Biomedical subjects
Publications and source records attributed to F Franchi.
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A double-blind, randomized, group comparative study was performed in hypogonadal male patients in order to compare the effects on sexual activity and mental state of testosterone undecanoate (TU) and mesterolone (M). The TU-treated group contained 12 patients, and the M-treated group contained 14 patients. The variables of sexual activity and of mental state were scored an evaluated statistically by means of the nonparametric randomization test for 2 independent groups. TU induced a marked improvement of the sexual activity and of the mental state. After 4 weeks of treatment the effects were significantly better than in the M-treated group: libido (p less than 0.001), erections (p less than 0.01), ejaculations (p less than 0.05) and mental state (p less than 0.001).
Although the role of biogenic amines in the regulation of gonadotropin release has been studied extensively, the precise role of dopamine (DA) in stimulating LHRH and/or LH release is still controversial. In the present study 6 eugonadal women, aged 20-30, were given an LHRH infusion on day 6 of the menstrual cycle and the pattern and magnitude of LH and FSH responses were estimated. On day 6 of the next cycle, the experiment was repeated and DA was also infused beginning 60 min after the start of the LHRH infusion. Following LHRH infusion plasma LH showed a marked and significant rise with a mean peak increment at 4 h, and with a cumulative response (CR) of 9136 +/- 955 mIU/ml/6h. The pattern of FSH response tended to parallel that of LH; however, mean peak increment at 4 h and a CR of 2640 +/- 169 mIU/ml/6h were markedly lower. Plasma prolactin levels remained unchanged. Addition of DA to LHRH at 60 min evoked a significantly greater mean peak LH increment at 4 h and a CR of 15514 +/- 1836 mIU/ml/6h (p less than 0.001). There were no significant changes in either mean FSH peak at 4 h or in the CR (3257 +/- 309 mIU/ml/6h). As expected, a highly significant (p less than 0.001) decrease in circulating PRL from 12.1 +/- 3.1 to 3.0 +/- 1.5 ng/ml was seen during DA infusion. In conclusion, DA given by iv infusion enhancement LH response to LHRH in eugonadal women under the conditions of the present investigation, supporting a role for a dopaminergic component in the control of LH release in women.
We evaluated the activity of ruboxyl (Rbx), a nitroxyl analogue of daunorubicin (Dauno), in experimental models of hepatic metastases from colorectal carcinoma (CRC) and compared it with its parent compound and with 5-fluorouracil (5FU). In mice treated by intraperitoneal injections Rbx and 5FU proved more effective than Dauno: the Index of Inhibition of Metastases in comparison with controls was 43% for Dauno, 70% for 5FU and 84% for Rbx. In BDIX rats implanted with the syngeneic cell line DHD K12/TRb, both Rbx and 5FU, administered as a continuous intravenous infusion for 7 days, reduced the development of liver metastases from a median of 23.8 +/- 2.16 for controls to 3.2 +/- 1.3 for 5FU and 1.0 +/- 1.4 for Rbx (p < 0.0001 versus controls for both treatments): the comparison of Rbx and 5FU showed a trend in favour of this new anthracycline. Median survival was prolonged from 40.6 +/- 3.4 days in controls to 56.0 +/- 5.8 days with Rbx and 58.0 +/- 4.69 days with 5FU. Considering that in a phase I study Rbx showed only minor and manageable toxic side effect, its activity in the clinical treatment of CRC metastases may deserve further attention.
BACKGROUND: Age-related physiological changes may lead to an increased toxicity of chemotherapy in the elderly, thus making tumor treatment difficult in this increasing subset of patients. OBJECTIVE: Since many trials claimed a favorable therapeutic index with raltitrexed, the aim of our preliminary study was to evaluate the anticancer activity and the toxic profile of this drug in the elderly. METHODS: Thirteen elderly patients with colorectal cancer, aged 75-90 years, were enrolled in a monochemotherapy treatment with raltitrexed. Due to their advanced age, the drug was administered with a 33% reduction of the dose. RESULTS: One partial response, four disease stabilizations, and two disease progressions were observed in 7 patients with advanced colorectal cancer. The patients with response or disease stabilisation had a satisfactory time to progression. Four out of 6 patients treated in the adjuvant setting for Dukes' C colorectal cancer remain disease free at observation periods of 15+ to 29+ months. Toxicity was virtually absent in all patients. CONCLUSIONS: The activity of monochemotherapy with raltitrexed appears to be appealing, above all because it is observed in the absence of toxicity. Though recent reports suggest some concern about severe complications of treatment with raltitrexed, administration of reduced doses of this drug seems to be a putative therapy for those patients who, because of their age, are highly susceptible to the adverse effects of chemotherapy.
The nature of the immune response to the tumor cell is complex and has yet to be clearly defined. Although past research has foscused on the cytotoxic effect of T lymphocytes versus tumor cells, it has been shown in animal studies that B lymphocytes may also be implicated. Lymphocytes from patients with respiratory and digestive tract tumors were studied. B and T lymphocytes of peripheral blood and of draining lymph node tumors were studied using the following techniques: E rosettes (marker for T cells); membrane Ig, EAC rosettes, aggregated-Ig (marker for B lymphocytes); PHA and PKW in vitro response of lymphocytes using tritiated thymidine incorporation. It was observed that both groups of patients had normal or depressed B and T populations. PHA response was depressed in the majority of the cases with lung tumor. No difference was observed between lymphocytes from peripheral blood and from lymph node suspensions. As in normal lymph nodes the EAC rosettes were constantly observed in the cortical area of lymph node draining tumors. The immune defect observed in part of these cases is discussed in relation to the local and general immunological factors probably responsible for this defect.
AIMS AND BACKGROUND: There is much interest in nitroxyl derivatives of cytotoxic agents. We evaluated the potential activity of magnizil, a derivative of 5-fluorouracil, on human gastrointestinal tumors in 3 different in vitro and in vivo experimental models. METHODS: The activities of magnizil and 5-fluorouracil were comparatively determined in vitro on the HT29 cell line by a clonogenic assay and on tumor clinical specimens by an antimetabolic assay. The activity of both the drugs against human tumors was also assessed in mice with the subrenal capsule assay. RESULTS: A similar cytotoxic activity was found for magnizil and 5-fluorouracil on the HT29 cell line. As regards human tumors, a lower activity was observed for the nitroxyl derivative than for 5-fluorouracil, with response rates of 25% and 50%, respectively, at comparable concentrations. Moreover, among the tumors transplanted in the subrenal capsule of mice, two were sensitive to magnizil and 3 to 5-fluorouracil. CONCLUSIONS: Even though experimental results on human tumors indicate a somewhat lower activity for magnizil than the parent compound, its low toxicity and the possibility to clinically use high doses suggest the opportunity to further investigate the potential of this new anticancer agent on larger series of colorectal cancers in experimental systems.
The sympathetic adrenal (SA) activity can be modulated by dopamine (DA) through D2 receptors. In man, using D2 antagonists, it has been demonstrated that endogenous DA plays an inhibitory modulation of the SA system during high degree of SA activation. D2 agonists are able to induce a decrease in norepinephrine (NE) release either in vitro or in vivo. This effect leads, in vivo, to a decrease in blood pressure (BP) and to an activation of arterial baroreceptors. Therefore, in vivo, the D2 mediated inhibition of epinephrine (E) release, which is clearly demonstrated in vitro, is overwhelmed by the baroreceptor-mediated activation of the splachnic nerve. As a consequence, the in vivo administration of D2 agonists can induce a different effect on the net peripheral sympathetic tone of an organ, depending on the balance between the degree of the baroreceptor-mediated sympathetic activation and the inhibitory D2-mediated inhibition of NE release at the tissue level. In the present paper we investigated the in vivo effect of placebo (PL) or acute oral bromocriptine (BC) administration on plasma CA and on the cardiac sympatho-vagal balance of 7 normal volunteers, as assessed by power spectral analysis of heart rate (HR) variability (autoregressive method), either in resting or sitting position. Low frequency (LF) and high frequency (HF) components, both expressed in normalized units (nU), and LF/HF ratio were calculated. BC caused a decrease in BP, plasma NE and no change in HR in resting and sitting position. Plasma E increased in sitting position. At the heart level, after BC, we observed, during rest, an increase in LF and LF/HF ratio and a decrease in HF while in sitting position LF did not increase further. These data show that BC, while reducing BP through a decrease of plasma NE, increases LF/HF ratio (sympathetic tone) without any change in heart rate. These data seem to confirm that BC causes an inhibitory modulation of the SA system acting predominantly at the periphery through D2 presynaptic receptors.
The possibility to administer chemo-hormone- and immunotherapy on an out-patient basis has greatly increased because of the progress reached in the management of the out-patient departments. The improved knowledges on tossicological, pharmacodynamic and therapeutic data as well as the advent of the cyclic schedules determined the feasibility of medical treatments even when they are combined with surgical and/or radiotherapeutic modalities. To the patient, the possibility to be carefully and effectively treated on out-patient clinic, renders more acceptable, both from a psychologic and economic point of view, even a prolonged combined treatment. On the same time, also the Institutions have some advantages both on their organization (a shorter median stay in hospital and consequently a reduced waiting list) and for their scientific program (increased number of patients who can be treated according to a therapeutic program, possibilities to obtain statistically valuable information on the treatment program of a given disease and on the knowledge of its natural history). The last five year increasing activity of the Out-Patient Clinic for Medical Oncology Treatment of the Istituto Nazionale Tumori of Milan is illustrated in Text-figure 1, while Text-figure 2 represents its actual organization; this is obviously of a multidisciplinary type, both on its diagnostic and therapeutic phase. Table 1 shows the activity carried out in 1975; it is noteworthy that 2,570 patients have been followed, thus accounting for a total of 20,164 medical examinations and/or intravenous drug administrations. Table 2 presents the incidence of the different types of neoplasia followed in the out-patient department: the large majority was represented by breast cancer (40%); followed by malignant lymphomas (31.5%) and pediatric tumors (7.5%). During 1975, 22 therapeutic protocols have been applied, 10 of which (table 4) required an initial hospitalization and 12 (table 5) could be entirely carried out in the out-patient department. As shown in Table 6 chest x-rays accounted for 52% and skeletal survey for 18% of the 11.906 radiological examinations. Table 7 shows the number of off-hand required radiological reports carried out for patients not geographically accessible who, in one signle day, could have their radiological, and medical examinations as well as their hemogram and treatment performed. A total 467 scintiscans have been required, 86% of which of the liver (table 8). The hemato-pathology unit counted out about 16,000 hemograms with platelets (table 9). The hemograms were always performed within 1-2 hours with immediate communication of the counts to the out-patient department. In order to modify clinical situations which were deteriorated because either of the disease or of the treatment 358 blood units were transfused.
In a 19 year old patient suffering from CMC since the first months of life, clinical improvement accompanied by correction of the immunologic defect was achieved by Transfer Factor therapy. After 12 months from the last administration of Transfer Factor the improvement persisted. The positive outcome of the treatment in this disease is not constant. Possibly only patients with cellular immunologic defects are susceptible of a favourable response, moreover it is thinkable that the quality of Transfer Factor and the dosage administered must play a role.
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The authors investigated the role of atrial natriuretic peptide (alpha-hANP 99-126) in essential hypertension by evaluating some hemodynamic and renal effects of acute peptide infusion (1 micrograms/kg for 1 min + 50 ng/kg for the following 20 min) in fourteen subjects: eight mild to moderate, untreated, essential hypertensives (EH) and six normotensive (N) controls, during 2 hour-clearance periods, the 1st after ANP infusion, the 2nd during placebo (PL) administration. The double-blind study was carried out after the patients had rested and fasted overnight. It showed no significant changes in heart rate (HR); instead, compared with placebo, mean blood pressure (MBP) decreased significantly in both groups, beginning from the 3rd min after ANP infusion was begun (N: PL = 87.04 +/- 1.7 mmHg, ANP = 80.9 +/- 3.7 mmHg, p less than 0.0001; EH: PL = 102.6 +/- 3.2 mmHg, ANP = 97.7 +/- 5.9 mmHg, p less than 0.01). Among the urinary parameters we considered, cyclic GMP (cGMP) increased after ANP infusion in all subjects (N: PL = 129.1 +/- 56.3 pmol/mL, ANP = 199.2 +/- 85.4 pmol/mL; EH: PL = 106.55 +/- 56.2 pmol/mL, ANP = 220.03 +/- 92.7 pmol/mL, p less than 0.05); diuresis showed a prompt and significant increase in EH (N: PL = 837 +/- 368 mL, ANP = 1066 +/- 340 mL; EH: PL = 713 +/- 286 mL, ANP = 1043 +/- 280 mL, p less than 0.005), and so did natriuresis (N: PL = 23 +/- 14.3 mEq/L, ANP = 33 +/- 14.6 mEq/L; EH: PL = 25.6 +/- 8.9 mEq/L, ANP = 41.9 +/- 13.8 mEq/L, p less than 0.01); urinary potassium excretion was significantly reduced in EH (N: PL = 18.7 +/- 12.9 mEq/L, ANP = 14.2 +/- 6.9 mEq/L; EH: PL = 16.5 +/- 7.9 mEq/L, ANP = 10.7 +/- 4.8 mEq/L, p less than 0.005), while no changes were noted in glomerular filtration rate (GFR), estimated as creatinine clearance, urinary magnesium, albumin and aldosterone excretion. To investigate other potential mechanisms involved in renal effects of ANP, the urinary excretion of both prostaglandins 6-cheto PGF1-alpha and thromboxane B2 (TXB2), and dopamine were studied. The results showed only a significant decrease of dopamine urinary excretion in EH after ANP administration (N: PL = 50.4 +/- 28.7 micrograms/L, ANP = 45.0 +/- 29.7 micrograms/L; EH: PL = 47.3 +/- 21.5 micrograms/L, ANP = 27.1 +/- 12.7 micrograms/mL, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
High free tryptophan (F-TRP) plasma levels are found in cancer patients (CP). F-TRP plasma concentrations are affected by the levels of its carrier, albumin (ALB), and free fatty acids (FFA) competing with TRP for ALB binding sites. The lack of correlation between F-TRP, ALB and FFA in CP suggests a tumor-dependent effect on the rise in F-TRP. To verify this hypothesis, F-TRP, ALB and FFA levels were assayed in 12 lung and 16 breast CP susceptible to radical surgery, before and 15 days after surgical removal of the tumor. F-TRP levels significantly decreased after tumor ablation. Since no correlation was found between F-TRP, ALB and FFA variations, it is conceivable that the tumor itself may be responsible for the high F-TRP levels in CP.
Four cases of multiple myeloma (MM) are reported in which the coexistence and/or the alternance of different plasma cell clones were observed. Genetic instability is typical of all tumors but in MM it is particularly striking due to the M component marker. In this respect, malignancies reveal the presence of an unremitting competition of different cell populations for the phenotype prevalence. When this phenomenon is related to the clinical picture it is possible, as in our cases, to ascertain that the appearance of new clones often corresponds to significant changes in the disease evolution.
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Six patients with high-risk multiple myeloma and one patient with primary amyloidosis were treated with a melphalan-peptichemio-prednisone association (PMP). The response trend seems promising, also in view of the low regimen bone marrow toxicity, but further studies could better evaluate the optimal PMP scheduling and peptichemio side effects.
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