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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 289 records · Page 16Linked to original sources

The role of autologous bone marrow transplantation in 46 adult patients with non-Hodgkin's lymphomas.

Forty-six patients with non-Hodgkin's lymphoma (NHL) were treated with autologous bone marrow transplantation (ABMT) in two different institutions. All patients were pretreated with conventional chemotherapy. Three different conditioning regimens were used, and 20 patients underwent bone marrow purging. Twelve patients were treated in first complete remission (CR); eight are in unmaintained CR 8 to 104 months after ABMT. Five patients were grafted in first partial remission (PR) after conventional therapy; all achieved CR, and all remain in prolonged CR (first CR for four patients, second CR for one patient). Of 21 patients with chemosensitive relapses, 13 patients are in prolonged unmaintained CR 8 to 94 months after ABMT. Eight patients with resistant disease remained uncured by ABMT; all eight died, six from progressive illness and two from toxicity. The current 3-year disease-free probability is 60% for all patients, 0% for refractory disease; 82% for first PR or CR, and 60% for sensitive relapses (SRs). These results confirm the efficacy of ABMT in the treatment of chemosensitive NHL with bad prognosis.

Adolescent↗

c-fms expression in acute leukemias with complex phenotypes.

The c-fms proto-oncogene product, which is the receptor for the macrophage colony-stimulating factor CSF-1, is always found expressed in acute myeloid leukemia cells, irrespective of their stage of differentiation according to the FAB classification (Dubreuil P, Torrès H, Courcoul M, Birg F, Mannoni P. Blood 1988;72:1081-1085). We have extended this study and looked for c-fms expression in poorly differentiated myeloid leukemias, in a series of acute leukemias of either T or B origin and in biphenotypic leukemias. We now report that expression of c-fms is still related to the myeloid origin of the leukemic proliferation, but that it can also be found in some acute leukemias presenting clonal rearrangements of the T cell receptor gene. Thus expression of the c-fms/CSF-1 receptor may not be exclusively a marker for myeloid proliferations.

Acute Disease↗

Carotid artery disease in patients with head and neck carcinoma.

Irradiation has been shown experimentally to cause accelerated development of atherosclerosis in exposed large arteries. However, occurrence of such an entity in carotid arteries of patients after treatment for head and neck carcinoma is unknown. Therefore, we reviewed 179 patient charts who had undergone head and neck operations with or without irradiation between 1979-1987. Of these 179 patients, 107 (59.8%) were dead at time of follow-up. Cause of death was unknown in 42 (40%) patients; in the remainder included: respiratory arrest--33; carcinoma-related--18; cardiac--6;pneumonia--7; and trauma--1. Average interval from treatment to death was 23.5 months. Of the 72 patients known to be alive, follow-up was obtained in 52 patients. Their average age was 64.9 years. Risk factors for atherosclerosis included: male gender--43; smoking--50; hypertension--9; diabetes--4; coronary artery disease--12; and peripheral vascular disease--4. Seventy-five per cent of these patients received postoperative irradiation. Average follow-up was 64.5 months. Duplex scans were performed on 34 patients. Three patients had common or internal carotid stenoses greater than 75 per cent. All of these patients had received irradiation and none of them were symptomatic. Seven patients had carotid stenoses between 50 to 75 per cent; five of these had received irradiation. Of these five patients, one had a stroke 60 months postoperatively, and one had a TIA 36 months postoperatively. The remaining 58 patients (of which 48 had irradiation) had carotid stenoses less than 50 per cent and none were symptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Mold contamination of automobile air conditioner systems.

Eight cars belonging to patients who were found to have exacerbation of allergic rhinitis and bronchial asthma after turning on the air conditioner in their cars were examined. Mold concentrations inside the passenger compartment with the a/c turned off and at different climate control settings were lower than concentrations in the outside air. After turning on the air conditioner to "Max", cultures obtained at various intervals revealed that mold concentrations decreased significantly with time. Furthermore, placement of a filter at the portal of entry of outside air significantly reduced the mold concentration in the passenger compartment.

Air Conditioning↗

A prospective randomized trial of doxorubicin versus idarubicin in the treatment of advanced breast cancer.

Seventy-six patients with advanced breast cancer were entered into the current study. They were randomized to receive either idarubicin (IDA) 45 mg/m2 orally or doxorubicin (DX) 75 mg/m2 intravenously (IV), both drugs being administered every 3 weeks. Among 37 evaluable patients who received DX treatment the overall response rate was 46%, whereas it was 21% in 34 evaluable patients treated with IDA. This difference was statistically significant. In previously untreated patients the response rate with DX was 60% compared to 29% with IDA. Patients with prior chemotherapy had 29% response rate to DX in contrast to 12% with IDA. The median time to response, the median response duration, and the median time to progression were similar in both groups. The median survival of all patients was 20 months in DX arm and 14 months in IDA arm (95% confidence limits 16.69-23.31 and 10.77-17.23, respectively; P = 0.09). Both treatments produced equivalent incidence and severity of myelotoxicity. Gastrointestinal toxicity and alopecia were significantly lower in patients receiving IDA. As for cardiotoxicity, four cases of congestive heart failure were recorded among patients treated with DX whereas no cases occurred in the IDA group. The results of this study indicate that, although DX remains the best single agent available in the treatment of breast cancer, IDA may have a role in selected patients with this disease.

Adult↗

Induction of immunotolerance in hemophilia for high titre inhibitor eradication: a long-term follow-up.

Three hemophiliacs with high titre inhibitor were treated with a medium-high FVIII dose schedule (100 IU/kg bw daily) with the aim of inducing the immunotolerance. These patients were followed-up extensively concerning their immunological status and HIV serology. In all of them the inhibitor disappeared and normal FVIII kinetics were obtained after 22, 15 and 29 months. After eradication of the inhibitor, no recurrence took place in any of the patients. All the patients were HIV Ab positive before the beginning of the treatment. In one of them CD4+ cells fell progressively 32 months after the treatment was started, a full-blown AIDS showed up, and the patient died 5 1/2 years after the beginning of the treatment. In the second and third patient the CD4+ cells varied widely but remained greater than 400/microliter during the whole immunotolerance treatment. The latter two patients are AIDS and ARC free so far, but patient No. 2 developed a mild-to-severe thrombocytopenia. Considering the high cost of the treatment and the possibility that such an intensive administration of FVIII concentrates might worsen the immunological status of patients, this therapeutic procedure should only be applied with caution.

Adult↗

[Bone marrow autograft treated with mafosfamide in the acceleration phase in chronic myeloid leukemia. Inversion of the clinical development].

A 21-year old male patient with Philadelphia chromosome-positive chronic myeloid leukaemia received an autologous bone marrow transplant in consolidation of the 2nd chronic phase. The bone marrow had been treated with mafosfamide in adequate doses. The post-transplantation course of the disease was marked by an inversion: the duration of the 2nd chronic phase was more than 4 times longer than that of the first one, suggesting some degree of effectiveness of autologous bone marrow transplantation performed in the 2nd chronic phase and/for of the in vitro treatment of the bone marrow with mafosfamide. Cytogenetic monitoring was pursued throughout the course of leukaemia: regression of the Philadelphia chromosome was only partial and transient, and 3 clones appeared, each of them involving chromosome 1, for which mafosfamide was most probably responsible.

Adult↗

Monoclonal antibodies against LFA-1 or its ligand ICAM-1 accelerate CD2 (T11.1 + T11.2)-mediated T cell proliferation.

Activation of human-purified T cells can be mediated by pairwise combinations of monoclonal antibodies directed against T11.1 and T11.2 epitopes on the CD2 molecule. Monoclonal antibodies (mAbs) reactive with either the alpha and beta chains of the lymphocyte-function-associated antigen-1 (LFA-1) molecule or one of its ligands, intercellular adhesion molecule-1 (ICAM-1), were found to accelerate anti-CD2-induced proliferation. This effect was seen on thymocytes and resting or preactivated T cells (phytohemagglutinin blasts and alloproliferative T cell clones) and could be observed, following the introduction of anti-LFA-1 or -ICAM-1 mAbs, up to 50 hr after the CD2 stimulatory signal. This effect was equally abrogated by 55 kDa anti-interleukin-2 (IL-2) receptor mAb, but neither the expression of IL-2 receptor nor the production of IL-2 was modified. The effects of anti-LFA-1 or anti-ICAM-1 on T cell activation through the CD2 pathway were therefore opposite to those observed in the CD3 pathway, where both mAbs strongly delayed T cell proliferation.

Antibodies, Monoclonal↗

[Current results and prospects of intra-arterial chemotherapy in hepatic metastases of carcinoma of the colorectum].

The development of safe arterial access devices and totally implantable or portable infusion pumps for intrahepatic chemotherapy has generated a renewed interest in regional treatment of liver metastases from colo-rectal primaries. Several phase II trials have been carried out, mostly using prolonged infusion of fluorinated pyrimidines showing very high activity for this method of treatment with response rates up to 80%. Randomized trials between systemic and regional therapy have confirmed the higher efficacy of arterial treatment in inducing objective responses but neither of the two studies with a follow-up long enough to assess survival data showed a clear advantage for the patients receiving intraarterial chemotherapy. Gastroduodenitis, ulcers and chemical hepatitis are frequently observed in patients treated with intrahepatic arterial chemotherapy but their incidence can be substantially reduced by a careful surgical procedure during the implant of the arterial catheter and by a close follow-up during chemotherapy. Since toxicity can be serious and no definitive improvement of survival has been shown, this modality of treatment is still applicable only in an investigational setting.

Antineoplastic Combined Chemotherapy Protocols↗

[Aztreonam and oxacillin in the treatment of febrile neutropenic patients with solid tumors].

22 consecutive febrile episodes in 21 neutropenic (PMN less than 1000/mmc) cancer patients, were treated with aztreonam and oxacillin. Nineteen patients were severely neutropenic (PMN less than 500/mmc). Cure was obtained in 86% of the febrile episodes, including 6/7 bacteriologically documented gram negative infections. No major side effects were observed. These results seem to indicate that aztreonam is effective as empiric treatment of gram negative infections in neutropenic patients. However, it must be used in combination with another antibiotic to ensure gram positive coverage.

Adult↗

Isolation and characterization of a cysteine proteinase from Fasciola hepatica adult worms.

Adult Fasciola hepatica worms contain multiple proteinases capable of degrading hemoglobin, immunoglobulins and collagen. Here we report the isolation and biochemical characterization of a cysteine proteinase from acidic extracts of these worms. The enzyme was purified to homogeneity by cation exchange and molecular sieve high-performance liquid chromatography. It eluted at a native molecular weight of approximately 14,500 and migrated as a single band at approximately 14,500 Da upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Activity was assessed by employing synthetic peptide substrates, such as carbobenzoxy-phenylalanyl-arginyl-7-amino-4-trifluoro-methylcoumarin, commonly used to assay other cysteine proteinases. The proteinase was maximally active at pH 6.0, with 50% or more of the activity detected between pH 4.5 and 7.5. Inhibition of activity at pH 5.5 was seen only with compounds known to inhibit cysteine proteinases. No effect was seen with inhibitors of aspartic, serine, or metalloproteinases. The purified enzyme was stable at acidic pH at 4 degrees C, 25 degrees C, -20 degrees C, and in 1 M urea.

Animals↗

[Chemotherapy of advanced ovarian carcinoma. II. Second-line treatment and new therapeutic modalities].

Despite the efficacy of cisplatin-containing regimens the majority of patients with advanced ovarian cancer will die of their disease because of its high recurrence rate. Salvage therapy, generally with cisplatin alone or in combination, is still discouraging. Among the drugs recently tried against this disease, mitoxantrone, ifosfamide and etoposide warrant further investigation because of their ability to induce responses in cisplatin refractory patients. While epirubicin, due to its lesser cardiotoxicity, can replace the parent compound, the exact role of cisplatin analogues is still controversial because their different toxicity does not necessarily imply a better therapeutic index. Intraperitoneal therapy is emerging as a new treatment effective in selected cases. Encouraging preliminary results have been reported with some biological response modifiers, such as interferons, interleukins and monoclonal antibodies. It is likely that in the near future information gained by both basic and clinical research will improve the prognosis of patients with ovarian carcinoma.

Antibodies, Monoclonal↗

A two-site monoclonal antibody ELISA for the quantification of the major Dermatophagoides spp. allergens, Der p I and Der f I.

A two-site monoclonal antibody (Mab) ELISA was developed to measure the Group I allergens from Dermatophagoides spp., Der p I from D. pteronyssinus and Der f I from D. farinae. Species-specific Mabs were used to coat microtiter plates which were then incubated with allergen or house dust extracts. Bound allergen was detected using a biotinylated Mab which recognized a common epitope on both Der p I and Der f I, followed by the addition of streptavidin-peroxidase and ABTS/H2O2 substrate. The assay had low non-specific binding (approximately 0.08 absorbance units) and had a sensitivity of 5 ng/nl for aqueous allergen extracts (equivalent to 0.1 microgram allergen/g dust). 53 dust samples were assayed using the Mab ELISA and an RIA previously described using 125I-labelled Mab. The results showed a very good quantitative correlation between the assays (r = 0.96, p less than 0.001 for Der p I; r = 0.92, P less than 0.001 for Der f I). A further 132 dust samples from a different geographical areas were also assayed by both methods and gave correlation coefficients of 0.90 (P less than 0.001) and 0.86 (P less than 0.001) for Der p I and Der f I, respectively. The Mab ELISA will be useful in epidemiological studies of allergic asthma, both in the assessment of levels of dust mite allergen present in houses and the efficacy of allergen avoidance regimes.

Allergens↗

Analysis of cytosolic ionized calcium variation in polymorphonuclear leukocytes using flow cytometry and Indo-1 AM.

The present report describes the increase in cytosolic-free calcium levels (Ca2+i) induced by chemoattractants in polymorphonuclear leukocytes (PMN) using the new fluorescent Ca2+ chelator Indo-1 AM. Increases in cytosolic Ca2+ were measured by flow cytometry. With this approach, 98% of PMN were found to respond to F-Met-Leu-Phe (FMLP) and leukotriene B4 (LTB4) stimulation. Although both substances induced a rapid and relatively homogeneous rise in Ca2+i, only FMLP gave a sustained Ca2+i rise, whereas that induced by LTB4 appeared transient. In addition, the combined use of wide-angle light scatter and electronic cell volume measurement allowed analysis of Ca2+i variations in the total peripheral blood cell population. The supernatant of a human fibrous histiocytoma cell line (GCT) was able to increase Ca2+ release in PMN. This activity may be ascribed to a new granulocytic activation factor, as neither human recombinant interleukin-1 alpha (IL-1 alpha), granulocyte-colony stimulating factor (G-CSF), nor granulocyte-macrophage-colony stimulating factor (GM-CSF), which were present in this supernatant, were able to induce a Ca2+i rise in PMN.

Calcium↗

T cell activation via the CD2 molecule is associated with protein kinase C translocation from the cytosol to the plasma membrane.

T cell activation via the CD2 molecule involves phospholipase C and phosphoinositide hydrolysis. Here we demonstrate that the triggering of subclones of the human T leukemia Jurkat cell line by anti-CD2 as well as anti-CD3 monoclonal antibodies is able to induce activation (i.e. translocation from cytosol to cell membrane) of protein kinase C (PKC), which is dependent on the formation of 1,2-diacylglycerol from inositol 4-5-bisphosphate. The kinetics of PKC translocation parallels the rise in intracellular calcium following both CD2 and CD3 stimulations. These results further demonstrate that CD2 and CD3 activation pathways use similar signal transduction mechanisms.

Antibodies, Monoclonal↗

Cholera toxin inhibits the increase in cytoplasmic free calcium induced via the CD2 pathway of human T-lymphocyte activation.

We investigated the action of cholera toxin on the intracellular ionized calcium [Ca2+]i increase induced by anti-CD2 and anti-CD3 monoclonal antibodies in the leukemic human T-cell line Jurkat. Cholera toxin inhibits in a dose-dependent manner these two pathways of human T-lymphocyte activation but with different half maximal inhibition doses (75 ng/ml for CD3, 30 ng/ml for CD2). This effect cannot be accounted for only by the increase in cAMP induced by cholera toxin because forskolin, which raises cellular cyclic adenosine monophosphate (cAMP) to the same levels, induced only a small inhibition of the [Ca2+]i increase in similar conditions. Cholera toxin induced a decrease in the surface expression of the CD3 molecule, suggesting a down-regulation of the CD3 molecules. On the other hand, the expression of CD2 remained unchanged. Cell surface disappearance of the CD3 molecule cannot account for all the inhibitory effects of cholera toxin because CD2 molecule expression was not affected (no modifications in the half maximal binding of anti-CD2 monoclonal antibodies). All together, these results suggest that cholera toxin acts on substrates, possibly G proteins, that could regulate the [Ca2+]i increase induced by anti-CD2 and anti-CD3 mAbs in Jurkat cells. In addition, the present study demonstrated that the rise in cellular cAMP partially inhibits the [Ca2+]i increase induced by anti-CD2 and anti-CD3 mAbs.

Antibodies, Monoclonal↗