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J M Ferrero

Publications and source records attributed to J M Ferrero.

33 records · Page 2Linked to original sources
PubMed1996

Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.

The role of the ATP-sensitive K+ current (IK-ATP) and its contribution to electrophysiological changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of IK-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of IK-ATP are simulated. Our results show that in normal ionic concentrations, only approximately 0.6% of the KATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg2+ counteract this shortening. Under conditions of high [K+]0, such as those found in early ischemia, the activation of only approximately 0.4% of the KATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of IK-ATP channels should play a significant role in action potential shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low ( < 1%). However, the results of the model suggest that activation of IK-ATP alone does not quantitatively account for the observed K+ efflux in metabolically impaired cardiac myocytes. Mechanisms other than KATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxic/ischemic situations.

Action Potentials↗
PubMed1995

[Is breast cancer prevention by tamoxifen possible?].

Breast cancer is a frequent disease especially in the Western world with an incidence that increases by 1% each year. Distressingly, even nowadays, 40% of patients with breast cancer will die of their disease. Postoperative adjuvant therapy and detection of non-palpable cancers by mass screening of women have improved patient survival but have not impinged upon the steady increase in incidence. Treatment before radiological detection could improve the chances of survival and even prevent the full-blown expression of the disease. The probability that a woman will develop breast cancer during her life-time is high but not evenly distributed. Knowledge of predisposing factors can help to identify those women subject to greater risk than the general population. The most important known risk factors are age, family history, factors related to ob-gyn antecedents, lifestyle, benign hyperplastic breast disease with or without atypia. These various risks, are often associated and cumulative. A woman who has already had breast cancer has a 3 to 5 times greater probability of developing cancer of the contralateral breast than the average woman. The second breast is therefore at risk in the same way as are the women with predisposing factors. Many clinical studies have demonstrated the benefits of postoperative adjuvant tamoxifen (TAM) in improving the disease-free interval and survival of patients. An analysis of the site of relapse has interestingly brought to light a marked decrease in the percentage of cancers of the contralateral breast. In order to establish whether TAM could prevent or delay the onset of high-risk women without detectable signs of illness into groups receiving either TAM or placebo. Is this ethically acceptable? The answer to this question rests heavily on an objective evaluation of the unwanted and beneficial side-effects of TAM in order to weigh up all pros and cons before initiating a trial.

Adult↗
PubMed1995

[Treatment of ifosfamide induced encephalopathy with methylene-blue].

The authors report a case of encephalopathy after treatment with ifosfamide treated by a methylene blue infusion. This side-effect is rare but influenced by high doses and short infusions of this drug. Recently, a treatment of ifosfamide encephalopathy with methylene blue has been reported. This case report confirms the interest of such a treatment.

Aged↗
PubMed1995

[Combination of mitoxantrone-vinorelbine as first-line chemotherapy for metastatic breast carcinoma].

A phase II trial was performed to assess the efficacy and toxicity of the combination mitoxantrone (MXN) and vinorelbine (VNR) as first-line chemotherapy for metastatic breast cancer. Forty-one patients with metastatic disease or local relapse recruited between March 1991 and April 1993 received a first-line chemotherapy treatment consisting in 12 mg/m2 intravenous (IV) bolus of MXN on day 1 followed by a 20-minute perfusion of 25 mg/m2 of VNR on days 1 and 8. Cycles were repeated every 21 days until evidence of disease progression or of severe toxicity. Thirty-seven patients were evaluable for response and all 41 for toxicity. An objective response was observed in 19 patients (51%; 95% confidence interval, 45 to 74%). The response was complete in a further 11 (30%). Median time to treatment failure was 9 months. Median survival was 14 months. There were no treatment-related deaths. Limiting toxicity was myelosuppression. Leukopenia occurred in 29 patients (71%) and was grade 3 or 4 in nine of these (15%). Grade 2 or 3 anemia was encountered in six patients (15%), grade 1 thrombocytopenia in one, neurotoxicity (constipation) in two, and grade 2 or 3 alopecia in 12 (29%). Nausea/vomiting requiring antiemetic treatment was experienced by only two patients (5%). There were two cases of septicemia treated by antibiotic therapy in hospital.

Adult↗
PubMed1994

[Epidemiology of cancer of the breast].

Breast cancer is a major public health problem. In 1980, breast cancer represented 18% of all cancers in women throughout the world. The worldwide incidence of breast cancer is increasing by 1.5% per annum and is influenced by geographical factors and by age. In France, this disease represents 19% of cancer deaths in women and is the commonest cause of cancer death in women. Several risk factors have been suspected, but many points remain obscure. The age of the menarche, the age of menopause, parity and the age of the first pregnancy influence the incidence of breast cancer. The use of oral contraceptives and hormone replacement therapy for menopause do not appear to affect the development of malignant breast disease, except, perhaps, in certain subgroups of patients, but this remains to be confirmed. The risk is increased by a fatty diet and by excessive alcohol consumption. It is now generally accepted that a family history of breast cancer is associated with an increased risk. In the future, a more precise understanding of genetic anomalies related to cancer will allow early diagnosis, particularly of familial forms. Many unresolved aspects of the risk factors of breast cancer could be elucidated by cohort studies.

Adult↗
PubMed1992

[Seraspenide (acetylSDKP): phase I-II trial study of inhibitor of hematopoiesis protects against toxicity of aracytine and ifosfamide monochemotherapies].

Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity.

Cytarabine↗
PubMed1990

[Cholecystocolic fistula: from symptoms to diagnosis].

We report 2 patients with a cholecystocolic fistula in whom diametrically opposite symptoms (isolated steator-rhea, jaundice and fever) were responsible for important clinical difficulties. These fistulae are far less common than cholecysto-duodenal fistulae. Endoscopic retrograde cholangiography was performed because of abnormal liver tests and led to diagnosis in both cases. Classical aerobilia was absent in both of our cases. Barium enema was disappointing (case n. 1), whereas technetium 99m scintiscan visualized the fistula (case n. 2). Two therapeutic approaches are possible in the case of cholecystocolic fistula. Surgery, usually combining cholecystectomy and extraction of common bile duct stones with the treatment of the fistula, may be performed systematically or in case of failure of sphincterotomy (case n. 1). On the other hand, endoscopical sphincteromy during endoscopic retrograde cholangiography, which, by reducing increased biliary pressure, may be sufficient to achieve spontaneous closure of the fistula in an elderly or high risk patient (case n. 2).

Aged↗
PubMedDate not supplied

Ectopic activity in ventricular cells induced by early afterdepolarizations developed in Purkinje cells.

The development of early afterdepolarizations (EADs) in Purkinje fibers and their propagation to ventricular muscle cells are studied by computer modeling. The Purkinje-ventricular system has been simulated by a two-dimensional model of a Purkinje fiber (PF) connected to a thin sheet of ventricular muscle tissue (VMT). EADs are induced in the PF by enhancing the fast second inward current, iCa,f, and blocking the delayed K+ current, iK, while the VMT is kept under physiological conditions. Different phenomena are observed depending on the EAD conditions applied. For 70% iK blockade and iCa,f enhancement greater than 60%, a single phase 3 EAD developed in the PF propagates to the VMT generating an ectopic beat. For 80% iK blockade and iCa,f enhancement in the range from 0% to 70%, multiple ectopic beats appear in the VMT. However, for iK blockades over 80%, action potentials in PF cells do not repolarize and the ectopic activity in the VMT disappears. In our simulations, the ionic mechanism underlying phase 3 EAD development is the reactivation of the fast sodium current in the PF. Our results demonstrate that there exists a critical range of EAD conditions that favor the development of EADs in the PF and their propagation to the VMT as ectopic activity. This phenomenon could underlie the genesis of some triggered arrhythmias.

Action Potentials↗
PubMedDate not supplied

Prognostic value of S-phase fraction in 920 breast cancer patients: focus on T1N0 status.

The aim of this study was to reexamine the prognostic role of tumor cell kinetics measured by S-phase fraction (SPF) and to establish its clinically relevant threshold values. SPF was determined by flow cytometry in a group of 920 consecutive breast cancer patients, all followed at our institute for 10 years (1988 to 1998). Mean age was 60.5 years (27-89 years). Median follow-up was 63 months (3-150 months). All patients had initial surgical treatment. SPF quartiles were: Q1=3.08%, median value = 5.98%, Q3=10.22%. A significant difference in overall specific survival was obtained between two populations divided by a cutoff at Q1 (p < 0.0001). A multifactorial analysis including SPF and known prognostic factors such as tumor size, node status, histological grade, ER and PR status was performed using the Cox model in a population of 719 patients: univariate analysis showed that each of these factors had significant influence on overall survival. Multivariate analysis selected three of them, ranked by decreasing order of hazard ratio (HR) value: SPF (HR: 3.88, p < 0.001), tumor size (HR: 2.49, p < 0.001) and nodal status (HR: 2.28, p < 0.001). In addition, when tumors were stratified according to SPF quartile values, there were statistically different overall survival curves in patients with small tumors (< 2 cm) and in axillary node-negative patients.

Biomarkers, Tumor↗
PubMedDate not supplied

Cisplatin nephrotoxicity: a multivariate analysis of potential predisposing factors.

STUDY OBJECTIVE: To evaluate the usefulness of biologic and pharmacologic parameters for early identification of cisplatin-induced renal dysfunction. DESIGN: Prospective evaluation of 62 consecutively admitted patients with cancer. SETTING: Cancer center. PATIENTS: Sixty-two consecutive patients with cancer (52 men, 10 women; mean age 61.9 yrs). INTERVENTIONS: Patients received cisplatin as a single short intravenous infusion every 3 weeks. One hundred twenty-one cycles were analyzed. The dosage in the first cycle ranged between 61 and 105 mg/m2 (mean 84 mg/m2). All patients received a standard hydration protocol. MEASUREMENTS AND MAIN RESULTS: Renal function was evaluated for each cycle before treatment (day 0) and before next cycle (day 21) based on the estimated creatinine clearance (Clcr). For each cycle, the weighted relative decrease (WD) of Clcr was calculated (WDClcr = 100 x [Clcr (day 0) - Clcr (day 21)]/[Clcr (day 0)](2). Total and ultrafilterable (UF) platinum were measured as a single-sample assay taken 16 hours after the end of cisplatin administration. The mean WDClcr was 0.07 min/100 ml (range -1.0 to +1.7 min/100 ml). The intensity of renal dysfunction evaluated by WDClcr was independent of cisplatin dosage, age, sex, body surface area, initial Clcr, and cycle number. Of interest, total and UF platinum concentrations were significantly correlated to WDClcr: the higher the platinum concentration, the greater the intensity of renal dysfunction. In stepwise regression analysis, UF platinum concentration was the only selected factor. The best prediction of UF platinum was obtained by stepwise regression including cisplatin dosage, initial Clcr, and cycle number (r=0.58, p<0.0001). CONCLUSION: We consider our results to be a first step toward a clinical strategy to identify patients at risk for renal dysfunction after cisplatin treatment.

Adult↗