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Biomedical subjects

P Dionigi

Publications and source records attributed to P Dionigi.

At least 19 recordsLinked to original sources

Cell proliferation and ploidy of human solid tumours: methodological experience with in vivo bromodeoxyuridine and DNA flow cytometry.

A sequential procedure for single and multiparameter flow cytometry (FCM) that allows detailed cell proliferation and DNA ploidy studies of human solid tumours is reported here. This description includes time collection and storage, tissue disaggregation and staining as well as FCM analysis of samples. The overall feasibility, together with some critical aspects of the DNA/bromodeoxyuridine (BrdU) in vivo assay for cell kinetic studies in human solid tumours, are reported, based on our experience in recent years. We found that the BrdU in vivo method, coupled with bivariate FCM for measurements, is a valuable approach for a 'dynamic' assessment of tumour cell proliferation in the clinical setting. Routine measurements can be achieved providing that well standardised tissue disaggregation and immunolabelling procedures are performed. In different solid tumours, cytokinetic results were satisfactory in 85% of cases as far as the BrdU-labelling index is concerned while 70% were acceptable for DNA synthesis time and tumour potential doubling time. Causes of failure are also considered and discussed. In order to guarantee the finest detection of aneuploidy, routine high resolution single-parameter DNA analysis is suggested. Our experience with further improvements in cell kinetic studies based on the possibility of gating the BrdU/DNA analysis for a subpopulation of interest (i.e. cytokeratin-positive cells in epithelial tumours) is also reported.

Bromodeoxyuridine

Impact of a programme of autologous blood donation on the incidence of infection in patients with colorectal cancer.

OBJECTIVE: To assess the effects of both autologous and homologous blood transfusion on the incidence of infective complications after elective operations for colorectal cancer. DESIGN: Prospective open study. SETTING: University hospital, Italy. INTERVENTIONS: Recording of variables known to influence the development of infection. MAIN OUTCOME MEASURES: Infective morbidity and mortality. RESULTS: Fifty-three patients (33%) deposited their own blood. Eighty-six of the 161 (53%) patients were transfused, 36 were given autologous blood, 48 homologous blood and 2 both autologous and homologous blood. These two were excluded from the analysis. Infective complications developed in 28 patients (17%), of which 7/75 (9%) were in patients who had not been transfused, 5/56 (14%) in patients given autologous transfusion, and 16/48 (33%) in patients given homologous transfusions (p < 0.001). Multivariate analysis identified homologous blood transfusion as the only variable significantly associated with the development of postoperative infective complications. No patient died. CONCLUSION: Transfusion of autologous blood was associated with significantly fewer postoperative infective complications than transfusion of homologous blood or no blood transfusion.

Adult

Use of subcutaneous implantable infusion systems in neoplastic and AIDS patients requiring long-term venous access.

OBJECTIVE: To evaluate the life span and complication rates of totally implantable infusion devices in patients with short bowel syndrome and in immunocompromised patients with AIDS, lymphoma, and myeloma who required long-term central venous access. DESIGN: Prospective open study. SETTING: University hospital, Italy. SUBJECTS: Group I - 5 patients with short bowel syndrome; group II - 11 patients with AIDS; and group III - 15 patients with lymphoma or multiple myeloma (1 of whom had 2 devices implanted). MAIN OUTCOME MEASURES: Duration of implantation and incidence of catheter-related complications. RESULTS: The mean duration/patient of the catheter was 422 days (range 20-1257) in group I; 104 days (range 43-262) in group II; and 415 days (range 62-1280) in group III. There were no catheter related complications in the patients in group I (short bowel syndrome). Of the 11 patients with AIDS (group II) 4 developed catheter related infections (0.32/100 catheter days), and 1 developed a thrombotic occlusion. All 5 catheters were removed (3 for infection). Of the 15 patients with lymphoma or myeloma who had 16 catheters implanted (group III), 1 patient developed 3 infective episodes (0.05/100 catheter days), 1 catheter migrated and 1 occluded. All 3 catheters were removed. CONCLUSION: Totally implantable infusion systems can safely be used for prolonged periods in immunocompromised patients, including those with AIDS if their life expectancy is reasonable.

Acquired Immunodeficiency Syndrome

[Nutritional support in acute pancreatitis].

Severe acute pancreatitis 3 or more Ranson's prognostic signs is characterized by a generalized hypermetabolic response and nutritional depletion leading to malnutrition and septic complications. Nutritional support has come to be a significant component of the treatment of acute pancreatitis. However the route of nutrient administration and composition of substrates administered remain controversial. Available data suggest that intravenous infusion of amino acids, glucose and fat emulsions alone or in combination does not stimulate exocrine pancreatic secretion. Similarly, enteral feeds should have low fat composition and be delivered distal to the ligament of Treitz. This review outlines the current body of specific literature and provides preliminary guidelines for the nutritional support of patients with acute pancreatitis.

Acute Disease

[Assessment of the nutritional status of the surgical patient].

Since malnutrition has been demonstrated as increasing surgical risk in terms of post-operative morbidity and mortality, simple and feasible methods of evaluating nutritional status have been investigated. Epidemiological studies, carried out mainly in populations with gastrointestinal diseases, allowed selection of some simple indices (weight loss, albumin, transferrin, circulating lymphocytes and delayed hypersensitivity response to cutaneous antigens) which are useful in assessing the patient's altered nutritional status. The same results can be obtained by clinical examination only, if this is conducted by a trained physician. The conclusions of investigations of nutritional assessment parameters and of multiparametric indices are controversial. Non-nutritional factors are often involved in the occurrence of post-operative complications, interfering with the predictive value of the nutritional status indicators.

Humans

[Hemodynamic changes in liver and multi-organ transplantation].

Multivisceral transplantation is a surgical technique developed as treatment for abdominal metastatic and/or multifocal malignancies. At present its clinical employment is reduced by our fragmentary knowledge of the intraoperative and postoperative outcome. The aim of this study is to compare intraoperative hemodynamic and respiratory changes during multivisceral transplantation (MTV, n = 12) and liver transplantation (OLTX, n = 14). The observations have been carried out a 4 phases: basal (I), visceral (II), reperfusion (III), final (IV). Phase I does not show differences between MTV and OLTX. In phase II MTV presents a lower temperature (T) and pulmonary arterial pressure (PAP) (p > 0.05). Phase III is marked by increasing T differences (p < 0.05), lower cardiac frequency (CF), pH and base excess (BE) (p < 0.05). PAP and cardiac output (CO) show a higher value in MTV (p < 0.05). Phase IV reports the vital signs close to normality in both groups, except pH in MTV (p > 0.05).

Animals

The role of surgery in the multimodal treatment of primary gastric non-Hodgkin's lymphomas. A report of 76 cases and review of the literature.

Seventy-six patients with primary gastric non-Hodgkin's lymphomas (PGL) were diagnosed, and 75 were treated between 1975 and 1985. According to the Working Formulation 22 patients had low-grade malignant histologic subtypes, 27 intermediate-grade, and 27 high-grade. Twenty-four cases were diagnosed by endoscopic biopsies, 52 through laparotomy biopsies. Forty-five underwent subtotal or total gastric resection; seven were considered unresectable at laparotomy; 23 did not undergo surgery because of the high operative risk, mainly due to advanced age and coexisting diseases; and one died of myocardial infarction a few days after admission, before starting therapy. All patients who did not undergo laparotomy were staged with bipedal lymphangiography or abdominal ultrasonography and/or computed tomography. Stage, evaluated according to the criteria of Musshoff, was I or II1 in 16 cases, II2 in five, and IV in the remaining 55. Treatment modalities included surgery (S), chemotherapy (CT), radiotherapy (RT), and combinations thereof in the following proportions: only S in ten cases, S + CT in 32 cases, S + RT in one case, S + CT + RT in two cases, CT only in 25 cases, CT + RT in five cases. No substantial differences in response to therapy and in survival were found in relation to the different treatments. Ten-year survival was 43% in Stage I or II and 20% in Stage IV. Of the 45 resected patients, five postoperative deaths were recorded (11%). No bleeding or perforations were observed in the 30 unresected patients, and survival of such cases compared with that of the resected ones. These findings, together with data from the literature, suggest that some of the advantages claimed for surgery in PGL (debulking and abatement of the risk of perforation or hemorrhage during CT or RT) have been overestimated in relation to the intrinsic surgical risk and to the possibility of anticancer therapy. Gastric resection may still be unavoidable as a diagnostic procedure in a minority of cases and may represent the primary therapeutic procedure in clinically assessed early-stage and low-risk patients, but it cannot be considered mandatory whenever possible merely for debulking purposes or to obviate possible perforation or hemorrhage. The CT and/or RT can be effective in unresected and even bulky cases, providing minimal risk of severe hemorrhage or perforation.

Adolescent

Prognostic significance of DNA content in large bowel carcinoma: a retrospective flow cytometric study.

Flow cytometric (FCM) determination of DNA content was performed on surgical specimens from 44 patients with previously untreated colonic carcinoma. For each tumor, cell suspensions were prepared from 2-4 40-microns thick sections obtained from formalin-fixed and paraffin embedded tissue samples. Aneuploidy was found in 47.2% of all the tumors and the aneuploid clone had a median DNA index of 1.49 (range: 1.24-1.93). Aneuploidy was found in 26.7% of highly differentiated tumors (WHO histologic classification), in 53.8% of moderately differentiated tumors and in 100% of poorly differentiated tumors (P = 0.04). The 33.3% of stages 1 + 2 (TNM) and the 70.6% of stages 3 + 4 tumors were aneuploid (P = 0.002). Median survival from surgery was 46.4 months for all patients. It was 18.8 months for patients with aneuploid tumors and 85.7 months for those with diploid tumors (P = 0.0002). FCM determination of DNA in colon carcinomas can easily be performed on archival histological material and provides prognostic information.

Adult

Cell kinetics in leukaemia and solid tumours studied with in vivo bromodeoxyuridine and flow cytometry.

During a 15-month period, we used in vivo bromodeoxyuridine (BUDR) infusion to study cell kinetics in 112 consecutive patients with various types of malignant tumours: acute leukaemia (50 patients), gastric cancer (42) and brain gliomas (20). The in vivo BUDR method requires that a single tumour sample be taken 4-6 h after infusion and that bivariate flow cytometry (FCM) be employed to measure simultaneously the percentage of BUDR-labelled cells (which are identified with a green fluorescent anti-BUDR monoclonal antibody) and their mean DNA content (following propidium iodide staining). This technique rapidly furnishes the labelling index (LI) and the DNA synthesis time (TS), from which the tumour potential doubling time (Tpot) and production rate (fractional turnover rate, FTR) are calculated. The procedure took 6-9 h to complete and there was no immediate toxicity from BUDR administration. Successful LI and TS determinations were obtained in 89 (80%) and 80 (72%) of the 112 patients, respectively. Correlations were sought between kinetic parameters and a number of pathological and clinical ones. In 34 patients with acute non-lymphoblastic leukaemias who were uniformly treated for remission (CR) induction and maintenance, proliferative activity, as measured by Tpot and FTR, was greater in responsive than in non-responsive patients, and in those who experienced CR for over 8 months than in those who had a shorter CR. Proliferative activity was also greater in patients with advanced gastric cancers than in those with more limited disease. No correlations between kinetic and clinical and pathological parameters were found in gliomas. These data indicate the in vivo BUDR infusion coupled with FCM measurements can be performed in clinical settings to obtain kinetic data rapidly in quite large patient series. This will probably allow the inclusion of kinetic data in clinical trials aimed at evaluating the prognostic relevance of these data.

Adolescent

Mechanisms of platelet activation by cultured human cancer cells and cells freshly isolated from tumor tissues.

We studied the effects on platelet function of cells isolated from freshly dissociated human tumor tissues (11 breast carcinomas, 9 colon carcinomas and 1 lymph node metastasis from melanoma) obtained at surgery as compared with cultured human tumor cells: namely, human melanoma 1402 cell line derived from a primary tumor and two lines derived from lymph node metastases (ME 7110/2 and Me 665/1) as well as a human hepatoma cell line (Hep G2). The three melanoma cell lines activated platelets by producing ADP, as evidenced by the inhibitory effect of apyrase and by the direct measurement of the agonist in the supernatants of tumor cell suspensions; this production was much greater by the cells derived from metastases than by the cells derived from the primary tumor. On the other hand, aggregation induced by Hep G2 hepatoma cells was unaffected by apyrase and was inhibited by hirudin or concanavalin A, suggesting that the cells aggregate platelets by producing thrombin, probably through tissue factor activity of the cells themselves. Cells isolated from 16 of the 21 human tumor tissues possessed a potent platelet-aggregating effect, which was not inhibited by apyrase, hirudin or concanavalin A, but was virtually abolished by the cysteine protease inhibitors iodoacetic acid or p-hydroxymercuri-phenylsulfonate. Collectively, our data demonstrate that cells isolated from freshly dissociated tumor tissues activate platelets through tumor-associated cysteine proteinases rather than by the ADP- or thrombin-dependent mechanisms characteristic of cultured human tumor cell lines.

Adenosine Diphosphate