Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers.

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidence of its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. This article discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapy products is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating the information given for a specific product, it is necessary to take into account further inherent characteristics of products and their application in clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/ subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data can serve as the basis for product-specific evaluation and cross-product comparability of individual products.

Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic.At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidenceof its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However,several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures acrossmanufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. Thisarticle discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison ofproducts from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapyproducts is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes,allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that thecomparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating theinformation given for a specific product, it is necessary to take into account further inherent characteristics of products and their applicationin clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data canserve as the basis for product-specific evaluation and cross-product comparability of individual products. (AU)

La prevalencia de las enfermedades alérgicas se ha incrementado drásticamente en los últimos 50 años y hoy pueden considerarse unaepidemia. Actualmente, la inmunoterapia específica con alérgenos (ITA) es el único tratamiento dirigido a la causa subyacente de lasenfermedades alérgicas y su superioridad se basa en resultados de ensayos clínicos/estudios observacionales que demuestran su eficaciay seguridad. Pero quedan aspectos sin resolver, como la armonización y estandarización de los procesos de fabricación y cuantificaciónentre fabricantes, la declaración homogénea de la potencia y el establecimiento de estándares internacionales de referencia. En este artículo se discuten aspectos relacionados con la medida del contenido de alérgenos mayores en los extractos de ITA, cuestionandosi, como base para elegir entre productos, es apropiada la comparación entre diferentes fabricantes. La estandarización alergénica escrucial para asegurar la calidad y, por tanto, la seguridad y eficacia de la ITA. Sin embargo, la falta de armonización en los procesos defabricación, la cuantificación alergénica, las diferencias regulatorias, la práctica clínica y el etiquetado, demuestran que comparar productosbasándose únicamente en la cantidad de alérgeno mayor no está justificado y es imposible. Además, cuando se evalúa la informaciónpara un determinado producto, deben tenerse en cuenta las características propias de cada producto y su uso clínico, como el estado dela modificación del extracto, la adición de adyuvantes, la vía de administración y la dosis acumulada. Solo datos clínicos convincentesdeben servir para la evaluación específica de cada producto o como base para la comparación entre productos. (AU)

[Peritoneal equilibrium test using icodextrin and glucose at different concentrations]. / Test de equilibrio peritoneal con icodextrina y glucosa a distintas concentraciones.

UNLABELLED: The aim of this study was to compare, under standard conditions (Peritoneal Equilibrium Test, "PET"), the peritoneal permeability to water and several solutes using icodextrin and glucose (3.86% and 1.36%) dialysates. The study includes 14 patients (3 women and 11 men), mean age 64 +/- 13 years, average time on peritoneal dialysis 23.5 +/- 17 months. PETs with icodextrin were performed in all of them (n = 14); PETs with 3.86% glucose were carried out in 7, and PETs with all the three solutions were performed in 5 patients. Samples were taken at 0, 30, 60, 120, 240 minutes, and after the rinsing procedure using 1.36% glucose in order to calculate the residual volume. RESULTS: Sodium concentration in the effluent and D/P sodium did not change significantly from minute 0 to 240 with icodextrin and 1.36% glucose; but with 3.86% glucose both sodium and D/P sodium decreased at thirty minutes, remained at the same levels till the 120 minutes and then had a tendency to increase. Glucose concentration and osmolarity in the effluent did not vary throughout the time with icodextrin, but progressively decreased during the 4-hour period with 3.86% and 1.36% glucose solutions. The drainage after the 4-hour period was higher for the 3.86% glucose (2,608 +/- 388 ml, p = 0.03) than for the 1.36% glucose (2,070 +/- 120 ml) or the icodextrin (2,212 +/- 213 ml). Low molecular weight permeability: D/P creatinine after the 4-hour dwell was significantly lower for the icodextrin (0.66 +/- 0.1, p = 0.05) than for the 3.86% glucose (0.71 +/- 0.1) or the 1.36% glucose (0.72 +/- 0.1). The creatinine clearance for 3.86% glucose (7.4 +/- 0.4 ml/min p = 0.007) was higher than for icodextrin (5.6 +/- 0.5 ml/min) or for 1.36% glucose (5.8 +/- 0.6 ml/min). The clearances for total protein, albumin and beta 2-microglobulin did not show significant differences between the solutions. CONCLUSIONS: Our study confirms that the icodextrin solution remains iso-osmolar with plasma during the 4-hour dwell. The sodium profile suggests that the ultrafiltration induced by icodextrin and 1.36% glucose depends on small pore-mediated sodium and water transport; on the other hand, 3.86% glucose also induces transport of water without solutes throughout the ultra-small aquaporin-mediated, pores, producing sodium dilution in the effluent. Ultrafiltration and solute clearances for icodextrin are lower than for 3.86 glucose during a 4-hour dwell.

Hipercalcemia hipocalciúrica familiar: a veces no es lo que parece / Familial hypocalciuric hypercalcemia: sometimes it is not what it seems

La hipercalcemia hipocalciúrica familiar (HHF) constituye una causa poco común de hipercalcemia. Su prevalencia se estima que es de 1:78.000 personas. Mostramos un caso con presentación atípica con confirmación mediante diagnóstico genético. Se trata de una mujer de 74 años con osteoporosis remitida al servicio de Endocrinología por sospecha de hiperparatiroidismo primario (HPTP). Presentaba una hormona paratiroidea (PTH) elevada (96,3 pg/ml-límites normales (LN): 15-65 pg/ml) con niveles de calcio, fósforo y magnesio normales, además de una calciuria elevada. Posteriormente presentó cifras de PTH normales, niveles de calcio elevados junto con calciurias normales-elevadas. El cociente aclaramiento de calcio/aclaramiento de creatinina (CCCR, en mmol/l) osciló entre 0,011-0,02 mmol/l. El CCCR < 0,01 es sugestivo de HHF, y el CCCR > 0,02 de HPTP; este cociente se ve limitado en el rango entre 0,01-0,02 mmol/l, motivo por el que se justifica solicitar la prueba genética en todos los pacientes con PTH normales o alt as, hipercalcemia y CCCR < 0,02, requisitos que cumplía nuestro caso índice (AU)

Familial hypocalciuric hypercalcemia (FHH) is an uncommon cause of hypercalcemia. Its prevalence is estimated to be 1:78,000 people. We describe a case with atypical presentation confirmed by genetic diagnosis. This is a case of a woman of 74 years of age with osteoporosis referred to the endocrinology service with suspected primary hyperparathyroidism (HPTP). She presented with a high level of parathyroid hormone (96.3 pg/ml, normal limits (NL): 15-65 pg/ml), with normal levels of calcium, phosphorus and magnesium, as well as a raised level of calciuria. She subsequently presented with normal levels of PTH, raised levels of calcium, combined with normal -high calciuria. The calcium/creatinine clearance ratio (CCCR, in mmol/l) varied between 0.011 and 0.02 mmol/l. A CCCR < 0.01 is suggestive of FHH, and a CCCR > 0.02, of HPTP. This ratio is within the range between 0.01 and 0.02 mmol/l, a reason which justifies requesting a genetic test in all patients with normal or high PTH, hypercalcemia and CCCR < 0.02, requirements which our index case meets (AU)

Síndrome de Cushing y necrosis avascular de cadera: presentación de 2 enfermos / Cushing's syndrome and avascular hip necrosis: presentation of two patients

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Test de equilibrio peritoneal con icodextrina y glucosa a distintas concentraciones / Peritoneal equilibrium test with icodextrin and glucose dialysates

El propósito de este trabajo ha sido comparar en condiciones estándar (test de equilibrio peritoneal) la permeabilidad para el agua y distintos solutos usando soluciones de Icodextrina y glucosa a las concentraciones de 3,86 por ciento y 1,36 por ciento. La muestra estaba formada por 14 pacientes (3 mujeres/11 hombres), edad 64 ñ 13 años, tiempo en diálisis peritoneal 23,5 ñ 17 meses. A los 14 pacientes se les realizó test de equilibrio peritoneal con Icodextrina, a 7 de estos también con 3,86 por ciento y a 5 de ellos el estudio completo con las tres soluciones. Se tomaron muestras en los minutos 0, 30, 60, 120, 240 y tras infusión de lavado de glucosa 1,36 por ciento para medir el volumen residual. Resultados: Tanto la concentración de Na como la relación D/P Na no varían desde el minuto 0 al 240 para la Icodextrina y glucosa 1,36 por ciento. Con la glucosa 3,86 por ciento bajan ya a los 30 minutos y permanece así hasta el minuto 120 que tiende a subir de nuevo. La glucosa y osmolaridad se mantienen a niveles similares al inicial con Icodextrina (y similares al plasma); en contraste, con ambas soluciones de glucosa va disminuyendo a lo largo de las 4 horas. El volumen de drenaje a las 4 horas fue superior (p = 0,03) con 3,86 por ciento (2.608 ñ 338 cc) al obtenido con 1,36 por ciento (2.070 ñ 120 cc) y con Icodextrina (2.212 ñ 213 cc). Referente a la permeabilidad para solutos de bajo peso molecular: D/P 4.ªh Cr inferior con Icodextrina (0,66 ñ 0,1 versus 0,71 ñ 0,1 (3,86 por ciento) versus 0,72 ñ 0,1 (1,36 por ciento) p = 0,05; ClCr superior con 3,86 por ciento (7,4 ñ 0,4 cc/m p = 0,007) en comparación con Icodextrina (5,6 ñ 0,5 cc/m) y con 1,36 por ciento (5,8 ñ 0,6 cc/m). Los aclaramientos de proteínas totales, albúmina y B2 microglobulina no mostraron diferencias. Conclusiones: Nuestro estudio confirma que la solución de Icodextrina es y permanece isoosmolar con el plasma a lo largo de un intercambio de 4 horas. El perfil de Na sugiere que la Icodextrina actúa a través del poro pequeño, con paso simultáneo de agua y Na, igual que la solución de glucosa 1,36 por ciento y distinta de la glucosa 3,86 por ciento que, al producir el transporte de agua sin solutos, diluye la concentración de Na del líquido de diálisis en las primeras dos horas. El aclaramiento de solutos y la UF con Icodextrina son inferiores a los obtenidos con glucosa 3,86 por ciento en un intercambio de 4 horas (AU)