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Biomedical subjects

F Conti

Publications and source records attributed to F Conti.

At least 325 records · Page 18Linked to original sources

The steady state properties of ion exchange membranes with fixed sites.

The properties of the steady states of a system composed of two solutions separated by a quite general type of ion exchange membrane having fixed sites are derived as functions of the compositions of the solutions and of the difference of electric potential between the two solutions. These properties are evaluated with the restraints that the membrane is solely permeable to cations or anions, no flow of solvent occurs, and the solutions contain no more than two permeant ionic species, which are monovalent. Under the assumptions that the difference of standard chemical potentials of the permeant species and the ratio of their mobilities are constant throughout the membrane, even when the spacing of sites is variable, explicit expressions are derived for the electric current, individual fluxes, and concentration profiles. An unexpectedly simple dependence of these expressions upon distribution of sites is found.

Chemical Phenomena↗

Neuronal and glial localization of NMDA receptors in the cerebral cortex.

The crucial role of glutamate receptors of the N-methyl-D-aspartate (NMDA) type in many fundamental cortical functions has been firmly established, as has its involvement in several neuropsychiatric diseases, but until recently, very little was known of the anatomical localization of NMDA receptors in the cerebral cortex of mammals. The recent application of molecular biological techniques to the study of NMDA receptors has allowed the production of specific tools, the use of which has much increased our understanding of the localization of NMDA receptors in the cerebral cortex. In particular, immunocytochemical studies on the distribution of cortical NMDA receptors have: 1. Demonstrated the preferential localization of NMDA receptors in dendritic spines, in line with previous work; 2. Disclosed a thus far unknown fraction of presynaptic NMDA receptors on both excitatory and inhibitory axon terminals: and 3. Shown that cortical astrocytes express NMDA receptors. These studies indicate that the effects of cortical NMDA receptor activation are not caused exclusively by the opening of NMDA channels on neuronal postsynaptic membranes, as previously assumed, and that the activation of presynaptic and glial NMDA receptors can contribute significantly to these effects.

Adult↗

Clinical relevance of radionuclide angiography and antimyosin immunoscintigraphy for risk assessment in epirubicin cardiotoxicity.

BACKGROUND: Cardiotoxicity is the major limiting factor in anthracycline chemotherapy of advanced neoplastic disease. Epirubicin shows a more favorable therapeutic index than does doxorubicin, but it is still cardiotoxic. Limited data regarding epirubicin cardiotoxicity are available, and suggested guidelines for doxorubicin with left ventricular ejection fraction (LVEF) measurement may not be empirically useful for epirubicin therapy. This study evaluates the diagnostic role of antimyosin immunoscintigraphy for early identification of patients at risk for late pump dysfunction from cardiotoxicity induced by high-dose administration of epirubicin up to high cumulative dosages. METHODS AND RESULTS: Chemotherapy with epirubicin was administered to 36 patients with cancer at a dosing rate of 160 mg/m2 as a bolus injection every 21 days to a cumulative dosage of 960 mg/m2. Radionuclide angiography (LVEF) and antimyosin immunoscintigraphy with heart-lung ratio (HLR) measurements were performed before chemotherapy, at intermediate cumulative epirubicin dosages, at the end of treatment, and during the follow-up. LVEF decreased significantly at the end of the treatment and after therapy discontinuation. HLR values were significantly increased at intermediate epirubicin dosage levels and continued to increase to the end of the treatment but thereafter remained substantially unmodified for 3 to 6 months after therapy discontinuation. A value of HLR >1.85 at intermediate epirubicin dosage level showed a sensitivity of 95% and a specificity of 57% as a predictor of late LVEF impairment. CONCLUSIONS: LVEF appears more useful at high cumulative dosages and during follow-up to monitor late pump dysfunction, whereas HLR may be effective during the early phase of the therapy in determining which patients are at risk for development of late cardiac dysfunction.

Adolescent↗

Calcitonin gene-related peptide (CGRP) in the cat neocortex: evidence for a sparse but widespread network of immunoreactive fibers.

The morphology, and laminar and topographic distribution of fibers containing calcitonin gene-related peptide (CGRP) immunoreactivity were studied by light and electron microscopic methods in the cerebral cortex of adult cats using a rabbit antiserum raised against the C-terminal region of the rat alpha-CGRP. At the light microscopic level, a sparse number of CGRP-positive fibers were observed in the frontal, parietal, and occipital cortices. They showed numerous irregularly spaced varicosities, were mostly oriented vertically, and in rare cases gave rise to boutons terminaux as they ascended toward the pial surface. At the border between layers I and II, they branched into horizontal fibers that could be followed for several hundred microns in layer I and gave rise to terminal clusters of boutons. In some sections, CGRP-positive fibers were seen in close association with blood vessels. At the electron microscopic level, CGRP immunoreactivity was found in axon terminals containing few mitochondria and clear synaptic vesicles. CGRP-positive axon terminals were very sparse, and mainly of small size. The majority formed conventional synapses, all of the asymmetric type. CGRP-positive fibers showed an uneven topographic distribution through the cortical mantle, with the frontal areas exhibiting the highest density and the occipital cortex the lowest. These results show that CGRP-containing axons are more widely distributed than previously thought since they were observed in all the cortical areas examined, and cast some doubts on the hypothesis that the functional role of this peptide is restricted to the processing of visceral sensory information.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vinorelbine and mitomycin C in anthracycline-pretreated patients with advanced breast cancer.

At present, there is no satisfactory treatment for advanced breast cancer patients who have become refractory to anthracyclines. Vinca alkaloids and mitomycin C (MMC) are among the drugs most frequently used in this setting. Recently, vinorelbine (VNR) has been reported to be highly active in advanced breast cancer. Sixty advanced breast cancer patients previously treated with anthracyclines have been exposed to VNR 25 mg/m2 i.v. on days 1 and 8, and MMC 10 mg/m2 i.v. on day 1, with cycles repeated every 4 weeks. There were 3 complete and 21 partial responses for an overall response rate of 40% (CI 95%: 28-52%). Median duration of response and median survival were 7 and 10 months, respectively. Myelosuppression was the dose-limiting toxicity, but it was generally mild to moderate. Although this combination appears to be effective and well tolerated, every effort should be made to further improve treatment results in anthracycline-pretreated advanced breast cancer.

Adult↗

Paclitaxel activity in anthracycline refractory breast cancer patients.

AIMS AND BACKGROUND: We investigated the efficacy and tolerability of two doses of paclitaxel, 175 mg/m2 and 135 mg/m2, over a 3-hr infusion, without prophylactic G-CSF, in heavily pretreated patients with anthracycline-resistant breast cancer. Although paclitaxel may share with anthracyclines a common mechanism of drug resistance, there is evidence that the two drugs are not completely cross resistant. METHODS: From July 1994 to January 1996, 42 patients were treated every 3 weeks, for a maximum of 6 cycles; paclitaxel dose was established according to pretreatment extension. RESULTS: In 41 assessable patients we observed 9 partial responses, for an overall response rate of 22% (95% CI, 10-34%). There was no difference in response rate between the two dose levels. Median duration of response was 9 months, median time to progression 5 months, and median survival 9 months. The dose-limiting toxicity was neutropenia, which was grade 3-4 in 40% (135 mg/m2) and 62% (175 mg/m2) of the patients (P = 0.28); neutropenic fever occurred in 24% of the patients, without significant differences between the two dose levels. Other toxicity was mild to moderate. CONCLUSIONS: Paclitaxel at doses of 175 mg/m2 or 135 mg/m2 is active and well tolerated in advanced breast cancer patients resistant to anthracyclines. The prophylactic use of colony-stimulating factors seems appropriate in heavily pretreated patients given the higher dose level.

Adult↗

Intracerebral diffusion of paramagnetic cationic liposomes containing Gd(DTPA)2- followed by MRI spectroscopy: assessment of pattern diffusion and time steadiness of a non-viral vector model.

Cationic liposomes are generally considered as the non-viral counterparts of the more common viral vectors used in several gene therapy protocols, but their use as delivery vehicles is limited by their efficiency even if they display a lower toxicity. However, cationic liposomes are promising delivery systems in cell biology due to their ability to incorporate small molecules into their inner aqueous spheres and to deliver them into cells. Additionally, on the external surface they can bind therapeutic molecules such as nucleic acids, oligonucleotides, plasmids, etc. through electrostatic interactions. The aim of this work was to study the diffusion properties of such vehicles in vivo with a non-invasive technique and to monitor their tissue migration in order to collect information to be further used in gene therapy procedures. For this purpose, cationic liposomes containing the paramagnetic contrast agent Gd(DTPA)2- (Gd(III)-diethylenetriamine-N,N,N',N",N"-pentaacetic acid) were investigated because of their extended paramagnetic persistency in vivo, compared to the use of the contrast agent alone, and they were used to monitor the diffusion of such vehicles in an animal model (rat model). In particular, these vectors were injected into the rat brain through a stereotactic frame in a preformed cavity mimicking the lesion which had originated after surgical removal of the primary tumor. For the purpose of comparison, the same injection procedure was also applied to a control series of animals without a preformed brain lesion. Pattern diffusion and steadiness of the reported paramagnetic cationic liposomes were studied by means of Magnetic Resonance Imaging (MRI) which allowed us to monitor their diffusion and assess their intracerebral time availability up to 24 hours.

Animals↗

[Gemcitabine in advanced stage soft tissue sarcoma: a phase II study].

PURPOSE: To assess the activity and toxicity of gemcitabine in locally advanced or metastatic soft tissue sarcoma patients (pts). PATIENTS AND METHODS: Gemcitabine was administered on days 1, 8, 15 every 4 weeks at a dose of 1.000/1.250 mg/m2, respectively, in pretreated or not pretreated pts. RESULTS: Eighteen pts entered this phase II trial; sixteen had been previously treated with anthracyclines and ifosfamide. A partial response was observed in a woman with fibrous malignant istocytoma, whereas in 7 pts the disease remained stable. Median time to progression was 4 months. The treatment was well tolerated. Grade 4 toxicity was not observed. CONCLUSIONS: These results do not suggest that gemcitabine, in the dose and schedule used in this trial, may be of value in the treatment of soft tissue sarcomas.

Antimetabolites, Antineoplastic↗