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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 325 records · Page 18Linked to original sources

Long-term systemic hypertension in children after successful repair of coarctation of the aorta.

The mechanisms responsible for long-term hypertension in children after successful repair of coarctation of the aorta have not yet been determined. We measured plasma renin activity and aldosterone, adrenalin, and noradrenalin concentrations both under basal conditions and in response to standing and treadmill exercise in 24 normal normotensive children, 16 normotensive postcoarctectomy children, eight hypertensive postcoarctectomy children, and seven children with essential hypertension. Exercise-induced changes in plasma renin activity, aldosterone, adrenalin, and noradrenalin were comparable in the four groups in spite of a significantly greater increase in systolic blood pressure in the children with hypertension. In response to standing, the plasma concentration of noradrenalin increased significantly in normotensive but not in hypertensive children. Hyperresponse of blood pressure to exercise in hypertensive postcoarctectomy children and children with essential hypertension is not related to abnormalities in the sympathetic nervous system or the angiotensin-aldosterone axis. Hypertension could be related to primary baroreceptor alterations, to structural changes in the arterial wall, or both. Twenty percent of normotensive postcoarctectomy children had a blood pressure hyperresponse to exercise and an abnormal noradrenalin response to standing similar to that seen in the hypertensive children. Follow-up of children after coarctectomy may elucidate whether these two abnormalities are indicators of an increased risk of developing long-term recurrent hypertension.

Aldosterone↗

In vitro chemical eradication of small cell lung cancer: application in autologous bone marrow transplantation.

Autologous bone marrow transplantation raises the question of the possible reinjection of tumour cells together with marrow. This paper investigates the ability of chemical compounds other than cyclophosphamide derivatives to eradicate small cell lung cancer (SCLC) in bone marrow. The responsiveness of SCLC lines to cis-platinum, doxorubicin, VP16, Celiptium (an ellipticine derivative), Ditercalinium, a new drug belonging to the pyridocarbazole series, and Asta Z were measured in an agar-agar clonogenic assay. Cis-platinum and Ditercalinium exhibited a high tumouricidal effect. The low cloning efficiencies of SCLC lines in an agar-agar clonogenic assay did not allow tumour cells to be detected among bone marrow cells with sufficient sensitivity. Therefore cis-platinum and Ditercalinium were tested on bone marrow-tumour cell mixtures cultured in a liquid medium allowing the detection of one tumour cell per 10(4) bone marrow cells. As cis-platinum exhibited a low myelotoxicity, it is proposed for purging bone marrows of patients with SCLC.

Antineoplastic Agents↗

Immune-deficiency in Hodgkin's disease (HD): a study of patients and healthy relatives in families with multiple cases.

In this study we evaluated some immunological features in both patients and healthy relatives within five families with multiple cases of Hodgkin's disease (HD). Such familial groups (at 'high risk' of HD), represent, in our opinion, a suitable opportunity to investigate the role of immune-deficiency in HD. The results obtained in the patient group confirm the well known persistent immune derangement in long term HD survivors. Regarding the group of relatives, we found a pattern similar to that of the patients. In particular, a decrease in the T helper lymphocyte subset and a lower response to Con-A mitogen were detected, which were statistically significant. These findings, confirmed in other studies of multiple case families, could support the hypothesis of a preexisting immune-deficiency in HD. This in turn would greatly contribute towards a better understanding of the role of immune-deficiency in the etiopathogenesis of the disease.

Adolescent↗

[Value of transcutaneous blood gas monitoring in fiberoptic bronchoscopy in intensive care patients].

Transcutaneous carbon dioxide and oxygen tensions (PtcCO2 and PtcO2) were monitored in seven critically ill patients under mechanical ventilation during fiberoptic bronchoscopy. In these conditions, both PtcO2 and PaO2 and PtcCO2 and PaCO2 correlated, with correlation coefficients of 0.964 and 0.793 respectively. Fiberoptic bronchoscopy induced an average fall in PtcO2 of 42 +/- 2.57 mmHg and an average increase in PtcCO2 of 12.1 +/- 1.89 mmHg; these two parameters returned quickly to their initial values after the procedure. Holter monitoring showed an arrhythmia in five of the seven patients. Continuous measurement of PtcO2 and PtcCO2 was a safe and reliable method for monitoring mechanically ventilated patients undergoing fiberoptic bronchoscopy.

Aged↗

Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial.

From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.

Adult↗

Growth response of human myeloid leukemia cells to colony-stimulating factors.

The effects of human recombinant granulocyte and granulocyte-macrophage- (G- and GM-CSF), and of purified macrophage-stimulating factors (CSF-1), were tested on populations of leukemia cells isolated from 18 patients with different types of acute myeloid leukemia. Cell proliferation and differentiation were studied by culturing the cells in suspension for 7 days in the presence of CSF or medium alone. Spontaneous cell proliferation, as assessed by tritiated thymidine uptake, was observed in 9 of the 18 cases. GM-CSF induced proliferation in seven of the nine cases without spontaneous growth and increased spontaneous proliferation in nine cases. G-CSF added alone was also found to strongly stimulate leukemic blast cell proliferation, in which a translocation involving the long arm of chromosome 17 was observed. Low levels of CSF-1 stimulation were also observed in some cases. No clear morphological modification supporting evidence of terminal differentiation was observed, whereas modulation of some cell surface antigens was detected by flow cytometry. Thus, most leukemia cells still depend on growth factors for their proliferation, GM-CSF appearing the most effective. On the other hand these factors were not able to induce terminal differentiation.

Antigens, Surface↗

Preferential response of acute myeloid leukemias with translocation involving chromosome 17 to human recombinant granulocyte colony-stimulating factor.

Induction of proliferation and differentiation in response to the addition of recombinant human granulocyte colony-stimulating factor (G-CSF) was studied by both suspension and semisolid cultures in a series of acute myeloid leukemias (AML). Induction of proliferation by G-CSF alone was observed in six of 27 cases of AML. All acute promyelocytic leukemias with the specific chromosomal translocation t(15;17) and one case of myelomonocytic leukemia with balanced chromosomal translocation involving chromosome 17 at band q12q21 were induced to proliferate strongly by the G-CSF. However, contrary to the long-term proliferative effect observed with granulocyte/macrophage colony-stimulating factor (GM-CSF), G-CSF activity can be characterized by its capability to initiate and promote the growth of responding AML cells but not to sustain long-term proliferation. Finally, no terminal differentiation was found, as assessed by morphology, cytochemistry, and cell surface marker analysis. These results indicate that G-CSF may be sufficient to provide a specific signal for induction of a transient proliferation in AML without induction of terminal differentiation. The cells with the highest response are clonal leukemia cells, all bearing a translocation involving the chromosome region 17q12q21 in which the G-CSF gene has been recently located.

Animals↗

Lack of differential sensitivity of normal hematopoietic stem cells and murine lymphoblastic leukemic cells to a lysosomotropic agent, N-dodecyl morpholine.

The effect of N-dodecyl morpholine (NDM), a lysosomotropic compound, on the clonogenic capacity of GK15, Sp2.0, Hb131, and L1210 lymphoblastic tumor cells and CFU-GM and CFU-S progenitor cells from DBA/2 mice was measured in order to evaluate the potential use of this compound for the purging of tumor-contaminated bone marrow (BM) in autologous BM transplantation. The growth of clonogenic tumor cells from all of the tested cell lines was inhibited with doses of NDM that also killed 100% CFU-GM and CFU-S, and no optimal dose could be found in this animal model to purge marrow while sparing sufficient stem cells to ensure engraftment in syngeneic BM transplantation.

Animals↗

Plantar lentiginous melanoma. A clinicopathologic study.

Twenty cases of plantar melanoma treated at Ellis Fischel State Cancer Center (EFSCC) since 1940 are analyzed to determine the clinical and histologic features of prognostic significance. The EFSCC experience confirms and extends the observations made in other recent studies of plantar melanoma. This clinical pathologic study suggests that one of the histologic patterns, the lentiginous growth pattern, shares some biologic features with lentigo maligna, namely the relatively indolent growth phase. Plantar melanomas may remain latent for a number of years making these patients good candidates for therapeutic cures if detected early.

Adult↗

[Autograft of bone marrow treated by in vitro chemotherapy (Asta Z 7557) for consolidation of acute leukemia in adults in the first complete remission].

Fourteen adult patients in first complete remission of acute leukemia (A.L.) [6 with acute lymphoblastic leukemia (ALL), 8 with acute non lymphoblastic leukemia (ANLL)] were consolidated with high dose cyclophosphamide and total body irradiation followed by autologous bone marrow transplantation (ABMT) with marrow cleansed in vitro by Asta Z 7557. According to our previously described protocol showing evidence for a wide range of sensitivity from patient to patient, the marrow of each individual patient was incubated with the highest tolerable dose of Asta Z 7557. This dose, individually determined, was defined as the dose sparing between 0 and 10% of CFU-GM (CFU-GM DL95). ABMT was not followed by maintenance therapy. Hematological reconstitution was significantly faster in ALL patients when compared to ANLL patients. Out of these 14 patients: 2 relapsed on months 5 and 15 respectively after ABMT, and 2 died in complete remission on months 3 and 16 respectively, of veno-occlusive disease and encephalitis. Ten patients (70%) remain in complete remission up to a median of 15 months +, with 4 patients over 24 months +.

Acute Disease↗

Two murine monoclonal antibodies to peripheral blood monocyte differentiation antigens discriminate within M5 acute non-lymphoid leukemia (ANLL) cells.

Two murine monoclonal antibodies (MoAbs), LAM3 and LAM7 of the IgG1 isotype, which were produced by immunization with normal peripheral blood monocytes (PBM), were assayed in their specificity by indirect immunofluorescence against a panel of normal as well as leukemic cells. Both LAM3 and LAM7 were reactive with PBM while LAM3 also recognized platelets. Neither MoAb showed reactivity with erythrocytes, granulocytes, or resting and mitogen activated B and T lymphocytes. The reactivity with bone marrow cells correlated with the degree of monocyte contamination. Among the 62 cases of leukemia tested, which included three cases of B-CLL, 19 cases of ALL, and 40 cases of ANLL, both MoAbs reacted highly homogenously only with M5b ANLL cells. These findings indicate that the two MoAbs, which recognize two distinct epitopes, represent useful markers in the differential diagnosis of M5b ANLL.

Acute Disease↗

Surface markers and cytotoxic activities of lymphocytes in monoclonal gammopathy of undetermined significance and untreated multiple myeloma. Increased phytohemagglutinin-induced cellular cytotoxicity and inverted helper/suppressor cell ratio are features common to both diseases.

To determine whether monoclonal gammopathy of undetermined significance (MGUS) resembles multiple myeloma (MM) with regard to phenotype and functional activity, 16 patients with MGUS and 16 with untreated MM were studied for surface markers and cytotoxic activities phytohemagglutinin-induced cellular cytotoxicity (PHA-ICC), antibody-dependent cellular cytotoxicity, natural killer (NK) activity. Our data showed a consistent immunological similarity between the two diseases. An increase in OKT8+ cells was evident in both patient groups and a significant reduction in the T4/T8 ratio, more pronounced in MM, was observed. Alterations in NK activity or ADCC were not found in MGUS or MM. A significant increase in PHA-ICC was demonstrated in the two diseases. The increase in PHA-ICC observed seems to be attributable to an increased frequency and/or lytic efficiency of PHA-ICC lymphoid effector cells. These data suggest that similar immunological alterations are common to the two diseases. The greater helper/suppressor ratio reduction observed in MM seems to be related to the more severe clonal proliferation in these patients.

Antibody-Dependent Cell Cytotoxicity↗