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Biomedical subjects

M Repetto

Publications and source records attributed to M Repetto.

At least 91 records · Page 5Linked to original sources
PubMed1988

Competition between recipient and donor cells after bone marrow transplantation for chronic myeloid leukaemia.

The cytogenetic and clinical course of three patients allografted for Ph positive chronic myeloid leukaemia are reported. All patients had a peculiar pattern of relapse. Two out of three patients had donor marrow graft pretreated with monoclonal antibody for graft versus host prevention. The cytogenetic relapse was invariably associated with major morphological changes in the marrow indicating that these were also haematological relapses. However, no changes in the peripheral blood count were observed. When relapse occurred in these patients, Ph positive marrow metaphases and host red blood cells ranged from 75% to 100% of the total cell population: thereafter they spontaneously reverted to complete chimaerism. Therefore the presence of leukaemic cells even in considerable amount was not sufficient, per se, to prevail over normal marrow. In addition these observations indicate that relapse was not associated with elimination of the graft: while haemopoiesis was entirely of recipient origin the donor normal stem cells were present and vital although functionally silent. These data suggest that, although TBI remains the more effective tool for eradicating the majority of leukaemic cells, haemopoietic competition between host and donor marrow may have a major impact on leukaemic relapse.

Acute Disease↗
PubMed1988

Regional pharmacokinetic selectivity of intraperitoneal cisplatin in ovarian cancer.

Five patients with intraabdominal ovarian cancer, 4 of whom with concomitant ascites, refractory to cisplatin-containing combination chemotherapy were treated with intraperitoneal cisplatin. Cisplatin, 90 mg/m2, was administered intraperitoneally in 2 liters of warm 0.9% NaCl with a 4-hour dwelling time on day 1 q 21 days. Platinum concentrations in plasma, ascites, ultrafiltrates of plasma and ascites, and urine were assayed by flameless atomic absorption spectrophotometry and determinations were verified by neutron activation analysis. Peak total and ultrafiltrable plasma platinum levels were 1.63 +/- 0.6 and 0.76 +/- 0.3 microgram/ml, respectively. Peritoneal clearance of total platinum (PA) was 21 ml/min whereas body clearance of total platinum was on the average 13.8 times PA, varying from 171 to 429 ml/min; the mean AUC (peritoneum) to AUC (plasma) ratio was 11 +/- 3. In 2 patients control of ascites was obtained, in 1 of these patients prior positive cytology became negative after her first intraperitoneal course. No nephrotoxicity was observed and gastrointestinal toxicity was mild. No catheter-related infections were observed. Intraperitoneal cisplatin therapy is well tolerated, pharmacokinetically rational and may be useful in managing ovarian cancer patients with malignant ascites or minimal residual disease at second-look laparotomy.

Aged↗
PubMed1988

Uncontrollable atmospheric conditions which can affect animal experimentation.

In our programs of investigation into mechanisms of molecular action of toxic substances, we have had occasion to observe the appearance of anomalous values in biochemical parameters, which we put down to cyclic rhythms or coincidences with the following phenomena: meteorological (storms), geological (earthquakes), and astronomical or phenological (eclipse and lunar phases). This work reviews such observations, which suggest that besides the environmental conditions of the animal room (illumination, humidity, temperature, noise) it is necessary to consider all the external circumstances which occur at the moment of the experiment.

Animals↗
PubMed1987

Human serum-dependent survival of GM-CFCs in vitro from patients with chronic granulocytic leukemia.

Bone marrow (BM) cells from 15 patients with chronic granulocytic leukemia (CGL) and 12 normal donors were placed in liquid culture for 4-7 days in the presence of fetal calf serum (FCS) or human AB serum. BM cells were plated in agar for GM-CFC growth at day 0, day 4, day 7 of culture, in the presence of human placenta conditioned medium (HPCM). The recovery of GM-CFCs on day 4 in FCS was 86 +/- 18 and 15 +/- 18% from normal or CGL BM cells respectively (p = 0.005). The recovery of GM-CFCs on day 4 in human AB serum was comparable for normal (66 +/- 48%) and CGL (69 +/- 32%) BM cells. Similar results were obtained on day 7 of culture. Cytochemical staining of agar plates showed a sharp drop of macrophage colonies in CGL BM cells kept in FCS cultures on day 4-7, when compared to both normal BM cells and baseline colonies. These data suggest that the survival in liquid culture of GM-CFCs from patients with CGL is dependent on a factor present in human and not in fetal calf serum. This is not the case for normal GM-CFCs.

Animals↗
PubMed1986

Bone marrow transplantation for chronic granulocytic leukemia.

Thirty patients with chronic granulocytic leukemia (CGL), were given cyclophosphamide 60 mg/kg on each of 2 consecutive days, followed by total body irradiation (TBI) 10 Gy and an HLA-identical bone marrow transplant (BMT). Eleven patients were in the accelerated phase of their disease (CGLacc) or in second/secondary chronic phase (CGL-2CP), with a median age of 33 years: four patients died of transplant related complications, and four of recurrent leukemia; three patients are alive and well 19, 31, 33 months from BMT. The actuarial 33-month survival is 27%. The actuarial relapse rate is 50%. Nineteen patients were in their first chronic phase (1CP), with a median age of 32 years: three died of graft versus host disease (GvHD), two of infection, and two of acute respiratory distress syndrome (ARDS); 12 are alive and well 6 to 29 months post-BMT. The actuarial 29-month survival is 63%. The actuarial survival of patients younger than 30 years is 63%, compared to 62% for patients older than 30 (P = 0.1). The survival of patients grafted within or after 24 months from the onset of CGL is respectively 87% and 45% (P = 0.04). None of the patients grafted in 1CP had a true hematologic-cytogenetic relapse. The Ph' chromosome was detected on one occasion in two patients 12, 13 months post-BMT: they both remain hematologically normal and Ph1-negative 3 to 6 months later, after discontinuation of cyclosporin A. This study confirms that survival exceeding 60% can be obtained in CGL in the first chronic phase, whereas less than 30% of patients will survive if grafted in accelerated, second/secondary chronic phase, mainly because of leukemic relapse. The duration of the disease seems to be relevant to the outcome of the transplant. The effect of post-transplant immunosuppression, in our case cyclosporin A, on the interaction between normal and Ph1-positive hemopoietic cells, may deserve further attention.

Adolescent↗
PubMed1986

Starch microsphere-induced arterial flow redistribution after occlusion of replaced hepatic arteries in patients with liver metastases.

In four patients with major anomalies of the hepatic artery undergoing intra-arterial chemotherapy, aberrant lobar vessels were ligated and catheters were inserted into the contralateral artery. Catheter perfusion scans performed early after ligation with 99mTc-macroaggregated albumin (MAA) showed a defective perfusion of the lobe supplied by the occluded artery (0.43, 0.23, 0.11, and 0.28, respectively, as compared to the contralateral lobe). Further MAA scans performed after catheter infusion of 90,000,000 parts of degradable starch microspheres (DSM) showed a near normal perfusion of the ischemic lobe (0.91, 0.96, 0.87, and 0.98). On the contrary, simple MAA scans performed in the first two patients 114 and 135 days after ligation showed a still defective arterial perfusion of the ischemic lobe (0.60, and 0.24). The DSM-induced redistribution of flow towards ischemic portions of the liver suggests a possible new role of DSM in regional treatment of liver tumors in cases with either occlusion of aberrant vessels or "hypovascular" tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

[Comparison of the performance of a totally implantable pump and conventional access systems in regional arterial chemotherapy of liver tumors].

Forty-nine patients with liver tumors have been submitted to regional arterial chemotherapy by means of either totally implantable Infusaid 400 pumps (29 casse) or implantable ports (20 cases). The latter were subsequently perfused with external pumps. There was one single major operative complication and no operative deaths. Most patients underwent continuous FUDR infusion. Access related complications in the Pump and Port groups respectively included 1 and 0 malfunctions, 7 and 2 seromas, 2 and 0 pocket necroses, 8 and 10 thromboses, 2 and 4 catheter dislocations, 0 and 2 portal breakages. Treatment was stopped for access related complications in 5 and 5 patients respectively. In most of those cases, however, more than 6 cycles of chemotherapy have been performed. The Infusaid 400 pumps showed a 12-month duration of 58.4% with a 13 month median versus 17% and 9 month median of the Ports. The difference was not significant. The new implantable systems give better results in comparison with traditional regional methods; the performance of the Port systems appear very similar to the totally implantable pumps, with an obvious advantage, however, for the pumps as far as quality of life is concerned.

Adenocarcinoma↗
PubMed1986

Competitive survival/proliferation of normal and Ph1-positive haemopoietic cells.

Bone marrow (BM) cells from 10 patients with Ph1-positive chronic granulocytic leukaemia (CGL) were placed in long-term cultures in the presence of fetal calf serum (FCS) and horse serum (HoS), or in the presence of human AB serum. The long-term cultures were started with three different cell combinations: (1) CGL BM cells (four cases), (2) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex-matched sibling (five cases), (3) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex mismatched sibling (five cases). Cytogenetic studies were performed at weeks 0, 3, 4 and 5 of culture. The results of this study can be summarized as follows: (a) Ph1-positive cells could be detected at any time of culture in all three of the described cell combinations; (b) a population of Ph1-negative cells of patient origin could be detected after 3-5 weeks of culture; (c) there was a trend for a better survival of Ph1-negative cells in cultures supplemented with FCS + HoS and, conversely, of Ph1-positive cells in cultures containing human serum. These results warrant further studies on the possibility of manipulating survival and proliferation of normal and leukaemic cells by varying the culture conditions.

Bone Marrow↗
PubMed1986

Inhibition of glucose-6-phosphatase and adenosine-triphosphatase activity in rats treated with toxic Spanish rapeseed oil or synthetic anilides.

After having demonstrated the impairment of the microsomal oxidation process in rats treated with toxic Spanish cooking oil or fatty acid anilides, we studied the possibility that the function of the cytoplasmic membrane had been affected. For this, the activities of glucose-6-phosphatase and adenosintriphosphatase were determined, these being enzymes of utmost importance in transport at the liver cell membrane level. Wistar rats received disease-related toxic rapeseed oil (1 mg/kg/day) or linoleilanilide (50 mg/kg/day) for 6 days, and the animals were sacrificed immediately after the administration period and after a 4-, 8- and 12-week latency period. Enzyme activities were measured in the membrane fraction of liver and lung. The results showed considerable reduction (up to 80%) in the activity of these enzymes, confirming that transport mechanisms through cell membranes must have been impaired.

Adenosine Triphosphatases↗
PubMed1986

Regional arterial chemotherapy of liver tumours. I. Performance comparison between a totally implantable pump and a conventional access system.

Thirty-nine patients with liver tumours have been submitted to regional arterial chemotherapy by means of either totally implantable Infusaid-400 pumps (22 c.) or implantable ports (17 c.). The latter were subsequently perfused with external pumps. There was one single major operative complication and no operative deaths. Most patients underwent continuous Fudr infusion. Access related complications occurred in both groups. Treatment was stopped for access related complications in 18.4% and 29.4% of cases out of the pump and port groups respectively. In most of those cases, however, several cycles of chemotherapy had already been performed. The Infusaid-400 pumps showed a 12-month functional duration of 57% with a 13-month median, the 10-month duration of ports being 67%. The difference was not significant. The new implantable systems give better results in comparison with traditional regional access methods, the functional performances of the port systems appearing very similar to the totally implantable pumps, with an obvious advantage for the pumps as far as quality of life is concerned.

Antineoplastic Agents↗
PubMed1985

Intrahepatic arterial flow distribution after ligation of a right replaced hepatic artery. A case report.

A basic requirement for arterial chemotherapy of liver tumors is complete catheter perfusion of the liver. In cases with atypical anatomy of the hepatic artery, it is frequently impossible to obtain this goal by means of a single catheter. In a patient with a right replaced hepatic artery, the aberrant vessel was ligated and the left hepatic artery was perfused through a catheter inserted into the gastroduodenal artery. Perfusion scans performed through the catheter 14 and 135 days after arterial ligation showed a fall in the arterial flow to the right liver (right/left ratio 0.43 and 0.60). In contrast, a nearly complete perfusion of the liver (0.91 right/left ratio) was obtained 28 days after ligation, when the perfusion scan was performed immediately after catheter infusion of 90,000,000 degradable starch microspheres (DSM: diameter = 40 m). DSM administration is supposed to increase back pressure in the lobe receiving native circulation, thus activating intrahepatic collateral flow to the ischemic lobe. As regards regional treatment of liver tumors, obvious conclusions are to be drawn.

Antineoplastic Agents↗