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Biomedical subjects

R Ridolfi

Publications and source records attributed to R Ridolfi.

At least 19 recordsLinked to original sources
PubMed2006

The application of environmental certification to the Province of Siena.

The SPIn-Eco project has provided very broad and precise data collection regarding the Province of Siena. These data and their elaborations have also been developed as a basis for the environmental certification of this organization. In this way, the Administration of the Province of Siena (the first Province in Italy) has reached its goal of obtaining better knowledge of the state of the system and of constructing its environmental management system (EMS) according to the environmental aspects directly and indirectly arising from the organization's activities. Indirect aspects are mainly related to the territorial monitoring and planning. Indicators based on the classical pressure-state-response approach, as well as more complex ones based on CO(2) balance, emergy and ecological footprint analyses, have been used to assess the environmental performance of the EMS. This paper presents how this EMS is constructed, as well as the indicators that are used to analyze the system, paying particular attention to sustainability indicators.

Conservation of Natural Resources↗
PubMed2006

The greenhouse gas balance of the Province of Siena.

There is a profound debate over how to assign greenhouse gas (GHG) responsibilities; therefore, we have decided to follow IPCC guidelines, as they offer the only standardized method. We have identified each type of greenhouse emission and its level of absorption. We have studied the province and its districts and municipalities. We have determined that the energy sector is that with the highest level of emissions, even if the per capita emissions of the Province of Siena are very low. This is caused by a very low level of industrialization and the presence of a local geothermal production of energy. In order to highlight this aspect, we have considered scenarios both with and without geothermal production. Our research was then focused on single districts (groups of homogenous municipalities) and municipalities, where we found great differences among the greenhouse emissions of the areas. We have constructed a map of the greenhouse emissions of the whole province. It has been interesting to note that there are 14 municipalities with net negative emissions, seven with low positive emissions, 12 with medium positive emissions and three with elevated positive emissions. These latter correspond to the main city and to two of the most industrialized municipalities.

Carbon Dioxide↗
PubMed2006

An environmental analysis for comparing waste management options and strategies.

The debate on different waste management practices has become an issue of utmost importance as human activities have overloaded the assimilative capacity of the biosphere. Recent Italian law on solid waste management recommends an increase in material recycling and energy recovery, and only foresees landfill disposal for inert materials and residues from recovery and recycling. A correct waste management policy should be based on the principles of sustainable development, according to which our refuse is not simply regarded as something to eliminate but rather as a potential resource. This requires the creation of an integrated waste management plan that makes full use of all available technologies. In this context, eMergy analysis is applied to evaluate three different forms of waste treatment and construct an approach capable of assessing the whole strategy of waste management. The evaluation included how much investment is needed for each type of waste management and how much "utility" is extracted from wastes, through the use of two indicators: Environmental yield ratio (EYR) and Net eMergy. Our results show that landfill is the worst system in terms of eMergy costs and eMergy benefits. Composting is the most efficient system in recovering eMergy (highest EYR) from municipal solid waste (MSW) while incineration is capable of saving the greatest quantity of eMergy per gram of MSW (highest net eMergy). This analysis has made it possible to assess the sustainability and the efficiency of individual options but could also be used to assess a greater environmental strategy for waste management, considering a system that might include landfills, incineration, composting, etc.

Conservation of Energy Resources↗
PubMed2003

Restored T-cell activation mechanisms in human tumour-infiltrating lymphocytes from melanomas and colorectal carcinomas after exposure to interleukin-2.

We investigated the effects of interleukin-2 (IL-2) exposure on T-cell signal transduction molecules and apoptosis markers in tumour-infiltrating lymphocytes (TIL) isolated from 20 melanoma and 16 colorectal carcinoma metastases and expanded in vitro for therapeutic reinfusion. Before IL-2 culture, TIL showed undetectable or very low levels of T-cell receptor (TCR) epsilon chain, p56(lck), Fas ligand (FasL) and Bax expression, while Bcl-2 values were elevated. Cancer cells were characterised by low or absent Fas and Bcl-2 and high Bax expression. Notably, they also expressed FasL. After 41-48 days of IL-2 culture, TCR epsilon chain and p56(lck) expression of TIL rose to median values of approximately 80 and 30% positive cells, respectively (P<0.001), FasL expression was detected in 45% cells from melanomas (P<0.001) and in 3% from colorectal carcinomas (P=0.09), and Bax-positive cells increased from 17.5 to 70% (P=0.005). Moreover, TCR zeta chain-positive cells were significantly increased from baseline (P=0.001), Bcl-2-positive cells dropped from 50 to 1% (P=0.007) and perforin content was high, while Fas expression was not significantly modified by IL-2 culture. In conclusion, our data suggest that the degree of immunosuppression in TIL from melanomas and colorectal carcinomas is very high, and the apoptosis markers' repertoire of cancer cells resembles that of immune-privileged tissue. Interleukin-2 culture appears to restore lymphocyte activation mechanisms, resulting in consistent FasL expression and perforin production.

Adult↗
PubMed2003

Quality of life evaluation in a randomised trial of chemotherapy versus bio-chemotherapy in advanced melanoma patients.

This study analyses the health related quality of life (HRQOL) of advanced melanoma patients, in a randomised trial comparing bio-chemotherapy (bio-CT) versus chemotherapy (CT). The trial enrolled 178 patients and the median survival was not statistically different between the two arms. HRQOL was assessed at baseline and before each cycle of therapy, using the Rotterdam Symptom Checklist (RSCL) questionnaire completed with 140 patients. At baseline, overall quality of life and psychological distress scores were the most impaired, compared with the normal population. During treatment, the difference between the two arms in the changes from baseline was statistically significant (P=0.03) only in the overall quality of life score, with a decrease of 6.28 points in the bio-CT arm. The mean values decreased significantly in all domains in bio-CT arm, but only in activity level and physical symptom distress scores in the CT arm. Testing HRQOL variables and prognostic clinical factors in a Cox model, only the serum level of lactic dehydrogenase, baseline overall quality of life and the physical symptom distress scores remained significant independent prognostic factors for survival. A score of less than 75 points in the overall quality of life and in the physical symptom distress domains was associated with a Hazard Ratio (HR) of 2.31 (95% Confidence Interval (CI): 1.09-4.90) and 1.92 (95% CI: 1.10-3.36), respectively.

Adult↗
PubMed2003

Chemotherapy and bio-chemotherapy in patients with advanced melanoma: combination therapy with a nitrosourea.

The treatment of advanced melanoma is still disappointing. In a multicenter randomized clinical trial to compare a chemotherapy (CT) with or without low doses of IL-2 and IFN (Bio-CT), the participating centers chose whether or not to add a nitrosourea, carmustine (BCNU) to the therapy. The aim of the present paper is to report the clinical results of the patients (pts) treated in both arms with BCNU. One hundred and seventy-six pts with advanced melanoma were enrolled in the study from 27 centers and a total of 18 pts also received BCNU in 3 centers. No further changes to the protocol criteria were allowed. One patient refused the treatment. No complete responses were observed. Irrespectively of the treatment arm, 9/17 pts showed a partial response to therapy (53%) (5/9 in the CT and 4/8 in the BioCT arm). The most important adverse events observed were hematological: 12 pts presented grade 3 (6 pts) or grade 4 (6 pts) leukocytopenia and 9 pts had grade 4 thrombocytopenia, all of which resolved spontaneously. The addition of a nitrosourea to CT or Bio-CT appears to improve response rates compared to the same regimens without nitrosourea. Patient tolerability is acceptable. Further studies using this combination are warranted.

Adult↗
PubMed2001

Intralesional granulocyte-monocyte colony-stimulating factor followed by subcutaneous interleukin-2 in metastatic melanoma: a pilot study in elderly patients.

AIM AND BACKGROUND: Recent data in the literature indicate that antigen-presenting cells (APC) are inactive in tumour tissue because of local immunosuppression. Tumour-infiltrating lymphocyte (TIL) signal activation transducing mechanisms are also seriously impaired. Administration of granulocyte macrophage-colony stimulating factor (GM-CSF) may lead to APC recovery and interleukin (IL)-2 may restore local TIL activation. Moreover, IL-2 increases the systemic lymphocyte population, an event that seems to correlate with a better prognosis. STUDY DESIGN: The present phase I-II study was carried out to examine whether intralesional injection of GM-CSF followed by subcutaneous IL-2 would induce a clinical response in advanced, pretreated elderly melanoma patients. METHODS: Sixteen patients over 60 years of age received intralesional GM-CSF (150 ng per lesion on day 1), generally divided between the two largest cutaneous lesions, followed by perilesional subcutaneous IL-2 (3,000,000 IU) for 5 days (days 3-7 inclusive) every 3 weeks. RESULTS: Four clinical responses [two partial (PR) and two minimal (MR)] (25%), which also involved lesions that had not been directly treated, and nine cases of stable disease were observed. The response duration for PR and MR was 9, 4, 4 and 2.5 + months, respectively. Stable disease (56%) recorded in the nine patients was short-term (3-6 months). Three patients rapidly progressed after two, two and one therapy cycles, respectively. The patient who reached the best PR had a fairly high absolute lymphocyte count (1600-2400/mm3). The second one, who reached complete remission after subsequent locoregional chemotherapy and hyperthermia, however, had a low absolute lymphocyte count that had doubled by the end of treatment. Blood lymphocyte values in the other patients were too varied to allow any correlation with clinical response. Therapy was well tolerated and only mild fever was observed, with the exception of one patient who had grade 3 fever, with muscle pain and arthralgia. CONCLUSIONS: Considering the very low toxicity observed, this treatment might be indicated in elderly patients for whom systemic therapy is no longer a viable option. Improved scheduling and timing could result from further studies.

Aged↗
PubMed1998

Adjuvant adoptive immunotherapy with tumour-infiltrating lymphocytes and modulated doses of interleukin-2 in 22 patients with melanoma, colorectal and renal cancer, after radical metastasectomy, and in 12 advanced patients.

Adoptive tumour infiltrating lymphocytes (TIL) in combination with a modulated dosage of interleukin-2 (IL-2) can be used with acceptable toxicity in the treatment of immunogenic tumours. Following an experience of reinfusion in advanced melanoma, colorectal and renal cancer patients, treatment was given to disease-free patients after metastasectomy. The high risk of relapse and favourable ratio between reinfused TIL and possible microscopic residual disease determined this choice of adjuvant treatment. A group of 12 patients with advanced disease (7 melanoma, 4 colorectal carcinoma, 1 kidney carcinoma) were treated with TIL (median 5.8 x 10(10) cells) and IL-2 (West's schedule) modulated towards a lower dosage (from 12 to 6 MIU/day) in order to maintain an acceptable level of toxicity. As treatment was well tolerated, it was offered to another 22 patients in an adjuvant setting after metastasectomy (11 melanoma, 10 colorectal carcinoma, 1 renal cancer), the median dose of TIL reinfused being 4.95 x 10(10) cells. No objective response was observed in advanced patients: all patients progressed after a median of 1.5 months (0-8 months) and median survival was 8 months (3-22+ months). Thirteen patients from the second group are still disease-free after a median of 23+ months (9+ - 47+ months). The remaining 9 patients relapsed after a median of 5 months (3-18 months). Toxicity was moderate as clinical and hepatic/renal function parameters were used to assess the need for dose reductions. Consequently, there was great diversity in IL-2 dosages administered. In particular, there seemed to be a difference in IL-2 doses administered between disease-free cases and those who progressed (17.5 MIU/day versus 7 MIU/day in melanoma patients; 11.2 MIU/day versus 7.1 MIU/day in colorectal cancer patients). By contrast, no differences were observed between number of TIL reinfused and clinical response. Phenotypical characteristics of reinfused TIL were similar to those reported in the literature: 97% were CD3 and 92% were CD8. Aspecific cytolytic activity was evaluated on 12 cases whereas, in 2 melanoma cases, autologous tumour tissue was available for the specific cytotoxicity test. Perforin levels in TIL measured at the end of culture were generally high or very high. Cytokine levels were measured on the supernatant at the end of culture, with an estreme variability in results. Finally, delta chain and p56lck were histologically assessed on the resected tissue from which TIL were cultivated. There were virtually none of the former and a complete absence of the latter, which concurs with data reported in the literature. The same immunocytochemical analysis was carried out on TIL at the end of culture. This time an almost complete restoration of both functions was seen, especially in melanoma patients, who are still free from disease. The study is on-going and it has been decided to focus on disease-free patients after metastasectomy in order to increase the number and possibility of clinical and histological correlations.

Adolescent↗
PubMed1997

Intraperitoneal carboplatin with or without interferon-alpha in advanced ovarian cancer patients with minimal residual disease at second look: a prospective randomized trial of 111 patients. G.O.N.O. Gruppo Oncologic Nord Ovest.

From June 1990 to October 1994, 111 advanced ovarian cancer patients with minimal (less than 2 cm) residual disease after platinum-based front-line chemotherapy and second-look laparotomy entered a cooperative randomized study aimed at evaluating the effectiveness and the toxicity of the addition of interferon-alpha2 to carboplatin, both intraperitoneally (ip) administered. Patients were randomized to receive either 3 courses of ip Carboplatin 400 mg/m2 Day 1 q 28 days (54 pts) (CBDCA) or ip interferon-alpha 25 x 10(6) U Day 1 + ip carboplatin 400 mg/m2 Day 2 q 28 days (57 pts) (CBDCA + IFN). Patients treated with interferon experienced more severe (WHO grade 3-4) leukopenia (28% vs 17.1%) and anemia (14% vs 4.2%). Fever (P = 0.000) and flu-like syndrome (P = 0.02) were significantly more frequent in the combination arm. No difference in gastroenteric, neurologic, or renal toxicity was observed. At a median follow-up time of 13 months (range 1-72) 71 patients showed a disease progression (31 CBDCA, 40 CBDCA + IFN) and 44 patients died (21 CBDCA, 23 CBDCA + IFN). Median progression-free survival was 11 months in the CBDCA group and 10 months in the CBDCA + IFN arm. Median survival was 22 and 29 months in CBDCA and CBDCA + IFN arm, respectively. In conclusion, intraperitoneal interferon-alpha does not seem to improve the results achievable with intraperitoneal carboplatin in this subset of patients, while the toxicity and the costs of the combination are consistently higher than with chemotherapy alone.

Adult↗
PubMed1994

A phase II study of advanced colorectal cancer patients treated with combination 5-fluorouracil plus leucovorin and subcutaneous interleukin-2 plus alpha interferon.

Twenty-one patients with advanced, pretreated colorectal cancer in disease progression were entered in a phase II study to investigate the use of 5-fluorouracil (5FU) + leucovorin with subcutaneous Interleukin-2 + alpha interferon (alpha-IFN). Eighteen of these patients were evaluable for response to treatment: 1 partial response (PR) (duration 8 months), 9 stable disease (SD) (median duration of 6.5 months, range 2-15) and 8 progressive disease (PD). The PR patient survived for 15 months, the SD patients for a median of 11 months and 8 months for PD patients. Toxicity evaluated in the 21 patients reached grade 4 for mucositis in two cases. Grade 3 toxicity was observed more frequently for fever (52.3%) and diarrhea (33.3%) and was most probably the result of the combined side-effect of chemotherapy and the biological response modifiers (BRMs). Treatment was, for the most part, carried out on an out-patient basis as originally planned. In 15 patients tests were carried out to verify whether any immuno-activation had taken place. Significant increases were found during the course of therapy regarding cluster of differentiation activation (HLA-DR, CD71, CS25). Different curves were observed during the course of treatment with respect to the CD8 value, which proved higher in SD patients than in PD patients. Our study would seem to suggest that the addition of BRMs to 5FU + leucovorin could increase survival. The next step, however, must be to determine lower doses of IL-2 for subcutaneous administration in order to reduce toxicity but maintain the same immunostimulation.

Adult↗
PubMed1992

Evaluation of toxicity in 22 patients treated with subcutaneous interleukin-2, alpha-interferon with and without chemotherapy.

Biological response modifiers (BRMs) have greatly modified the immunotherapy of tumors. Interleukin-2 (IL-2) has brought about metastasis regression in some cases of malignant tumors, however, when given systemically, it results in high toxicity. More recently, the subcutaneous administration of IL-2 (combined with alpha-interferon, alpha-IFN) seems to be capable of offering the same chances of therapeutic response, but this time with a lower level of toxicity. The Authors report an evaluation of toxicity in 22 patients treated with a combination of IL-2 + alpha-IFN i.m. with or without chemotherapy. The side-effects present in the majority of cases were: fever, diarrhea and asthenia. Approximately 50% of the patients had nausea/vomiting, mucositis, skin rashes, and slight leukopenia. The following side-effects were noted to a much lesser degree, thrombocytopenia, alterations in hepatic and dizziness and cystitis. Only one patient reached 4th degree toxicity, with mucositis, asthenia and skin rash. All the other patients received the treatment without suspensions for toxicity. Biological evaluations will enable us to determine in the future, the cases which can benefit from therapeutic intensification and thus it would seem opportune at this time to use therapy with acceptable toxicity.

Adult↗
PubMed1991

Chemotherapy with 5-fluorouracil and streptozotocin in carcinoid tumors of gastrointestinal origin: experiences with 13 patients.

The Authors report their experiences on the treatment of 13 consecutive cases of gastro-intestinal carcinoid tumors observed over the last 11 years. The primary sites were as follows: intestine (5 cases), appendix (3 cases), colon (1 case) and peritoneum (4 cases); only 3 patients presented systemic signs. Ten patients in advanced phase were treated with a chemotherapeutic regimen containing 5-fluorouracil (5-Fu) and streptozotocin (STZ). One case was excluded from the study because of a concomitant gastric carcinoma. Of the 9 evaluable patients, two achieved partial remission (22%) with a duration of 18+ and 66 months respectively; 4 (44.5%) had stable disease for periods ranging from 7 to 40 months and 3 cases progressed. Severe toxicity (thrombocytopenia and diarrhea) occurred in 2 cases and disappeared with the suspension of therapy. The systemic signs disappeared with treatment and did not appear in 2 cases out of 3. The prospective of the employment of new drugs such as alpha-interferon and, above all, somatostatin provides hope that this uncommon disease may have an improved response rate to treatment in the future.

Adult↗
PubMed1986

Combination chemotherapy in advanced ovarian carcinoma.

Ovarian carcinoma is the fifth most common cause of death among women in western countries. It is often diagnosed in an advanced stage (FIGO Stage III and IV) and requires effective chemotherapy as first-line treatment. The advent of cis-platin combined with adriamycin and cyclophosphamide has remarkably increased the response rate in advanced disease. The authors report 31 cases of epithelial ovarian neoplasia, without prior chemotherapy, treated with cis-platin, adriamycin and cyclophosphamide (PAC I). Of the 30 evaluable patients, 15 had clinical complete remissions (cCR = 50%), 10 clinical partial remissions (cPR = 33%) and 5 no response (NR = 17%). The total response (cCR + cPR) was equal to 83%. Twelve of the 15 patients in cCR underwent second-look laparotomy; in 8 of these cases, histologic and cytologic confirmation of CR was obtained. PAC I was found to be a highly effective therapeutic regimen with moderate toxicity. The individual toxicity reported was gastroenteric (nausea and vomiting), but transitory. No chronic toxic side-effects from cisplatin or adriamycin were noted. However, more definitive results must be obtained to verify its impact on the prolongation of survival.

Adult↗
PubMed1986

Chemotherapy of advanced gastric cancer: a study of 43 consecutive cases treated with fluorouracil, adriamycin and mitomycin C (FAM).

All consecutive patients with advanced gastric carcinoma who came to the Oncology Dept. of the "L. Pierantoni Hospital" in Forlì, between June 1, 1980 and August 30, 1983, were treated with 5-fluorouracil, adriamycin and mitomycin C (FAM). None of the patients had previously received chemotherapy. The dominant location of metastasis was the liver in 21 pts (48.8%), the abdomen in 15 pts (34.8%) and distant organs in 7 pts (16.2%). The schedule of FAM regimen used was: 5 Fluorouracil, 600 mg/m2, days 1, 8, 29, 36; Mitomycin C 10, mg/m2, day 1; Adriamycin, 30 mg/m2, days 1, 29. Complete remission (CR) was reached in 2 pts (4.6%) with a median length of response (m.l.r.) of 55 weeks (range 20-90), partial remission (PR) in 9 pts (20.9%) with a m.l.r. of 15.1 weeks (2.2-60), no change (N.C.) in 19 pts (44%) with a m.l.r. of 10 weeks (2.2-54) and progression (P) in 13 pts (30.2%). Median survival of patients in CR + PR considered together was 48 weeks (12 months), for the NC pts 20 weeks (5 months) and for those in P 14.1 weeks (3.5 months). The authors reached the conclusion that gastric carcinoma may be treated with FAM both for palliation and to improve survival even if in a small number of patients.

Adult↗
PubMed1984

A retrospective study of FAM regimen in 38 patients with advanced gastric cancer.

Gastric carcinoma has a very poor prognosis, with a survival rate at 5 years of 13%. Various chemotherapy regimens have been used in the advanced stages of the disease. The best results were obtained using the FAM combination. We treated 38 patients with advanced measurable gastric cancer using the FAM combination and obtained 23.67% complete plus partial remission (CR + PR) (32% with more restrictive criteria for eligible patients) and 34% no change. The median length of response was 30 weeks in CR patients (range 20-100) and 26 weeks (range 12-34) in PR patients. Responsive patients (CR + PR) had a median survival of 12.3 months (range 5-22) compared to nearly 4 months (range 2-8) for unresponsive patients.

Adult↗