PubMed Health⌕ Search

Biomedical subjects

G Gasparini

Publications and source records attributed to G Gasparini.

At least 19 recordsLinked to original sources
PubMed2006

Local infusion of norepinephrine reduces blood losses and need of transfusion in total knee arthroplasty.

Blood loss after total knee arthroplasty (TKA) is often associated with cardiovascular complications and a high transfusion rate of allogenic blood. In our study we focused our attention on developing a new intra-surgical procedure that appears safe, easy to perform and effective in the reduction of bleeding in TKA. We evaluated 84 patients who underwent TKA and met our inclusion criteria; they were assigned to two groups: 55 controls in which a saline solution was used to wash the surgical field before tourniquet release, and a second group of 29 patients, in which a saline solution containing a low dose of norepinephrine was locally applied before tourniquet release. The local administration of a low dose of norepinephrine has induced a significant reduction of perioperative blood loss and blood transfusion requirements; in addition, this method was characterised by the absence of complications or adverse effects. In conclusion, our data suggest that intraoperative local administration of a low dose of norepinephrine could represent an effective and safe method of reducing blood loss and preventing blood transfusions in patients with TKA.

Aged↗
PubMed2005

Gefitinib (ZD1839) combined with weekly epirubicin in patients with metastatic breast cancer: a phase I study with biological correlate.

PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% of invasive breast carcinomas and it is correlated with hormone resistance and poor prognosis. EGFR suppression by gefitinib, a quinazoline derivative that inhibits phosphorylation of the specific receptor, represents a novel therapeutic strategy. A dose-finding study was performed to evaluate the combination of gefitinib with weekly epirubicin in patients with pretreated metastatic breast cancer. METHODS: Fifteen patients were enrolled at four sequential dose levels. Gefitinib was administered orally, at the fixed daily dose of 250 mg. The starting dose of epirubicin was 20 mg/m2. Escalating dose levels of epirubicin were planned by increments of 5 mg/m2 per level, up to the maximum tolerated dose (MTD). Pharmacodynamic studies were performed by determining serum and tissue ERBB2 and EGFR. RESULTS: At the first three dose levels tested no patient experienced a dose-limiting toxicity (DLT). In cohort 4, two patients experienced DLTs (grade 4 dyspnea and asthenia, grade 3 diarrhea and thrombocytopenia) identifying the MTD of epirubicin as 35 mg/m2. Of the 14 cases assessable for response, partial response was documented in two patients, and stable disease in seven, giving an overall disease control rate of 64.2%. The comparison of pre- and post-therapy ERBB2 and EGFR values was not statistically significant between the subgroups of patients regarding responsiveness to treatment. CONCLUSIONS: The recommended dose of epirubicin for phase II studies is 30 mg/m2 in combination with gefitinib at the daily dose of 250 mg. Pharmacodynamic studies did not identify any biomarker predictive of response.

Adult↗
PubMed2005

The role of 5-fluorouracil (5-FU) reintroduction with irinotecan or oxaliplatin in truly 5-FU-refractory advanced colorectal cancer patients.

OBJECTIVES: Although several evidences have demonstrated a synergistic activity of 5-fluorouracil with irinotecan and oxaliplatin, thus explaining the use of this drug combination in the first-line treatment of advanced colorectal cancer, the need for the reintroduction of 5-FU in the second-line setting is more questionable. METHODS: We retrospectively evaluated the outcome of patients developing progressive disease while on an infusional 5-FU-based front-line chemotherapy and subsequently treated with one of the four following chemotherapy regimens: irinotecan, oxaliplatin and irinotecan or oxaliplatin both combined with the de Gramont schedule (LV5-FU2). RESULTS: 225 patients (137 males and 88 females), were eligible for analysis. Second-line chemotherapy consisted of irinotecan in 79 patients (35%, group A), oxaliplatin in 47 patients (21%, group B), irinotecan with LV5-FU2 in 53 patients (24%, group C) and oxaliplatin with LV5-FU2 in the remaining 46 cases (20%, group D). The response rate to second-line chemotherapy was obtained in 6/79 patients (8%) in group A, in 4/47 patients (9%) in group B, in 11/53 patients (21%) in group C and in 10/46 patients (22%) in group D (p = 0.04). CONCLUSIONS: These data suggest that reintroduction of 5-FU could increase irinotecan and oxaliplatin activity in patients progressing during a 5-FU-based first-line chemotherapy.

Adult↗
PubMed2005

Clinical benefit of intermittent administration of imatinib in a patient with metastatic gastrointestinal stromal tumour.

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours of the gastrointestinal tract, resistant to conventional chemotherapy and radiotherapy, but responsive to imatinib. Acquired resistance to imatinib has been reported in some patients, and several studies have suggested the possibility of overcoming imatinib resistance by increasing the dose of the drug. This case shows the possibility of obtaining clinical benefit with intermittent administration of imatinib in a patient who developed acquired resistance to a high dose of the drug.

Aged↗
PubMed2005

Predictors of drop-out in overweight and obese outpatients.

OBJECTIVE: To investigate the impact on drop-out rates of several baseline clinical characteristics of a sample of overweight and obese outpatients. DESIGN: Retrospective clinical trial. SUBJECTS: The charts of 383 patients aged 15-82 y attending an outpatient clinic for the treatment of obesity were examined from the first clinical evaluation until 1 y of diet ambulatory treatment. MEASUREMENTS: We characterised the participants at baseline on the basis of their somatic characteristics, socioeconomic status, obesity-related diseases and dietary habits. The most significant factors resulting in univariate statistical analysis (waist, body mass index (BMI), full-time job, depressive syndrome, number of obesity-related diseases, daily frequency of fruit consumption) were then examined as independent variables in direct multiple logistic regression with the dependent variable drop-out. RESULTS: The 1-y drop-out rate was 77.3%. A total of 87 patients completed the follow-up study. The noncompleter patients had slightly lower BMI and waist circumference mean values, and they were further regularly employed in full-time jobs, while the completer patients were principally pensioners and housewives. Drop-outs had a lower number of obesity-related diseases and as a result were less depressed. By the logistic regression, full-time job is the best predictor of premature withdrawal (odds ratio=2.40). Age, gender, anthropometric measurements, lifestyle and dietary habits did not result as significant predictors of drop-out. CONCLUSION: The overweight and obese outpatients at higher risk of ambulatory treatment drop-out are more likely to work full hours, have less obesity-related complications and be less depressed. In our study, the full-time job condition seems to be the strongest predictor of premature withdrawal.

Adolescent↗
PubMed2005

Therapy of breast cancer with molecular targeting agents.

Invasive breast cancer is a heterogeneous disease sustained by intercorrelated and complex growth pathways. Classically, human breast carcinoma has been classified for therapeutic purposes in two distinct categories: one hormone-correlated, the other hormone-uncorrelated. However, the recent advancements of the technology applied to molecular biology by genomic and proteomic analyses have suggested that many more factors are involved in breast cancer growth and progression and that some clusters of these distinguish subgroups of patients at different prognosis. The knowledge of the diversities between tumor and normal tissue of origin is the key to identify novel targets for new selective therapeutic strategies. In fact, the principal goal of molecular-targeted therapy is the suppression of the transformed phenotype minimally affecting normal cells. This review focuses on the molecular targeting compounds directed against the known molecular pathways involved in breast cancer such as: type I growth factors (HER-2/neu; epidermal growth factor receptor [EGFR]), angiogenesis, cyclooxigenase-2 (COX-2) and farnesylation. Presently, trastuzumab is the first agent approved for therapy of HER-2/neu overexpressing tumors. Several other compounds directed against different targets have entered clinical evaluation and the preliminary results are here presented and commented. The major challenges on the clinical development of targeted therapy include the proper selection of patients, the identification of the optimal dosage and schedule of administration, the combinations with conventional treatments and the more appropriate therapeutic strategy.

Angiogenesis Inhibitors↗
PubMed2005

Clinical utility of IVUS in 2005.

Intravascular ultrasounds (IVUS) allowed an innovative visualization of coronary artery disease. This technique developed first in the research field and, then, it was introduced in clinical practice as a supplement to coronary angiography in diagnosis of the severity of ischemic heart disease. The characteristic tomographic view of coronary plaque supplied by IVUS allowed to overcome the limitations of coronary angiography and to add important supplemental information in understanding the mechanism of action of several interventional devices. In this review we analyze current indications of use of IVUS in clinical practice and the future applications of IVUS-related techniques for the diagnosis of coronary artery disease.

Humans↗
PubMed2005

[The senologist surgeon].

Senology is going to be an independent branch, but resistances to the acknowledgement of the senologist as a devoted professional are still under way. Nevertheless, in the last 20 years an irreversible educational training was traced out. The senologist is not only the surgeon who operates on the breast: he is also a clinician, a researcher and a philosopher. Restricting the senologist's role to that of a knife-user is by far reductive, as this does not put in its true light his huge knowledge: senology is first of all a cultural item. Europe is going to set up independent Breast Units because this is the only way to offer excellent services, whose final result will be the reduction of mortality and the improvement of quality of life.

Breast Neoplasms↗
PubMed2004

Acute myocardial infarction probably caused by paradoxical embolus in a pregnant woman.

A 19 year old pregnant woman presented to the coronary care unit with an acute anterior myocardial infarction. She was treated with primary percutaneous transluminal coronary angioplasty of the proximal left anterior descending coronary artery. Ultrasound examination showed patent foramen ovale (PFO) and atrial septal aneurysm. The patient was a heterozygote carrier of factor V Leiden. Despite the lack of a clear clue, it was considered that the pathophysiological cause of this infarction was a paradoxical embolus in the left coronary artery. Pregnancy and factor V Leiden carriership are associated with increased risk of venous thromboembolism and the association between PFO and atrial septal aneurysm is a strong risk factor for systemic embolisation.

Adult↗
PubMed2002

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: a low cost effective regimen.

Recently, we reported a highly active regimen in advanced gastric cancer including a weekly administration of cisplatin, epidoxorubicin, leucovorin, 5-fluorouracil with the support of filgrastim. In order to simplify the administration and to decrease the toxicity of these drugs, mainly epidoxorubicin-induced alopecia, we designed a regimen including an infusional 5-fluorouracil schedule according to the de Gramont regimen, cisplatin and mitomycin C replacing epidoxorubicin. Forty-five patients with advanced or metastatic gastric cancer were treated with cisplatin 50 mg m(-2) i.v. on day 1, every 2 weeks, 6S-stereoisomer-leucovorin 100 mg m(-2) i.v. followed by 5-fluorouracil 400 mg m(-2) i.v. bolus and 600 mg m(-2) i.v. in a 22-h infusion, on days 1 and 2, every 2 weeks, and mitomycin C 7 mg m(-2) i.v. bolus on day 2, every 6 weeks. Grades 3-4 toxicities (National Cancer Institute-Common Toxicity Criteria) consisted mainly of neutropenia and thrombocytopenia. Five patients had a complete response and 16 had a partial response for an overall response rate of 46.7% (95% confidence interval, 32.1-61.2%). The median survival was 11 months. The combination of cisplatin, 5-fluorouracil and leucovorin according to de Gramont, and mitomycin C seems to be an active and safe regimen in the treatment of advanced gastric cancer. Because of its low cost it may be suggested for patients not enrolled into clinical trials.

Adult↗
PubMed2002

Anti-angiogenic therapy: rationale, challenges and clinical studies.

Physiological angiogenesis occurs during embryogenesis, wound healing and reproductive functions in adults. Abnormal angiogenesis takes place in certain chronic diseases (diabetes, psoriasis, rheumatoid arthritis, etc.) and tumours. Genetic changes and local stresses including hypoxia, glucose deprivation and oxidative stress play a pivotal role in angiogenesis switch, which is necessary for tumour development and is rate-limiting for tumour progression. Angiogenesis is tightly regulated by pro- and anti-angiogenic growth factors with a series of complex and interrelated steps. Activated endothelial cells (ECs) migrate as a solid cord and, subsequently, form lumina; the sprout tips then anastomose to form vessel loops or networks. One of the final events is the laying down of a basement membrane and the structural support of pericytes. The molecular alterations that sustain angiogenesis represent novel targets for rationally designed anti-cancer treatment strategies. Inhibition of angiogenesis presents certain advantages on conventional therapies, such as the direct accessibility from the circulation, and the potential low rate of drug resistance related to the genetic stability of ECs. Certain anti-angiogenic compounds were found to have potent anticancer property in in vivo experimental studies. Nevertheless, in contrast to preclinical studies, the first generation of anti-angiogenic drugs tested in clinical trials have shown a moderate activity in advanced disease partly due to suboptimal schedules of therapy or biases in study design.

Angiogenesis Inhibitors↗
PubMed2002

Doxorubicin-docetaxel sequential schedule: results of front-line treatment in advanced breast cancer.

OBJECTIVE: We conducted a multi-institutional phase II study to evaluate the tolerability and activity of a sequential schedule of treatment with doxorubicin and docetaxel in chemotherapy-naive women with advanced breast cancer. METHODS: A total of 73 patients with PS (ECOG) 0-2, aged <70 years and adequate bone marrow, renal, liver and cardiac functions were included in the study (13 stage III B and 60 stage IV). The schedule of administration was doxorubicin 50 mg/m2 by intravenous (i.v.) 30 min injection on day 1 followed the day after by docetaxel 75 mg/m2, by i.v. 60 min infusion. Cycles were repeated every 28 days. RESULTS: Overall, the median number of administered cycles was 6 (range 1-14). The most common toxicity was hematological, with 56.2% of the patients who experienced grade 3-4 neutropenia. However, febrile neutropenia occurred only in 2.8% of the cases. The median cumulative dose of doxorubicin was 350 mg/m2 (range 50-700 mg/m2). Eleven patients (15.4%) were documented to have >10% but <20% decrease in the left ventricular ejection fraction. No case of congestive heart failure was recorded. No patient experienced treatment-related death. Among the 68 evaluable patients, the overall objective response rate was 73.5% (95% confidence limits: 63-84%): 10 patients (14.7%) obtained a complete remission and 40 (58.8%) had a partial response. Only 10 patients (14.7%) experienced progressive disease. The median duration of response was 10 months (2-54+). CONCLUSION: This sequential treatment with doxorubicin and docetaxel is an effective, feasible and a well-tolerated regimen. The main toxicity was neutropenia. The lack of cardiotoxicity is an important advantage of such a doxorubicin-docetaxel combination and it justifies phase III comparative studies with other anthracyclines/taxanes containing schedules in both advanced and early-stage breast cancer.

Adult↗
PubMed2002

Evaluation of homologous bone graft versus biomaterials in the aesthetic restoration of the middle third of the face.

BACKGROUND: Bone deficits of the midface can be observed following tumor surgery, facial traumas or malformations, and can determine aesthetic deformities requiring surgical corrections. The goal of this study is to illustrate the 23 years experience of the Maxillo-Facial Department of the "La Sapienza" University of Rome, in surgical correction of middle third bone loss for aesthetic improvement, and to compare postsurgical results from the use of biomaterials and homologous bone grafts. METHODS: From January 1977 to January 2000, 18 patients were surgically treated with bone grafts for bone deficit of the midface requiring aesthetic improvements, and 23 received biomaterial placement in the same district. A retrospective analysis regarding aesthetic improvements following corrective (reconstructive) surgery was carried out in order to compare long-term results obtained with bone grafts and biomaterials. RESULTS: Of the 19 implants of the zygomatic bone, 1 patient suffered from infection, observ-ed on the 8th day, following iliac bone graft in the maxillary area. Of the 32 prostheses, 7 became infected and in 1 case the material became exposed: Proplast(R) became infected 2 times, Gore-tex(R) 3 times and 1 time became exposed; 2 of the 24 Medpor(R) implants resulted in infection. The employment of bone graft obtained a good short term aesthetic result. Medpor(R) employment, was evaluated as an optimal aesthetic improvement. We cannot evaluate the results obtained with Gore-tex(R) and Proplast(R) because of the few cases treated. Anyway we consider unsatisfactory the corrections obtained with these 2 materials. CONCLUSIONS: Homologous bone grafts are still considered as the best choice when a further fixture positioning is planned for prosthetic rehabilitation of the alveolar ridge of the upper jaw or mandible. At the present time, some biomaterials are the definitive solution for restoring facial harmony in the 3 spatial dimensions.

Biocompatible Materials↗
PubMed2001

Clinical significance of determination of surrogate markers of angiogenesis in breast cancer.

Compelling experimental and clinical data support the concept that breast carcinoma, as most of the other solid tumors, needs to develop the angiogenic phenotype for invasiveness, progression and metastasis. Several studies have determined intratumoral microvessel density by panendothelial markers and immunohistochemical techniques, with most of them showing that the degree of vascularity is associated with prognosis of the patients operated of early-stage invasive breast cancer. More recently, certain angiogenic peptides have been assessed in human breast cancer: vascular endothelial growth factor (VEGF), platelet derived-endothelial cell growth factor (PD-ECGF, also known as thymidine phosphorylase, TP) and fibroblast growth factor family (FGFs). Among these, the most studied is VEGF, which appears to be a powerful prognostic indicator. Little data are available on the clinical significance of naturally occurring antiangiogenic factors, with few studies reporting on interleukin-12 and thrombospondins. In vivo techniques for dynamic assessment of tumor blood network are presently under extensive research, in particular for monitoring activity of inhibitors of angiogenesis. The methods of assessment of angiogenic activity and the results of published clinical studies in peer reviewed Journals with a computerized overview of literature will be presented. Overall, the results of the reported studies suggest that human breast cancer is an angiogenic-dependent tumor for which antiangiogenic therapy represents a promising novel antitumoral therapeutic strategy.

Biomarkers, Tumor↗
PubMed2001

Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs.

Angiogenesis is essential for tumour growth, invasion, and metastasis. Tumour blood vessels show many differences from normal vessels and are not genetically unstable, so they form a potentially key area for therapy of all types of cancer including leukaemias. Here we review current knowledge on the multiple pathways controlling tumour angiogenesis and assess which are the most clinically relevant. We also review the clinical evidence that angiogenesis affects the behaviour of cancer. Retrospective studies on intratumoral vascularisation suggest that it is an independent prognostic factor that merits prospective validation. Also, the presence of vascular endothelial growth factor in high concentrations in primary cancers is associated with poor prognosis. Key targets for drug development, current clinical trials, and the problems of developing drugs that do not have direct cytotoxic effects are reviewed. Recommendations are made on organising and monitoring antiangiogenic trials.

Antineoplastic Agents↗
PubMed2001

Metronomic scheduling: the future of chemotherapy?

Tumour endothelium is a new target for anticancer treatments. Proliferating endothelial cells from the tumour, even if qualitatively different from those of blood vessels in the normal tissue of origin, remain putatively normal and genetically stable cells. The results of recent experimental studies have suggested that frequent administration of certain cytotoxic agents at low doses (a tenth to a third of the maximum tolerated dose), known as 'metronomic' chemotherapy, increases the antiangiogenic activity of the drugs. The effects of these metronomic schedules of cytotoxic agents may be further enhanced by concurrent administration of novel, selective, treatments that inhibit, at a molecular level, the processes of tumour formation and growth eg angiogenesis, growth factor pathways, and other signal transduction cascades. The need to treat patients for long periods also supports the use of metronomic scheduling for chemotherapy, to minimise toxicity and to target both proliferating tumour cells and endothelial cells. This review describes the experimental studies involving metronomic schedules of chemotherapy, alone and in combination with angiogenesis inhibitors, and suggests a new therapeutic anticancer paradigm for controlling cancer by long-term therapy, based on the development of combinations of metronomic cytotoxic agents with individually tailored compounds designed to target specific molecules.

Angiogenesis Inhibitors↗