Search PubMed⌕ Search

Biomedical subjects

F Conti

Publications and source records attributed to F Conti.

At least 55 records · Page 3Linked to original sources
PubMed2000

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation: a report of three cases.

BACKGROUND/AIMS: Post-transplant lymphoproliferative disorders (PT-LPD) are a well-known complication of organ transplantation. Their incidence after liver transplantation in adults ranges from 1.8 to 4%. Reduction of immunosuppression led to remission in a few cases. Other treatments include chemotherapy, interferon alpha therapy and/or intravenous-immunoglobulins, or antiviral drugs. However, monoclonal antibodies directed against B-cell specific antigens have rarely been used in those patients. Our aim was to study the feasibility and efficacy of Rituximab, a new, promising human chimeric antibody that recognizes the CD20 antigen, for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation. METHODS: Rituximab (IDEC-C2HB8; Roche Laboratories, Neuilly-sur-Seine, France) was administered at a 375 mg/m2 dose on days 1, 8, 15, and 22, in an outpatient setting, in three patients with PT-LPD. The tumor was classified as polymorphic PT-LPD in two cases and PT-LPD with features of large cell lymphoma in one case. All the tumors expressed the CD20 antigen and were EBV-related, and the clonality was confirmed in all three cases. The 4 injections of the anti-CD20 monoclonal antibody were associated with reduced immunosuppression in the three patient. RESULTS: The treatment with Rituximab was well tolerated without any side effects. The two patients with polymorphic PT-LPDs underwent rapid complete remission, whereas the treatment modalities were ineffective in the patient with the large-cell non-Hodgkin-lymphoma. CONCLUSION: These results must be confirmed in a larger cohort of liver transplant recipients suffering from lymphoproliferation. However, they indicate rapid efficiency of Rituximab in association with reduced immunosuppression in these disorders.

Adult↗
PubMed2000

Etorphine increases the number of mu-opioid receptor-positive cells in the cerebral cortex.

Imunocytochemical techniques were used to determine whether agonist-induced activation of mu-opioid receptors alters the number and distribution of mu-opioid receptor-positive cells in the rat cerebral cortex. In untreated rats, mu-opioid receptor immunoreactivity was localized to neuronal perikarya and dendrites and to neuropilar punctate structures. mu-Opioid receptor-positive neurons were mostly in layers II and III and exhibited a bipolar or bitufted morphology. In rats treated with the mu-opioid receptor agonist etorphine (0.1mg/kg intraperitoneally) and perfused after different survival periods, there was an enhancement of immunostaining for mu-opioid receptors observed at 15min, reaching a maximum at 60min, and which returned to normal at 480min. Etorphine-induced effects included an increase in the intensity of cellular and neuropil staining; statistical analysis showed that the number of mu-opioid receptor-positive cells in etorphine-treated groups was significantly higher than in controls or saline-treated rats. In animals that received both etorphine and the mu-opioid receptor antagonist naloxone, the pattern of mu-opioid receptors immunoreactivity was similar to that of untreated animals. This study shows that the number of mu-opioid receptor-positive cells is significantly increased following etorphine treatment and suggests that agonist treatment may be exploited to increased immunostaining of mu-opioid receptors and also of other G-protein coupled receptors.

Animals↗
PubMed2000

Effect of long-term feeding with acetyl-L-carnitine on the age-related changes in rat brain lipid composition: a study by 31P NMR spectroscopy.

Changes in brain lipid composition have been determined in 24 months-old Fischer rats with respect to 6 months-old ones. The cerebral levels of sphingomyelin and cholesterol were found to be significantly increased in aged rats, whereas the amount of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and phosphatidic acid appear to be unaffected by aging. Long-term feeding with acetyl-L-carnitine was able to reduce the age-dependent increase of both sphingomyelin and cholesterol cerebral levels with no effect on the other measured phospholipids. These findings shown that changes in membrane lipid metabolism and/or composition represent one of the alterations occurring in rat brain with aging, and that long-term feeding with acetyl-L-carnitine can be useful in normalizing these age-dependent disturbances.

Acetylcarnitine↗
PubMed2000

MR spectroscopy: a powerful tool for investigating brain function and neurological diseases.

Magnetic resonance spectroscopy (MRS) has attracted much attention in recent years and has become an important tool to study in vivo particular biochemical aspects of brain disorders. Since the proton is the most sensitive stable nucleus for MRS, and since almost all metabolites contain hydrogen atoms, investigation by in vivo 1H MRS provides chemical information on tissue metabolites, thus enabling a non-invasive assessment of changes in brain metabolism underlying several brain diseases. In this review a brief description of the basic principles of MRS is given. Moreover, we provide some explanations on the techniques and technical problems related to the use of 1H MRS in vivo including water suppression, localization, editing, quantitation and interpretation of 1H spectra. Finally, we discuss the more recent advancement in three major areas of neurological diseases: brain tumors, multiple sclerosis, and inborn errors of metabolism.

Brain↗
PubMed2000

Suppression of humoral immunization against encapsulated xenogeneic hepatocytes and prolongation of their function by 2-week cyclosporine treatment in the rat.

BACKGROUND: Xenogeneic liver transplantation may induce immune reactions not only against the grafted liver but also against the proteins that it synthesizes. We investigated whether 2-week cyclosporine treatment could suppress immunization and improve graft function in a xenogeneic hepatocyte transplantation model. METHODS: Free or encapsulated human hepatoma cells (HepG2) were cocultured for 28 days with splenocytes from Lewis rats or implanted for 60 days into the peritoneum of Lewis rats. RESULTS: Anti-HepG2 and antialbumin antibodies were detected in the supernatants of rat splenocytes that were cocultured with HepG2 cells and in the serum of rats that had undergone transplantation with HepG2 cells. Cyclosporine suppressed this antibody production both in vitro and in vivo. Human alpha-GST blood levels, which reflect hepatocyte injury, were low in cyclosporine-treated animals but high when encapsulated HepG2 cells were transplanted without cyclosporine therapy. Western blots revealed human albumin from day 3 to day 60 in the serum of rats treated with cyclosporine, but not after day 30 in untreated rats. CONCLUSIONS: Xenogeneic hepatocytes induce a humoral response that impairs their viability and function. A 2-week course of cyclosporine suppresses this immune response and improves graft function for up to 60 days.

Animals↗
PubMed2000

First-line chemotherapy with vinorelbine and paclitaxel as simultaneous infusion in advanced breast cancer.

Based on preclinical data showing a synergistic activity of simultaneous administration of vinorelbine and paclitaxel, we carried out a phase II trial in previously untreated advanced breast cancer patients. Treatment consisted of vinorelbine 25 mg/m(2) and paclitaxel 150 mg/m(2), both drugs given by intravenous infusion over 3 h on day 1, with cycles repeated every 3 weeks. Granulocyte colony-stimulating factor, 300 microg subcutaneously, was given on days 7-12 to the first 10 patients. From October 1995 to January 1997, 43 patients with advanced breast cancer entered the study, and 41 were evaluable for response. We obtained 2 complete responses (5%) and 18 partial responses (44%), for an overall response rate of 49% (95% CI 34-64%). Median time to response, time to progression and survival were 2, 7 and 22 months, respectively. Myelosuppression was the dose-limiting toxicity, with G4 neutropenia in 21% and neutropenic fever in 7% of the patients. Other toxicities were mild. Simultaneous infusion of vinorelbine and paclitaxel is a well-tolerated and active regimen in metastatic breast cancer, with overall results similar to those reported with more toxic regimens; furthermore, it may be a good option in patients with anthracycline contraindications.

Adult↗
PubMed2000

Safety profile and causes of withdrawal due to adverse events in systemic lupus erythematosus patients treated long-term with cyclosporine A.

Several case reports and uncontrolled trials have established the use of cyclosporine A (CsA) in systemic lupus erythematosus (SLE) but some concerns have been raised because of its kidney damaging effects. We here report the results of a retrospective follow-up study designed to assess the safety profile and causes of discontinuation due to adverse events in SLE patients treated with CsA. We treated 56 SLE patients with oral CsA at doses of 3-5 mg/kg for an average of 26 months. Adverse events not leading to the discontinuation of therapy were observed in 62.5% of the patients, the most frequent being hypertrichosis. CsA was stopped because of the occurrence of side effects in 9/56 (16%) of the patients. The most common were nephrotoxicity (3/9) and the occurrence of tremors (3/9). These effects were always reversible within three months of CsA withdrawal. The patients who were older than 40 y had a significant slightly increased risk of stopping CsA therapy for any adverse events (RR 1.08; CI 95% 1.03-1.14). In comparison with previous studies, this study involved a larger cohort of SLE patients who were evaluated for a longer period of follow-up, and confirmed the good tolerability of CsA in these subjects.

Adolescent↗
PubMed2000

Cellular volume determination of alginate-entrapped hepatocytes by MRI diffusion measurements.

Cellular volume of hepatocytes entrapped in alginate gel beads were evaluated under in vivo conditions in samples having different cell densities by applying mathematical models to the diffusion data obtained by magnetic resonance imaging (MRI). The calculated average volume is in good agreement with the values from the literature-- being closer to the data relative to living tissue than to isolated cells. The non invasive characteristics of magnetic resonance imaging make this method particularly well suited to obtain information from the intact system.

Alginates↗
PubMed2000

[Reconstructive surgery of the mitral and tricuspid valves with a Cosgrove-Edwards flexible ring].

BACKGROUND: Mitral and tricuspid valve asymmetric annular dilation represents the most important mechanism which produces insufficiency. Recent computerized in vitro and in vivo three-dimensional models have been developed in order to better understand the competing factors (annular dilation, displacement of papillary muscles, left and right ventricular geometry). The leading cause of mitral and tricuspid competence is a sphincteric action of both annuli, during systole and diastole, the loss of which produces asymmetric dilation and therefore the absence of cusp coaptation. The Cosgrove-Edwards dynamic ring corrects, alone or in combination with other procedures on the valves, this patho-anatomic feature in a physiological way by restoring the normal annular dimensions and the sphincteric movements during the cardiac cycle. METHODS: Between June 1998 and May 1999, 30 adult patients underwent mitral (n = 20, Group I) or tricuspid valve repair (n = 10, Group II). Regurgitation was due to a degenerative disease in 13 Group I patients and to ischemic (n = 3), congenital (n = 2) or dilated cardiomyopathy (n = 2) in the others. In Group II the leading cause of insufficiency was functional regurgitation in 7 patients and organic in 3. Associated procedures were carried out in 4 Group I patients and in all Group II patients. Regurgitation was evaluated by transesophageal echocardiography before, during and 3 months after operation. The maximal regurgitant area (MRA) and the grade of insufficiency were evaluated using the equation: MRA < 2 cm2 = grade 0, MRA > 2 < 4 cm2 = 1+, MRA > 4 < 7 cm2 = grade 2+, MRA > 7 < 10 cm2 = 3+, MRA > 10 cm2 = 4+. RESULTS: The operative mortality was 0%. One Group I patient died 3 months after operation due to bronchopneumonia. No patient was reoperated on for plasty failure in both groups during the follow-up. Mitral insufficiency was absent (grade 0) in 17 Group I patients and mild (grade 1+) in 3 at the end of operation. At 3-month postoperative transesophageal echocardiographic control mitral insufficiency was absent in 14 patients, mild (1+) in 4 and moderate (2+) in 2. MRA was 3 cm2 in the 2 patients operated on for dilated cardiomyopathy and < 3 cm2 in the others. Preoperative tricuspid insufficiency of grade 4+ in all Group II patients became absent in 9 of them either at the end of operation or at 3-month postoperative control. CONCLUSIONS: The Cosgrove-Edwards dynamic ring as isolated device or in combination with other plasty mitral or tricuspid procedures is a safe, simple, and reproducible method to restore the distorted motion of valvular annuli. It preserves the sphincteric mechanism of the valve and allows for the coaptation of cusps. Although in a small number of patients and for a short period of follow-up our experience corroborates what other more consistent series of patients operated on have shown.

Adult↗
PubMed1999

Costs and outcomes of liver transplantation in adults: a prospective, 1-year, follow-up study. GRETHECO study group.

BACKGROUND: Orthotopic liver transplantation (OLT) is widely used to treat patients with end-stage liver disease. However, data on the cost of the procedure are fragmentary. We evaluated the costs, as calculated from resource use, and outcomes of OLT in adults, from registration on the transplant waiting list to the end of the 1st-year of follow-up after the transplant. METHODS: Two parallel cohort studies were conducted from 1994 to 95. All patients ages 18 years and older, on the waiting list (n=33) according to national criteria or having undergone transplants (n=38) were followed for 1 year or until either the transplant (waiting list cohort) or death (waiting list and transplantation cohorts). RESULTS: Eighty percent of the patients undergoing transplants were alive after 1 year, and no patient died while on the waiting list. However, the estimated cost of the procedure was high: more than 55,000 pound silver for the 1st year after OLT, to be added to 5,500 pound silver for evaluation and further costs motivated by the planned transplant during an average 6.5 months on the waiting list. Age over 40 and a baseline Child-Pugh score of 10 and over were predictive of high costs. The proportion of costs associated with immunosuppressive therapy and rejection were very high. CONCLUSIONS: This medical and economic cohort study suggests that OLT is still expensive; the study identifies sources of extra cost that could be limited either by improved selection of patients or, in the future, by technological advances in immunosuppressive therapy that help avoid medical complications. It also suggests the situation is precarious, with outcomes and costs being very sensitive to variation in graft availability.

Adolescent↗
PubMed1999

Neuronal, glial, and epithelial localization of gamma-aminobutyric acid transporter 2, a high-affinity gamma-aminobutyric acid plasma membrane transporter, in the cerebral cortex and neighboring structures.

Neuronal and glial high-affinity Na+/Cl(-)-dependent plasma membrane gamma-aminobutyric acid (GABA) transporters (GATs) contribute to regulating neuronal function. We investigated in the cerebral cortex and neighboring regions of adult rats the distribution and cellular localization of the GABA transporter GAT-2 by immunocytochemistry with affinity-purified polyclonal antibodies that react monospecifically with a protein of 82 kDa. Conventional and confocal laser-scanning light microscopic studies revealed intense GAT-2 immunoreactivity (ir) in the leptomeninges, choroid plexus, and ependyma. Weak GAT-2 immunoreactivity also was observed in the cortical parenchyma, where it was localized to puncta of different sizes scattered throughout the radial extension of the neocortex and to few cell bodies. In sections double-labeled with GAT-2 and glial fibrillary acidic protein (GFAP) antibodies, some GAT-2-positive profiles also were GFAP positive. Ultrastructural studies showed GAT-2 immunoreactivity mostly in patches of varying sizes scattered in the cytoplasm of neuronal and nonneuronal elements: GAT-2-positive neuronal elements included perikarya, dendrites, and axon terminals forming both symmetric and asymmetric synapses; nonneuronal elements expressing GAT-2 were cells forming the pia and arachnoid mater; astrocytic processes, including glia limitans and perivascular end feet; ependymal cells; and epithelial cells of the choroid plexuses. The widespread cellular expression of GAT-2 suggests that it may have several functional roles in the overall regulation of GABA levels in the brain.

Animals↗
PubMed1999

Ongoing prothrombotic state in patients with antiphospholipid antibodies: a role for increased lipid peroxidation.

We measured the urinary excretion of Isoprostane F2alpha-III and Isoprostane-F2alpha-VI, two markers of in vivo lipid peroxidation, and the circulating levels of the prothrombin fragment F1+2, a marker of thrombin generation, in 18 antiphospholipid antibodies-positive patients, in 18 antiphospholipid antibodies-negative patients with systemic lupus erythematosus, and in 20 healthy subjects. Furthermore, 12 patients positive for antiphospholipid antibodies were treated with (n = 7) or without (n = 5) antioxidant vitamins (vitamin E at 900 IU/d and vitamin C at 2, 000 mg/d) for 4 weeks. Compared with antiphospholipid antibodies-negative patients, antiphospholipid antibodies-positive patients had higher urinary values of Isoprostane-F2alpha-III (P =. 0001), Isoprostane-F2alpha-VI (P =.006), and plasma levels of the prothrombin fragment F1+2 (P =.0001). In antiphospholipid-positive patients, F1+2 significantly correlated with Isoprostane-F2alpha-III (Rho =.56, P =.017) and Isoprostane-F2alpha-VI (Rho =.61, P =.008). After 4 weeks of supplementation with antioxidant vitamins, we found a significant decrease in F1+2 levels (P <.005) concomitantly with a significant reduction of both Isoprostane-F2alpha-III (P =.007) and Isoprostane-F2alpha-VI (P <.005). No change of these variables was observed in patients not receiving antioxidant treatment. This study suggests that lipid peroxidation might contribute to the activation of clotting system in patients positive for antiphospholipid antibodies.

Adolescent↗
PubMed1999

Bile acids modulate the interferon signalling pathway.

We have previously shown that cholestasis and bile acids inhibit 2', 5' oligoadenylate synthetase (OAS) activity in the liver and in primary hepatocyte cultures. Here, we assessed the influence of bile acids on interferon (IFN) pathway activation in three hepatoma cell lines. In HepG2 cells, bile acids (100-200 micromol/L) inhibited IFN-induced 2',5' OAS activity to an extent depending on their surface activity index. In Western blot analysis, IFN-induced expression of two major antiviral proteins, MxA and OAS p100, was reduced by 54% +/- 8% and 44% +/- 12%, respectively, when cells were preincubated for 4 hours with 100 micromol/L chenodeoxycholic acid (CDCA). In the same conditions, CDCA did not modify the IFN-induced signal transducers and activators of transcription (STAT)s tyrosine phosphorylation. In contrast, it reduced IFN-induced MxA promoter activity by 60%. The inhibitory effect of CDCA was not mediated by a 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA)-sensitive protein kinase C (PKC)-dependent pathway. Finally, using CHO cells stably expressing a functional human bile acid carrier (Na+-dependent taurocholate cotransporting polypeptide [NTCP]), we found that bile acid inhibition of the IFN pathway occurred in the range of more physiological concentrations (12-50 micromol/L). In summary, our results provide strong evidence that bile acids inhibit the induction of proteins involved in the antiviral activity of IFN. This might partly explain the lack of responsiveness to IFN therapy in some patients with advanced chronic viral liver diseases.

2',5'-Oligoadenylate Synthetase↗
PubMed1999

Tonic and phasic tetrodotoxin block of sodium channels with point mutations in the outer pore region.

Tonic and use-dependent block by tetrodotoxin (TTX) has been studied in cRNA-injected Xenopus oocytes expressing mutants W386Y, E945Q, D1426K, and D1717Q, of the outer-pore region of the rat brain IIA alpha-subunit of sodium channels. The various phenotypes are tonically half-blocked at TTX concentrations, IC50(t), that span a range of more than three orders of magnitude, from 4 nM in mutant D1426K to 11 microM in mutant D1717Q. When stimulated with repetitive depolarizing pulses at saturating frequencies, all channels showed a monoexponential increase in their TTX-binding affinity with time constants that span an equally wide range of values ([TTX] approximately IC50(t), from approximately 60 s for D1426K to approximately 30 ms for D1717Q) and are in most phenotypes roughly inversely proportional to IC50(t). In contrast, all phenotypes show the same approximately threefold increase in their TTX affinity under stimulation. The invariance of the free-energy difference between tonic and phasic configurations of the toxin-receptor complex, together with the extreme variability of phasic block kinetics, is fully consistent with the trapped-ion mechanism of use dependence suggested by and developed by. Using this model, we estimated for each phenotype both the second-order association rate constant, kon, and the first-order dissociation rate constant, koff, for TTX binding. Except for mutant E945Q, all phenotypes have roughly the same value of kon approximately 2 microM-1 s-1 and owe their large differences in IC50(t) to different koff values. However, a 60-fold reduction in kon is the main determinant of the low TTX sensitivity of mutant E945Q. This suggests that the carboxyl group of E945 occupies a much more external position in the pore vestibule than that of the homologous residue D1717.

Animals↗