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Biomedical subjects

F Fiore

Publications and source records attributed to F Fiore.

54 records · Page 3Linked to original sources
PubMed1993

Hemangiomas of the maxillofacial area. Usefulness of 99Tcm-labelled red cell scintigraphy.

Recent work reports the usefulness of radionuclides in the study of hepatic hemangiomas. In particular, 99Tcm-red blood cell (RBC) scintigraphy is useful to evaluate the vascularization and to plan the therapy. The aim of this paper is to confirm the usefulness of 99Tcm-RBC scans in the detection and follow-up of maxillofacial hemangiomas. Results using this technique in a selected group of patients with maxillofacial hemangiomas are reported.

Adolescent↗
PubMed1993

[Apropos of preventive ophthalmologic interventions in the child population of compulsory school age. Authors' experience].

The results are reported of work carried out during the last five years by the Center of Social Ophthalmology, director Prof. G. Scuderi, which is part of the II Division of the Ophthalmologic Clinic of Rome University "La Sapienza" with the object of trying out together with territorial units a model of preventive intervention acting as a filter for specialized university facilities. In other words, already existing facilities and medical personnel were to be used and trained for specific methods and techniques. From 1985 through 1990, 787 children selected by ophthalmologic screening by school doctors among the compulsory school population of the RM 3 and 5 districts were seen and submitted to periodic checks. This cohort included children aged 5 to 14 without significant differences in sex distribution and with prevalence of the 8 to 10 year olds. Each subject was submitted to complete eye examination including refractometry and orthoptics, color vision, biomicroscopic and ophthalmoscopic examination. The principal findings show that about 36% of subjects examined have a natural vision of 11/10 while the high percentage of ametropia observed was mainly represented by astigmatism and hypermetropy, albeit of minor intensity. Strabismus was found in 2.79% and implied marked visual deficit that was often refractory to any type of treatment. In addition, the prevalence was determined of other abnormalities concerning eye motility, color vision and pathologies involving anterior segment and eyeground. In their conclusion, the authors stress the rarity of organic ocular pathology in children (mostly represented by inflammatory changes of the adnexes and conjunctiva) whereas amblyopia was one of the main causes of visual deficit in children. They stress the importance of early therapeutic intervention in order to allow complete visual rehabilitation. The results of the clinical model for prevention were excellent so that it can even be proposed for large scale prevention of amblyopia.

Adolescent↗
PubMed1989

Calitoxin, a neurotoxic peptide from the sea anemone Calliactis parasitica: amino acid sequence and electrophysiological properties.

We have isolated a new toxin, calitoxin (CLX), from the sea anemone Calliactis parasitica whose amino acid sequence differs greatly from that of other sea anemone toxins. The polypeptide chain contains 46 amino acid residues, with a molecular mass of 4886 Da and an isoelectric point at pH 5.4. The amino acid sequence determined by Edman degradation of the reduced, S-carboxymethylated polypeptide chain and tryptic and chymotryptic peptides is Ile-Glu-Cys-Lys-Cys-Glu-Gly-Asp-Ala-Pro-Asp-Leu-Ser-His-Met-Thr-Gly-Thr- Val-Tyr - Phe-Ser-Cys-Lys-Gly-Gly-Asp-Gly-Ser-Trp-Ser-Lys-Cys-Asn-Thr-Tyr-Thr-Ala- Val-Ala - Asp-Cys-Cys-His-Glu-Ala. No cysteine residues were present in the peptide. Similarly to other sea anemone toxins, calitoxin interacts, in crustacean nerve muscle preparations, with axonal and not with muscle membranes, inducing a massive release of neurotransmitter that causes a strong muscle contraction. The low homology of CLX with RP II and ATX II toxins has implications regarding the role played by particular amino acid residues.

Amino Acid Sequence↗
PubMedDate not supplied

Preclinical pharmacokinetics and metabolism of a potent non-nucleoside inhibitor of the hepatitis C virus NS5B polymerase.

The disposition of compound A, a potent inhibitor of the hepatitis C virus (HCV) NS5B polymerase, was characterized in animals in support of its selection for further development. Compound A exhibited marked species differences in pharmacokinetics. Plasma clearance was 44 ml min-1 kg-1 in rats, 9 ml min-1 kg-1 in dogs and 16 ml min-1 kg-1 in rhesus monkeys. Oral bioavailability was low in rats (10%) but significantly higher in dogs (52%) and monkeys (26%). Compound A was eliminated primarily by metabolism in rats, with biliary excretion accounting for 30% of its clearance. Metabolism was mainly mediated by cyclohexyl hydroxylation, with N-deethylation and acyl glucuronide formation constituting minor metabolic pathways. Qualitatively, the same metabolites were identified using in vitro systems from all species studied, including humans. The low oral bioavailability of compound A in rats was mostly due to poor intestinal absorption. This conclusion was borne out by the findings that hepatic extraction in the rat was only 30%, intraperitoneal bioavailability was good, and compound A was poorly absorbed from the rat isolated intestinal loop, with no detectable intestinal metabolism. Compound A was not an inhibitor of major human cytochrome P450 enzymes, indicating minimal potential for clinical drug-drug interactions. The metabolic clearance of compound A in rat, dog and monkey hepatocytes correlated with the systemic clearance observed in these species. Since compound A was very stable in human hepatocytes, the results suggest that it will be a low clearance drug in humans.

Animals↗
PubMedDate not supplied

The role of granulocyte growth factors in the treatment of non small cell lung cancer.

In the past years granulocyte growth factors have been introduced in clinical practice. Their use is intended to reduce the risk of infection related to chemotherapy and to increase the dose-intensity of chemotherapy agents. Very few randomized trials have been reported in advanced non small cell lung cancer on chemotherapy plus or minus granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor. No benefit for granulocyte growth factors use was observed in terms of response rate and survival. Recently, several investigators used growth factors to support new promising drug combinations including vinorelbine, gemcitabine, taxol or taxotere. However, outside controlled clinical trials the role of granulocyte growth factors in the treatment of non small cell lung cancer should be within the American Society of Clinical Oncology guidelines.

Adult↗
PubMedDate not supplied

Single-agent gemcitabine as second-line treatment in patients with advanced non small cell lung cancer (NSCLC): a phase II trial.

BACKGROUND: Although the use of salvage chemotherapy in advanced non-small cell lung cancer (NSCLC) is controversial, pretreated symptomatic patients often need some kind of treatment to achieve symptoms relief. Gemcitabine is one of the most active new drugs in advanced NSCLC and preliminary reports suggest that it is active also in patients previously treated with platinum compounds. AIM: to evaluate activity and toxicity and the effect on quality of life of gemcitabine in platinum-pretreated patients with advanced NSCLC. METHODS: single-stage phase 2 trial with p0 = 5%, p1 = 20%, alfa = 5%, beta = 10%; 34 patients required and 4 objective responses expected to warrant further studies. Gemcitabine was administered at dose of 1000 mg/m2, i.v., d 18-15, every 4 weeks, for a maximum of 6 cycles. Quality of life was measured by EORTC C-30 and LC-13 questionnaires. RESULTS: from September 1996 to July 1998, 30 patients have been enrolled. There were 6 (20% exact 95% CI 8-39%) partial responses (2 responses were in pts with brain metastases and 2 in patients progressed during first-line chemotherapy). All patients (but one died because myocardial infarction, progressed; median time to progression was 10 weeks (95% CI 7-12); 28 patients died; median survival was 22 weeks (95% CI 17-29). Quality of life analysis showed no significant change but for the improvement of cough after 3 cycles of chemotherapy. There was no severe toxicity. CONCLUSION: gemcitabine is active as second line for patients with advanced NSCLC who received platinum-based first line treatment. In view of such results randomized trials comparing gemcitabine versus best supportive care are warranted.

Adult↗
PubMedDate not supplied

Single agent docetaxel plus granulocyte-colony stimulating factor (G-CSF) in previously treated patients with advanced non small cell lung cancer. A phase II study and review of the literature.

The use of salvage chemotherapy in advanced non small cell lung cancer (NSCLC) is controversial. However, many patients need to be treated in order to achieve relief of their symptoms. Docetaxel (taxotere) is one of the most active drugs for the treatment of advanced NSCLC and several studies have also shown its effectiveness in pretreated patients. In the present study, 23 patients were treated in order to evaluate both the effectiveness and toxicity of the single agent docetaxel. Furthermore, granulocyte-colony stimulating (G-CSF) factor was administered in order to reduce neutropenia related to docetaxel. Docetaxel was administered intravenously at a dose of 100 mg/m2, on day 1, and it was repeated every 3 weeks. G-CSF was administered for primary prophylaxis of neutropenia at the standard dose of 30 mg/day from day 4 to day 10 of each cycle. The treatment was tolerated well and 5 (21.7%) partial responses were obtained. The median time to progression and the median survival time were 3 and 5 months, respectively. The main side effect noted was fatigue, the intensity of which was grade 2 in 43.4% of cases and grade 3 in 8.7% of patients, respectively. One patient (4.3%) had grade 4 cutaneous toxicity. No cases of grade 4 neutropenia were reported. In conclusion, docetaxel is active when used for salvage chemotherapy in advanced NSCLC whilst concurrent primary prophylactic administration of granulocyte-colony stimulating factor seems to decrease severe neutropenia.

Adult↗
PubMedDate not supplied

Phase I clinical trial of liposomal daunorubicin in hepatocellular carcinoma complicating liver cirrhosis.

Chemotherapy has been proposed for patients with hepatocellular carcinoma (HCC) associated with well-compensated cirrhosis who are unsuitable for locoregional treatments. Anthracyclines are the most active agents against HCC, although their toxicity is often unpredictable; thus, there is a need for new active drugs with a safe toxicity profile. The liposomal formulation of the anthracycline daunorubicin has low systemic toxicity and is taken up strongly by the liver. We started a phase I study with liposomal daunorubicin (starting dose 80 mg/m2 every 21 days) in patients with hepatocellular carcinoma and Child-Pugh stage A or B liver cirrhosis. At the starting dose, we recorded dose-limiting toxicities (1 hyperbilirubinemia, 1 prolonged prothrombin time, 1 persisting grade 3 neutropenia) in 3 out of 4 patients. Thus, according to protocol, we went down to the dose level of 60 mg/m2 but still 2 out of 3 patients had unacceptable toxicity (1 hypertransaminasemia, 1 hyperbilirubinemia with encephalopathia). Finally, we treated 4 more patients at the dose level of 40 mg/m2 and again we recorded liver toxicity in three of them. Overall haematological toxicity was mild and significant non-haematologic toxicities, other than hepatic, were not recorded. The toxicity profile observed warns against further assessment of liposomal daunorubicin in patients with hepatocellular carcinoma and liver cirrhosis.

Aged↗
PubMedDate not supplied

Neoadjuvant chemotherapy for intermediate/high-grade soft tissue sarcomas: five-year results with epirubicin and ifosfamide.

BACKGROUND: Neoadjuvant chemotherapy for intermediate/high-grade soft tissue sarcomas (STS) may provide some advantages for facilitating the surgical resection of the tumor and for disease control. However its role as induction therapy before surgery should still be proved. PATIENTS AND METHODS: Twenty-one patients with intermediate/high-grade STS and tumor size > or = 5 cm were consecutively treated from 1997 to 2001 with neoadjuvant chemotherapy based on epirubicin 60 mg/m2/day on days 1 and 2 and ifosfamide 1.8 gr/m2/day on days 1 through 5 every three weeks. Evaluation of objective tumor response and toxicity were carried out according to WHO criteria. RESULTS: Nine partial responses were documented; stable disease in 11 patients, progressive disease in one patient. Apart from nine cases of grade 4 neutropenia, the treatment was generally well-tolerated. Twelve patients underwent conservative and limb salvage surgery. CONCLUSION: This therapeutic approach seems to be effective in facilitating surgery. Neutropenia was the most significant toxicity but it was preventable or medically treatable with G-CSF support.

Adult↗
PubMedDate not supplied

Growth hormone in inflammatory bowel disease.

Crohn's disease and ulcerative colitis are inflammatory diseases of the gastrointestinal tract characterized by chronic relapsing inflammation and catabolism. Growth hormone/insulin-like growth factor-I axis is important in inflammatory bowel disease, because of the effects on epithelial cell kinetics, collagen deposition and immunomodulation. The potential of growth hormone as a therapeutic option in inflammatory bowel disease has been proven in various clinical settings. Acquired growth hormone resistance in inflammatory bowel disease seems to be mediated by a combination of undernutrition and active inflammation. In particular, proinflammatory cytokines, such as TNF-a and interleukin-6, have been implicated as potential mediators of growth hormone resistance. The introduction of anti-TNF-alpha monoclonal antibodies has proven very efficacious in patients with inflammatory bowel disease. By reducing cytokines levels in inflammatory cells of intestinal mucosa, infliximab could interfere with cytokine-induced growth hormone resistance. Recent in vivo data have shown that acquired growth hormone resistance in patients with inflammatory bowel disease may be reversed after the administration of anti-TNF-alpha therapy.

Animals↗
PubMedDate not supplied

A multicentric phase II clinical trial on intra-arterial hepatic radiotherapy with 90yttrium SIR-spheres in unresectable, colorectal liver metastases refractory to i.v. chemotherapy: preliminary results on toxicity and response rates.

BACKGROUND: In patients locally progressing after two lines of chemotherapy, some locoregional approaches showed encouraging results in terms of local control of disease. The aim of our study was to evaluate toxicity, clinical response and quality of life in 48 patients with unresectable colorectal liver metastases submitted to selective internal radiotherapy (SIRT). MATERIALS AND METHODS: Up to now 35 patients with unresectable colorectal liver metastases, refractory to two lines of chemotherapy, underwent intra-arterial infusion of resin microspheres with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood tests, a PET scan and arteriography of celiac trunk, hepatic and superior mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR-spheres injection. Other exclusion criteria were liver dysfunction and anatomical vascular anomalies. The clinical response was evaluated by CT-scan following the RECIST criteria. Median follow-up was 4 months. RESULTS: Median number of metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement < 25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%. No operative mortality occurred; early toxicity (within 48 hours) was 20.6%, shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with chronic pain, jaundice and nausea being the most frequent. All the toxic events were graded 2 or 3 according to the WHO scale. Preliminary results were available in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a stable disease, while progression of disease, was observed in 12.5% of the patients. CONCLUSION: SIRT is a safe treatment in terms of acute and late toxicity. Intra-arterial microspheres could represent a good therapeutic option for patients with progressing liver metastases only, after two lines of systemic chemotherapy.

Antineoplastic Agents↗
PubMedDate not supplied

Does cyclosporin A have any effect on accelerated atherosclerosis in absence of graft rejection? Pathologic and morphometric evaluation in an experimental model.

BACKGROUND: The effects of cyclosporin A on accelerated atherosclerosis were studied in an experimental model of aortic isotransplantation. METHODS: Seventy-six Lewis rats were studied. Forty-one abdominal aortic isografts were performed and divided into five groups: 2-day isografts and 15- and 100-day isografts with and without cyclosporin treatment. The remaining rats were divided into seven groups: 15- and 100-day sham-operated, with and without cyclosporin administration; 15- and 100-day animals with cyclosporin treatment only; and normal controls. Cyclosporin was injected subcutaneously in doses of 10 mg/kg daily for the first 15 days and afterward every other day. Longitudinal sections of the proximal anastomosis and cross sections of the midgraft region were measured with a semiautomatic image-analyzer. RESULTS: Histologic analysis showed that accelerated atherosclerosis was not observed either in NT2 rats or in nontransplanted animals. In the 15-day isografts, accelerated atherosclerosis was present in the perianastomotic tract of the recipient aorta in nine of nine NT15 rats, whereas it was found only in three of nine T15 animals (p < 0.02). Histomorphometric analysis showed that accelerated atherosclerosis was less pronounced in the T100 isografts than in the NT100 ones, this difference being significant at the recipient anastomotic side only (p < 0.0005). CONCLUSIONS: The present results support the hypothesis that cyclosporin, at immunosuppressant and nontoxic doses, can delay the onset and progression of accelerated atherosclerosis and that its effects are more significant at the recipient side of the anastomosis where accelerated atherosclerosis begins to develop.

Anastomosis, Surgical↗
PubMedDate not supplied

Carboplatin plus oral etoposide in elderly patients with advanced non small cell lung cancer. A phase II study.

More than 30% of lung cancers arise in patients over 70 years old. Elderly patients are not considered to tolerate chemotherapy, are generally excluded from clinical trials, and are not considered eligible for aggressive cisplatinbased chemotherapy in clinical practice. The aims of the present study were to test the activity and toxicity of a combination of carboplatin and oral etoposide in patients over 70 years old with advanced non small cell lung cancer. Carboplatin was given at a dose of 300 mg/m2, i.v., at day 1, and oral etoposide (50 mg capsules) at a total dose of 100 mg/die from day 1 to day 7, recycled every 4 weeks. Fourteen patients entered the study. Median age was 73 years (range 70-77), 42.9% of patients had at least one concomitant illness. The trial, according to the Gehan design, was terminated earlier because no objective response was observed among the first 14 patients. We reported, according to intent to treat analysis, 2 stable and 12 progressive diseases. Median time to progression was 2 months and median survival 6 months. Remarkable hematological toxicity was recorded. Finally, we do not recommend the combination of carboplatin and oral etoposide, at the doses and schedule used in the present study, in the treatment of elderly patients with advanced NSCLC. The combination might be reconsidered using a different etoposide schedule with chronic administration (21 days).

Adenocarcinoma↗