Standardization of rat blood clotting tests with reagents used for humans.
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Biomedical subjects
Publications and source records attributed to J González-Llaven.
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Between August 1994 and June 1999, 56 patients were prospectively randomized to receive ifosfamide 10 g/m2 + GM-CSF 5 microg/kg/day (IFO+GM-CSF n = 28) and cyclophosphamide 4 g/m2 + GM-CSF 5 microg/kg/day (CY+GM-CSF n = 28). Both groups were comparable for age, gender, diagnosis, disease stage and previous chemotherapy. The IFO+GM-CSF group demonstrated a shorter median interval between therapy and apheresis (10 days (8-14) vs 13 days (8-25) P = 0.002), median number of doses of GM-CSF (9 (7-13) vs 15 (9-31) P = 0.001), median of days with aplasia (0.5 (0-10) vs 6 (0-21) P = 0.001), median days with fever (0 (0-6) vs 3 (0-9) P = 0.006) and median of days using i.v. antibiotics (0 (0-11) vs 7.5 (0-19) P = 0.002). The median MNC yield was similar in both groups. The CD34+ cell yield was better in the CY+GM-CSF group (3.14 (0.9-11.8) vs 5.33 (0. 08-32)) but not at significant levels (P = 0.1). White blood cell hematopoietic recovery was more rapid in the CY+GM-CSF group (16 (10-22) vs 13 (10-24) P = 0.02). Platelet engraftment was similar in both groups. Costs of mobilization and transplantation were almost the same: $28 570 ($18 527-$47 028) and $30 020 ($17 281-$67 591), respectively (P = 0.9). There were no differences in disease-free survival and overall survival between both groups. Mild and transient non-hematological toxicity (hemorrhagic cystitis, decrease in serum creatinine clearance and CNS dysfunction) was seen most frequently in the IFO+GM-CSF group.
The existence of population variations in cyclosporine pharmacokinetics could be expected, as this drug, similar to nifedipine, is biotransformed by cytochrome P-450 subfamily 3A4, and the existence of interethnic variability in nifedipine disposition has been demonstrated previously. The bioavailability of oral cyclosporine was studied in 23 healthy Mexican volunteers receiving 7.5-mg/kg doses of cyclosporine. Blood samples were drawn over 24 hours, and concentration of cyclosporine in whole blood was determined by a radioimmunoassay using monoclonal antibodies specific for the unchanged drug. The bioavailability of cyclosporine exhibited wide interindividual variability. Maximum concentration (Cmax) ranged from 528 ng/mL to 2,689 ng/mL, area under the concentration-time curve (AUC) ranged from 6,550 ng.hr/mL to 18,562 ng.hr/mL, and time to reach Cmax (tmax) ranged from 1 to 8 hours. Half-life (t1/2) exhibited less important variations, ranging from 4.4 to 9.1 hours. The bioavailability of oral cyclosporine in Mexicans was higher than that reported for white populations under similar conditions. The present results suggest the existence of interethnic variability in the pharmacokinetics of cyclosporine, as is the case with nifedipine.
In this report we show the chromosomal changes seen in a group of 303 Mexican patients with de novo Acute Myeloblastic Leukemia (AML). Two hundred forty-two patients were diagnosed and treated at two hospitals affiliated with the Instituto Mexicano del Seguro Social (IMSS). These are the Centro Medico Nacional Siglo XXI and Centro Medico La Raza Hospitals; the remaining 61 patients were diagnosed and treated at the Hospital General de Mexico (HGM). Clonal abnormalities were detected in 75.6% of the patients; this result agrees with what has been reported in other large series of AML studies. The incidence of changes per hospital was similar in patients from the IMSS hospitals (72-75%), while an increase was seen in patients from the HGM (85.2%). The chromosomal changes seen in this study in order of frequency were: t(15;17)[18.8%], t(9;22)[9.2%], miscellaneous chromosomal changes (mainly rearrangements of chromosomes 1,2,3,12y17)[8.2%], abnormalities of 16q22 [7.3%], t(8;21)[6.3%], -7/del(7q)[5.6%], t(6;9)[5.3%], and abnormalities of 11q23 [4.6%]. We reported an increase in the incidence of certain types of chromosomal changes seen in cases of AML, in comparison with reports from other countries. These differences could be due to methodological variations, although ethnic, socioeconomic and nutritional differences must not be disregarded. We support this finding when comparing distribution of changes in the population of patients seen in the IMSS hospitals with those from the HGM; the main difference lies in the socioeconomic level.
PURPOSE: To compare the clinical patterns and survival of young and adult (AP) versus paediatric (PP) patients with paroxysmal nocturnal haemoglobinuria (PNH). PATIENTS AND METHODS: The clinical records of 117 patients (82% AP, 18% PP) seen in four cities of the Mexican Republic were analysed, the clinical course and survival of both groups being compared. RESULTS: No sex difference was found in the two patient-groups: 51% and 52% males, 49% and 48% females in AP and PP, respectively. The onset of PNH had similar distribution for the two groups of patients: aplastic form, 45% in AP and 62% in PP; cytopenias, 24% in AP versus 27% in PP; haemolysis, 28% in AP and 9% in PP, and thrombosis, 3% in AP versus 0% in PP. The clinical features with significant difference were: anaemic+haemorrhagic syndrome (39 AP (40%) vs 14 PP (67%), p = 0.02), initial diagnosis of immunologic thrombocytopenic purpura (7 AP (7%) vs 7 PP (33%), p = 0.003), and death rate (17 AP (18%) vs 8 PP (38%), p = 0.04). The actuarial survival curves showed significant differences between both groups (p = 0.045, Cox-Mantel), with estimated 10-year survival of 81% for AP and 55% for PP, and 15-year survivals of 64% for AP and 55% for PP. CONCLUSIONS: Seemingly, PNH in paediatric age has poorer prognosis than in adults, which is associated to higher incidence of fatal haemorrhages due to thrombocytopenia.
Lymphocyte subsets were enumerated in a group of 31 patients with aplastic anemia. Abnormal numbers of immunoregulatory T-cells were found in some patients: 26% of them showed a reversed helper/suppressor ratio. Seven of 18 patients showed significantly decreased proliferation in response to PWM; this hyporesponsiveness was present in 75% of patients with a reversed helper/suppressor ratio and in 10% of those with a normal helper/suppressor ratio (R = 0.66, P = 0.008). Eight of 18 patients showed suppressor activity over PWM-induced allogeneic cell proliferation. This suppressive activity did not correlate with T-cell phenotype. Of the patients with a low number of T-cells, 73% had responded to treatment, whereas of those patients with a normal number of T-cells, 26% had responded (P = 0.016). The results are consistent with abnormal immune response in selected patients with aplastic anemia, and suggest a possible influence of T-cells on disease process.
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BACKGROUND: The use of conventional cyclosporine (Sandimmune) requires great care, as this drug exhibits a narrow therapeutic index and wide interindividual variability in its pharmacokinetics. Recently, a new microemulsion formulation (Neoral) was developed. With this formulation, cyclosporine is absorbed at the small intestine without the presence of bile. Therefore, the objective of this study was to compare the bioavailability of cyclosporine after the administration of conventional and microemulsion formulations in healthy Mexican volunteers in order to approach the optimal dosage regimen of microemulsion in the Mexican population. METHODS: The trial was conducted using 23 healthy volunteers according to a randomized crossover design. Volunteers received one 7.5-mg/kg dose as each formulation, with a 1-week washout period between treatments. Blood samples of 0.5 mL were obtained according to the following schedule: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 h after medication. RESULTS: These indicated that Cmax and AUC0-24 values were higher with the microemulsion than with the conventional formulation. CONCLUSIONS: The microemulsion had a better absorption profile than the conventional formulation, because plasma levels with the conventional formulation demonstrated oscillations rather than reflecting an erratic absorption. Lower doses of the microemulsion are required to obtain Cmax values similar to those obtained with conventional cyclosporine.
BACKGROUND: Bone marrow transplantation (BMT) is the therapy of choice for patients with chronic myeloid leukemia (CML) who have a human leukocyte antigen (HLA)-identical donor and are under 50 years of age. METHODS: Here, 45 patients with CML were treated with busulfan (Bu) 16 mg/kg and cyclophosphamide (Cy) 120 mg/kg before allogeneic BMT from an HLA-identical sibling 27 (60%) or a 1-antigen mismatch donor 18 (40%). Eighteen patients (40%) were in the early chronic phase (CP) and 27 (60%) in late CP. We used cyclosporin-A (CsA) in 20 patients and cyclosporin-A-methotrexate (CsA-MTX) in 25 for graft-vs.-host disease (GVHD) prophylaxis. RESULTS: We observed a high incidence of acute and chronic GVHD (69% and 67%, respectively). A multivariate analysis identified differences in the sex of the donor and the recipient (p = 0.03) and grade III-IV acute GVHD (p = 0.0001) as significant adverse influences on disease-free survival. Age, sex, chronic GVHD, disease phase, one antigen-mismatch and use of CsA or CsA-MTX had no statistical significance. The 3-year probabilities of relapse, disease-free survival, and overall survival were 11%, 55%, and 60%, respectively. Transplant-related mortality occurred in 31% of the cases. The high frequency of GVHD is explained by HLA determination by serological typing, differences in sex between the donor and recipient, and a high proportion (40%) of 1 antigen-mismatch donors. CONCLUSIONS: BMT is a procedure feasible for patients with CML in early and late chronic phase and even in those with an HLA non-identical donor. Strategies directed to decrease acute GVHD could improve the outcome of these patients.
BACKGROUND: This study was carried out to assess the isolation rate of bacterial and fungal causative agents in Mexican neutropenic adults with hematological neoplasia. METHODS: A prospective observational survey involving 120 consecutive episodes of febrile neutropenia during 1 year was carried out. These episodes were observed in 630 patients discharged with diagnoses of leukemia or lymphoma, or after bone-marrow transplantation. RESULTS: At least one pathogen was isolated in 42 of 120 episodes (35%), and was present in 39 patients with acute myeloid leukemia (AML) (43%), acute lymphoblastic leukemia (ALL) (23%), and in patients who underwent bone-marrow transplantation (20%). Primary bacteremia was the most frequent cause of fever (24 episodes, 57%), followed by intravascular device-related infections (5 episodes, 17%), and soft-tissue infections (5 episodes, 15%). Escherichia coli (33%) was the most frequently isolated agent of primary bacteremia, followed by coagulase-negative Staphylococcus (29%), and Klebsiella oxytoca (16%). Fungal infection was responsible for five events (4%): two episodes of pneumonia (Penicillium marneffei and Aspergillus fumigatus, one event each); two cases of fungemia, one due to Candida tropicalis and one to Rhodotorula gluttinis, and one cryptococcal meningitis event. CONCLUSIONS: The isolation rate, approximately 30%, was in accordance with previous reports; similar percentages of Gram-positive and Gram-negative isolates were found. A remarkably low rate of viridans group streptococci and fungal agents was observed, despite the fact that neutropenia is the main risk factor for infection due to these agents. Studies reporting local microbiological findings are necessary because they support an antibiotic choice for prophylaxis or therapy more accurately than reports from other areas.
Forty five adult patients with low risk acute lymphoblastic leukemia were treated with prednisone, vincristine and adriamycin. 91 per cent (41 patients) obtained complete remission with a mean survival was of 39 months. The side effects of treatment were minimal and less patient had to delay his chemotherapy. This regimen of treatment is a good option for adults patients with low risk acute lymphoblastic leukemia, in consequence of: a) high value of complete remission and its duration. b) the mean survival obtained and the probability of cure. c) the absence of severe side effects and without necessity of support therapy or hospitalization.
A double-blind, placebo-controlled randomized study of danazol was performed to determine if the drug has a therapeutic effect in patients with myelodysplastic syndromes (MDS). Fifty evaluable patients with MDS were randomized to receive, a single daily oral dose of either danazol (600 mg/day) or matching placebo. Treatment was continued, when possible, for a period of 6 months. Response was based on clinical course, peripheral blood counts with white blood cells differential, platelet, reticulocyte at specified intervals. Repeat bone marrow aspirates and biopsy were also done. Significant differences was observed between the treatment groups in response to test drug. Increase in hemoglobin, granulocytes, platelets and improvement in survival was noted in danazol group. Side effects were minimal. Our study suggests that danazol exerts a beneficial therapeutic effect in patients with MDS.
A multivariate analysis of clinical, biochemical and hematologic data was performed in 138 patients with myelodysplastic syndromes (MDS) in order to evaluate their prognostic significance. The most important individual variables, isolated in a previous univariate analysis, were placed in a multiple regression modeling procedure to identify major prognostic factors. Multivariate analysis tends to identify prognostic variables containing significant predictive information. Characteristics were examined on both continuous and binary bases. The FAB classification was the first parameter entered in regression equations of both models, followed by platelet count, systemic symptoms, bone marrow blast and infection. Our analysis confirms FAB classification as the best prognostic factor in MDS. It supports the previously predictive value of platelet count, hemoglobin level and bone marrow blast and recognizes the importance of systemic symptoms and infection as prognostic characteristics in MDS.