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Biomedical subjects

P Lira

Publications and source records attributed to P Lira.

At least 19 recordsLinked to original sources

Genomic organization of the CC chemokine mip-3alpha/CCL20/larc/exodus/SCYA20, showing gene structure, splice variants, and chromosome localization.

We describe the genomic organization of a recently identified CC chemokine, MIP3alpha/CCL20 (HGMW-approved symbol SCYA20). The MIP-3alpha/CCL20 gene was cloned and sequenced, revealing a four exon, three intron structure, and was localized by FISH analysis to 2q35-q36. Two distinct cDNAs were identified, encoding two forms of MIP-3alpha/CCL20, Ala MIP-3alpha/CCL20 and Ser MIP-3alpha/CCL20, that differ by one amino acid at the predicted signal peptide cleavage site. Examination of the sequence around the boundary of intron 1 and exon 2 showed that use of alternative splice acceptor sites could give rise to Ala MIP-3alpha/CCL20 or Ser MIP-3alpha/CCL20. Both forms of MIP-3alpha/CCL20 were chemically synthesized and tested for biological activity. Both flu antigen plus IL-2-activated CD4(+) and CD8(+) T lymphoblasts and cord blood-derived dendritic cells responded to Ser and Ala MIP-3alpha/CCL20. T lymphocytes exposed only to IL-2 responded inconsistently, while no response was detected in naive T lymphocytes, monocytes, or neutrophils. The biological activity of Ser MIP-3alpha/CCL20 and Ala MIP-3alpha/CCL20 and the tissue-specific preference of different splice acceptor sites are not yet known.

Alternative Splicing↗

[Comparative study of health care costs for patients using home oxygen therapy or those in waiting lists].

BACKGROUND: Home oxygen therapy is the only intervention that significantly prolongs survival of patients with chronic obstructive pulmonary disease. Since this therapy is expensive, it is imperative to calculate its cost-benefit ratio. AIM: To compare health care costs for patients in a home oxygen therapy program, with those of a similar group of patients in a waiting list for this therapy. MATERIAL AND METHODS: A retrospective analysis of 21 patients on home oxygen therapy for 36 months or less and a group of 13 patients in the waiting list during a similar lapse. Medical consultations, drugs delivered and the cost of oxygen therapy were considered among ambulatory costs. Hospitalization costs included the number of days on regular or intermediary care beds, laboratory tests and drugs delivered. RESULTS: The annual health care costs for patients on home oxygen therapy were 709,656 Chilean pesos and the costs for patients in the waiting list were 797,320 Chilean pesos. CONCLUSIONS: The overall health care costs of home oxygen therapy are similar to the cost required by patients with chronic obstructive pulmonary disease remaining in waiting lists.

Aged↗

Genomic organization and biological characterization of the novel human CC chemokine DC-CK-1/PARC/MIP-4/SCYA18.

The chemokines are a group of chemotactic molecules that appear to regulate the directed movement of white blood cells in vitro and in vivo and may therefore play important roles in inflammation and immunity. The genes encoding the chemokines are clustered in close physical proximity to each other. A large cluster of human CC chemokine genes resides on chromosome 17. We have used this information in a positional cloning approach to identify novel chemokine genes within this cluster. We constructed a YAC contig encompassing the MIP-1alpha (HGMW-approved symbol SCYA3) gene region and used exon trapping and sequence analysis to isolate novel chemokine genes. Using this approach, a gene encoding a chemokine named MIP-4, based on its homology with MIP-1alpha (49.5% identity at the nucleotide level and 59.6% at the predicted amino acid level), was found. The MIP-4 gene (HGMW-approved symbol SCYA18) consists of three exons spread over 7.1 kb and is separated from the MIP-1alpha gene by 16 kb. The MIP-4 gene encodes a 750-bp mRNA that is expressed in lung and macrophages but not in brain or muscle. The mRNA encodes an 89-amino-acid protein and includes a predicted signal peptide of 21 amino acids. Recombinant or synthetic MIP-4 induced calcium mobilization in naive and activated T lymphocyte subpopulations in vitro. Injection of synthetic MIP-4 into the peritoneal cavity of mice led to the accumulation of both CD4(+) and CD8(+) T lymphocytes, but not monocytes or granulocytes. These observations provide new information concerning the arrangement of the CC chemokine gene cluster on human chromosome 17 and indicate that the MIP-4 gene product is chemotactic in vivo for both CD4(+) and CD8(+) T lymphocytes and may therefore be implicated in both humoral and cell-mediated immunity.

Amino Acid Sequence↗

[Imipenem/cilastatin versus ceftazidime-amikacin in the treatment of febrile neutropenic patients].

AIM: To compare the efficacy of imipenem/cilastatine and ceftazidime-amikacin in the treatment of febrile neutropenic patients. DESIGN: Open, prospective and randomized clinical study. PATIENTS: Fifty two patients (26 female) aged 16 to 80 years old with 60 episodes of neutropenia were studied. They were randomly assigned to receive imipenem/cilastatine in doses of 500 mg iv qid or the combination of ceftazidime 1 to 1.5 g iv tid and amikacin 7.5 mg/kg iv bid. RESULTS: Global response to initial therapy was 53% in patients receiving imipenem/cilastatine and 37% in those receiving ceftazidime-amikacin (p = ns). When other antimicrobial were added, a 90 and 85% infection eradication success was achieved respectively. Six febrile episodes in the group receiving imipenem/cilastatine and 12 episodes in the group receiving ceftazidime-amikacin had Gram positive cocci as the sole infectious agent (p < 0.04). A lower duration of neutropenia had a favorable influence on treatment outcome. Three patients receiving imipenem/cilastatine (10%) and four receiving ceftazidime-amikacin (13%) died. Superinfections and toxicity related to antibiotics were minimal in both groups. CONCLUSIONS: Imipenem/cilastatine and the combination of ceftazidime with amikacin were equally effective in the treatment of febrile episodes in neutropenic patients.

Adolescent↗

[Allogenic bone marrow transplantation in the treatment of malignant hematologic disease].

We have treated 28 patients (pts) with malignant hematological diseases with allogeneic bone marrow transplantation (BMT). 18 pts had acute lymphoblastic (ALL) and non lymphoblastic leukemia (ANLL), 5 chronic myeloid leukemia (CML), 2 severe aplastic anemia (SAA), 1 myelodisplasia, 1 Fanconi's anemia and 1 advanced Non Hodgkin's lymphoma. All but three received the graft from HLA identical sibling donors. We used conditioning with total body irradiation and chemotherapy (cyclophosphamide, cytarabine and etoposide) in 17 pts and chemotherapy alone in 11. 24 pts had full hematological recovery 18 to 25 days post BMT. 15 pts died after BMT as a consequence of toxicity or early infection (4), graft failure (2), graft versus host disease (4) or relapse (5). Actuarial event free survival for the group with favorable prognosis (SAA, ALL and ANLL in first or second remission and CML in chronic phase) is 57% at 36 months. Allogeneic BMT is an effective and feasible therapeutic procedure for selected patients with hematological malignancies.

Actuarial Analysis↗

[Chronic myeloid leukemia: cytogenetic and molecular study and its relationship with the disease course].

The aim of this study was to perform a cytogenetic and molecular study in patients with chronic myelogenous leukemia and to seek a possible relation between bcr gene break points and the clinical evolution of the disease. The cytogenetic study allowed to establish the presence of Ph chromosome and the molecular study localized the break point in bcr region of chromosome 22 using the Southern technique, hybridizing with bcr fragment derived probes bcr1 and bcr2. Forty eight patients were studied, 27 male (aged 46.5 years) and 21 female (aged 56). Forty seven patients were Ph +. A rearrangement in 3' bcr region was found in 25 patients and in 5' region in 23. During the follow up period 20 patients developed a blast crisis or accelerated phase. In 11 of these the rearrangement was in region'3 and their chronic phase lasted a mean of 33.1 months; in 9 the rearrangement was in region 5' and their chronic phase lasted 44.1 months. There were no differences in event-free survival between those with rearrangement in region 3' or 5', however these was a tendency towards a longer chronic phase duration in those with 5' breaks. The lack of correlation between the location of break points and the evolution of the disease may be due to a selection of patients with a better evolution and the exclusion of those with a rapid progression to blast crisis or accelerated phase.

Adult↗

[Infective complications of the use of permanent central venous catheters in oncology].

We analyzed the infectious complications associated with the use of permanent central venous catheters (PVC) in pediatric and adult cancer patients. 62 patients used 74 PVC (54 external, 20 subcutaneous), which were in place for an average of 200 days with a total observation period of 14,876 days, 152 febrile episodes occurred during this period, 87 in neutropenic patients (less than 500 neutrophils/mu, FN+) and 65 in non neutropenic patients (FN-). The incidence of bacteremia was 32% in febrile episodes in the first group (FN+C+ and 41% in the second (FN-C+). Overall there were 3.7 episodes of bacteremia per 1000 catheter days. We found a statistically significant difference in the incidence of bacteremia between the external and subcutaneous PVC in favor of the latter among patients over 15 years of age but not in the pediatric group. 14 PVC had to be removed due to an infection, 8 in patients with bacteremia and 6 in patients with exit site infections. We conclude that the use of PVC in the care of cancer patients is beneficial and safe, with a low incidence of infectious complications.

Adolescent↗

[Intravascular coagulation in acute promyelocytic leukemia: analysis of coagulation and fibrinolysis parameters].

Eight pts with acute myeloid leukemia were studied to assess coagulation and fibrinolysis disturbances as a cause of hemorrhages associated to thrombopenia. Fibrinogen, products of fibrinogen to fibrin degradation, D-dimer, antithrombin III, protein C, plasminogen and alpha-2 antiplasmin determinations were performed at admission, during and after chemotherapy. All pts were on heparin during induction chemotherapy. Coagulation activation, which increased with the onset of chemotherapy (increases in D-dimer) and a decreasing trend at the end of the antileukemic therapy (normalization of fibrinogen levels) was observed. During the whole observation period alpha-2 antiplasmin levels remained very low. No significant changes were observed in antithrombin III or protein C levels. In conclusion, disseminated intravascular coagulation with associated thrombopenia is an important event in acute leukemia and an increased fibrinolytic activity due to low alpha-2 antiplasmin levels may take part in the genesis of hemorrhage. These data suggest that both heparin administration and the use of antifibrinolytic drugs may have a therapeutic effect.

Adolescent↗

[Cytogenetic studies in myelodysplasias].

Cytogenetic studies were performed in 29 patients with myelodysplasia, 12 males and 17 females with a mean age of 61 years. The distribution of patients according to FAB groups were as follows: refractory anemia (RA) 7, sideroblastic refractory anemia SRA) 6, refractory anemia with excess blasts (RAEB) 12 and refractory anemia with transformation excess blasts (RAEB-t) 4. Cytogenetic anomalies were found in 48% over all, 78% in patients with RAEB and RAEB-t forms and only 23% in patients with simpler forms of myelodysplasia. Multiple and complex chromosomal alterations were found in 50% of abnormal studies, only in patients with complex forms. In general, structural rearrangements and deletions were less frequent than numeric defects, with a slight preponderance of chromosomal losses. Alterations of chromosomes 5, 7, 28, 21, 22, 8, 11 and 15 were the most commonly observed. Survival was decreased from 60 months in patients with normal karyotype to 6 months in those with chromosomal alterations. Thus, chromosomal abnormalities are related to excess blasts and to survival in patients with myelodysplasia.

Adolescent↗

[Human recombinant erythropoietin (rH-EPO) in chronic hemodialysis patients].

We studied 7 patients on chronic hemodialysis before and after 12 weeks of therapy with human recombinant erythropoietin. The drug was administered intravenously, 3 times a week at doses increasing from 50 to 125 U/kg. Dialysis was performed for 4 hr, 3 times a week and no blood transfusions were used during the study. An increased tolerance to daily physical activities was observed in all patients. Hematocrit increased from 19 +/- 3.4 to 28 +/- 4.1 and hemoglobin from 6.7 +/- 1.3 to 9.4 +/- 1.5, p less than 0.01. No changes were detected in blood pressure, weight, liver function tests and nutritional values. No patient developed either absolute (ferritin less than 30 ng/ml) or relative iron deficiency (transferrin saturation less than 20%) during the study. Efficiency of dialysis remained unaltered. No secondary effects from the drug were observed. Thus, this study confirms the clinical usefulness of human recombinant erythropoietin in patients with chronic renal failure and anemia on chronic dialysis.

Adult↗

[Myelodysplasias: clinical experience with 35 patients].

Myelodysplasia, characterized by varied reductions of peripheral blood elements with normal or hypercellular bone marrow, is relatively frequent among older patients and may evolve to acute leukemia. We reviewed findings in 35 patients whom, according to the FAB classification were distributed as follows: simple refractory anemia (RA) 34%, sideroblastic refractory anemia (SRA) 14%, refractory anemia with excess blast forms (RAEB) 31%, chromic myelomonocytic leukemia (CMML) 12% and refractory anemia with excess blast forms in transformation (RAEBT) 9%. Cytogenetic studies performed in 16 patients were abnormal in 5 (31%), all among patients with poor prognosis forms of the disorder. All patients had anemia; thrombopenia and neutropenia were more frequent in subtypes RAEB, CMML and RAEBT). Mean survival rate was 30 months, significantly greater in RA and SRA compared to the other groups. Infections and development of acute leukemia were the causes of death.

Actuarial Analysis↗

[Paroxysmal nocturnal hemoglobinuria presenting as acute renal failure].

We report a patient who developed acute renal failure at the first severe hemolytic crisis associated to paroxysmal nocturnal hemoglobinuria. The associated histologic findings on electron microscopy and immunofluorescence are discussed as an insight to possible pathogenic mechanisms.

Acute Kidney Injury↗

[Beta 2 microglobulin in some hematologic neoplasms].

Beta 2 microglobulin is a low molecular weight protein integrating the light chain HLA antigens. Its serum concentration is increased in different neoplasias and in renal failure. Using solid phase RIA we determined the concentration of beta 2 microglobulin in plasma and spinal fluid of 57 healthy individuals and patients with hematologic neoplasia. Serum levels were 1.34 +/- 0.34 mg/l and spinal fluid levels were 1.3 +/- 0.7 mg/l in healthy subjects. Serum levels in 29 patients with myeloma was 7.51 mg/l, significantly higher in those with renal failure (12.35 mg/l) compared to those without (4.54). In 30 patients with non-Hodgkin lymphoma the mean serum levels were 2.90 mg/l, significantly greater in those with active disease (3.18) than in those with remission (1.5). No difference was found according to the degree of malignancy. Patients with acute lymphatic leukemia had elevated values of beta 2 microglobulin while the disease was active (3.37 mg/l), decreasing to normal levels after remission (1.79 mg/l). Spinal fluid levels of beta 2 microglobulin were elevated only in patients with central nervous system involvement. Our results indicate that serum levels of beta 2 microglobulin are helpful in patients with hematologic neoplasia in assessing the activity of the disease and tumor mass, especially in multiple myeloma.

Adolescent↗

[Deficiency of folates in pregnancy: effect of supplementary folic acid].

Higher folate needs are present during pregnancy, which may lead to tissular deficiency in the mother and to depleted newborn folate reserves. The aim of this work was to assess the prevalence of folate deficiency and to establish the rates of serum and red cell folate in two groups of mothers and newborn infants, one receiving only iron and the other iron and folate during pregnancy. The rates of serum and red cell folate found at the end of pregnancy were significantly higher in the group which received folate; however, the percentage of cases with tissular folate deficiency was low in both groups, with no significant difference (3.8% and 1.3%, respectively). These findings, along with the lack of effect of supplemental folate on erythropoiesis, pose some questions on the usefulness of supplemental folate during pregnancy in our country.

Adult↗