers are also found. The observed pharmacokinetic differences between healthy subjects and patients with epilepsy are likely to be related to induction of metabolism of valnoctamide stereoisomers by carbamazepine.

Administration, Oral↗
PubMed1997

Elevation of plasma carbamazepine concentrations by ketoconazole in patients with epilepsy.

The effect of ketoconazole (200 mg/d orally for 10 days) on the plasma concentrations of carbamazepine (CBZ) and its active metabolite carbamazepine-10,11-epoxide (CBZ-E) was assessed in eight patients with epilepsy stabilized on CBZ therapy. Administration of ketoconazole was associated with a significant increase in plasma CBZ concentrations (from 5.6 +/- 1.9 to 7.2 +/- 2.9 micrograms/ml on day 10 [means +/- SD, P < 0.02]), whereas plasma concentrations of CBZ-E were unchanged. After ketoconazole was discontinued, plasma CBZ levels decreased to pretreatment values. This interaction was probably mediated by an inhibiting action of ketoconazole on cytochrome CYP3A4, the main enzyme responsible for CBZ metabolism.

Adult↗