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Biomedical subjects

M Venturini

Publications and source records attributed to M Venturini.

At least 91 records · Page 5Linked to original sources
PubMed1994

Hyaluronidase as an antidote to extravasation of Vinca alkaloids: clinical results.

Skin necrosis is a recognized potential consequence of an inadvertent extravasation of Vinca alkaloids in the surrounding tissues during i.v. administration. Experimental studies suggest that hyaluronidase, an enzyme that degrades hyaluronic acid and improves the absorption of locally injected drugs, can reduce the risk of progressing to skin necrosis. On this basis, we used this enzyme as a local treatment after extravasations of Vinca alkaloids in seven patients. No patient suffered from subsequent skin necrosis. To the best of our knowledge, this is the first clinical report confirming the positive findings of experimental studies on the effectiveness of this antidote.

Extravasation of Diagnostic and Therapeutic Materi↗
PubMed1994

A pilot study of accelerated cyclophosphamide, epirubicin and 5-fluorouracil plus granulocyte colony stimulating factor as adjuvant therapy in early breast cancer.

32 consecutive early breast cancer patients were treated to evaluate the feasibility of an accelerated CEF regimen (cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2 and 5-fluorouracil 600 mg/m2) given intravenously every 2 weeks for six cycles together with granulocyte colony stimulating factor, 5 micrograms/kg/day subcutaneously from day 4 to day 11. One hundred and eighty two out of 192 planned cycles (95%) were administered. Toxicity was mild: no cases of grade IV non-haematological toxicity and only one episode of grade IV granulocytopenia were observed. Delays or dose reductions of anti-neoplastic drugs occurred in 14 cycles (7.7%). The mean duration of six cycles of treatment was 71 days (planned 70) and 93% of average planned dose intensity was actually administered. The short course CEF therapy is a feasible, well tolerated outpatient chemotherapy regimen, allowing a 46% increase in dose intensity compared with a standard CEF regimen given every 3 weeks. A randomised study comparing this regimen to a standard CEF regimen is now in progress in early breast cancer patients.

Adult↗
PubMed1994

Granulocyte-macrophage colony-stimulating factor (GM-CSF) allows acceleration and dose intensity increase of CEF chemotherapy: a randomised study in patients with advanced breast cancer.

A randomised study was conducted in 62 patients with advanced breast cancer to assess whether granulocyte-macrophage colony-stimulating factor (GM-CSF) would yield an increase in the dose intensity of a standard-dose CEF regimen through an acceleration of chemotherapy administration. Patients received CEF (cyclophosphamide 600 mg m-2, epidoxorubicin 60 mg m-2 and fluorouracil 600 mg m-2) i.v. on day 1 or the same chemotherapy, plus GM-CSF 10 micrograms kg-1 s.c. starting from day 4, repeated as soon as haematopoietic recovery from nadir occurred. Patients in the CEF + GM-CSF group received chemotherapy at a median interval of 16 days compared with 20 days in the control group. This led to a significant increase (P = 0.02) in the dose intensity actually administered in the third, fourth and sixth cycles: +28%, +25%, +20% respectively. Non-haematological toxicity was mild. GM-CSF had to be reduced or suspended in 50% of patients because of toxicity. Haematological toxicity, mainly cumulative anaemia and thrombocytopenia, was manageable. An increase in response rate for patients with measurable disease, of borderline statistical significance (P = 0.088, P for trend = 0.018), from 42% in the CEF group to 69% in the CEF + GM-CSF group, was observed. This randomised trial indicates that GM-CSF is useful for chemotherapy acceleration. Accelerated CEF + GM-CSF is a moderately dose-intensive regimen that can be administered in an outpatient clinic and is associated with a high objective response.

Adolescent↗
PubMed1994

Angiosarcoma of the residual breast after conservative surgery and radiotherapy for primary carcinoma.

BACKGROUND: Angiosarcoma of residual breast, arising after conservative surgery and radiotherapy for early breast cancer, is a rare tumor, with only 14 cases having so far been documented. The first was observed in 1987 and 7 of the 14 were reported in 1992 alone. METHODS: Here, we present an additional case developing in residual breast 3.3 years after lumpectomy and radiotherapy. The other fourteen are reviewed. RESULTS: Review of data from this series of patients reveals a higher incidence of breast oedema (67%) than that reported in the literature (4%). Another unusual finding is the shorter mean latency period (time interval from radiotherapy to onset of angiosarcoma) noted here (6 years) compared to the more than 10 years reported for other secondary angiosarcomas. CONCLUSIONS: In view of the widespread use of radiotherapy after breast-conserving surgery, and also its lack of benefit in terms of overall survival, every novel complication should be investigated. Given the apparent rise in incidence of this rare tumor over the last few years, doctors should be aware of the phenomenon in order to recognize and define it.

Aged↗
PubMed1994

[Role of magnetic resonance in the follow-up o hepatocarcinoma treated with percutaneous ethanol injection (PEI) or transarterial chemoembolization (TACE)].

The purpose of this study was to assess Magnetic Resonance Imaging (MRI) patterns of hepatocellular carcinoma (HCC) treated with percutaneous ethanol injection (PEI) or Transarterial Chemoembolization (TACE) and, consequently, the potential role of MR Imaging in the follow-up of these lesions. HCC treated with PEI. Thirty-one patients with a single small HCC lesion underwent MR Imaging at 0.5 T before and after PEI. In all cases before and after treatment contrast enhanced Computed Tomography (CT) and US-guided fine-needle biopsy were performed. Twenty-seven of 31 HCC lesions in which complete tumor necrosis was obtained with PEI showed homogeneous hypointensity on SE T2-weighted MR images. This feature corresponded to an unenhanced and low-attenuation area on follow-up contrast-enhanced CT scans. All these lesions were negative for malignant cells at fine-needle biopsy follow-up. In four HCCs, high-signal areas on SE T2-weighted images and high-attenuation areas on contrast-enhanced CT scans were observed, suggesting the presence of residual tumor tissue; these lesions were positive for malignant cells at 6-month fine-needle biopsy. In each case, incomplete tumor necrosis was confirmed at pathologic examination of the surgical specimen. HCC treated with TACE. Twenty-one patients with a total of 36 HCC lesions underwent plain and Gadolinium-enhanced MR Imaging before and after TACE. 10 HCC lesions were later surgically resected; 26/36 lesions underwent MR, CT and angiographic follow-up. At short-term follow-up exams (15-30 days), hypointensity was present on enhanced SE T1 weighted sequences in those lesions (5/10) in which complete tumor necrosis was histologically confirmed. In the remaining 5/10 HCC lesions, persistent viable tumor portions were found at pathology. These areas corresponded to areas on hyperintensity of Gadolinium-enhanced SE T1-weighted images. Hypointensity on both SE T2-weighted and enhanced SE T1-weighted images was a characteristic pattern on long-term follow-up MR images in 21/26 unresected lesions; this finding was correlated with devascularization at angiography; the presence of hyperintense areas on SE T2 weighted and enhanced SE T1-weighted images corresponded to the persistence of hypervascular (viable) areas at angiography.

Adult↗
PubMed1993

In Saccharomyces cerevisiae, protein secretion into the growth medium depends on environmental factors.

In the budding yeast Saccharomyces cerevisiae the cell wall, mainly composed of mannoproteins and glucans, constitutes a barrier to protein excretion in the growth medium. In this paper we have studied the effects of different environmental parameters on excretion of Escherichia coli beta-galactosidase obtained by exploiting the glucoamylase II signal sequence. Excretion of the unglycosylated beta-galactosidase was detectable only in cells grown in rich medium, was affected by temperature (36 degrees C > 30 degrees C >> 24 degrees C) and slightly stimulated by reducing agents. On the contrary, glycosylated proteins, such as alpha-galactosidase and glucoamylase II, were excreted to a good extent under all tested conditions of medium composition, growth temperature and pH. These data indicate that optimization of environmental parameters may help the excretion of heterologous proteins, offering advantages for protein purification.

Culture Media↗
PubMed1993

Potentiation of tumour necrosis factor-mediated cell killing by VP16 on human ovarian cancer cell lines. In vitro results and clinical implications.

Synergism between recombinant human tumour necrosis factor (rHuTNF) and DNA topoisomerase II inhibitor VP16 during the killing of cells has been studied in six human ovarian cancer cell lines (A2774, A2780, SW626, IGROV-1, SKOV3, Pa1) and a cervical carcinoma cell line (Me180). Studies were performed using an assay of colony formation inhibition (drug treatment for 1 h) and a growth inhibition assay (continuous exposure for 20 h). Concomitant treatment of cells with VP16+rHuTNF enhanced cell killing in all the cell lines tested--an effect observed in both short- and long-term cytotoxicity assays. This study suggests that the activity of VP16 in ovarian cancer cell lines might be enhanced by rHuTNF in in vitro models.

Cell Survival↗
PubMed1993

High dose-intensity chemotherapy, with accelerated cyclophosphamide-doxorubicin-etoposide and granulocyte-macrophage colony stimulating factor, in the treatment of small cell lung cancer.

15 patients with small-cell lung cancer were treated with an "accelerated" chemotherapy consisting of standard-dose cyclophosphamide-doxorubicin-etoposide administered every 15 days (as opposed to the usual 21-day intervals) along with granulocyte-macrophage colony stimulating factor (10 micrograms/kg/day) administered prophylactically subcutaneously from day 4 to 13. The primary objective of this study was to examine the possibility of achieving a 50% dose-intensity increase by a shortening of chemotherapy intervals. 9 patients were not able to complete the planned six courses of chemotherapy owing to cumulative haematological toxicity. In fact, while leukopenia was acceptable and constant during treatment, both thrombocytopenia and anaemia progressively worsened with subsequent courses, becoming particularly severe after the 4th cycle when interruption of the treatment was often required. 13 patients who completed four courses of chemotherapy received a median of 96% of the planned dose-intensity. This corresponded with an average relative dose-intensity actually delivered of 1.44 compared with the planned dose-intensity of a standard cyclophosphamide-doxorubicin-etoposide every 21 days. In conclusion, acceleration of cyclophosphamide-doxorubicin-etoposide chemotherapy combined with granulocyte-macrophage colony stimulating factor can lead to a significant increase of dose-intensity but it is feasible only for a limited number of courses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Feasibility of a cyclophosphamide methotrexate and 5-fluorouracil regime intravenously administered with and without granulocyte-colony stimulating factor in surgically treated breast carcinoma].

The aim of this study was to evaluate the feasibility of CMF 1.8-28 regimen, with all three drugs administered intravenously (IV), and to compare the hematologic toxicity of this regimen with or without G-CSF. Patients aged 18 to 65 years with histologically proven breast cancer treated by surgery and without distant metastases were eligible for the study. All patients had to have normal white blood cells (WBC) count (WBC > or = 3000/mm3 and/or neutrophils > or = 2000), and platelets (Plt) counts (> or = 100,000/mm3), and adequate renal and hepatic function. The toxicity was recorded according to World Health Organization Scale. CMF 1.8 regimen was: cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5-fluorouracil 600 mg/m2. The drugs were given IV on day 1 and 8, and cycles repeated every 28 days. G-CSF (5 micrograms/kg/day) was administered subcutaneously from day 9 to 20, starting from the second cycle of chemotherapy. A complete blood count with white-cell differential and platelet count was obtained twice a week. For each patient bone marrow toxicity variables recorded during the first cycle (without G-CSF) were compared with values during the second cycle (with G-CSF). One of 10 entered patients, 1 was not evaluated due to missing data on hematologic toxicity. All patients received chemotherapy with or without G-CSF at the scheduled 28th day. Treatment with G-CSF after CMF 1.8 regimen resulted in a significantly WBC's earlier nadir (average day of nadir 14 vs 17; p = 0.0005), while there was no difference in the average values of WBC at the nadir. Moreover, the average value of platelets recorded at the nadir was significantly lower with the use of G-CSF (average No. of platelets/mm3; 185,111 vs 116,000; p = 0.001). Complete hematologic recovery without and with G-CSF was reached on day 25 and 20 respectively (p = 0.001). CMF 1.8 with IV cyclophosphamide is a feasible regimen with and without G-CSF and can be used in adjuvant setting instead of "classic" CMF in order to improve the low compliance observed when cyclophosphamide is given by mouth. As reported by others, we observed that after standard chemotherapy G-CSF anticipated the nadir of WBC and hastened hematologic recovery (WBC > 3000 and Plt > or = 100,000).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

[Primary empty sella syndrome. Report of 6 cases].

The extension of the suprasellar subarachnoid space through an incompetent diaphragma sellae into the sella turcica is defined as empty sella syndrome (ESS). The primary form arises in the absence of previous pituitary surgery or irradiation. Predominance of obese, middle aged, often multiparous women are generally observed; clinically headaches and slight endocrine alterations are frequent but not characteristic symptoms. Rarely liquor rhinorrhea or visual campimetric defects may occur. The authors report six cases observed in their Departments of Internal Medicine during the last two years; they discuss the aspecific symptoms of presentation and the associated pathologic conditions. Standard skull X rays were negative in half the cases showing the overall poor sensitivity of this examination in detecting ESS. According to the literature no evident abnormality of hypophyseal basal hormone levels was found. Diagnosis was done by high resolution TC or MR which now must be preferred to pneumoencephalography (PEG). Three patients had peculiar pathologic conditions associated with ESS: a very high suspicion of partial insipidus diabetes was made in a man with hypo-osmolar polyuria; one patient without related humoral symptoms had a duodenal carcinoid endoscopically removed and in another primary ESS was associated with Hashimoto thyroiditis. These last two pathologies were never related before associated to primary ESS. The authors conclude that primary ESS is most often a diagnosis made by serendipity, lacking specific signs and or symptoms, whenever an imaging technique (TC or MR) is employed for detecting an unrelated endocranic pathology or the content of an enlarged sella turcica.

Aged↗
PubMed1992

Randomised comparison of weekly bolus 5-fluorouracil with or without leucovorin in metastatic colorectal carcinoma.

148 patients with advanced untreated colorectal cancer were randomised to receive a weekly bolus of 5-fluorouracil (5-FU) 600 mg/m2 alone, with or without leucovorin (LV) 500 mg/m2. 5-FU plus LV produced a higher response rate than 5-FU alone: 23% (5 complete response, 11 partial response) vs. 8% (2 complete response, 4 partial response) (P = 0.03) out of 70 and 72 evaluable patients, respectively. Median survival was 11 months in both groups and median time to progression was not significantly different (P = 0.08). The combined regimen was more toxic than 5-FU alone, as evidenced by (a) a higher percentage of grade 3-4 diarrhoea, 19.5% vs. 8.5% (P = 0.045) and conjunctivitis, 26.5% vs. 5.6% (P = 0.0025); (b) the recording of one toxic death in the combined arm; and (c) the reduction of the median dose intensity of 5-FU actually delivered during the first 2 months of treatment. We conclude that 5-FU plus LV at a price of a higher toxicity is more active than 5-FU alone without improving survival and progression-free survival.

Adult↗
PubMed1992

An outpatient phase I study of a subcutaneous interleukin-2 and intramuscular alpha-2a-interferon combination in advanced malignancies.

The aim of this phase I study was to exploit the potential efficacy of an alpha-2a-interferon (alpha-2a-IFN)-subcutaneous interleukin-2 (IL-2) combination, bypassing the toxicity usually associated with bolus or continuous infusion of IL-2. Therefore, nineteen patients with metastatic malignancies (7 melanomas, 6 renal cell carcinomas and 6 soft tissue sarcomas) were treated according to a dose escalating schedule of subcutaneous IL-2 combined with intramuscular alpha-2a-IFN for 5 days/week for 3 consecutive weeks. Cycles were repeated every 2-4 weeks unless disease progressed. Alpha-2a-IFN (3 MU/die) was given continuously, including during the rest weeks. IL-2 doses were started at 2 MIU/day/sqm and the MTD of 6 MIU/day/sqm was progressively reached. The dose of IL-2 was given twice daily every 12 hours. Both of the cytokines were administered in an outpatient setting. The main side effects were fever, chills, fatigue, hypotension, nausea and vomiting. Toxicity was correlated with IL-2 dose level. It was found to be mild at 2 and 4 MIU/day/sqm, while, in contrast, grade III toxicity was observed only at the highest dose of 6 MIU/day/sqm. However, this grade III toxicity was manageable and did not prevent continuation of the treatment as long as the dose was not increased above 6 MIU/day/sqm. Three patients, one with melanoma and two with renal cell carcinomas, obtained clinical partial responses. In eight patients, stable disease, and in the remaining eight, progression, were observed. The data suggest that the combined use of the two BRMs has manageable side effects and would seem to be efficacious. A phase II study at the recommended dose of 6 MIU/day is now necessary.

Adult↗
PubMed1992

Potentiation by tumor necrosis factor of mitoxantrone cytotoxicity to human ovarian cancer cell lines.

The cytotoxic activity of human recombinant tumor necrosis factor (rHuTNF) (from 0.01 to 10000 U/ml) was assayed on six human ovarian cancer cell lines and one human cervical carcinoma cell line using a crystal violet assay. rHuTNF was cytotoxic to four cell lines (A2780, A2774, SW626, PA1), while 3 cell lines (IGROV1, SKOV3, Me180) were marginally sensitive to its activity. However, under the same experimental conditions rHuTNF markedly enhanced the cytotoxicity of mitoxantrone, a chemotherapeutic drug targeted at DNA topoisomerase II, in six cell lines. The potentiation of mitoxantrone cytotoxicity was not caused by increased drug accumulation after rHuTNF treatment. No significant increase in cytotoxicity to Me180 cell line was seen when rHuTNF was added to mitoxantrone.

Drug Screening Assays, Antitumor↗
PubMed1992

Potentiation of topoisomerase I and II inhibitors cell killing by tumor necrosis factor: relationship to DNA strand breakage formation.

Recombinant human tumor necrosis factor (rHuTNF) synergistically potentiates the cytotoxicity of the topoisomerase I inhibitor camptothecin, and the topoisomerase II inhibitors epidoxorubicin, etoposide, mitoxantrone, ellipticine, actinomycin D and 4'-(9-acridinylamino)methanesulfon-m-anisidide on A2780 human ovarian cancer cell line. Similar synergy was not observed with a combination of rHuTNF and cis-platinum or mitomycin C. When A2780 cells were incubated with rHuTNF simultaneously with camptothecin or mitoxantrone or VP16, increased numbers of DNA single-strand breaks were produced. rHuTNF alone did not induce DNA strand breakage. These data provide evidence that the enhancing effect of rHuTNF is closely related to the DNA damage mediated by topoisomerase-targeted drugs. These observations may have relevance for ovarian cancer treatment.

Camptothecin↗
PubMed1992

An analysis of prognostic factors in response to conservative treatment of postmastectomy lymphedema.

Postmastectomy lymphedema of the upper limb is usually managed conservatively. Patients are often advised to use elastic bandages or sleeves during the day: elastic compression is, in fact, generally considered the mainstay of lymphedema therapy by authors who advocate the addition of cyclical instrumental or physical treatments, such as pneumatic compression or manual lymphatic drainage. The results of elastic compression, however, have never been extensively analyzed. In the present study, we describe the patterns of response during six months of use of a standard elastic sleeve in a series of 120 patients with postmastectomy lymphedema. Univariate and multivariate analyses were performed to identify possible prognostic factors for a better or worse response. Overall, limb measurements were reduced by 14.7 percent, with weight gain after surgical treatment resulting as the only significant independent negative factor: patients who did not increase weight after mastectomy achieved nearly a 25 percent reduction of lymphedema. These results should be considered during the selection of patients for protocols of lymphedema treatment and the analysis of results.

Aged↗
PubMed1991

A pilot study of mitomycin, ifosfamide and cisplatin as outpatient combination chemotherapy for advanced non-small cell lung cancer.

Twenty-one patients with advanced stage, non-small-cell lung carcinoma were treated with a chemotherapy regimen including: mitomycin (6 mg/m2), ifosfamide (3 g/m2), cisplatin (80 mg/m2). The regimen was administered on an outpatient basis. Two patients were lost to follow-up. Among the 29 patients evaluable for response we registered a response rate of 36.8%; 36.8% of patients had stable disease, and 15.7% progressed during treatment. Median duration was 8.7 months and median survival was 11 months. Toxicity was low and easily manageable on an out-patient basis.

Aged↗