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Biomedical subjects

M Navarrete

Publications and source records attributed to M Navarrete.

At least 19 recordsLinked to original sources

Factor X deficiency: clinical manifestation of 102 subjects from Europe and Latin America with mutations in the factor 10 gene.

Inherited factor X deficiency (FXD) is a rare (1:1,000,000) recessive bleeding disorder. The clinical and laboratory phenotypes of FXD are poorly correlated and few regional studies on the genotype and the clinical manifestations of FXD are known. To understand the association between clinical manifestations and causative genotype, detailed evaluation of bleeding pattern in a high number of patients is needed. This international study analysed the phenotype and genotype of 102 subjects from Central Europe (Germany, Poland and Slovakia) and Latin America (Costa Rica and Venezuela) with causative mutations in the F10 gene, via sequencing. Twenty-eight homozygous, seven compound-heterozygous and 67 heterozygous FXD subjects were characterized. Twenty-nine different causative mutations, including 15 novel mutations, were analysed. Spontaneous bleeding symptoms in 42 symptomatic individuals (26 homozygous, seven compound heterozygous and nine heterozygous) comprised easy bruising (55%), haematoma (43%), epistaxis (36%), haemarthrosis (33%), intracranial haemorrhage (ICH; 21%), and gastrointestinal (GI) haemorrhage (12%). The manifestation of bleeding symptoms in 9 of 67 (13%) symptomatic heterozygous subjects is described. The bleeding patterns of the enrolled patients showed differences that are associated with the types of F10 mutation, and the corresponding genotypes. The homozygous patients were evaluated for genotype-phenotype correlation. The results suggested that ICH seems to be associated with the F10 mutation Gly380Arg, and possibly with the mutations IVS7-1G>A and Tyr163delAT. A tentative association of other mutations to severe symptoms such as haemarthrosis and GI haemorrhage is reported. The severity of FXD, the genotype-phenotype association, and the results of regional studies are discussed.

Adolescent↗

Trapping of the OH radical by alpha-tocopherol: a theoretical study.

The antioxidant activity of alpha-tocopherol against the damaging hydroxyl radical was analyzed theoretically by hybrid density functional theory, following the direct dynamics method, where the thermal rate constants were calculated using variational transition-state theory with multidimensional tunneling. We found that the OH radical is only slightly or not at all selective, attacking by different mechanisms at several positions of the alpha-tocopherol molecule, giving competitive reactions. The most favorable pathways are the hydrogen abstraction reaction from the phenolic hydrogen and the electrophilic addition onto the aromatic ring. We propose a final rate constant, the sum of the competitive hydrogen abstraction and addition reactions, > or =2.7 x 10(8) M(-1) s(-1) at 298 K, where the hydrogen abstraction reaction represents only 20% of the total OH radical reaction. This result indicates that, molecule by molecule, in an apolar environment, alpha-tocopherol is less effective than coenzyme Q (which presents a rate constant of 6.2 x 10(10) M(-1) s(-1) at 298 K) as a scavenger of OH radicals. It was also found that both mechanisms are not direct but pass through intermediates in the entry channel, with little or no influence on the dynamics of the reactions. The hydrogen abstraction reaction also presents another intermediate in the exit channel, which may have a significant role in preventing the pro-oxidant effects of alpha-tocopherol, although less important than with free radicals other than OH.

Antioxidants↗

Clinical epidemiology of childhood cancer in Central America and Caribbean countries.

BACKGROUND: Countries with scarce resources have the right to appropriate essential health care but very few reports discuss how this can be achieved. We assessed the survival of a large cohort of pediatric oncological patients to provide hard data on which to base realistic evaluation and planning schemes. PATIENTS AND METHODS: This multicenter retrospective survey covered consecutively diagnosed and treated patients admitted to eight national level hospitals in seven countries in Central America and the Caribbean. The research protocol was discussed extensively, so the data to be collected and the criteria for their evaluation were clearly pre-defined. We analysed 2214 patients diagnosed between 1996 and 1999 with various cancers, classified as hemato-oncological disorders (70%) and solid tumors (30%). RESULTS: Three-year overall survival was 48.4% [standard error (SE) 1.3]. Detailed analysis of acute lymphoblastic leukemia highlighted the wide intercountry variability: 3-year survival was 62.2% (SE 5.3) in Cuba, 74.2% (SE 3.3) in Costa Rica, 61.7% (SE 4.9) in Nicaragua, and lower in the other four countries. CONCLUSIONS: The yield of diagnostic-therapeutic protocols depends largely on the context of care in which they are applied. This paper documents the importance of including epidemiological research in interventions for cooperation in complex health areas such as pediatric oncology.

Caribbean Region↗

Variation in indoor thoron levels in Mexico City dwellings.

This paper presents the results obtained for thoron concentration in 50 single-family dwellings in normal occupancy conditions (open house conditions), measured by a passive electret system (type E-PERM, SSTB configuration) in a 2001-2002 monitoring survey in the Metropolitan Zone of Mexico City. The results show the general log-normal distribution of integrated indoor thoron concentration with annual arithmetic and geometric means of 82 and 55 Bq m(-3), respectively, with ranges from 8 to 234 Bq m(-3) higher than world average of 3 Bq m(-3). The seasonal variation shows the minimum mean values in the summer season that were 35% lower than in autumn.

Air Pollutants, Radioactive↗

Safety conditions for irradiation, transporting, and melting of sintered TeO2 during the industrial production of 131I.

The development of a program to produce 131I by neutron activation of previously sintered TeO2, was started at the Nuclear Center of Mexico 3 y ago. Since then, the problems related to producing high purity, sintered TeO2 for neutron activation, transport of the activated samples and melting of the samples to retrieve the 131I have been satisfactorily solved. The main problems, related to health physics, arise when the process is conducted on a daily basis. Described are the irradiation conditions for sintered TeO2, retrieval of the sample from the pool, and the transport of the radioactive source after a 4-d cooling time. The radiation dose in the room where the hot cell is located increases from 2 microSv h(-1) (0.2 mrem h(-1)) to 4 microSv h(-1) (0.4 mrem h(-1)) during the melting of the radioactive (131+131m)TeO2, and the pumping out and dissolution of gaseous 131I. These measurements are below the maximum permissible levels and the ALARA concept has been assured through each step of the process and no leaks have been found in the system.

Hot Temperature↗

Transmission study of Andes hantavirus infection in wild sigmodontine rodents.

Our study was designed to contribute to an understanding of the timing and conditions under which transmission of Andes hantavirus in Oligoryzomys longicaudatus reservoir populations takes place. Mice were caged in test habitats consisting of steel drums containing holding cages, where seronegative rodents were exposed to wild seropositive individuals by freely sharing the same cage or being separated by a wire mesh. Tests were also performed for potential viral transmission to mice from excrement-tainted bedding in the cages. Andes virus transmitted efficiently; from 130 attempts with direct contact, 12.3% resulted in virus transmission. However, if we consider only those rodents that proved to be infectious, from 93 attempts we obtained 16 infected animals (17.2%). Twelve of them resulted from intraspecies O. longicaudatus encounters where male mice were differentially affected and 4 resulted from O. longicaudatus to Abrothrix olivaceus. Experiments using Abrothrix longipilis as receptors were not successful. Transmission was not observed between wire mesh-separated animals, and mice were not infected from excrement-tainted bedding. Bites seemed not to be a requisite for oral transmission. Genomic viral RNA was amplified in two out of three saliva samples from seropositive rodents, but it was not detected in urine samples obtained by vesicle puncture from two other infected rodents. Immunohistochemistry, using antibodies against Andes (AND) hantavirus proteins, revealed strong reactions in the lung and salivary glands, supporting the possibility of oral transmission. Our study suggests that AND hantavirus may be principally transmitted via saliva or saliva aerosols rather than via feces and urine.

Animals↗

Cutaneous presentation of follicular lymphomas.

The description of primary cutaneous follicular lymphoma has raised interest in the differential diagnosis of this versus disseminated follicular lymphoma involving the skin. We report here on four cases of Stage IV follicular lymphoma, diagnosed in skin biopsy, in which cutaneous lesion was the most noticeable feature of clinical presentation. In all cases, the morphological features were superimposed over typical nodal follicular lymphoma. Apart from classic B-cell markers, they were characterized by CD10 and bcl6 positivity, markers of follicle germinal center cells; and bcl2 expression, with a corresponding t(14;18) translocation in three of three cases examined. In all four cases, bone marrow study and clinical staging revealed disease that had disseminated since diagnosis. Follow-up showed relapsing cutaneous and nodal disease in two cases. The only difference observed with a control group of 10 cases of primary cutaneous follicular lymphoma was the absence in this group of t(14; 18). Disseminated classical follicular lymphoma has to be considered in the differential diagnosis of follicular lymphoma presenting in the skin. This series of cases suggests that the presence of t(14;18) could imply the existence of disease that has disseminated beyond the skin and that cases harboring this translocation could be candidates for systemic polychemotherapy.

Adult↗

Cutaneous follicular B-cell lymphoma: description of a series of 18 cases.

The lack of precise and homogeneous criteria for the recognition of primary cutaneous follicular lymphoma has hindered gaining data on the frequency and clinical and molecular features of this entity. In the course of a review of a series of primary cutaneous lymphoma from different Spanish hospitals, we collected a series of 18 cases of primary cutaneous follicular lymphoma and analyzed its clinical, morphologic, and biologic characteristics. In this review only cases with a follicular pattern of growth, germinal center cytology, and restriction to the skin in a minimum follow-up of 6 months have been included. Cases of primary cutaneous follicular lymphoma were characterized by the expression of classic markers of the germinal center, such as bcl6, CD10, and the presence of aggregates of follicular dendritic cells. They frequently express bcl2 protein, although classical t(14;18) was not found in any of the cases analyzed. Analysis of the bcl6 noncoding first exon showed somatic mutations in two of four cases analyzed, as would be expected in lymphoma deriving from the germinal center. Clinically, most cases showed initial involvement of the head and neck, with relapses in eight cases (involving the skin in five cases, both skin and lymph node in two cases, and lymph node in one case). No death attributable to the tumor was recorded. These data seem to imply that follicular lymphoma may present initially in the skin, lacking the characteristic t(14;18) and having a relatively indolent course. Recognition of these tumors and elucidation of their molecular alterations could lead to properly adapted staging and treatment protocols for these patients.

Adult↗

Urinary selenium excretion in patients with cervical uterine cancer.

In this work, we report on a relationship between urinary selenium and the development of cervical uterine cancer. A simple chemical method was developed to concentrate trace amounts of selenium from relatively large urine samples by use of small activated carbon filters. When these filters are irradiated with thermal neutrons, selenium can be determined either by 77mSe (t1/2 = 17.5 s) or 75Se (t1/2 = 120 d). In this article, we report the results for 82 urine samples from women with cervical uterine cancer in several stages of development and from healthy controls. These results show a statistically significant increase of selenium excretion in cancer patients as compared to controls. Urinary selenium excretion is highest for patients in the intermediate stages of the disease.

Adult↗

Antibodies anti-Chlamydia pneumoniae and anti-Mycoplasma pneumoniae in patients with negative serology for hantavirus. Retrospective study.

The seroprevalence of Chlamydia pneumoniae and Mycoplasma pneumoniae in hantavirus seronegative patients, who had symptoms and signs compatible with pneumonia was established. For this purpose we used the indirect fluorescent antibody test. Titers > or = 1:16 for C. pneumoniae and M. pneumoniae were found in 8.6% and 17.1% of the serum, respectively, showing evidence of recent or current infection.

Adolescent↗

Flow cytometry in the bone marrow evaluation of follicular and diffuse large B-cell lymphomas.

BACKGROUND AND OBJECTIVES: Bone marrow biopsies are routinely performed in the staging of patients with lymphoma. Despite the lack of evidence for its usefulness, many institutions include flow cytometry (FC) of bone-marrow aspirates in an attempt to increase sensitivity and specificity. The aim of this study is to evaluate the usefulness of FC for the assessment of bone-marrow involvement by lymphoma in follicular (FL) and diffuse large B-cell lymphomas (DLBCL). DESIGN AND METHODS: Seventy-nine bone marrow biopsies from 65 patients diagnosed with FL or DLBCL were examined to compare histology and FC for the assessment of bone-marrow involvement by lymphoma. RESULTS: Bone marrow histology showed involvement (BM+) in 16 cases (20.3%), lack of infiltration (BM(-)) in 52 cases (65.8%) and undetermined or undiagnosed for involvement (BMu) in 11 cases (13.9%). FC was positive for involvement in 28 cases (35.4%) and negative in 51 cases (64.6%). 65 cases (95%) showed concordance between the results of morphology and FC (BM(+)/FC(+) or BM(-)/FC(-)). No BM(+)/FC(-) cases were observed. 3 cases showed discrepant results (BM(-)/FC(+)). In these 3 cases the molecular studies (PCR) demonstrated clonal rearrangement of the heavy immunoglobulin chain (IgH) and/or bcl2-IgH in agreement with the flow results. Among the 11 cases with BMu, all but 2 were FC(+) and concordance with the PCR results was seen in 9 cases (81.9%). INTERPRETATION AND CONCLUSIONS: We conclude that FC is just as sensitive or perhaps slightly more sensitive than histology in the detection of bone marrow involvement in FL and DLBCL. FC studies may be warranted in those cases in which the morphology is not diagnosed. The clinical relevance of the small clonal B-cell population in patients without histologic bone marrow involvement (BM(-)/FC(+) cases) remains an open question.

Bone Marrow↗

Equity in the financing of social security for health in Chile.

Real public health spending has more than doubled since 1990, raising concerns about the targeting of public subsidies. This study examined the degree of equity in the financing of FONASA, the public insurer, which in 1995 covered 8.6 million beneficiaries, or 62% of the country's population. Study results, covering calendar year 1995, indicated that (1) government health subsidies were well-targeted, with about 90% reaching the indigent and 8% going to other, low-income beneficiaries; (2) only 2.5% of government subsidies leaked to higher-income, non-beneficiaries of FONASA (people covered by private insurers known as ISAPRES, otherwise covered, or without any coverage); (3) overall, FONASA's contributing beneficiaries (i.e. the indigent aside) self-financed their health benefits, although higher-income beneficiaries were providing significant cross-subsidies to low-income ones, making the internal financing of FONASA somewhat progressive; (4) the indigent received the highest amount of annual net benefits per capita, followed by low-income beneficiaries; and (5) the evasion of FONASA's payroll tax was pervasive, although public providers delivered care on an equal basis irrespective of the patients' contributions to FONASA. FONASA's finances would improve significantly if affiliation to health social security by both dependent and independent workers was made compulsory.

Ambulatory Care↗

Disseminated histoplasmosis in infants.

BACKGROUND: Disseminated histoplasmosis usually occurs in immunocompromised patients who reside in Histoplasma capsulatum-endemic regions. It has also been described in immunocompetent infants after exposure to a large inoculum of the pathogen resulting in case fatality rates of 40 to 50%. METHODS: From 1983 through 1996 all infants with documented disseminated histoplasmosis were treated with amphotericin B followed by daily ketoconazole for 3 months. Immunologic workups were performed at the time of diagnosis and at 4 to 6 weeks of therapy. Surviving patients were followed for at least 1 year. Time to resolution of signs and symptoms was recorded, as were complications. RESULTS: We managed 40 patients with disseminated histoplasmosis. The age in months at diagnosis was 15.3+/-10.2 (mean +/- SD), and 24 were male. All patients were from endemic regions and they presented with fever, spleen and/or liver enlargement and hematologic abnormalities. Diagnosis was made by histology and culture of bone marrow, spleen, lymph node, bronchoalveolar or liver samples. Twenty patients presented with T cell deficiency that resolved at 4 to 6 weeks of therapy in all of the retested patients, and 10 of 12 tested patients had hyperglobulinemia that resolved. Thirty-five (88%) patients were cured by treatment; 4 died and 1 relapsed. CONCLUSIONS: Disseminated histoplasmosis should be considered in infants from endemic areas who present with fever, hepatosplenomegaly and hematologic abnormalities. These patients develop transient hyperglobulinemia and T cell deficiency that resolve with treatment. Treatment with amphotericin B followed by an oral azole for 3 months is effective in most patients.

Amphotericin B↗

[Hantavirus in Chile: review and cases analysis since 1975].

Since the identification of the first case of Hantavirus infection in Chile in 1995, a great advance in the knowledge of the disease natural history has occurred. There is evidence to suppose that the infection by Andes virus in suburban areas of Argentina and Chile, whose natural reservoir is Oligoryzomys longicaudatus, has been present but unidentified for a long time. We describe a serologically proven case occurred in 1975. The clinical presentation of the disease slightly differs from that described for Hantavirus Pulmonary Syndrome (HPS), caused by Sin Nombre virus in the USA. There is a wider range of presentation forms including, besides HPS, mild and asymptomatic cases, a greater proportion of renal involvement and pediatric cases. Therefore the epidemiological scenario would be an endemic disease with fluctuations that follow changes in rodent population and their interactions with humans.

Adolescent↗