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Biomedical subjects

E Gómez-Morales

Publications and source records attributed to E Gómez-Morales.

11 recordsLinked to original sources
PubMed2001

Tumor necrosis factor-alpha levels in long-term marrow cultures from patients with aplastic anemia: modulation by granulocyte-macrophage colony-stimulating factor.

We have previously shown that the levels of hematopoietic progenitors in long-term marrow cultures (LTMC) from patients with aplastic anemia (AA) are drastically reduced, as compared to normal LTMC. We have also reported that when LTMC from AA patients are supplemented with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) there is an increase in colony-forming cell (CFC) levels. However, such a stimulation is only transient and it is followed by an inhibition in CFC growth. Based on these observations, in the present study we have tested the hypothesis that the levels of tumor necrosis factor-alpha (TNF-alpha), an inhibitor of hematopoiesis, are increased in AA LTMC and that such levels are further increased after rhGM-CSF has been added to the cultures for several weeks. Accordingly, we have determined the levels of TNF-alpha in the supernatant of LTMC established from normal (n = 8) and AA (n = 6) bone marrow and in AA LTMC supplemented with rhGM-CSF (n = 6). At the time of culture initiation, TNF-alpha levels were below detection in all the samples analyzed. After 5 weeks of culture, TNF-alpha levels in normal LTMC were very low, with a median of 7.3 pg/mL. In contrast, AA LTMC contained higher levels of TNF-alpha (median of 49.6 pg/mL). In keeping with our hypothesis, addition of rhGM-CSF to AA LTMC resulted in a significant further increase of TNF-alpha levels (median of 135.4 pg/mL). Our results demonstrate an inverse correlation between reduced hematopoiesis in AA LTMC and increased levels of TNF-alpha in this culture system. Based on the results presented here, together with previous reports indicating that TNF-alpha is a potent inducer of apoptosis in hematopoietic progenitor cells, it seems reasonable to suggest that TNF-alpha is implicated in the pathophysiology of AA.

Adult↗
PubMed2001

Severe hematopoietic alterations in vitro, in bone marrow transplant recipients who develop graft-versus-host disease.

Graft-versus-host disease (GVHD) is currently one of the major obstacles for successful allogeneic bone marrow transplantation (BMT). GVHD results from a complex set of interactions between donor T cells and a variety of target tissues from the host. To gain a better understanding of the biology of the human hematopoietic system in GVHD patients, in the present study we have determined the progenitor cell content in bone marrow (BM) samples from BMT recipients, with and without GVHD, and followed their growth kinetics in Dexter-type long-term marrow cultures (LTMC). We have also assessed some aspects regarding the composition of the hematopoietic microenvironment developed in vitro. As compared to normal subjects, BMT recipients showed decreased numbers of myeloid, erythroid, and multipotent progenitor cells. Interestingly, progenitor levels were significantly lower in GVHD patients (7% of the levels in normal marrow) than in those without GVHD (44% of the levels in normal marrow). When marrow cells from BMT recipients were cultured in LTMC, hematopoiesis was sustained at lower levels and for shorter periods of time, as compared to cultures from normal subjects. The hematopoietic deficiencies observed in this in vitro system were also more pronounced in GVHD patients. In terms of the microenvironment elements, reduced numbers of fibroblastic progenitors and adherent stromal cells were observed in BMT recipients, as compared to normal subjects, who showed 7 colony-forming unit fibroblast (CFU-F)/10(5) marrow cells and 320,000 adherent cells in LTMC. Again, GVHD patients showed more severe deficiencies (0.16 CFU-F/10(5) marrow cells and 34,000 adherent cells in LTMC) than patients without GVHD (2 CFU-F/10(5) marrow cells and 122,000 adherent cells in LTMC). Our results demonstrate that the hematopoietic system of BMT recipients is impaired, both in terms of its in vitro composition and function, and that these deficiencies are clearly more pronounced in patients with GVHD than in those without GVHD. Finally, although the evidence is still preliminary, our results also indicate that the severity of the hematopoietic alterations may be greater in acute GVHD than in chronic GVHD.

Acute Disease↗
PubMed1999

Effect of recombinant human granulocyte macrophage-colony stimulating factor in long-term marrow cultures from patients with aplastic anemia.

The hematopoietic system in patients with aplastic anemia (AA) shows both quantitative and qualitative deficiencies, i.e., reduced numbers of hematopoietic progenitor cells (HPC) and impaired HPC proliferation in long-term marrow cultures (LTMC). Since recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) has been shown to be a potent stimulator of normal hematopoiesis, both in vivo and in vitro, in the present study we wanted to assess the possibility of stimulating hematopoiesis in LTMC from 17 patients with AA, by weekly addition of rhGM-CSF (10 ng/ml). In LTMC from 11 patients (group of responders), rhGM-CSF induced a significant increase (4.8-fold, compared with untreated cultures) in the levels of myeloid progenitor cells; in contrast, in six patients (group of nonresponders), myeloid progenitors were refractory to this cytokine. In the group of responders, rhGM-CSF also induced a pronounced increment in the levels of nonadherent and adherent cells (5.99- and 5.18-fold, respectively, compared with untreated cultures). Among the different myelopoietic lineages, rhGM-CSF preferentially stimulated the macrophagic lineage; this was evident both at the progenitor and mature cell levels. Interestingly, the effect of rhGM-CSF in LTMC from AA patients was only transient. Indeed, the effects mentioned above were observed only during the first three weeks of culture; afterwards, myeloid progenitor and nonadherent cell levels in treated cultures declined, practically reaching the levels observed in untreated cultures. At the moment, we do not know whether this transient stimulatory effect is due to the production of inhibitory cytokines, by macrophages generated in response to rhGM-CSF, or to the exhaustion of the HPC pool in AA cultures. In all 17 patients, rhGM-CSF had no effect on the kinetics of erythroid or multipotent progenitor cells. These results are in keeping with clinical studies in which it has been observed that most AA patients treated with rhGM-CSF show increments in circulating monocytes and granulocytes, as well as in bone marrow cellularity. However, little or no effect is observed on erythropoiesis. The actual mechanisms involved in the in vitro effects of rhGM-CSF on myeloid progenitor cells from AA bone marrow are still not completely understood. Future studies on this issue should be encouraged, since they may help to understand the in vivo (clinical) effects of this cytokine.

Anemia, Aplastic↗
PubMed1998

Deficient proliferation of myeloid, erythroid, and multipotent progenitor cells in long-term marrow cultures from patients with aplastic anemia treated with immunosuppressive therapy.

By using Dexter-type long-term marrow cultures (D-LTMC), it has been shown previously that hematopoietic progenitor cells (HPC) from patients with aplastic anemia (AA) have a deficient proliferation in vitro. The studies reported to date, however, have focused exclusively on granulomonocytic progenitors and no information exists on erythroid or multipotent progenitor cells. On the other hand, in such studies, the input progenitor cell numbers were significantly below normal levels, thus suggesting that the rapid disappearance of myeloid progenitor cells from AA D-LTMC could also be due, at least in part, to their reduced number at culture onset. In the present study, we have followed the kinetics of myeloid, erythroid, and multipotent progenitors, from 24 AA patients subjected to immunosuppressive therapy (including patients that achieved complete, partial, or no remission at all), throughout a seven-week culture period. For analysis, we grouped all the patients based on their initial content of all three types of progenitors. Thus, we were able to evaluate separately the kinetics of these cells in D-LTMC from patients with normal and subnormal levels of progenitor cells. At the time of marrow sampling, most patients showed decreased levels of HPC; in fact, only 21%, 8%, and 16% of them showed normal levels of myeloid, erythroid, and multipotent progenitors, respectively. When cultured in D-LTMC, HPC from all AA patients analyzed showed a relatively fast disappearance from the cultures. Indeed, myeloid progenitors could be detected for only six weeks, whereas erythroid and multipotent progenitors disappeared from the cultures after two and one weeks of culture, respectively. In contrast, in normal marrow D-LTMC, myeloid, erythroid, and multipotent progenitors were detected for at least seven, five, and three weeks, respectively. Such a deficient proliferation was observed even in cultures of AA patients that contained normal levels of HPC at culture onset. Interestingly, no correlation was found between HPC proliferation in D-LTMC and response to treatment. Thus, the results of this study indicate the presence of a functional in vitro deficiency in the hematopoietic system of patients with AA, including those that achieved partial or complete remission after immunosuppressive treatment. Furthermore, this work suggests that such a proliferation deficiency is more pronounced in erythroid and multipotent progenitors than in their myeloid counterparts.

Adult↗
PubMed1997

Cytogenetic findings in 303 Mexican patients with de novo acute myeloblastic leukemia.

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.

Acute Disease↗
PubMedDate not supplied

[Evaluation of a program for monitoring of nosocomial infections].

The results of two nosocomial infection surveillance programs are presented. They were conducted sequentially during a period of eight months, in a general hospital in Mexico City. The purpose of the study was to evaluate the results of a previously installed program based on the investigation of the incidence of episodes of nosocomial infections through the results of the investigation of the prevalence of these episodes. The observed prevalence and incidence rates and the calculated incidence rate were 23 percent, (127 episodes in 547 patients); 4.52 percent (134 episodes in 2,963 discharges) and 4 percent. The commonest problems detected by both studies were surgical wound and urinary tract infections. Pseudomonas and coagulase negative Staphylococcus were isolated most frequently during each period. It is concluded the system based on the investigation of the incidence of nosocomial infections works adequately in this hospital. The advantages of the design of the prevalence system are discussed, since it permitted the analysis of the infection risk associated to different invasive procedures. The odds ratio for acquiring respiratory infection was 152 (C.I. 95%: 31,732) in patients that underwent tracheostomy, 20 (C.I. 95%: 4 90) in patients with respirator, 34 (C.I. 95%: 8,142) in patients with endotracheal tube and 33 (C.I. 95%: 8,137) in patients with nasogastric tubes.

Cross Infection↗
PubMedDate not supplied

[Treatment of paroxysmal nocturnal hemoglobinuria with antilymphocyte globulin].

OBJECTIVE: To evaluate the effectiveness of antilymphocyte globulin therapy (ALG) in patients with paroxysmal nocturnal hemoglobinuria (PNH). DESIGN: Prospective, non-controlled trial. SETTING: Hematology Service, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City. PATIENTS: Six patients were included. The median age was 37.5 years and the male/female ratio was 1:1. All the patients had clinical disease consistent with PNH (hemolytic anemia with some degree of transient or persistent pancytopenia) and also erythrocytes with enhanced sensitivity to complement mediated lysis in vitro, as documented by either the Ham test or the sucrose lysis assay. The criterion for severity was the existence of continuous hemolysis in all and transfusion requirements of two or more packed red cells per month in four cases. Prior to ALG therapy, androgens and/or steroids had been given to five patients with no improvement. INTERVENTION: A single batch of ALG was used during the trial (E 0034, Lymphoglobulin Mérieux, Lyon, France). Patients received an infusion of 10 mg/kg per day in a 20 hours lapse during four consecutive days. Also 500 mg/day of methylprednisolone were started simultaneously with the ALG; it was given for seven days and was gradually tapered off and stopped on day 30. MEASUREMENTS: The increases in hemoglobin, granulocytes and/or platelets as well as decreases in red cell transfusion requirements were used to evaluate the results of therapy. RESULTS: Two patients suffered anaphylaxis after the first administration of ALG and were withdrawn from the study. Two of the four remaining patients responded, one response was total and the other minimal. The responses were transient, and no response was seen in the follow-up of 11-14 months. CONCLUSION: ALG therapy for PNH in the doses and time periods used by us had no beneficial effect in patients with a severe form of PNH.

Adult↗
PubMedDate not supplied

[Interferon in the eradication of the Philadelphia chromosome in chronic myeloid leukemia].

OBJECTIVE: To evaluate if human recombinant interferon alpha (IFN) combined with chemotherapy is able to suppress the Philadelphia chromosome clone in patients with chronic myeloid leukemia (CML). MATERIAL AND METHODS: The cytogenetic evolution in 53 patients with CML in chronic phase de novo was studied. They received one of three treatment schemes: a) induction of remission with daunorubicin, vincristine, cytosine arabinose and prednisone (DOAP) and maintenance with IFN (n = 12); b) induction with busulfan (BUS) or hydroxyurea (HYDX) and maintenance with IFN (n = 26); c) induction with DOAP and maintenance with BUS (n = 15). RESULTS: The remission was seen two to six months after the start of treatment: 10 had complete remission, six a partial one, 14 a minor remission and 23 none. The 16 with complete or partial response received treatment with IFN. None of the 15 cases maintained with BUS had complete or partial response. The proportion of cases with complete response (3/12) was slightly lower in patients treated with intensive chemotherapy (BUS/HIDX/IFN) than in those receiving conventional treatment (7/26). CONCLUSIONS: Our results showed that: a) IFN in combination with chemotherapy induced partial or complete response in 30% of our cases; and b) intensive chemotherapy combined with IFN was not superior in terms of a cytogenetic response to treatment with monodrugs (BUS/HIDX) and IFN.

Adolescent↗
PubMedDate not supplied

[Blood erythropoietin levels in healthy subjects studied in the valley of Mexico].

Erythropoietin (EPO) is the hematopoietic growth factor that regulates red cell production. There is a direct relationship between its secretion and tissue hypoxia. Above sea level, oxygen concentration diminishes. This causes an increase of hemoglobin and hematocrit; this effect could be the consequence of higher EPO levels. Currently, evaluation of baseline serum EPO levels is very important in the differential diagnosis of anemia and erythrocytosis. The purpose of the present work was to report the EPO levels on a group of healthy blood donors living in Mexico City, 2,240 m above sea level. Two-hundred twenty blood donors were selected to measure serum EPO; there were 168 males and 52 females. Median EPO levels of the entire population were 7.5 mU/mL (percentile interval, PI, 1-18). Median EPO levels were 7.6 (PI 1-18) and 7.5 (PI 1-16.9) for men and women, respectively. We did not find differences in serum EPO levels among previous reports in other populations and the values determined in this study.

Adolescent↗
PubMedDate not supplied

[5 episodes of transient aplastic anemia in 3 patients].

We report five episodes of severe aplastic anemia (AA) followed by spontaneous remission in three patients. They were classified as transient aplastic anemia (TAA). Two were females and one male of 32, 56 and 41 years of age, respectively; the man had two recurrences. They had been in contact with insecticides, solvents or drug ingestion. The three had fever, anemia and muco-cutaneous purpura. Supportive measures were used (transfusion of packed red blood cells and platelets, antibiotics, corticosteroids and danazol, the latter two given for ten days in three episodes). They showed spontaneous remission after 16 to 45 days of evolution. The patients did not suffer infection or myeloproliferative disorders which might explain the AA. Transient AA is infrequent and should be considered a variant of AA.

Adult↗