Biomedical subjects
Publications and source records attributed to G Bogliolo.
The Authors report their experience with the use of the Olympus Endoloop HX-20L for the prevention of haemorrhages after endoscopic polypectomy. They emphasize the utility of this therapeutic device that will find its right application only in a well selected group of patients.
The Authors report their experience of endoscopic polipectomy. This technique represents a gold standard treatment for polyps of the colon-rectum because it is safe and effective, being correlated with low-risk of complications as perforation and hemorrhage. Hospitality stay was only 24-48 hours. The polyps were histologically examined and grade of dysplasia was determined. The patients underwent surgical resection of the colon when an invasive carcinoma was found.
Haemotoxicity is usually the primary and dose-limiting side-effect of docetaxel (TXT) a semysyntetic analogue of paclitaxel which has acquired an important role in anticancer treatment. This research presents the results of an in vitro toxicity study of TXT on myeloid progenitors obtained from healthy volunteers and assayed as CFU-GM. Peripheral blood mononucleated non-adherent cells (MNAC) were incubated for 24 h at standard conditions with increasing concentrations of TXT and then cultured for CFU-GM assay. At every concentration severe CFU-GM growth inhibition was observed. In a second set of experiments MNAC were sequentially exposed to TXT and then to doxorubicin or cisplatin or vinorelbine or etoposide at appropriate concentrations. In a third set the sequence of exposure was reversed. No difference of CFU-GM growth inhibition was observed between the alternate sequences. These findings suggest that the toxicity on CFU-GM in vitro growth of TXT combinations with other anticancer drugs is sequence-independent.
It is generally agreed that chemotherapy prolongs survival and relieves symptoms more than the best supportive care in advanced colorectal cancer. Since its introduction over 35 years ago, 5-fluorouracil (5-FU) has been the only effective chemotherapeutic option available for the treatment of advanced colorectal cancer. Efforts have focused on the use of various 5-FU-based regimens. A commonly used regimen, frequently extolled as the "gold standard" for clinical trials in advanced colorectal cancer, is the Mayo Clinic regimen; this option has, however, been associated with considerable dose-limiting toxicity. Another approach has involved 5-FU administration by continuous intravenous infusion. In this paper we present our experience on 10 Dukes D colorectal cancer patients treated with 24-hour continuous infusion of biomodulated 5-FU delivered in an ambulatory setting with an intravenous infusional pump. The number of treated patients was admittedly not sufficient to evaluate the clinical response of this 5-FU chemotherapeutic regimen. This is not the goal of our work; however, other rationale for adopting this approach is justified: the regimen has a favourable toxicity profile and can provide considerable benefit in terms of improved quality of life while at the same time the health care costs are alleviated since hospitalization is generally not required.
Authors report their experience in the treatment of adenomas with severe dysplasia and early cancer of the colon-rectum confirming that the endoscopic resection of these lesions is safe and curative when completely removed and no submucosal invasion is found. Between 1995 and 1999, 219 patients underwent colonoscopy and 287 polyps were removed. Histologic examination showed 217 adenomatous polyps (75.6%), 58 non adenomatous (20.2%) and 12 early carcinomas (4.2%). Severe dysplasia was found in 15 adenomas. There were no complications. The Authors focused on 12 patient with early carcinoma and 15 with severe dysplasia. The mean follow-up was 34 months. No recurrences were observed, supporting that this procedure is the treatment of choice in selected cases.
Association of all-trans retinoic acid (ATRA) and amifostine (AMF) might be an alternative in treatment of myelodisplatic syndromes. In this study we undertook a preliminary in vitro research on the effects of a combination of ATRA and AMF on normal hemopoietic progenitors. Mononuclear, non-adherent cells from peripheral blood of normal volunteers, were incubated with AMF, at a the concentration of 500 microM and then cultured for CFU-GM and BFU-E growth adding to culture dishes before gelling ATRA at the concentration 10(-6) and 10(-12)M. Controls were cultures not pre-incubated with AMF, cultures incubated with AMF without addition of ATRA and cultures without addition of any drug. ATRA addition did not have significant effects on hemopoietic progenitors growth. Association of ATRA and AMF do not appear to synergize to stimulate in vitro growth of hemopoietic progenitors.
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Acivicin (AVC), a L-glutamine antagonist, is an intriguing antimetabolite coupling cell growth inhibition activity with differentiating effects. In this in vivo study the influence of acivicin on mice bone marrow hemopoietic progenitors was tested. 10 mg/kg b.w./day of acivicin were i.p. injected in B6D2F1 mice for nine days. Leucocyte and reticulocyte level (in peripheral blood), CFU-S (multipotent stem cells) and GM-CFU (granulocyte-macrophage committed progenitors) content in bone marrow were determined during drug administration and for 14 days thereafter. All tested populations decreased severely during the first days of treatment. The drop was particularly striking for bone marrow CFU-S. The recovery of hemopoietic progenitors, however, began while AVC was still administered. These results suggest that the effects of acivicin on normal mouse hemopoietic system are mainly inhibitory, causing considerable myelosuppression.
For a long time some pesticides (chlordane, lindane, DDT) have been associated with bone marrow aplasia. Little is known on the toxic activity of the herbicides s-triazines on hemopoiesis. We studied the effect of one of these compounds (atrazine) on mouse hemopoietic progenitors (CFU-S and GM-CFC) and on peripheral blood (leukocytes and reticulocytes) after a single i.p. injection of 58.65 mg/kg. The peripheral blood leukocyte level was not modified; on the contrary, reticulocytes dropped severely but recovered promptly. Hemopoietic progenitors were severely hit but they recovered and reached normal levels in a few days. Our results demonstrate a hemotoxic effect of atrazine. However, more data are needed, especially in experiments with chronic exposure.
Trimetrexate (2, 4, diamino -5- methyl - 6 [3, 4, 5, trimethoxyanilino) methyl] quinazoline) (TMQ) is a non-classic folate antagonist that is used as an antineoplastic and antipneumocystis agent with promising results. TMQ and methotrexate (MTX) toxicities are comparable. Leucovorin (N-5-formyltetrahydrofolate) (LV) is used to prevent the toxic effects of MTX. In this study the effects of LV on TMQ induced hemopoietic progenitor damage are studied in a murine model. Changes of pluripotent stem cells (colony forming units spleen, CFU-S), granulocyte-macrophage committed progenitors (GM-CFC), erythroid committed progenitor (BFU-E) levels in the bone marrow were followed after administration to mice of a single dose of TMQ or of simultaneous injection of TMQ and LV. Results show that the latter significantly reduces the effects of the former on peripheral blood cells and on hemopoietic progenitors.
Several antiviral compounds showed a toxicity or hemopoietic progenitor cells, 2', 3' Dideoxycytidine (ddc) is the most potent drug in vitro against human T cell lymphotropic viruses and is now being tested on patients with AIDS and AIDS-related complex. We studied its toxicity on mouse hemopoietic progenitors. Results reported here show a toxic activity of ddc but further studies are required to ascertain whether this toxicity is of significance during clinical application.
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Data are presented on the general and hematological toxicity of a cisplatin (DDP), 5-fluorouracil (5-FU) and alpha interferon (IFN-alpha) association in patients with stage III B or IV non small cell lung cancer (NSCLC). Twenty patients received DDP (100 mg/mq i.v., day 1) and 5-FU (750 mg/mq/day i.v. continuous infusion, days 1 to 4). In ten of these patients IFN-alpha (3 MU s.c., three times weekly, days 1 to 21) was added. General and hematological toxicity was of a similar degree in both groups. Recombinant granulocyte colony stimulating factor (G-CSF; 5 micrograms/kg b.w. s.c. days 7 to 18) induced a sharp increase in peripheral blood GM-CFU level in patients receiving DDP and 5-FU but not in DDP, 5-FU, IFN-alpha treated patients. The results appear to indicate that IFN-alpha modulation of a DDP, 5-FU combination induces an acceptable degree of toxicity.