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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 253 records · Page 14Linked to original sources
PubMed1991

Combination chemotherapy with oral idarubicin and cyclophosphamide for metastatic breast cancer.

A group of 40 women with objectively measurable metastatic breast cancer was treated with idarubicin, 35 mg/m2 on day 1, and cyclophosphamide, 200 mg/m2 on days 2-5, both drugs being administered orally every 3 weeks. Of 37 evaluable patients, 4 (10.8%) achieved a complete response and 14 (37.8%) a partial response, for an overall response rate of 48.6% (95% confidence interval, 37.45%-59.75%). In previously untreated patients the response rate was 58.3%, whereas it was 44% in patients previously exposed to cytotoxic drugs. The median duration of response was 6.5 months, and the median survival of all patients was 10.5 months. Moderate nausea and vomiting were common. Diarrhoea, which occurred in 37% of the patients, was usually short-lived. Alopecia was generally mild, myelosuppression was the dose-limiting toxicity. Grade 3-4 leukopenia occurred only in pretreated patients. In previously untreated patients it was generally of grade 1-2. Laboratory evidence of cardiotoxicity (greater than or equal to 20% decrease in the left-ventricular ejection fraction from the baseline value) was observed in 3 out of 26 patients, who had at least two determinations of the left-ventricular ejection fraction, and was transient in nature. No cases of congestive heart failure were observed. These results indicate that the combination of idarubicin + cyclophosphamide represents a practical and effective regimen to be used in selected patients with advanced breast cancer.

Administration, Oral↗
PubMed1991

Use of flagellin-enriched antigens in a rapid, simple and specific quantitative enzyme immunoassay for Lyme disease antibodies in human serum samples.

An enzyme immunoassay (EIA, ELISA) using microwells coated with a flagellin-enriched fraction of B. burgdorferi and absorbent-containing sample diluent for the quantitative determination of Lyme disease (LD) IgG and IgM antibodies in human serum samples was described. This LD EIA required three 15-minute incubations at room temperature, followed by a 1-step normalization of photometer readings to EIA units (EU/ml). Compared with tests using the whole bacterial extract as antigens and a sample diluent containing 6% BSA, this new LD EIA revealed lower values for 20 syphilis (SS) and 21 normal serum samples (NS) but about the same for 21 Lyme disease (LD) samples, allowing lower cut-off points which would place almost all these SS and NS samples below while almost all LD samples above the positive cut-off point. The LD EIA results of larger numbers (67 to 291) of mixed samples correlated with results of four reference EIA. However, the LD EIA gave lower (2 to 4 fold) reactivities (index values) with SS and NS samples but higher values with positive serum samples than reference EIA. Thus, this LD EIA showed improvements in both specificity and sensitivity over other tests compared.

Adjuvants, Immunologic↗
PubMed1991

Cell surface expression of ICAM-1 (CD54) and LFA-3 (CD58), two adhesion molecules, is up-regulated on bone marrow leukemic blasts after in vivo administration of high-dose recombinant interleukin-2.

High-dose recombinant interleukin-2 (rIL-2) therapy can induce long-term remission in patients with melanoma and renal and colon cancer. More recently, in vivo IL-2 therapy was shown to induce complete or partial remission in some cases of relapsed chemotherapy-resistant acute myeloid leukemia. We have investigated the phenotypic modifications of bone marrow cells obtained from five patients with acute myeloid leukemia in relapse receiving high-dose i.v. rIL-2. We found that, in three of five patients, IL-2 could induce, in vivo, an increase in the expression of CD54/ICAM-1 and to a lesser extent of CD58/LFA-3 on bone marrow leukemic blasts. This demonstrates that rIL-2 modifies directly or indirectly the expression of the cell surface molecules of the tumor cells themselves. Upregulation of such adhesion molecules could account for the enhancement of cell interactions between the tumor and effector cells such as T, natural killer, and phagocytic cells as well as being indicators of differentiation signaling.

Antigens, CD↗
PubMed1991

Additive effects of psychostimulants, parent training, and self-control therapy with ADHD children.

Utilizing a double-blind, placebo design, the effects of a high (0.8 mg/kg) and a low (0.4 mg/kg) dose of methylphenidate alone and in combination with behavioral parent training plus child self-control instruction were evaluated with 96 attention deficit hyperactivity disorder children. No evidence of the superiority of the combined conditions relative to medication alone was found. Some limited support was found for the hypothesis that the effects of a high dose of psychostimulant medication could be achieved by combining the low dose with a behavioral intervention. The importance of the latter finding is highlighted by the fact that both the benefits and untoward effects of the psychostimulants appear to increase with the dose.

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

Feasibility of autologous bone marrow transplantation for early consolidation of follicular non-Hodgkin's lymphoma.

In contrast to intermediate- and high-grade non-Hodgkin's lymphomas (NHL), patients with follicular lymphomas retain a poor prognosis in the long run. Several reports suggested that they are incurable by conventional chemotherapy. 10 patients with follicular NHL were autografted for consolidation of early remission. One of these patients treated in 1979 received the TACC regimen with unpurged marrow. The other 9 (8 in first, 1 in second remission) treated since July 1987 received the BEAM regimen followed by autologous bone marrow transplantation (ABMT) with marrow purged in vitro by mafosfamide at levels individually adjusted. There were no toxic deaths. 8 patients remain in unmaintained CR 15 to 43 months post-ABMT-2 are beyond 2 years. The patient autografted in 1979 has relapsed 9 yr later. ABMT is feasible with no indue toxicity for consolidation of follicular NHL early in first remission, as an alternative aggressive strategy. Further studies and a longer follow-up will be needed to evaluate its antitumor efficacy.

Adult↗
PubMed1991

Epirubicin and DTIC (EDIC) for advanced soft-tissue sarcomas.

Fifty-six patients with measurable advanced soft-tissue sarcomas were treated with epirubicin, 90 mg/m2 intravenously on day 1, and DTIC, 250 mg/m2 intravenously on days 1-5, with the entire regimen repeated every 3 weeks. The overall response rate in 52 evaluable patients was 48% with 9 complete remissions. Noncardiac toxicity was limited predominantly to vomiting, alopecia and myelosuppression. Laboratory evidence of cardiotoxicity [greater than or equal to 20% decrease in left-ventricular ejection fraction (LVEF) from the baseline value] was observed in 4 out of 39 patients who had at least two determinations of LVEF, at a median dose of 1,305 mg/m2. Two patients had clinical congestive heart failure at cumulative dose of 1,440 and 1,620 mg/m2. These findings suggest that the combination of epirubicin and DTIC is an active regimen in soft-tissue sarcomas, and provide further evidence that epirubicin is a doxorubicin analogue with reduced cardiac toxicity, but preserved efficacy in this disease.

Adolescent↗
PubMed1991

Evaluation of immune parameters in HIV+ subjects reporting adverse reactions to sulfamethoxazole.

Trimethoprim-sulfamethoxazole (TMP-SMX) is frequently used in human immunodeficiency virus (HIV)-infected patients (HIV+) for treatment or prophylaxis of Pneumocystis carinii pneumonia (PCP). Up to 80% of those patients report adverse reactions to that drug combination. To test the hypothesis that these reactions are immunologically mediated, we quantitated specific IgG and IgE SMX-human serum albumin (HSA) antibodies and immune complexes (IC) in HIV+ patients and in HIV controls. Patients with mild HIV disease had elevated specific SMX-HSA IgG and IC levels compared with those having severe disease or with controls. Conversely, patients with severe HIV disease had statistically elevated levels of specific IgE when compared with patients having milder disease or with controls. There were no differences in either specific antibody or IC levels between patients reporting adverse reactions and those who did not. Results suggest that there are increased levels of SMX-HSA-specific antibodies in some HIV+ patients. The presence of these antibodies appears to be related to severity of disease, rather than clinically significant drug sensitivity.

Antigen-Antibody Complex↗
PubMed1991

Basidiomycete allergy: identification and characterization of an important allergen from Calvatia cyathiformis.

Basidiomycetes were not considered as major aeroallergen sources until spore traps revealed the prevalence of basidiospores, which were in some cases associated with epidemic outbreaks of asthma. More recently, we established that approximately one third of subjects with respiratory allergic disease were skin prick test positive to basidiospore extracts. Bronchial challenge with these extracts induced reversible immediate and late phase bronchospasm in sensitive subjects. Screening individual RAST-positive sera for reactivity to immunoprinted Calvatia cyathiformis spore extract indicated that a basic component with pI 9.3 reacted with 63% of test sera. Further analysis by RAST and immunoprint (IP) inhibition showed that this component, Cal c Bd9.3, appeared to cross-react with spore extracts from 3 of 5 other species tested. To isolate this component for additional analysis, a protocol was used with two sequential stages of preparative isoelectric focusing (IEF) followed by hydrophobic interaction chromatography. This yielded purified Cal c Bd9.3 that retained IgE-binding activity by IP, was a single band by IEF and SDS-PAGE (16 kD) analysis when stained with Coomassie blue. Double diffusion in gel with rabbit antiserum to Cal c BD9.3 demonstrated a single precipitin band in crude extract that was identical to that obtained with purified Cal c Bd9.3. By IP this antiserum recognized pure Cal c Bd9.3 and the 9.3 band in crude extracts from C. cyathiformis and 3 other species, corroborating the cross-reactivity. However, other bands were also recognized. These studies indicate that basidiospores are major fungal aeroallergens, many of which contain a common basic allergen to which most sensitized subjects react.

Allergens↗
PubMed1991

Acceleration of hemopoietic recovery after autologous bone marrow transplantation by low doses of peripheral blood stem cells.

Twenty patients with advanced malignant disease submitted to autologous bone marrow transplantation with marrow either unpurged (10 patients) or purged in vitro with mafosfamide (10 patients) after ablative chemotherapy, received simultaneously autologous peripheral blood stem cells (PBSC) collected during one to three 3 h cytapheresis procedures. The kinetics of the hematological recovery of these patients were compared to those of a group of patients suffering from similar diseases and grafted in the same institution with either unpurged marrow only (14 patients) or purged in vitro with mafosfamide (six patients). The median times to reach 10(9)/l leukocytes, 0.5 x 10(9)/l polymorphs, and 50 x 10(9)/l platelets were reduced by 10, 10, and 13 days, respectively, in patients transfused with both autologous bone marrow and peripheral blood stem cells as compared to those receiving bone marrow only. A reduction in the numbers of days spent in hospital post-transplantation (p less than 0.01), of days of fever greater than 38 degrees C (p = NS), and of platelet (p = 0.07) and of red blood cell transfusions (p less than 0.01) were also observed in the group of patients grafted with bone marrow and PBSC.

Adolescent↗
PubMed1991

Complications of CAPD in children: six years experience in Caracas, Venezuela.

Forty-three ESRD children received treatment with CAPD from November 1984 through July 1990. Mean patient age was 10 years (range 2-17 years) and total observation period (consolidated for the whole group) was 683 months. Double cuff Tenckhoff catheters were used as access. The most common complication was peritonitis with an overall rate of one episode per 5.6 patient/months. Important correlation was found between incidence of peritonitis and socioeconomic status assessed by Graffar Index (G.I.). Patients with lowest socioeconomic status (GI of IV and V) had one episode of peritonitis per 2.9 patient/months. Patients with GI of III had one episode per 5.2 patient/months and patients with the best socioeconomic status (GI of I and II) had only one episode per 11.6 patient/months. Other complications were the following: Infections: 18 exit site infection, 5 exit site granuloma and 5 tunnel abscess. Catheter malfunction: 17 obstructions, 5 migrations and 2 ruptures. Others: 3 peritoneal hemorrhages, 1 intestinal perforation, 3 eventrations, 4 inguinal hernias and 1 right pleural effusion. In this last patient, pleurodesis was unsuccessfully attempted with homologous blood. We conclude that patients with very low socioeconomic status are poor candidates for CAPD and should be considered preferably for hemodialysis.

Adolescent↗
PubMed1991

Coexpression of the genes for interleukin 6 and its receptor without apparent involvement in the proliferation of acute myeloid leukemia cells.

Leukemic cells isolated from patients with either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL) were screened for their capacity to express the interleukin 6 (IL-6) and IL-6 receptor genes, both at the RNA and protein levels. Variable levels (10 to greater than 600 U/ml) of an IL-6 activity, inhibited by neutralizing anti-IL-6 antibodies, were detected in AML cell supernatants using the B9 cell bioassay. High levels (greater than 100 U/ml) were observed in differentiated (M4 and M5 stages) AML, as well as in less mature (M1 and M2 stages) AML. Detection of the IL-6 transcript correlated with the biological activity. In addition, both IL-6 activity and IL-6 mRNA were detected in "fresh" leukemic cells, indicating that the glycoprotein was actually synthesized in vivo. In contrast, the IL-6 gene was less frequently expressed in ALL. The IL-6 receptor gene was transcribed in both AML and ALL; binding experiments showed that the protein was present at the cell surface. The spontaneous in vitro proliferation of leukemic cells coexpressing the transcripts for IL-6 and its receptor was not significantly inhibited by a neutralizing anti-IL-6 antibody, suggesting that IL-6 is not primarily implicated in the proliferation of the leukemic clone via an autocrine loop. Synthesis of IL-6 could, however, confer on leukemic cells a selective growth advantage through activation of the cytokine cascade.

Antigens, CD↗
PubMed1991

Amocarzine investigated as oral onchocercacidal drug in 272 adult male patients from Guatemala. Results from three dose regimens spread over three days.

The clinical investigations with three types of a three days regimen of amocarzine permitted to adjust the fixed dosing to the body weight related dosing and subsequently the administration of amocarzine from fasting state to drug intake after food. The main objective to reach a dose with predictable and sustained absorption was achieved, and this in turn proved to be onchocercacidal and safe. A combined clinicopharmacokinetic study showed enhancement and consistency of amocarzine absorption after food. Quantitative assessment of the urinary excretion confirmed the presence of the N-oxide metabolite, which qualitatively was visible by a urine colorimetry. This assay proved useful for drug monitoring. Ultrasonography of onchocercal skin nodules detected changes within the nodules following amocarzine therapy. Histology after nodul-ectomy at four months post-therapy showed that 57% of the female worms were dead, 24% necrobiotic, and 19% alive; male worms were more necrobiotic. Skin microfilariae were reduced within one week to about 10% of the initial level and after one year they remained at about 20%. Skin punch biopsies on day 5 showed that most microfilariae were dead or moribund. Ocular reduction of microfilariae was also observed, although it was slower than in the skin. The visual acuity improved within the one year's observation time. Ocular and clinical tolerability was good, with one exception of neurological disturbance, which was fully reversible. Sequential testing of the liver function showed average values within the normal range. In conclusion, a repeat low dose regimen of amocarzine (3 mg/kg twice daily post-prandially for three consecutive days) was well absorbed with predictable plasma levels, macro- and microfilaricidal with good local and systemic tolerability in patients with moderate to heavy onchocerciasis. Amorcarzine is recommended for further clinical investigations, particularly in females and juveniles. Urine colorimetry and nodular ultrasonography are recommended for optional monitoring of amocarzine.

Administration, Oral↗
PubMed1991

Identical utilization of T-cell receptor gene regions in B-lymphoid blast crisis of chronic myeloid leukemia and B-precursor acute lymphoblastic leukemia.

The configuration of the T-cell receptor (TCR) beta, gamma and delta chain genes was analyzed in 16 cases of B-lymphoid blastic crisis of chronic myeloid leukemia (BC-CML) for a better definition of the biological aspects of this cellular population, in comparison with the molecular features of B-precursor acute lymphoblastic leukemia (ALL). All cases displayed B-phenotypic features, were Ph'-positive and had a rearranged configuration of the breakpoint cluster region (bcr) and of the immunoglobulin heavy chain gene region (JH). The TCR beta chain gene was rearranged in four cases (25%), all of which displayed a monoallelic rearrangement involving the J beta 2 region. The TCR gamma chain gene was rearranged in 13 cases (81%); 13 rearranged alleles utilized the J1/2 regions, while the remaining five utilized JP1. The V regions of the group I were mostly involved. The TCR delta chain gene was rearranged or deleted in 15 cases (94%); the 10 rearranged chromosomes displayed exclusively two patterns referable to partial recombinations, a V2-(D)-D3 and a (D)-D3 type. These two configurations are predominant in B-precursor ALL (75% of rearranged chromosomes) and almost absent in T-ALL. Taken together, these results document the close similarities between the genotypic features of B-lymphoid BC-CML and B-precursor ALL, not only in terms of the incidence of rearrangement but more relevantly with regard to the choice of regions involved in the recombinations. This aspect is particularly evident at the TCR delta locus level.

Blast Crisis↗
PubMed1991

Medulloblastoma presenting as blindness of rapid evolution. A case report.

An 18-year-old man reported rapid decrease of visual acuity that progressed to total blindness in 1 month. Computed tomographic scanning showed two neoplastic masses: a large one, intra- and suprasellar, and a smaller cerebellar nodule. Histologically, the former proved to be a large metastasis of the small cerebellar medulloblastoma, which infiltrated and compressed the chiasm. Direct compression of the optic pathways by metastasis of a medulloblastoma is a rare event.

Adolescent↗
PubMed1991

LH-RH analogue Zoladex in the treatment of pre- and perimenopausal women with metastatic breast cancer (results of the Italian Cooperative Study).

From May 1987 to May 1989 sixty one pre- and perimenopausal women with advanced or recurrent breast cancer entered in an open non comparative study. They were treated, as a first-line therapy, with goserelin (Zoladex ICI-118630) a long acting gonadotropin-releasing hormone (LH-RH)-analogue in a depot formulation. Fifty three patients were evaluable for response; median age at entry was 41 years (range 28-56). Serum concentrations of 17 beta estradiol, LH and FSH were significantly suppressed within the first four weeks of therapy and remained suppressed for the whole duration of treatment. Subjective responses were observed, such as pain reduction and/or performance status improvement in 58% of patients. Overall objective response (CR + PR) occurred in 16 (30.2%) patients in all major sites of disease with a median time to response of 12 weeks (range 8 to 48 weeks) and a lifetable median duration of response of 36 weeks (range 16 to 76 weeks). The lifetable median time to progression was 17 weeks (range 5 to 76 weeks). Goserelin depot was well tolerated with no withdrawal due to possible adverse reactions. The observed subjective and objective response rates are comparable to those induced by surgical oophorectomy. Goserelin provides a well tolerated medical alternative to ovarian ablation, without the morbidity associated to surgery. In conclusion the present paper suggests that this innovative chemical estrogen deprivation, in premenopausal breast cancer patients, might be favorably investigated as an adjuvant therapy in future clinical trials.

Adult↗
PubMed1991

Human placental low molecular weight factors inhibit the entry into cell cycle of murine pluripotent stem cells.

In 1977, Frindel et al. reported the presence in fetal calf bone marrow of a low molecular factor, the tetrapeptide Ac-N-Ser-Asp-Lys-Pro (AcSDKP), capable of inhibiting in vivo the hematopoietic pluripotent stem cell (CFU-S) recruitment into DNA synthesis and to increase the survival of mice which had received lethal doses of cytosine arabinoside (AraC), a phase-specific drug. Considering the potential clinical importance of CFU-S proliferation inhibitor during anticancer chemotherapy and the importance of monitoring the inhibitor by immunological methods, we tried to determine if a similar inhibitor is present in humans. Preliminary results indicate the presence in human placenta of an inhibitor coeluted with AcSDKP and which is effective in inhibiting murine CFU-S.

Amino Acid Sequence↗