Trombocitopenia fetal/neonatal aloinmune. Revisión a propósito de un caso / Foetal/neonatal alloimmune thrombocytopenia. A review and case report

La trombocitopenia fetal/neonatal aloinmune (TFNA) es la causa más frecuente de trombocitopenia grave en el recién nacido. Es un proceso agudo donde las plaquetas fetales son destruidas durante la gestación por un anticuerpo de tipo IgG presente en la madre aloinmunizada. En la raza caucásica, tiene especificidad frente al antígeno específico plaquetar HPA-1a en más del 80% de los casos. La hemorragia intracraneal, que ocurre hasta en un 30%, es la complicación más grave, con un 10% de mortalidad y un 20% de secuelas neurológicas irreversibles. El alto riesgo de repetición de hemorragia grave en futuras gestaciones obliga a plantearse profilaxis o tratamiento antenatal. El diagnóstico precoz puede permitir administrar un tratamiento eficaz basado en la transfusión de plaquetas de fenotipo HPA compatible o de inmunoglobulinas endovenosas. Presentamos el caso de una gestante de 27 años, que en la semana 35 de su segunda gestación fue diagnosticada por ecografía de hidrocefalia fetal bilateral. En la cesárea realizada en la semana 36, el neonato presentó hematomas en hombro y glúteo izquierdos, macrocefalia con fontanelas a tensión y salida de líquido cefalorraquídeo hemorrágico tras la colocación de un catéter de derivación externo. El hemograma reveló trombocitopenia grave (9 x 109/L). Ante sospecha clínica de TFNA, se transfundieron plaquetas de donante no fenotipado para el HPA-1a y se inició tratamiento con inmunoglobulinas endovenosas, con recuperación de la trombocitopenia, pero con secuelas neurológicas probablemente irreversibles. El estudio inmunohematológico confirmó el fenotipo materno HPA-1a negativo, el fenotipo neonatal HPA-1a positivo y la presencia de aloanticuerpos anti-HPA-1a en el suero materno. La profilaxis y el tratamiento continúan siendo, en la actualidad, motivo de discusión y controversia, así como la posibilidad de realizar un cribado antenatal (AU)

Foetal/neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia in the newborn. It is an acute disorder which implies that foetal platelets are destroyed during the pregnancy due to a maternal alloimmune IgG antibody. More than 80% of Caucasians are HPA-1a specific. Intracranial haemorrhage, which occurs in 30% of cases, is the most serious complication, with a 10% mortality rate or a 20% rate of irreversible neurological sequels. The high risk of a recurrence of serious bleeding in future pregnances led us to consider prophylaxis or prenatal treatment. An early diagnosis of this process allows an effective therapy to be carried out based on the infusion of compatible phenotype HPA platelets or endovenous immunoglobulins. We present the case of a 27 year old pregnant woman, who in the 35th week of a second pregnancy was diagnosed using echography with a bilateral foetal hydrocephaly. After caesarean delivery in the 36th week, the newborn presented haematomas in the left shoulder and gluteus, macrocephalia with tension of the fontanellas and hemorrhagic cerebrospinal fluid after insertion of an external ventricular derivation catheter. The haemogram revealed a severe trombocytopenia (9 x 109/L). In the light of clinical suspicion of foetal/neonatal alloimmune thrombocytopenia, infusion was made of platelets from a non-phenotyped donor for the HPA-1a system, and an endovenous immunoglobulin treatment was followed, with a recovery of platelet counts, but with neurological sequels that are probably irreversible. The immunohaematologal study confirmed the negative HPA-1a maternal phenotype, the neonatal HPA-1a positive phenotype and the presence of anti-HPA-1a alloantibodies in the maternal serum. Nowadays, the prophylaxis and treatment continue to be a controversial issue that is open to discussion, as is the possibility of implementing antenatal screening (AU)

[Foetal/neonatal alloimmune thrombocytopenia. A review and case report]. / Trombocitopenia fetal/neonatal aloinmune. Revisión a propósito de.

Foetal/neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia in the newborn. It is an acute disorder which implies that foetal platelets are destroyed during the pregnancy due to a maternal alloimmune IgG antibody. More than 80% of Caucasians are HPA-1a specific. Intracranial haemorrhage, which occurs in 30% of cases, is the most serious complication, with a 10% mortality rate or a 20% rate of irreversible neurological sequels. The high risk of a recurrence of serious bleeding in future pregnancies led us to consider prophylaxis or prenatal treatment. An early diagnosis of this process allows an effective therapy to be carried out based on the infusion of compatible phenotype HPA platelets or endovenous immunoglobulins. We present the case of a 27 year old pregnant woman, who in the 35th week of a second pregnancy was diagnosed using echography with a bilateral foetal hydrocephaly. After caesarean delivery in the 36th week, the newborn presented haematomas in the left shoulder and gluteus, macrocephalia with tension of the fontanellas and hemorrhagic cerebrospinal fluid after insertion of an external ventricular derivation catheter. The haemogram revealed a severe trombocytopenia (9 x 109/L). In the light of clinical suspicion of foetal/neonatal alloimmune thrombocytopenia, infusion was made of platelets from a non-phenotyped donor for the HPA-1a system, and an endovenous immunoglobulin treatment was followed, with a recovery of platelet counts, but with neurological sequels that are probably irreversible. The immunohaematologal study confirmed the negative HPA-1a maternal phenotype, the neonatal HPA-1a positive phenotype and the presence of anti-HPA-1a alloantibodies in the maternal serum. Nowadays, the prophylaxis and treatment continue to be a controversial issue that is open to discussion, as is the possibility of implementing antenatal screening.

[Incidence and mortality due to cancer in Navarre, 1998-2002. Trends in the last 30 years]. / Incidencia y mortalidad por cáncer en Navarra, 1998-2002. Evolución en los últimos 30 años.

Between 1998-2002, 16,952 new cases of cancer were registered in Navarre. In men, the most frequently diagnosed cancers were in the following order: prostate, lung, colon and rectum, bladder and stomach, which accounted for 63.2%. In women, the sites were breast, colon and rectum, corpus uteri, stomach and ovary, which accounted for 57.6% of the cases. In the same period, 1998-2002, 4,127 men and 2,470 women died from cancer. Sixty percent of all deaths due to malign tumours in men were due to cancer of the lung, prostate, colon and rectum, stomach and bladder. In women this was due to cancers of colon and rectum, breast, stomach, pancreas and lung, which accounted for 49% of the cases. In men in Navarre there has been an increase in the incidence rates of cancer of the prostate, kidney and non-Hodgkin lymphoma. Avoidable cancers such as those related to smoking (lung, oral cavity and pharynx or pancreas) continue to rise, and represent a greater global risk of dying from cancer in the latest period studied than in the decades of the 1970s and 1980s. From 1995 up to the present, mortality due to cancer has moved from occupying the second place to become the first cause of death among men in Navarre. The global risk of death due to cancer in men is now equal to the first period studied, 1975-1977. Amongst women the global risk of death due to cancer fell by 25% between 1975 and 2002, basically at the cost of breast and stomach cancer. Tumours related to smoking increased both in mortality and in incidence and appear as a significant health problem amongst women in Navarre. Breast cancer has increased in incidence, with lower mortality figures than those of the first period 1975-1977. Invasive cancer of the cervix remains at very low rates in comparison with many European countries, including Spain. In both sexes colorectal and skin cancer has increased, while the incidence and mortality of stomach cancer continues to fall.

Incidencia y mortalidad por cáncer en Navarra, 1998-2002. Evolución en los últimos 30 años / Incidence and mortality due to cancer in Navarre, 1998-2002. Trends in the last 30 years

entre 1998-2002 se registraron 16.952 nuevos casos de cáncer en Navarra. En los hombres, los cánceres más frecuentes diagnosticados fueron, por este orden próstata, pulmón,colon y recto, vejiga y estómago, que sumaron el 63,2% de todos los casos de cáncer. En mujeres las localizaciones de mama, colon y recto, cuerpo de útero, estómago y ovario sumaron el 57,6% del total de los casos. En el mismo periodo, 1998-2002, fallecieron por cáncer 4.127 hombre y 2.470 mujeres. el 60% de todas las muertes producidas por tumores malignos en hombres se debieron a las localizaciones de pulmón, próstata,colon y recto, estómago y vejiga. En las mujeres las localizaciones de colon y recto, mama,estómago, páncreas y pulmón, sumaron el 49% de las defunciones por cáncer. En los hombre de Navarra han aumentado las tasas de incidencia del cáncer de próstata, riñón y linfoma no Hodgkin. Cánceres evitables, como los relacionados con el hábito de fumar (pulmón,cavidad oral y faringe o páncreas),continúan en ascento, y representan mayor riesgo global de morir por cáncer en el último periodo estudiado que en las décadas de los años 1970 y 1980. A partir de 1995 y hasta la actualidad, la mortalidad por cáncer pasó a ocupar el segundo lugar a ser la primera causa de muerte por cáncer en hombres se ha igualado al primer periodo estudiado 1975-1977. Entre las mujeres el riesgo gloval de muerte por cáncer descendió un 25% entre 1975 y 2002, a costa fundamentalmente del cáncer de mama y de estómago. Los tumores relacionados con el hábito de fumar muestran incrementos tanto en la mortalidad como en la incidencia y emergencia como un problema importante de salud entre las mujeres de Navarra. Ha aumentado la incidencia de cáncer de mama, en cambio en la mortalidad se sitúa en cifras inferiores a las del primer periodo 1975-1977. El cáncer invasivo de cérvix se mantiene en tasas muy bajas respecto a muchos países europeos, incluida España. En ambos sexos ha aumentado el cáncer colorrectal y el melanoma mientras que continúa el descenso de la incidencia y mortalidad por cáncer de estómago

Between 1998-2002, 16,952 new cases of cancer were registered in Navarre. In men, the most frequently diagnosed cancers were in the following order: prostate, lung, colon and rectum, bladder and stomach, which accounted for 63.2%, In women, the sites were breast, colon and rectum, corpus uteri, stomach and ovary, which accounted for 57,6% of the cases. In the same period, 1998-2002m 4,127 men and 2,470 women died from cancer. Sixty percent of all deaths due to malign tumours in men were due to cancer od the lung, prostate, colon and rectum, stomach and bladder. In women this was due to cancers of colon and rectum, breast, stomach, pancreas and lung, which accounted for 49% of the cases. In men in Navarre there has been an increase in the incidence rates of cancer on the prostate, kidney and non Hodgkin lymphoma. Avoidable cancers such as those related to smoking (lung, oral cavity and pharynx or pancreas) continue to rise, and represent a greater global risk of dying from cancer in the latest period studied than in the decades of the 1970s and 1980s. From 1995 up to the present, mortality due to cancer has moved from occupying the second place to become the first cause of death among men in Navarre. The global risk of death due to cancer in men is now equal to the first period studied 1975-1977. Amongst women the global risk of death due to cancer fell by 25% between 1975 and 2002 basically at the cost of breast and stomach cancer. Tumours related to smoking increased both in mortality and in incidence and appear as a significant health problem amongst women in Navarre. Breast cancer has increased in incidence, with lower mortality figures than those of the first period 1975-1977. Invasive cancer of the cervix remains at very low rates in comparison with many European countries, including Spain

Diferencias en el manejo del infarto agudo de miocardio según la edad en los hospitales de Navarra. Estudio IBERICA / Differences in the management of acute myocardial infarction according to age in the hospitals of Navarre (Spain). The IBERICA study

Fundamento y objetivo: estudio de las características de los episodios de infarto agudo de miocardio (IAM) producidos en Navarra en el año 1997 por edad. Material y métodos: investigación de los casos de IAM mediante la revisión de las historias clínicas y de los Boletines Estadísticos de Defunción. Resultados: en 1997 se registraron 903 casos de IAM en Navarra (509 hospitalarios y 394 extrahospitalarios). El 54,8% de las personas que presentaron un IAM falleció en los primeros 28 días del inicio de los síntomas, letalidad que aumentó con la edad (el 36% en menores de 65 años y el 71,9% en los mayores de 75 años). Uno de cada 3 varones ingresados por IAM y 1 de cada 2 mujeres tenían 75 años o más. El factor de riesgo coronario más frecuente entre los pacientes jóvenes fue el tabaquismo y en ancianos la hipertensión arterial. La edad fue un importante condicionante para la utilización de trombólisis (el 46,7% en menores de 60 años frente al 20,2% en mayores de 75 años). Se observó un menor uso de antiagregantes y bloqueadores beta y un mayor uso de inhibidores de la enzima de conversión de la angiotensina y nitratos entre los mayores de 75 años, tanto en el momento del ingreso como en el del alta. Conclusiones: los datos sobre los tratamientos aplicados a pacientes ancianos muestran un menor seguimiento de las recomendaciones de las guías de práctica clínica que lo observado entre los pacientes más jóvenes. Existe la necesidad de optimizar la aplicación de las guías de tratamiento del infarto agudo de miocardio en los pacientes ancianos en Navarra

Background and objective: to describe the characteristics of episodes of acute myocardial infarction (AMI) occurring in 1997 in Navarre according to age. Material and methods: a search was made for possible cases of AMI through a review of patients' medical records and death certificates. Results: in 1997, 903 cases of AMI were registered in Navarre (509 hospital cases and 394 outside the hospital). A total of 54.8% of patients with AMI died in the 28 days following the onset of the symptoms and lethality increased with age (36% in those aged below 65 years and 71.9% in those aged more than 75 years). One out of every three men admitted for AMI and one out of every two women was aged 75 years or more. The most frequent coronary risk factor in younger patients was smoking and that in the elderly was hypertension. Age was a factor determining the use of thrombolytic therapy (46.7% in those below 60 years of age versus 20.2% in those over 75). A lower use of antiagregants and beta-blockers and a higher use of angiotensin-converting enzyme inhibitors (ACEI) and nitrates was observed in patients over 75 years of age, both during admission and after discharge. Conclusions: data on the treatments applied to elderly patients with AMI in Navarre show a lesser adherence to the recommendations of the care guidelines than was observed amongst younger patients. There is a need to optimise the application of AMI treatment guidelines in elderly patients in Navarre

El infarto de miocardio en la población de 25-74 años de Navarra. Incidencia, letalidad y tratamiento en el periodo 1997-98. Estudio IBERICA / Myocardial infarction in the population aged 25-74 in navarra. Incidence, lethality and treatment in the period 1997-98. IBERICA study

El objetivo principal de este trabajo fue determinar la incidencia de infarto de miocardio en la población de 25-74 años de Navarra, la letalidad a los 28 días y las características del tratamiento aplicado en los hospitales durante los años 1997-1998. Se realizó una búsqueda de los posibles casos de infarto de miocardio en los servicios hospitalarios que los atienden, mediante la revisión de las historias clínicas. Los casos letales que no llegaron a los hospitales se investigaron a través de los boletines estadísticos de defunción, completándose la información sobre los mismos a través de los médicos de familia. Se registraron 1.059 eventos coronarios, que correpondían a una tasa cruda de ataque de 238 casos por 100.000 entre las mujeres. Entre los pacientes varones que llegaron vivos a los hospitales, el 50 por ciento fumaban, el 41 por ciento presentaban hipercolesterolemia, el 35,9 por ciento eran hipertensos y el 16 por ciento diabéticos. Entre las mujeres, que presentaban una edad media más alta, la hipertensión arterial fue el factor de riesgo más frecuente, el 66 por ciento. Durante la hospitalización se realizó trombolisis en el 39,2 por ciento de los pacientes, angioplastia primaria o deresacte en el 4,6 por ciento; se administraron aspirina u otros antiagregantes al 94,2 por ciento de los pacientes, ß-bloqueantes, al 60,6 por ciento y el IECA al 37,4 por ciento. Este trabajo ha mostrado que la frecuencia de infarto de miocardio en Navarra es inferior a la registrada en muchos países europeos y norteamericanos y concordante con las bajas tasas de mortalidad por esta causa. En los años 1997 y 1998 se observo una alta implementación de las recomendaciones de las guías de atención de esta enfermedad en lo relativo al uso de terapias eficaces cuando se analizan los datos globalmente. Se han observado, sin embargo, y con la excepción del uso de antiagregantes, variabilidad hospitalaria en el uso de la terapia trombolítica y de terapias adjuvantes como los betabloqueantes o IECA, y en el uso de técnicas diagnósticas como la arteriografía (AU)

[Myocardial Infarction in the population aged 25-74 in Navarra. Incidence, lethality and treatment in the period 1997-98. IBERICA study]. / El infarto de miocardio en la población de 25-74 años de Navarra. Incidencia, letalidad y tratamiento en el periodo 1997-98. Estudio IBERICA.

The principal aim of this study was to determine the incidence of Myocardial Infarction in the population aged 25-74 in Navarra, lethality after 28 days, and the characteristics of the treatment applied in the hospitals during the years 1997-1998. A search was conducted for possible cases of heart attack in the hospital services responsible for attending to them, by means of a review of clinical histories. The lethal cases that did not reach the hospitals were researched through the statistical bulletins of deaths, with the information on these deaths completed through the family doctors. 1,059 coronary events were registered, which corresponded to a crude rate of attack of 238 cases per 100,000 amongst men and 59 cases per 100,000 amongst women. Amongst the male patients who reached hospital alive, 50% were smokers, 41% showed hypercholesterolaemia, 35.9% were hypertense and 16% were diabetic. Amongst the women, who showed a higher average age, arterial hypertension was the most frequent risk factor, with 66%. During hospitalisation thrombolysis was carried out on 39.2% of the patients, primary or rescue angioplasty on 4.6%; aspirin or other anticoagulants were administered to 94.2%, beta-blockers to 60.6% and IECA to 37.4%. This study has shown that the frequency of Myocardial Infarction in Navarra is lower than that registered in many European and North American countries, and is concordant with the low rates of mortality due to this cause. Global analysis of the data shows that a high implementation of the care guidelines for this disease with respect to the use of efficient therapies could be observed in the years 1997 and 1998. Nonetheless, with the exception of the use of anticoagulants, hospital variability has been observed in the use of thrombolytic therapy and adjuvant therapies such as the beta-blockers or ACE Inhibitor, and in the use of diagnostic techniques such as arteriography.

Preparation of Ulex europaeus lectin-gliadin nanoparticle conjugates and their interaction with gastrointestinal mucus.

One approach to improve the bioavailability and efficiency of drugs consists of the association of a ligand (i.e. lectins), showing affinity for biological structures located on the mucosa surfaces, to nanoparticulate drug delivery systems. In this context, Ulex europaeus lectin-gliadin nanoparticle conjugates (UE-GNP) were prepared with the aim of evaluating their in vitro bioadhesive properties. The lectin was fixed by a covalent procedure to gliadin nanoparticles by a two-stage carbodiimide method. Typically, the amount of bound lectin was calculated to be approximately 15 microg lectin/mg nanoparticle, which represented a coupling efficiency of approximately 16% of the initial lectin concentration. In addition, the activity of these conjugates was tested with bovine submaxillary gland mucin (BSM) and the level of binding to this mucin was always much greater with UE-GNP than with controls (gliadin nanoparticles). However, the presence of 50 micromol fucose, which is the reported specific sugar for U. europaeus lectin, specifically inhibited the activity of these conjugates and, therefore, the UE-GNP binding to BSM was attenuated by 70%. These results clearly showed that the activity and specificity of U. europaeus lectin was preserved after covalent coupling to these biodegradable carriers.

Properties of glutaraldehyde cross-linked vicilin nano- and microparticles.

The influence of some selected factors on the properties of nano- and microparticles obtained from vicilin (storage protein from Pisum sativum L.) has been studied. These systems were prepared by coacervation followed by a cross-linking step with glutaraldehyde. Stabilized vicilin particles could be formed very rapidly after a short exposure to a low glutaraldehyde concentration. Nevertheless, particles increased in size with time of reaction and with an increase in glutaraldehyde concentration. On the other hand, the cross-linking process greatly influenced particle stability when incubated in the presence of trypsin. In this case, degradation followed a square-root-time relationship, suggesting enzymatic attack at the surface and in the interior of the matrix. The influence of the particle size on the tryptic degradation was also investigated and led to similar conclusions. Thus, microparticles showed a more rapid degradation than might be anticipated considering particle diameter alone.

Antioxidants in some pharmaceuticals, cosmetics and food from the European market.

A specific and sensitive reverse phase HPLC method (AO-1) for the quantitative determination of ten phenolic antioxidants and propyl paraben in fatty products (food, pharmaceuticals and cosmetics) has been developed. Extraction with acetonitrile from a hexane dilution of the products; acetic acid-water-acetonitrile-methanol solvent system and detection at 280 nm and quantification by internal standard procedure (reference compound: DMP, dimethylphenol) were used. Good resolutions for all peaks, especially BHT and DG, and no interferences with others common additives were achieved. Mean recoveries, by addition of standards to sample at 20, 50 and 100 micrograms/g, were 96-101% (BHT, 84-86%); minimal quantifiable levels were 0.5-1.6 micrograms/g. Two simple isocratic methods for the confirmation of data obtained by AO-1 were also developed: AO-2 for seven phenolic antioxidants and propyl paraben with DMP as internal standard, AO-3 for four lipophilic antioxidants with di-tert-butylphenol (DTBP) as internal standard.

[Melanotic medulloblastoma. Ultrastructural and histochemical study of a case]. / Meduloblastoma melanótico. Estudio ultraestructural e inmunohistoquímico de un caso.

A electron microscopic and immunohistochemical study of a Melanotic medulloblastoma is reported. The cerebellar tumor was located in the vermis of a 6-year-old boy, dead 11 months after diagnosis. The tumor consisted of medulloblastoma-like areas with focal differentiation and pseudoepithelial structures pigmented with melanin. Electron microscopy showed melanosomes and tight junctions in pigmented areas. On immunohistochemistry, the cytoplasm of melanotic cells were positive to S-100 protein and the differentiated glial cells to GFAP. The tumor histogenesis, its relationship with other pigmented tumors of the CNS and their low frequency is commented on.