Biomedical subjects
Publications and source records attributed to F Simone.
High-dose cyclophosphamide can be used to obtain haematological stem cells from the peripheral blood. In this paper we analyse the dynamics of appearance of cells with these characteristics, together with the impact of this drug on the immunological system. Cyclophosphamide seems to possess immunomodulating effects even at high doses.
The vagal cardiac activity was compared in two groups of patients with a history of syncope. Sixty-one patients (Group A) experienced vasovagal reactions induced by head-up tilt, 61 sex and age-matched patients (Group B) did not. No significant differences in vagal cardiac activity between two groups were found. Group A was further subdivided into two subgroups: A1 (14 patients) with stronger, and A2 (47 patients) with smaller cardioinhibition. Again, vagal cardiac activity was not different between two subgroups. Thus, the baseline vagal cardiac activity ('tone') seemed not to be helpful in predicting the susceptibility to vasovagal orthostatic syncope and in discriminating the patients with stronger cardioinhibition.
Lonidamine (LND), previously reported as a useful antitumor substance in combination with physical or chemical agents, has been studied for its capacity in increasing pharmacological elimination in vitro of residual tumor cells from human bone marrow. Different drugs were tested in association with LND against mixtures of human bone marrow and a tumor cell line, clonogenic human leukemic blast progenitors, and normal human bone marrow precursors. The results demonstrated that LND increased the efficacy of anthracycline derivatives (Adriamycin, Mitoxantrone) both on the tumor cell line and on the leukemic blast progenitors, while VP-16 or ASTA-Z 7654 was not affected by the same substance. The toxicity on normal stem cells reflected that of each drug and was not modified by the addition of LND. While a consistent dose-dependent CFU-GM reduction was observed immediately after treatment with the different drugs, a complete recovery was reached after 7 and 14 days of long-term marrow cultures. Because of the low toxicity and the efficacy demonstrated in association with certain agents in increasing tumor cell elimination in vitro, LND could play an important role in in vitro purging prior to autologous bone marrow transplantation.
The feasibility and the antileukemic activity of a double sequential autograft has been evaluated in 3 patients affected by AML in first hematological relapse. Bone marrow collection and cryopreservation was performed twice: during first complete remission (CR) and during second CR. At the time of relapse patients underwent first ABMT with BAVC preparative regimen achieving a second CR without any remarkable complications. After 4, 5 and 4 months respectively a second ABMT was performed with a different preparative regimen, consisting of cyclophosphamide and fractionated total body irradiation (Cy + F-TBI). A delay in platelet recovery was observed after the second procedure as compared to the first, while neutrophils recovery was comparable. 1 patient died in CR (on day +91 after second ABMT) of interstitial pneumonitis. 2 patients are alive and well without evidence of disease after 46 and 53 months of unmaintained second CR. This experience shows the high antileukemic potential of treatment with a double sequential autograft; 2 relapsed patients in fact are long-term survivors with a second CR longer than the first.
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Two AML patients, whose leukemic clonogenic cells totally reacted to the anti-lactofucopentaose III S4-7 monoclonal antibody (MoAb), underwent autologous bone marrow transplantation, in first complete remission, after in-vitro purging with S4-7 MoAb and complement. After ablative chemotherapy (BAVC regimen) and reinfusion of S4-7 purged cells, regeneration of marrow cells occurred with prompt recovery of granulopoiesis and erythropoiesis. A more delayed platelet recovery was observed. The two patients are in complete remission at 20 and 11 months from ABMT. The results indicate that immunologic purging with S4-7 MoAb is safe and suitable for selected AML patients undergoing ABMT.
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The efficacy of autologous bone marrow transplantation in leukemia and lymphoma may depend upon the selective elimination of malignant cells from human bone marrow in vivo and in vitro. A cyclophosphamide derivative (ASTA-Z 7654) and etoposide (VP16-213) have been tested on lymphoma and leukemia cell lines in a model that may represent a bone marrow situation in complete remission. The influence of different concentrations of normal mononuclear cells and tumor cells in this model and the activity of the two chemotherapeutic agents in the presence of bone marrow cells or peripheral blood cells were evaluated. A major inhibitory effect was observed using the two agents in combination; low doses of ASTA-Z and VP16 consecutively added to the mixture of malignant cells and normal mononuclear cells resulted in a greater elimination of tumor line cells than with ASTA-Z alone at the current 100 micrograms/ml dose. In contrast, no major toxicity on normal human bone marrow precursors was observed; the effect of treatment on hemopoietic recovery with the two agents either alone or in combination was evaluated on CFU-GM growth after long-term bone marrow cultures. Despite a profound growth inhibition at day 0, a recovery was observed in all cases after 7 or 14 days. The use of multiple chemotherapeutic agents in the treatment of bone marrow in vitro could decrease the possibility of malignant cells surviving while sparing normal bone marrow precursors.
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Thirteen patients with AML in first relapse were treated with high dose combination chemotherapy followed by cryopreserved autologous bone marrow transplantation (ABMT). The first four patients received the COATA-Roma regimen, consisting of CTX, VCR, CA, 6-TG and ADM; nine additional patients received the BAVC regimen consisting of BCNU, AMSA, VP-16 and CA. A median of 1.6 X 10(8) fractionated nucleated bone marrow cells/kg body weight were reinfused. The median of GM-CFU-C recovered was 4.7 X 10(4)/kg. Out of 13 patients, 10 (76.9%) achieved CR, 3 had profound aplasia and died from hemorrhagic or infectious complications. Of the 10 patients who achieved CR, 1 died after 1 week from heart failure, 5 relapsed respectively 17, 20, 21, 21, 42, weeks after ABMT, 4 are still in CR after 2+, 14+, 17+, and 120+, weeks. Of the 9 patients treated with BAVC regimen, 8(88.8%) achieved CR. Four patients relapsed after a median of 19.7 weeks and 4 are still in complete remission. Of interest is the fact that the second complete remission of one patient is longer than the first one, despite the fact that marrow was not purified by any in vitro treatment. In conclusion we can say that BAVC regimen is highly effective in obtaining second complete remission in patients with AML and prolonged disease free survival can be achieved at least in a small number of cases.
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On the basis of an existential analysis (Daseinanalyse), the authors consider the suicide, at age 42, of Cesare Pavese, one of the most important Italian poets and writers of the post-World War II period. It is found that in his poems, his novels, and particularly his letters and diary the idea of suicide was present in his consciousness since adolescence; year by year it is possible to follow the development of his ideas and fantasies about suicide. Incapable of establishing authentic communication with others, Pavese narrowed his existential horizon to the point of being less and less capable of living in the world and projecting himself into the future. From these considerations it is concluded that Pavese's acute feeling of incapacity caused him to have lasting experiences of failure that brought him to view suicide as the only way to free himself from his own torment.
After pointing out that in literature studies concerning the anthropo-phenomenologic aspects of the existence of subjects suffering from epilepsy are very scanty, the Authors dwell upon the opportunity of deepening this study which may allow a better knowledge of the complex problems of the patient. These problems should be neglected if only the biologic side of the disease was taken into consideration.
The Authors discuss the case of a 23-year-old man who manifested the characteristic symptomatology of a progressive mental deterioration and disorders in behaviour displaying themselves as apathy, speechlessness, progressive detachment from environment and considerable slovenliness. It has been also emphasized a situation which suggest Kleist's melokinetic apraxia. In addition to usual routine laboratory studies, the patient underwent a EEG, an encephalography and psychodiagnostic investigations executed by a means of series of tests in order to ascertain his intellectual efficiency and outline his psychological profile. On the basis of the investigations made and after a discussion concerning possible differential diagnoses, the Authors have reached the conclusion that it is an uncommon case of juvenile Pick's disease.
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