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To analyze the temporal trends of premature mortality from diabetes in Costa Rica in the period 2000-2020, at a national level and by province, and the effect of the COVID-19 pandemic on diabetes mortality during the year 2020.We studied the temporal trends of mortality from diabetes in Costa Rica in the period between 2000 and 2020. Age-standardized mortality rates and corresponding 95% confidence intervals were calculated for each year, sex and province.We analyzed the data of 17,968 deceased persons. The mean age was 72.5 years (range 1 to 109 years), and 51.5% of the population (n = 9253) was younger than 75 years. In both men and women, we observed a significant decrease in mortality from 2000 to 2014, followed by the opposite trend from 2014 to 2020, with average yearly increases of 13.9% in men and 11.6% in women.Premature mortality from diabetes has been growing from 2014. The COVID-19 pandemic changed the mortality pattern, increasing premature diabetes deaths in Costa Rica in 2020.

The HLA system shows the most extensive polymorphism in the human genome. Allelic and haplotypic frequencies of HLA genes vary dramatically across human populations. Due to a complex history of migration, populations in Latin America show a broad variety of admixture proportions, usually varying not only between countries, but also within countries. Knowledge of HLA allele and haplotype frequencies is essential for medical fields such as transplantation, but also serves as a means to assess genetic diversity and ancestry in human populations. Here, we have determined high-resolution HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies in a sample of 713 healthy subjects from three Mestizo populations, one population of African descent, and Amerindians of five different groups from Costa Rica and Nicaragua and compared their profiles to a large set of indigenous populations from Iberia, Sub-Saharan Africa, and the Americas. Our results show a great degree of allelic and haplotypic diversity within and across these populations, with most extended haplotypes being private. Mestizo populations show alleles and haplotypes of putative European, Amerindian, and Sub-Saharan African origin, albeit with differential proportions. Despite some degree of gene flow, Amerindians and Afro-descendants show great similarity to other Amerindian and West African populations, respectively. This is the first comprehensive study reporting high-resolution HLA diversity in Central America, and its results will shed light into the genetic history of this region while also supporting the development of medical programs for organ and stem cell transplantation.

A total of 110 Costa Rican Mestizos from the province of Guanacaste were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, and -DRB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identified was A*24:02:01-B*35:12:01-C*04:01:01-DRB1*04:07:01G, with an estimated frequency of 2.73%. No deviation from Hardy-Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database under the population name "Costa Rica Guanacaste Mestizo" and the identifier AFN3609.

También puede accesar el texto completo en este link: https://www.sciencedirect.com/science/article/abs/pii/S1877959X16301509?via%3Dihub This study focuses on the detection and identification of DNA and antibodies to Ehrlichia spp. in samples of blood bank donors in Costa Rica using molecular and serological techniques. Presence of Ehrlichia canis was determined in 10 (3.6%) out of 280 blood samples using polymerase chain reaction (PCR) targeting the ehrlichial dsb conserved gene. Analysis of the ehrlichial trp36 polymorphic gene in these 10 samples revealed substantial polymorphism among the E. canis genotypes, including divergent tandem repeat sequences. Nucleotide sequences of dsb and trp36 amplicons revealed a novel genotype of E. canis in blood bank donors from Costa Rica. Indirect immunofluorescence assay (IFA) detected antibodies in 35 (35%) of 100 serum samples evaluated. Thirty samples showed low endpoint titers (64–256) to E. canis, whereas five sera yielded high endpoint titers (1024–8192); these five samples were also E. canis-PCR positive. These findings represent the first report of the presence of E. canis in humans in Central America. Este estudio se centra en la detección e identificación de ADN y anticuerpos contra Ehrlichia spp. en muestras de donantes de bancos de sangre en Costa Rica utilizando técnicas moleculares y serológicas. La presencia de Ehrlichia canis se determinó en 10 (3,6%) de 280 muestras de sangre utilizando la reacción en cadena de la polimerasa (PCR) dirigida al gen conservado dhr ehrlichial. El análisis del gen polimórfico ehrlichial trp36 en estas 10 muestras reveló un polimorfismo sustancial entre los genotipos de E. canis, incluidas las secuencias de repetición en tándem divergentes. Las secuencias de nucleótidos de los amplicones dsb y trp36 revelaron un nuevo genotipo de E. canis en donantes de bancos de sangre de Costa Rica. El ensayo de inmunofluorescencia indirecta (IFA) detectó anticuerpos en 35 (35%) de 100 muestras de suero evaluadas. Treinta muestras mostraron títulos bajos de punto final (64–256) a E. canis, mientras que cinco sueros arrojaron títulos altos de punto final (1024–8192); estas cinco muestras también fueron positivas para E. canis-PCR. Estos hallazgos representan el primer informe de la presencia de E. canis en humanos en América Central. Universidad Nacional, Costa Rica Escuela de Medicina Veterinaria

A total of 155 Nicaraguan Mestizos from across the country were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, and -DRB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identified was A*24:02:01-B*40:02:01-C*03:05-DRB1*04:07:01G, with an estimated frequency of 2.26%. No deviation from Hardy-Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database under the population name "Nicaragua Mestizo" and the identifier AFN3610.

A total of 125 Costa Ricans of Amerindian descent were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, and -DRB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identified was A*24:02:01-B*40:02:01-C*03:05-DRB1*04:07:01G, with an estimated frequency of 8.26%. A deviation from Hardy-Weinberg Equilibrium was detected at the DRB1 locus (p = 0.099). The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database under the population name “Costa Rica Amerindians” and the identifier AFN3608.

A total of 221 Costa Rican Mestizos from the Central Valley were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, -DRB1, and -DQB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identified was A*24:02:01-B*40:02:01-C*03:05-DRB1*08:02:01-DQB1*04:02:01, with an estimated frequency of 2.04%. No deviation from Hardy-Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database under the population name “Costa Rica Central Valley Mestizo” and the identifier AFN3606.

Anticoagulant activity of enoxaparin is not routinely monitored even when previous studies have shown a high pharmacological variability. The aim of this study is to determine the prevalence of non-therapeutic anti-Xa levels among medical patients using enoxaparin as anticoagulant therapy and to point out potential risk factors related to the risk of having a sub-therapeutic level.Anti-Xa levels were measured in a cohort of sixty patients with medical indication for enoxaparin. Patients were categorized according to anti-Xa levels as follows: suboptimal anticoagulation (0.5 IU/ml), optimal anticoagulation (between 0.5 and 1.2 IU/ml) or overanticoagulated (1.2 IU/ml). Demographic and clinical variables and the use of concomitant medications were described for each group. Univariate and multivariate analysis were performed to assess the relationship between sub-optimal anticoagulation and potential predictive variables. A linear regression analysis was done to assess the relationship between anti-Xa activity, age, weight, body mass index, administered dose/weight and creatinine clearance.The mean anti-Xa activity was 0.71±0.32 UI/ml. Thirty one percent of patients had anti-Xa levels out of the therapeutic range, most of them (twenty-eight percent of total population) with a sub-therapeutic level. None of the variables were associated with the risk of a sub-therapeutic anti-Xa level.Almost one third of patients receiving enoxaparin had anti-Xa levels out of the therapeutic range. We need more studies to determine the clinical relevance of these findings.

The human leukocyte antigen (HLA) system is the most polymorphic in humans. Its allele, genotype, and haplotype frequencies vary significantly among different populations. Molecular typing data on HLA are necessary for the development of stem cell donor registries, cord blood banks, HLA-disease association studies, and anthropology studies. The Costa Rica Central Valley Population (CCVP) is the major population in this country. No previous study has characterized HLA frequencies in this population. Allele group and haplotype frequencies of HLA genes in the CCVP were determined by means of molecular typing in a sample of 130 unrelated blood donors from one of the country's major hospitals. A comparison between these frequencies and those of 126 populations worldwide was also carried out. A minimum variance dendrogram based on squared Euclidean distances was constructed to assess the relationship between the CCVP sample and populations from all over the world. Allele group and haplotype frequencies observed in this study are consistent with a profile of a dynamic and diverse population, with a hybrid ethnic origin, predominantly Caucasian-Amerindian. Results showed that populations genetically closest to the CCVP are a Mestizo urban population from Venezuela, and another one from Guadalajara, Mexico.

Thrombotic disease is a multifactorial condition that involves both classical and genetic risk factors. We studied the association between the classical risk factors of hypertension and smoking, and polymorphisms on the genes of the angiotensin-converting enzyme (ACE), the beta-chain of fibrinogen (FG), and the plasminogen activator inhibitor-1 (PAI-1) in patients with venous and arterial thrombosis. The present investigation is a retrospective case-control study. A total of 340 participants were analyzed, including 162 patients and 178 healthy controls. Hypertension and smoking showed a significant association with thrombotic disease (p0.05) but FG level was found significant risk factor only for the venous thrombosis (VT) group (p0.04). Significant differences between thrombotic groups were found for the studied polymorphisms of PAI-1 (p0.0014), but for both FG beta-chain gene polymorphisms, none of the molecular analyses showed a positive sample for any mutating allele (p0.05). For the ACE polymorphism, the I allele present a protective effect in the general thrombotic group. This is one of the first reports in a Latin-American population dealing with these molecular markers and thrombotic diseases.

SummaryHaemophilia is the most frequent hereditary haemorrhagic illness and it is due to the deficiency of coagulation factors VIII (haemophilia A, HA) or IX (haemophilia B, HB).The prevalence of this disease varies according to the country, those having better survival rates having also higher prevalences. Specifically in Costa Rica, there are around 130 HA and 30 HB families. This study reports the prevalence and a spatial distribution analysis of both types of the disease in this country. The prevalence of haemophilia in this country is 7 cases per 100 000 men, for HA it is 6 cases per 100 000 and for HB it is 1 case per 100 000 male inhabitants. The prevalence of this disease is low when compared with other populations. This low prevalence could be due to the many patients that have died because of infection with human immunodeficiency virus during the 1980s. The prevalence of haemophilia in Costa Rica is almost one half of that present in developed countries. Nevertheless, the ratio between HA and HB follows world tendency: 5 : 1. In this study, nationwide geographical distribution maps were drawn in order to visualize the origin of severe cases and how this influences the pattern of distribution for both types of haemophilia. By means of these maps, it was possible to state that there is no association between the sites of maximum prevalence of mutated alleles and ethnicity. With this study, haemophilia prevalence distribution maps can be used to improve efforts for the establishment of hemophilia clinics or specialized health centers in those areas which hold the highest prevalences in this country. Also, this knowledge can be applied to improve treatment skills and offer the possibility of developing focused genetic counseling for these populations.

In this study, eight common polymorphisms associated with venous thrombosis (VT) and thrombophilia factors were analyzed in a Costa Rican case-control study. With the use of polymerase chain reaction (PCR) methods the polymorphisms were detected in 120 patients and 133 controls (mean age

Fisiologicamente, los receptores de quimiocinas se expresan en diferentes tipos de leucocitos; los receptores median la quimiotaxis de las celulas T y los fagocitos a las areas de inflamacion (Hurk 1994). Estudios previos han demostrado que el alelo CCR5-Δ32 ocasiona un cambio de marco de lectura y genera una proteina no funcional que conduce a la perdida de la expresion y funcion de CCR5, dando lugar a una proteina truncada que no se expresa en la superficie celular (Samson et al 1996). La variante CCR5 delta 32 ha sido asociado en multiples enfermedades donde el factor inflamatorio juega un componente importante (Wheeler et al 2007).

Las hemoglobinopatías son alteraciones de las cadenas de globina que componen la hemoglobina, dentro de las alteraciones más comunes destacan las talasemias y la drepanocitosis. En el CIHATA se realizó un estudio retrospectivo de las muestras analizadas por electroforesis de hemoglobina durante el período 2011-2013, en donde se obtuvo un total de 2345 muestras analizadas, de las cuáles el patrón electroforético más frecuente fue el de Hb AA2, con un valor A2 promedio de (4.8±0.8%), compatible con el diagnóstico de β talasemia menor; seguido por el patrón asociado a portadores Hb S. En menor cantidad se observaron resultados de Hb AC, AF, AA2F, entre otros. Los patrones se distribuyeron a lo largo del país, pero localizados mayormente en la región central (sesgo relacionado a mayor área de atracción). Es importante la detección de los patrones anormales, pues aunque no se asocien con un cuadro clínico, en condiciones de hipoxia o estrés fisiológico si se pueden presentar complicaciones graves y sobre para brindar consejo genético. Esta actualización brinda un panorama de la frecuencia de hemoglobinopatías circulantes en Costa Rica durante los últimos años. Se debe procurar la recopilación de información clínica, y demográfica completa de todos los pacientes, con el fin de hacer reportes de caso completos que puedan ayudar en el óptimo abordaje diagnóstico de los pacientes y familiares.

Hemophilia Aand B are X-chromosome linked bleeding disorders caused by deficiency of the respective coagulation factor VIII and IX. Affected individuals develop a variable phenotype of hemorrhage caused by a broad range of mutations within the Factor VIII or Factor IX gene. Here, were report the results of the molecular diagnosis in a five Costa Rican families affected with Hemophilia. Methods of indirect and direct molecular diagnosis are applied in three Hemophilia A and two Hemophilia B families from Costa Rica as well as preconditions, practicability and facilities of this diagnosis. In two families with Hemophilia A and both families with Hemophilia B the causative mutation could be detected by Southern blotting, polymerase chain reaction or sequence analysis. One Hemophilia A family could only analyzed by linkage analysis using genomic markers. Rev. Biol. Trop. 52(3): 521-530. Epub 2004 Dic 15.La hemofilia A y B es una enfermedad hemorrágica hereditaria ligada al cromosoma X, producida por la deficiencia del factor VIII o IX, respectivamente. Los individuso afectados presentan un fenotipo de hemorragia variable causada por el amplio espectro de mutacionesdentro del gen del factor VIII o IX. Se reportan los resultados preliminares del diagnóstico molecular de familias hemofilicas costarricenses. Se demuestran los hallazgos obtenidos por medio de diagnóstico molecular directo e indirecto en tres familias con hemofilia A y dos con hemofilia B; así como las precondiciones y facilidad de este diagnóstico. En dos familias con hemofilia A y dos con hemofilia B, la mutación responsable pudo ser detectada por medio de Southern Blot, por la reacción en cadena de la polimerasa o por secuenciación genética. Una familia con hemofilia A pudo ser analizada solamente por medio de análisis indirecto por medio de marcadores genéticos intragénicos y extragénicos.

Individuals belonging to six different Amerindian tribes and two African groups of Costa Rica were genotyped for factor V Leiden (FV), factor V haplotype HR2 (FV HR2), Factor II 20210G>A (FII), the methylenetetrahydrofolate reductase (MTHFR), factor VII polymorphisms (FVII IVS7, FVII R353Q), factor XIII (FXIII V34L), and the insertion/deletion (I/D) polymorphism of the gene of angiotensin converting enzyme (ACE). Clear differences in the prevalence were found and are first reported. The prevalence of some of the established genetic risk factors was low in Amerindians of Costa Rica (ACE) or even absent (FVL, FII), and others (MTHFR, FVHR2) had an extremely high prevalence. People of African origin carried very rare FVL or FII polymorphisms, but the DD genotype of ACE is the highest reported. Concerning the protective factors, the QQ genotype of FVII R353Q was absent in Amerindians, but the protective 7/7 genotype of FVII IVS7 frequently found. Novel alleles of FVII IVS7 (4, 8, and 9 monomers) were found. Intertribal heterogeneity was observed that may reflect the evolutionary history of these tribal groups and their admixture with other populations.

SummaryHaemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII (FVIII). It is caused by FVIII gene intron 22 inversion (Inv22) in approximately 45% and by intron 1 inversion (Inv1) in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous regions, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The aim of this study was to analyze the presence of these mutations in 25 HA Costa Rican families. Patients, methods: We studied 34 HA patients and 110 unrelated obligate members and possible carriers for the presence of Inv22or Inv1. Standard analyses of the factor VIII gene were used incl. Southern blot and long-range polymerase chain reaction for inversion analysis. Results: We found altered Inv22 restriction profiles in 21 patients and 37 carriers. It was found type 1 and type 2 of the inversion of Inv22. During the screening for Inv1 among the HA patient, who were Inv22 negative, we did not found this mutation. Discussion: Our data highlight the importance of the analysis of Inv22 for their association with development of inhibitors in the HA patients and we are continuous searching of Inv1 mutation. This knowledge represents a step for genetic counseling and prevention of the inhibitor development.

Intracranial hemorrhage (ICH) is a severe complication of Factor X (FX) deficiency. We report 6 homozygous patients with central nervous system (ICH) bleeds. Five patients are homozygous for the mutation Gly380Arg and one for the novel deletion Tyr163delAT. We describe the association of these mutations with ICH bleeding.

Aim: The epidemiological behavior of malignant tumors in Costa Rica has undergone an important change during the last years; breast carcinoma has increased its incidence, occupying the second place in malignancies in women and the first one in mortality. This type of tumor can be studied by several immunohistochemistry markers, such as the expression of different hormonal receptors by neoplastic cells (estrogen receptors, progesterone receptors and Human Epidermal Growth-Factor Receptor type 2, HER2). Carcinomas which do not express any of these three receptors have a worse prognosis. Objectives for this study were to determine the main characteristics of these tumors, named triple negative carcinomas, and to define their relevance within breast carcinomas. Methodology: Data was collected from a ll women with breast cancer diagnosed, with immunohistochemistry studies, from January 1 st , to December 31 st , 2006, at the Pathology Department of the San Juan de Dios Hospital. Patient´s age, histological type and degree of differentiation, were taken into account for each case. Triple negative carcinomas were considered separately, and statistical analysis was made with Epi Info 3.3.4 software. Results: During the above mentioned period, 221 patients were diagnosed with breast cancer, 40 of them were identified as having triple negative carcinomas, which meant an incidence of 18% (C.I. 95%, 12.79 – 23.40), and had an average of 54 years old (C.I. 95%, 50 - 58 ), a median of 52 years old and a mode of 48 years old. Triple-negative cancer was more related with ductal infiltrating histological type: 67.5% (C.I. 95%, 51.73-83.26), followed by infiltrating lobular, with 12.5% (C.I. 95%, 4.18 – 26.80), medullary, with 5%, and less related are papillary type and spindle cell metaplastic carcinoma. According to the degree of differentiation, there were 23 grade-3 cases, 8 grade-2 cases, and 3 grade-1 carcinomas. Conclusion: Triple negative breast cancers are an aggressive group of tumors, which manifest at younger ages, have larger tumor size, are of higher histological grade, and mostly are infiltrating ductal carcinomas. Due to the fact that this was based only on determination of hormonal receptors and HER2, other tests might be necessary such as CK5/6 and 17 stains to check basal-like carcinoma cases. Also, this study shows a higher prevalence for infiltrating lobular carcinomas than other studies, so that other tests could be done such as e-cadherin, to verify the cases of lobular carcinomas, thereby increasing reliability of results.

The new HLA-A*74:23 allele differs from the closest allele A*74:01 by a nucleotide change in exon 3 at codon 97.

Justificación y objetivo: El comportamiento epidemiológico de los tumores malignos del país ha presentado un cambio en los últimos años; el cáncer de mama ha aumentado su incidencia hasta colocarse como el segundo tumor maligno más frecuente en la mujer y el primero en mortalidad. Este tipo de tumor tiene características que se pueden estudiar con las técnicas de inmunohistoquímica, como son la expresión de receptores en las células neoplásicas (estrógenos, progesterona y el HER2 o receptor 2 del factor de crecimiento epidérmico humano). Los carcinomas que no expresan ninguno de estos tres receptores tienen un peor pronóstico. El estudio tiene como objetivos conocer las principales características de este grupo de tumores denominados triples negativos, y determinar su relevancia dentro del grupo total del carcinoma de mama. Materiales y métodos: Se recolectaron los casos diagnosticados de cáncer de mama en mujeres, en el periodo comprendido entre el 1 de enero y el 31 de diciembre de 2006, en el Hospital San Juan de Dios, en el Servicio de Patología, que dispusieran de estudios inmunohistoquímicos. Se consideró la información acerca de la edad de las pacientes, así como el tipo histológico y grado de diferenciación de cada uno de los tumores. Se separó el grupo correspondiente a los tumores triple negativo y se realizaron los análisis estadísticos por medio del programa Epi Info 3.3.4. Resultados: De una población de 221 pacientes diagnosticadas con cáncer de mama en el periodo mencionado, se presentaron 40 pacientes con cáncer de mama triple negativo, resultando en una incidencia de un 18% (I.C. 95%, 12,79 - 23,40) y una edad promedio de 54 años (I.C. 95%, 50 - 59), con una mediana de 52 y una moda de 48. El cáncer de mama triple negativo tuvo una relación mayor con el tipo histológico ductal infiltrante, con un 67,5% (I.C. 95%, 51,73- 83,26); seguido por el lobulillar infiltrante, con un 12,5% (I.C.95%, 4,18 - 26,80); el medular con un 5% (I.C. 95%, 0,61 - 16,92), y con menos relación el tipo papilar y el metaplásico fusocelular, ambos con un 2,5% (I.C. 95%, 0,06 - 13,16). Con respecto al grado de diferenciación, hubo 23 casos con grado 3, 8 con grado 2 y 3 con grado 1.Conclusiones: Los cánceres de mama triple negativo son un grupo de tumores agresivos, que se manifiestan a edad más temprana, con mayor tamaño, grado histológico alto, principalmente son carcinomas ductales infiltrantes. Debido a que el estudio se basó solo en pruebas de receptoreshormonales y HER-2, se podría realizar otras pruebas como tinción de CK5/6 y 17, para comprobar los casos de carcinomas basales. Además, se observa que los carcinomas lobulillares infiltrantes muestran una mayor prevalencia que en otros estudios, de manera que se podrían efectuar pruebas como la e-cadherina, para comprobar los casos de carcinomas lobulillares y aumentar la fidelidad de este estudio. Aim: The epidemiological behavior of malignant tumors in our country has undergone an important change during the last years, Breast carcinoma has increased its incidence, occupying the second place in malignancies in women and the first one in mortality. This type of tumor has characteristic features from the immunohistochemistry, standpoint since they can express different receptors such as estrogens, progesterone and HER2 or receptor 2 of epidermal human growth factor. It is known that carcinomas that do not express any of these 3 receptors have worse prognosis. Our objective is to define the main characteristics of the so called triple negative tumors and determine their rol within the total group of breast carcinomas. Methodology: All cases of breast cancer seen at the Pathology Department of the Hospital San Juan de Dios, from January 1 to December 31, of 2006 were included if they had immunohistochemistry studies. The age of the patient;s, and the histological type and degree of differentiation of each one of the tumors was recorded. The triple negative group was separated and an statistical analyses was undertaken utilizing the Epi Info 3.3.4 program. Results: Of 221 patients diagnosed with breast carcinomas, 40 patients were identified as triple- negative cancer, giving an incidence of 18% (I.C. 95%, 12,79 - 23,40), they had an average age of 54 years (I.C. 95%, 50 - 58 ) with a median of 52 and mode of 48. Likewise, triple-negative cancer individuals were more related with ductal infiltratiing: 67,5% (I.C. 95%, 51,73-83,26), followed by unfiltrating lobular:12,5% (I.C.95%, 4,18 - 26,80), medular, 5 % and with other such as papillary Regarding the degree of differentiation, 23 cases were III degree, 8 were II degree , and 3 were I degree. Conclusion: Triple-negative breast cancers affect young women, are of higher histological grade, have larger tumor size and have a more aggressive clinical behavior, and preferentially they are of infiltrating ductal histological type. The incidence in our study seems to be higher than the one reported in the world literature. Due to the fact that this was based only on determination of receptors, other tests might be necessary such as CK5/6 and 17 stains to verify the cases. In addition, in this study a high proportion of tumors were of lobular type, other tests might be indicated such as e-cadherin to verify the cases of lobular carcinomas to increase in this way the reliability of results. Universidad de Costa Rica. Caja Costarricense de Seguro Social. UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicina UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Hematología y Trastornos Afines (CIHATA)

Se evalúo la técnica de Reacción en Cadena de la Polimerasa (PCR) para el diagnóstico de Mycobacterium tuberculosis y micobacterias atípicas en tejidos parafinados. Para ello se analizaron 7 casos del Hospital San Juan de Dios (HSJD) con diagnóstico sugestivo de tuberculosis y se compararon los resultados obtenidos por PCR con el diagnóstico histopatológico y la historia clínica de los pacientes. De los siete casos analizados, tres resultaron positivos para M. tuberculosis, tres para micobacterias atípicas y un caso resultó negativo. Para evaluar la sensibilidad y especificidad de la técnica se necesita un estudio con un mayor número de muestras pero se pudo demostrar que es posible realizar el diagnóstico molecular de tuberculosis en muestras fijadas en nuestro país, sin embargo se debe de considerar ésta como una herramienta diagnóstica que se debe complementar con la historia clínica de cada paciente.

The congenital Factor VII deficiency (FVIID) is a rare hemorrhagic disorderwith an autosomal recessive pattern of inheritance and a prevalence of 1:500,000. In 1994 the International Greifswald Registry of congenital FVII deficiency was initiated [1]. We analyzed the phenotype and genotype of subjects,who presented with reduced FVII activities.

La mutación del gen de la protombina (PTG20210A), es un importante marcador asociado a un mayor riesgo de trombosis. Objetivo: se presenta el caso de una paciente con eventos trombóticos. Materiales y métodos: La paciente con historia de tromboflebitis y abortos sin factores de riesgo conocidos para ello. Se realizaron análisis de coagulación y estudios moleculares para el factor V Leiden (FVL), la mutación C677T de la metilentetrahidrofolato reductasa (MTHFR C677T) y de la mutación de PTG20210A. También, se analizaron tres hijos de ella. Resultados: La mutación del FVL no fue encontrada en este paciente ni en ningún miembro de su familia. La paciente es heterocigota para la MTHFR C677T y homocigota para la variante PTG20210A. Tres hijos suyos son heterocigotas para esta última mutación. Conclusiones: La variante de la PTG20210G se asociada con eventos de trombosis venosa. En el presente caso, ha sido importante este hallazgo para determinar las medidas terapéuticas de esta paciente y para tomar medidas preventivas de eventos trombóticos en los miembros de su familia que la portan.

Individuals belonging to six different Amerindian tribes and two African groups of Costa Rica were genotyped for factor V Leiden (FV), factor V haplotype HR2 (FV HR2), Factor II 20210GA (FII), the methylenetetrahydrofolate reductase (MTHFR), factor VII polymorphisms (FVII IVS7, FVII R353Q), factor XIII (FXIII V34L), and the insertion/deletion (I/D) polymorphism of the gene of angiotensin converting enzyme (ACE). Clear differences in the prevalence were found and are first reported. The prevalence of some of the established genetic risk factors was low in Amerindians of Costa Rica (ACE) or even absent (FVL, FII), and others (MTHFR, FVHR2) had an extremely high prevalence. People of African origin carried very rare FVL or FII polymorphisms, but the DD genotype of ACE is the highest reported. Concerning the protective factors, the QQ genotype of FVII R353Q was absent in Amerindians, but the protective 7/7 genotype of FVII IVS7 frequently found. Novel alleles of FVII IVS7 (4, 8, and 9 monomers) were found. Intertribal heterogeneity was observed that may reflect the evolutionary history of these tribal groups and their admixture with other populations.

Eight common polymorphisms of known myocardial infarction (MI)risk factors (factor V Leiden (FVL), factor V HR2 (FVHR2),factor II 20210G>A (FII),factor VII IVS7 (FVII IVS7),factor VII Arg353Gln (FVII), factor XIII Val34Leu (FXIII),Methylenetetrahydrofolate reductase C677T (MTHFR), Angiotensin Converting Enzyme (ACE))and environmental risk factors were analyzed in a MI patients of Costa Rica.This case-control study included 186 MI subjects,95 of them Se estudiaron ocho polimorfismos comunes asociados como factores de riesgo para el infarto al miocardio (IM):factor V Leiden (FVL),factor VHR2 (FVHR2), factor II 20210G>A (FII),factor VII IVS7 (FVII IVS7), factor VIIArg353Gln (FVII),factor XIIIVal34Leu (FXIII), metilentetrahidrofolato reductase C677T (MTHFR), enzima convertidora de la angiotensina (ACE) y factores ambientales de riesgo,en pacientes costarricenses.Este es un estudio de casos y controles,donde participan 186 pacientes,95 de ellos con edades

Hemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII. The disease is caused by Factor VIII gene intron 22 inversion in approximately 50% of the patients and by intron 1 inversion in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous region, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The goal of the present study was to analyze the presence of these mutations in 15 HA severe Costarrican families. Methods: We studied 122 unrelated HA patients and obligate or possible carriers for the presence of intron 22 or intron 1 by Southern blotting and polymerase chain reaction (PCR). Results: We found altered intron 22 restriction profiles by Southern analyses in 14 of the families, 12 cases type 1 (Figure 1) and 2 cases type 2 inversion. During the screening for intron 1 inversion among the HA patient, who were intron 22 inversion negative, we did not identified this mutation. Interpretation and Conclusions: This report is the first in our haemophilia families dealing with mutations in the intron 22 and intron 1. Our data highlight the importance of the analysis of intron 22 inversion for the association with development of inhibitors in the HA patients and we are continuous searching of intron 1 mutation. This will benefit both genetic counselling and the study of the relationship between genotype and inhibitor development. Fig. 1 Southern blot of HA-I showing the intron 22 inversion of the factor VIII gene. Lane 1 and 2 normal Lane 3: heterozygote carrier and lane 4: patient with the altered fragment, (inversion of the intron 22). Fig. 1. Southern blot of HA-I showing the intron 22 inversion of the factor VIII gene. Lane 1 and 2 normal Lane 3: heterozygote carrier and lane 4: patient with the altered fragment, (inversion of the intron 22).

La ‘era posgenómica’ ha impactado las ciencias biológicas y biomédicas desde la identificación de un significativo componente de variabilidad genética interindividual. La Farmacología no escapa a esta realidad, y esta ciencia, en conjunto con la Toxicología, ya desde hace varios años ve desarrollados campos como la Farmacogenética y la Farmacogenómica. Dichas disciplinas estudian la influencia de la variabilidad genética de la población respecto a la respuesta que se tiene ante el contacto con los fármacos y las sustancias tóxicas. Las variantes genéticas, reflejadas en el polimorfismo de los genes, tienen implicaciones en el manejo de xenobióticos en el organismo y además determinan las respuestas aumentadas, normales o disminuidas durante la administración de algunos fármacos. Muchos genes se relacionan con reacciones adversas y fallas terapéuticas de fármacos administrados a dosis predeterminadas y siguiendo protocolos establecidos. Es por esto que las herramientas de caracterización genética molecular se aplican en muchos países con el fin de adaptar estos protocolos a cada individuo, es decir, personalizar la terapia farmacológica, donde las dosificaciones son evaluadas de acuerdo con las características genéticas de la persona, para evitar o prevenir reacciones adversas en individuos predispuestos. Costa Rica es un país que hace grandes esfuerzos para brindar una atención médica de primer mundo a sus habitantes, sin embargo, el campo de la Farmacogenética aún no se ha desarrollado en nuestro medio. No obstante, el Centro Nacional Innovaciones Biotecnológicas financia un proyecto pionero junto con la Universidad de Costa Rica, para desarrollar la aplicación de esta disciplina en el país. El presente artículo presenta las bases biológicas y la utilidad clínica de la Farmacogenética, así como detalles de las iniciativas para el desarrollo de esta disciplina en Costa Rica. The ‘post-genomic era’ has had an impact on biological and biomedical sciences since the recognition of a significant interindividual genetic variation. Pharmacology has not escaped this influence. This discipline, together with toxicology, has seen the development of areas such as pharmacogenetics and pharmacogenomics for several years now. These disciplines study the influence of the population’s genetic variability on the response people have to drugs and toxic substances. Different polymorphisms (genetic variants) in genes involved in the handling of xenobiotics in the body are able to determine an exaggerated, normal or reduced response to a certain dose of any drug. Many genes have been associated with poor response to pre-determined dosing protocols or with hypersensitivity reactions. Because of this, molecular genetics characterization tools are applied in many countries to adapt this protocol individually, i.e. a personalized pharmacology, where dosages are evaluated according to the genetic determinants a person carries in order to avoid or prevent adverse reactions in predisposed individuals. Costa Rica is a country that makes great efforts 208 Acta méd. costarric Vol 54 (4), octubre-diciembre 2012 to give first-world medical care to its residents, but the field of pharmacogenetics has not been developed in our medium yet. Notwithstanding, the National Center for Biotechnology Innovations is currently funding a pioneering joint project with the University of Costa Rica in order to develop the application of this discipline in the country. This article presents the biological basis and clinical utility of pharmacogenetics, as well as the details regarding the efforts that are being made to develop this discipline in Costa Rica. UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones Farmacéuticas (INIFAR)