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Biomedical subjects

F Mauro

Publications and source records attributed to F Mauro.

At least 37 records · Page 2Linked to original sources

The importance of heterogeneity and of multiple site sampling in the prospective determination of deoxyribonucleic acid flow cytometry.

Multiple fresh specimens from 59 nonsmall cell carcinomas of the lung, 38 carcinomas of the gastric tract and 55 carcinomas of the colon and rectum were analyzed by deoxyribonucleic acid (DNA) flow cytometry (FC) after radical resection to evaluate tumor ploidy as an independent prognostic factor. The minimum follow-up period was five years (range of five to ten years). Aneuploidy was observed in 98.0 percent of carcinomas of the lung, in 70.9 percent of carcinomas of the colon and rectum and in 63.1 percent of carcinomas of the gastric tract. FC DNA heterogeneity, in terms of different number of DNA stem lines or different DNA indices between core and periphery, or both, was found in 50.0 percent of carcinomas of the lung, 47.0 percent of carcinomas of the colon and rectum and in 34.5 percent of carcinomas of the gastric tract. A diploid pattern was more frequently observed in less advanced stages of the gastrointestinal tract. By univariate analysis (Kaplan-Meier), patients with carcinoma of the lung with hypodiploid or hypertetraploid peaks, or both, and aneuploid gastric tumors had poorer prognosis. These differences were only marginally significant. Cox analysis demonstrated that the single most important prognostic variable for predicting the overall survival rate was the stage of disease. Tumor DNA content can be considered a marker of advanced stages, particularly in tumors of the gastrointestinal tract, but there is no evidence that it is an independent prognostic variable able to predict long term survival in patients who have been radically resected.

Adenocarcinoma↗

[Effects of beta blocking agent iontophoresis by modulated sinusoidal current].

The action of the transcutaneous application of propranolol using modulated sinusoidal current iontophoresis was studied. When this way of administration is used, the drug, while maintaining its negative chronotropic effect, loses the negative inotropic one. Investigations were performed on 58 men aged 32 to 62 who underwent an aortocoronary bypass for myocardial ischemia. Thirty-four patients had already had myocardial infarction. The drug reduced the heart rate and increased cardiac contractility. Moreover, the study showed that only the levogyral isomer of propranolol (the only active one) passes through the skin.

Adrenergic beta-Antagonists↗

[Meteoropathy: a syndrome continuously on the increase].

The authors describe the different kinds of meteoropathies, pointing out how these disorders are becoming ever more frequent in countries belonging to the consumer and welfare society due to the progressive lowering of body resistance and immunologic responses. These "unfavourable meteosyndromes", as meteoropathies should be called, develop when wave disturbances arrive, and are more manifest and persistent in subjects with neurologic disturbances, i.e. in the presence of anxiety, stress, hypertension, coronary artery disease, arthropathy, hyperthyroidism, etc. The different moments in which meteoropathies are more frequent and the possible therapies are also discussed.

Climate↗

Cytokinetic investigation of lung tumors using the anti-bromodeoxyuridine (BUdR) monoclonal antibody method: comparison with DNA flow cytometric data.

In order to investigate the cytokinetics of malignant tumors and non-malignant lesions of the lung, tissue samples from 57 patients affected by non-small-cell carcinoma (NSCLC), small-cell carcinoma (SCLC), and benign and inflammatory lesions have been analyzed using the BUdR monoclonal antibody (MAb) method. This method is based on the preparation, at the time of surgery, of viable monocellular suspensions (using collagenase and DNase treatment) and the concomitant administration of BudR. The percentage of BudR-labelled cells was monitored by fluorescent microscopy using an FITC-labelled second antibody. In NSCLC, each histological group showed a wide range of labelling index (LI) values. On the contrary, SCLC exhibited a more homogeneous kinetic behaviour as evidenced by a narrowly distributed, higher LI. Tumors shown to be diploid by flow cytometry did not show a lower LI than aneuploid tumors. Furthermore, differences were constantly observed between the S-phase percent calculated using BUdR and that calculated using the DNA flow cytometric (FC) histogram, the latter always showing higher S-phase values. In an attempt to study the intra-tumor proliferative heterogeneity, multiple-site sampling was performed. Proliferative heterogeneity seemed to be higher inter-tumor than intra-tumor. Finally, a positive correlation (p less than 0.05) was found between LI and the actual doubling time (DT) of the primary tumor mass, evaluated using sequential radiographs. In conclusion, the present BUdR method can be considered a useful source of relevant information on in vivo cell growth, in parallel to other clinical (DT) and biological (DNA content) approaches.

Adenocarcinoma↗

Flow cytometric analysis in colorectal carcinoma: prognostic significance of cellular DNA content.

The prognostic value of DNA ploidy status was evaluated prospectively in 70 patients with colorectal carcinoma. Cellular DNA content was measured by flow cytometry from fresh specimens with multiple site sampling. Seventy-five percent of cases exhibited a DNA aneuploid pattern. In a univariate analysis, DNA ploidy status showed a statistically significant correlation with survival (p less than 0.05), weaker than Dukes' stage (p less than 0.001). No correlation was observed between survival and presence of multiple DNA stemlines. In a multivariate analysis, Dukes' stage was the strongest prognostic indicator (p = 0.01) while DNA ploidy status did not show an independent prognostic value. It is concluded that DNA ploidy status is associated with pathological features of aggressive malignancy, but it does not have a determinant role in predicting survival.

Adenocarcinoma↗

Sequential evaluation of gastric intraluminal prostaglandin E2 release, acid secretion and DNA-flow cytometry in N-methyl-N-nitro-N-nitrosoguanidine gastric carcinogenesis in the rat.

The study was initiated to evaluate the sequential changes of gastric intraluminal prostaglandin E2 (PGE2), gastric acid secretion and of the DNA-flowcytometric patterns during gastric carcinogenesis induced by 45-week N-methyl-N-nitro-N-nitrosoguanidine (NG) administration in the rat. Twenty male chronic gastric fistula Sprague-Dawley rats received NG solution (120 mg/l) for 45 weeks and 20 were used as controls. Samples of gastric juice (1 h) were obtained from all animals under basal conditions and every 5 weeks until the end of the experiment. Aliquots of gastric juice were titrated with 0.1 N NaOH. Other aliquots were extracted with ethylacetate and processed for specific PGE2 RIA. On the day following gastric juice collection a gastric lavage and gastric biopsies (n = 4) were obtained through the fistula and processed for flowcytometry. All surviving animals were killed after 45 weeks and histology was obtained. The incidence of cancer in NG treated chronic gastric fistula rats was 66%. Flowcytometry segregated at an early stage (30-35 weeks) those animals which were to develop gastric carcinoma from those which were not. Administration of NG decreased gastric secretion volume, acid and intraluminal PGE2 concentration both in animals developing and not developing cancer. During the last 10 weeks a sharp rise in gastric intraluminal PGE2 concentration was observed in tumor-bearing animals only probably due to production by tumor cells. Prostaglandin deficiency may contribute to the NG-induced mucosal damage and may be involved in gastric carcinogenesis.

Animals↗

Flow cytometric DNA analysis of the human cervix affected by human papillomavirus and/or intraepithelial neoplasia.

The relative DNA contents of 164 cellular samples from 59 patients affected by the viral cytopathic effects (VCE) of human papillomavirus (HPV) infection and/or by cervical intraepithelial neoplasia (CIN) and 12 cellular samples from 12 normal donors were analyzed by flow cytometry (FCM) with the aim of correlating the cytometric measurements with the morphologic and etiologic parameters. The unselected group of 59 patients was found to be characterized by statistically significant differences in average ages in the VCE and CIN (31.4 years) and CIN only (44.8 years) subgroups. Of the pathologic samples, 32 (54%) exhibited at least one cell subpopulation with an abnormal DNA content; in all but 2 of those cases, a diploid cell subpopulation was also present. The results indicate a relationship between the FCM ploidy and the morphologic classification, as shown by the increase in the occurrence of subpopulations with abnormal DNA contents from VCE only (38%) to VCE + CIN 1 (57%), to VCE + CIN 2/3 (70%). These results suggest that cytometric parameters, in association with the determination of the HPV types and in parallel to the colpocytohistopathologic criteria, can contribute to a more accurate characterization of cervical lesions in diagnostic and prognostic terms.

Adolescent↗

Cytogenetic follow-up after allogeneic bone-marrow transplantation for Ph1-positive chronic myelogenous leukemia.

Serial cytogenetic studies were carried out on 36 patients with Ph1-positive chronic myelogenous leukemia treated with allogeneic bone-marrow transplantation from unlike sex (21 patients) or like sex (15 patients) donors. Fourteen of the 21 sex-mismatched and 12 of the 15 sex-matched donor marrows were T cell depleted. Disease relapse was documented in 19 of the 26 patients who received T cell-depleted marrow, and in none of the 10 patients who received non-T cell-depleted marrow. In the group of patients with unlike sex donor, a triple donor/normal recipient/Ph1-positive recipient or a double donor/Ph1-positive recipient chimerism was documented during the subsequent months, while on alpha-interferon treatment for relapse. Two of these patients subsequently showed a complete disappearance of the Ph1 chromosome. Unstable and/or stable, clonal or non-clonal chromosome changes were detected in Ph1-positive cells from 12 of the 19 patients who relapsed. Analysis of the identified stable changes showed a non-random distribution of breakpoints with clustering to chromosome nos. 1, 4, 7 and 12.

Adolescent↗

[Primary duodenal lymphoma. Communication of a case].

Primary malignant lymphoma of the duodenum is a rarity. A case of primary non-Hodgkin lymphoma of the duodenum is reported. Symptoms, signs, radiographic and endoscopic findings are discussed. C.T. with C.V.P. were performed in addition to subtotal pancreatico-duodenectomy Follow-up, after one year, did not show any signs of recurrence.

Aged↗

Automatic analysis of flow cytometric DNA histograms from irradiated mouse male germ cells.

An automatic procedure for recovering the DNA content distribution of mouse irradiated testis cells from flow cytometric histograms is presented. First, a suitable mathematical model is developed, to represent the pattern of DNA content and fluorescence distribution in the sample. Then a parameter estimation procedure, based on the maximum likelihood approach, is constructed by means of an optimization technique. This procedure has been applied to a set of DNA histograms relative to different doses of 0.4-MeV neutrons and to different time intervals after irradiation. In each case, a good agreement between the measured histograms and the corresponding fits has been obtained. The results indicate that the proposed method for the quantitative analysis of germ cell DNA histograms can be usefully applied to the study of the cytotoxic and mutagenic action of agents of toxicological interest such as ionizing radiations.

Animals↗

Radiation-induced diploid spermatids in mice.

Diploid elongated spermatids of mice were enriched by flow cytometry and cell sorting using a new type of sorter (Partec). The sorted abnormal spermatids were identified morphologically and by nuclear area integration. The radiation-induced increase in the frequency of diploid elongated spermatids was monitored with time following acute X-ray exposure of mice. Dose-response curves for acute 60Co-gamma and 14 MeV neutron irradiations yielded an RBE value of 4.3 for the doubling of the control level.

Animals↗

A stochastic model of the acquisition of drug resistance during antineoplastic chemotherapy.

A stochastic model is proposed to simulate the phenomenon of acquisition of genetic resistance by a tumor cell population treated with antineoplastic cytotoxic agents. In the model, stochastic differential equations are numerically integrated to simulate the expected response after treatment with two different agents. The model takes into account the initial number of cells, the sequence of the agents, the time intervals between administrations, the birth and death rates of the untreated cells, the probabilities of mutations to resistance, and the induced cell-killing kinetics. Satisfactory demonstration runs of the model indicate that it could represent a useful tool in verifying the results of experimental and clinical chemotherapy courses and planning treatment strategies.

Antineoplastic Agents↗

Mathematical models of cell survival after ionizing radiation: application to radiotherapy planning.

The work described here represents an attempt to use mathematical models of single-cell survival for radiotherapy planning. The aim of the study is to develop a procedure in which the distribution of the effects achieved by optimizing physical radiation dose is implemented by taking into account radiobiological terms. An algorithmic model has been developed to evaluate the probability of tumor control and of excessive damage to normal tissue on the basis of the linear-quadratic model of cell survival. In its present preliminary form, the procedure can be used to predict differential isoeffect distributions obtained by varying the total dose and the fraction size of multifraction radiotherapy courses. This approach can also be used to extract from historical clinical results, by maximum-likelihood methods, parameters related to the cellular response to radiation (for instance, alpha and beta of the linear-quadratic model).

Cell Survival↗

Applicability of local hyperthermia as adjuvant to systemic chemotherapy.

With the aim of verifying the in vivo applicability of local hyperthermia combined with chemotherapy, 13 patients with superficial metastases from different histologic types of carcinoma, mostly from head and neck cancer, were entered in a pilot study. The chemotherapeutic regimen was cis-platinum, 20 mg/m2/d X 5 days, bleomycin, 10 mg/m2 on days 8 and 12, methotrexate, 100 mg/m2 on day 15, followed after 24 by folinic acid. Hyperthermia, using a microwave apparatus, and chemotherapy were delivered simultaneously. Objective remissions were achieved in 54% of patients, within the hyperthermia field (1 CR and 6 PR). No serious toxicity was noted. Methotrexate distribution after local hyperthermia was evaluated in 8 patients. Response duration was not gratifying, except for patients successively treated with radiation. In conclusion, the combination of chemotherapy plus local hyperthermia deserves subsequent evaluation as part of adjunctive programs.

Aged↗

Radiotherapy and hyperthermia. Analysis of clinical results and identification of prognostic variables.

Site- and tumor-specific data obtained from two groups of patients with head and neck and melanoma lesions, respectively, showed that both immediate response and response duration were enhanced by the addition of heat. Two important variables, however, such as tumor volume and "isoeffect thermal dose" appeared to influence local tumor control. The volume effect was less pronounced in the lesions treated with radiotherapy plus heat than in those treated with radiotherapy alone, suggesting that the addition of heat was more damaging to the large than to the small lesions. Furthermore, a striking isoeffect thermal dose-response relationship was shown in head and neck lesions. Those data were collected and used to design a mathematical model relating the probability of local control to clinical and treatment variables. The analysis shows that, by using the same radiation parameters, the probability of local tumor control is a function of both "isoeffect thermal dose" and tumor volume.

Carcinoma, Squamous Cell↗

Prognostic significance of flow cytometry in lung cancer. A 5-year study.

Flow cytometrically determined cellular DNA content has been measured on specimens from 101 patients affected by lung cancer (40 epidermoid cell carcinoma, 22 adenocarcinoma, 21 large cell carcinoma, 11 small cell carcinoma, and seven undifferentiated carcinoma), and one by mesothelioma. Ninety-eight of 102 (96%) patients with neoplastic disease evidenced the occurrence of at least one cytometrically aneuploid cell subpopulation. Fifty-five of 102 (54%) cases evidenced the occurrence of multiclonality, that is, the presence of more than one aneuploid stem cell line. However, the incidence of multiclonality in lung carcinoma was statistically different in surgical cases (where multiple site sampling from the primary and lymph nodes was possible) in comparison to the nonsurgical ones (e.g., bronchial washing): 48/77 (62%) and six of 24 (25%), respectively. Therefore, only the 77 surgical patients were used for further analysis. The cases were classified according to the DNA index (DI) in the following way: Group A (tumors with one or more stem lines with DI ranging from 1 to 2) and Group B (tumors with at least one stem line with DI less than 1 or greater than 2). A significant correlation has been found between the cytometric ploidy condition so defined (Groups A and B) and the tumor mass doubling time (DT), Group B being associated with fast growing tumors (DT lower than 90 days). A statistically better 12-month survival rate (5-year maximum follow-up) was observed in Group A (88%) in respect to Group B (47%) and is evident in the patient survival time course. A better prognostic indication can be achieved by stratifying the patients according to both the cytometric ploidy condition and the tumor DT. Flow cytometric data can usefully contribute to the prognostic assessment of lung carcinoma provided that representative cellular material is collected by multiple site sampling.

Actuarial Analysis↗

Flow cytometric analysis of the effects of 0.4 MeV fission neutrons on mouse spermatogenesis.

(C57Bl/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons ranging from 0.05 to 2 Gy, and testis cell suspensions were prepared for cytometric analysis of the DNA content 2-70 days after irradiation. Various cell subpopulations could be identified in the control histogram including mature and immature spermatids, diploid spermatogonia and spermatocytes, tetraploid cells and cells in the S-phase. Variations in the relative proportions of different cell types were detected at each dose and time, reflecting lethal damage induced on specific spermatogenetic stages. The reduction of the number of elongated spermatids 28 days after irradiation was shown to be a particularly sensitive parameter for the cytometrical assessment of the radiosensitivity of differentiating gonia. A D0 value of 0.13 Gy was calculated and compared with data obtained after X-irradiation, using the same experimental protocol. In the latter case a biphasic curve was obtained over the dose range from 0.25 to 10 Gy, possibly reflecting the existence of some cell population heterogeneity. RBE values were estimated at different neutron doses relative to the radiosensitive component of the X-ray curve, and ranged from 3.3 to 4, in agreement with data in the literature. Genotoxic effects were monitored 7 days after irradiation by a dose-dependent increase of the coefficient of variation (CV) values of the round spermatid peak, reflecting the induction of numerical and structural chromosome aberrations, and 14 or 21 days after irradiation by the detection of diploid elongated spermatids, probably arising from a radiation-induced complete failure of the first or second meiotic division.

Animals↗