Gamma heavy-chain disease accompanied with follicular lymphoma: a case report

Heavy chain diseases (HCD) are B-cell lymphoprolipherative disorders characterized by the production of monoclonal heavy chains without associated light chains. Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm. The monoclonal component is not always detectable by serum electrophoresis, and often an immunofixation procedure is necessary to detect this component. Prognosis is variable, and no established guidelines for follow-up are available. We describe a case of a challenging diagnosis of γ-HCD due to the absence of clinical signs frequently reported in the disease (anaemia and palatal oedema among others). Haematological malignancy was the first suspicion but bone marrow examination was negative. In addition, the presence of an autoimmune bicytopenia and a Klinefelter syndrome complicated the clinical context of the patient. A thoracoabdominal computed tomography reported many small adenopathies whose pathological and immunohystochemical study revealed a follicular lymphoma. Shortly after, serum inmunofixation secondary to an abnormal electrophoretic pattern revealed a gamma paraprotein without light chains. Eventually, γ-HCD in association with follicular lymphoma was the final diagnosis. This is the first case reporting this association

Description of interference in the measurement of troponin T by a high-sensitivity method

Introduction: Measurement of high-sensitivity troponin T (hs-TnT) has become an essential step in the diagnosis of acute myocardial infarction. This high-sensitivity method allows quantifying the concentration of troponin T in blood of healthy subjects with a lower inaccuracy compared to previous reagent generations. However, the presence of certain compounds in the sample may interfere with the result. We present a patient who had repeatedly high concentrations of hs-TnT in the serum sample that did not agreed with the signs and symptoms. In addition, ultrasensitive troponin I concentration was undetectable. Materials and methods: To investigate the presence of an interfering compound, different analysis were carried out. In order to discard macro complexes in the sample, the serum was precipitated with polyethylene glycol. In addition, the serum was incubated with Scantibodies Heterophilic Blocking Tube, which can block heterophilic antibodies. Finally, a size exclusion chromatography of the sample was performed by the manufacturer. What happened: The interfering substance was allocated into fractions with proteins of 150kDa, corresponding to high molecular weight proteins like immunoglobulin G (IgG). This compound was responsible for the falsely elevated hs-TnT results and it affected only the high-sensitivity methods. Main lesson: The detected interfering compound was probably an IgG. This type of interference must be kept in mind in front of discordant results, even if they are extremely rare. Therefore, interdisciplinary cooperation between clinicians, laboratory and manufacturer is essential

Glucagon stimulation test to assess growth hormone status in Prader-Willi syndrome

Growth hormone deficiency (GHD) must be confirmed before starting treatment in adults with Prader-Willi syndrome (PWS). Most studies use the growth-hormone-releasing hormone plus arginine (GHRH-arginine) test. No data are available on the glucagon stimulation test (GST) in PWS. We compared the utility of fixed-dose (1 mg) GST versus GHRH-arginine test in diagnosing GHD. Adults and late adolescents with PWS underwent both tests on separate days. In the GHRH-arginine test, GHD was defined according to body mass index. In the GST, two cutoffs were analyzed: peak GH concentration 90 kg). We analyzed 34 patients: 22 weighing ≤ 90 kg and 12 weighing > 90 kg. In patients weighing ≤ 90 kg, the two tests were concordant in 16 (72.72%) patients (k = 0.476, p = 0.009 with GST cutoff 90 kg, the two tests were not concordant with GST cutoff 90 kg, the < 1 ng/mL cutoff seems better. Larger studies are necessary to establish definitive glucagon doses and cutoffs, especially in extremely obese patients

Gamma heavy-chain disease accompanied with follicular lymphoma : a case report

Heavy chain diseases (HCD) are B-cell lymphoprolipherative disorders characterized by the production of monoclonal heavy chains without associated light chains. Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm. The monoclonal component is not always detectable by serum electrophoresis, and often an immunofixation procedure is necessary to detect this component. Prognosis is variable, and no established guidelines for follow-up are available. We describe a case of a challenging diagnosis of γ-HCD due to the absence of clinical signs frequently reported in the disease (anaemia and palatal oedema among others). Haematological malignancy was the first suspicion but bone marrow examination was negative. In addition, the presence of an autoimmune bicytopenia and a Klinefelter syndrome complicated the clinical context of the patient. A thoracoabdominal computed tomography reported many small adenopathies whose pathological and immunohystochemical study revealed a follicular lymphoma. Shortly after, serum inmunofixation secondary to an abnormal electrophoretic pattern revealed a gamma paraprotein without light chains. Eventually, γ-HCD in association with follicular lymphoma was the final diagnosis. This is the first case reporting this association

El Flamenco. Baile, Música y Lírica. Precedentes histórico-culturales y primer desarrollo histórico (1780-1890)

Estudio de los precedentes y primer desarrollo histórico del Flamenco que aúna investigación y divulgación. Coordinado por Miguel Ángel Berlanga, del Departamento de Hª y Ciencias de la Música de la Universidad de Granada, quien es autor del capítulo dedicado al baile. Participan Norberto Torres (la guitarra flamenca y preflamenca), Ramón Soler (lírica flamenca y preflamenca), Guillermo Castro (música flamenca y preflamenca) y Eugenio Cobo (el flamenco en la literatura). Prólogo de Cristina Cruces Roldán (Universidad de Sevilla).Study of the precedents and first historical development of Flamenco. It combines research and divulgation. Coordinated by Miguel Ángel Berlanga, from the Department of Musicology, University of Granada, who is also the author of the chapter dedicated to flamenco and pre-flamenco dance. With the participation of Norberto Torres (flamenco and pre-flamenco guitar), Ramón Soler (flamenco and pre-flamenco lyrics), Guillermo Castro (flamenco and pre-flamenco music) and Eugenio Cobo (flamenco in literature). Foreword by Cristina Cruces Roldán (University of Seville).Fundación UNICAJA / Colaboración de Asociación Amigos del Flamenco de Extremadura - Unión Cultural y Centro de Documentación, Cácere

Usefulness of salivary cortisol as a marker of secondary adrenal insufficiency in paediatric patients

Background: The main cause of adrenal insufficiency (AI) in paediatric patients is prolonged treatment with corticosteroids. Determination of plasma cortisol (PC) during ACTH test is the most used adrenal function indicator in clinical practice. However, determination of salivary cortisol (SC), a simple test especially useful in children in order to avoid invasive procedures, can be used as an alternative technique for the diagnosis of adrenal disease. Methods: A two-year prospective study (January 2014-January 2016) in paediatric patients (2-18 years of age) treated with corticosteroids for more than fifteen days, who were investigated for suspected AI. Low-dose ACTH test was used to determine adrenal function and samples for SC and PC were obtained simultaneously in basal situation and during the test (at 30, 60 and 90 minutes). Results: 230 samples (118 PC-112 SC) of 30 studies belonging to 20 patients (4 males), mean age 10.93 years &plusmn; 3.69 SD. Pearson&rsquo;s correlation coefficient showed a positive correlation between PC and SC (r = 0.618, p &lt; 0.001). All the studies with some determination of PC higher than 18 &mu;g/dL (n = 8) had a SC peak higher than 0.61 &mu;g/dL with a specificity of 66.67% and a sensitivity of 93.94% (ROC analysis). Conclusion: Measurement of SC is a less invasive, easier and quicker test than PC to measure plasma free cortisol levels. In our study, a SC peak in low-dose ACTH test higher than 0.61 &mu;g/dL was able to discriminate patients without AI, and proved to be a useful tool in the initial evaluation of children with suspected AI.Introduction The activation of the hypothalamic-pituitary-adrenal axis in response to critical illness and the resulting release of cortisol from the adrenal cortex are essential to stress adaptation. Adrenal insufficiency (AI) is described as the inability of adrenal glands to produce an appropriate hormonal secretion not only under stress but also in basal situation. Therefore, a low baseline plasma cortisol (PC) (&lt; 5 &mu;g/dL) and a poor cortisol response to stimulation with exogenous adrenocorticotropic hormone (peak &lt; 18 &mu;g/dL) are some of the defining criteria of this condition [1,2]. It is well known that the main cause of AI in paediatric patients is prolonged treatment with exogenous corticosteroids, which is an iatrogenic cause derived from the increasing complexity of paediatric pathologies and the increased use of prolonged high-dose corticosteroid therapy. In clinical practice, adrenal function is usually assessed by the total PC (determined by low-dose ACTH test). This implies the placement of a vascular access which is often a traumatic experience for children. PC includes protein-bound fraction and serum-free cortisol. The latter constitutes the biologically active form of the hormone and is responsible for glucocorticoid activity on peripheral organs. Most of the circulating cortisol is bound to plasma proteins (over 90%), such as cortisol-binding globulin (CBG) and albumin, whereas only about 10% of circulating cortisol is free. Hence, the measurement of plasma-free cortisol level has been considered more representative of adrenal function (especially in critically ill adults and children) [1,2], because some conditions, such as hypoalbuminaemia or hypoproteinaemia (frequent in critically ill patients or in patients with cirrhosis), may lead to misinterpretation of adrenal function with an overestimation of the prevalence of AI. But the direct measurement of free PC is a laboratory-dependent and time-consuming procedure that is not available for routine use. Salivary cortisol (SC) is one of the several indirect methods available to determine free PC [3], as SC levels accurately reflect free PC [4] even in cases of hypoalbuminaemia or CBG abnormality [1,5]. For this reason, in the last years, this technique (SC) has been introduced as a non-invasive tool in the diagnosis of adrenal cortical disorders, for its simplicity and applicability in the paediatric population. However, few studies to date have evaluated the usefulness of SC as a diagnostic method in children with AI. No interactions between exogenous corticoids and SC have been described [6]. The aim of the present study was to assess the usefulness of determining salivary cortisol levels as a diagnostic tool in children with suspected secondary iatrogenic AI.&nbsp

Experiencia en la evaluación de tutores de especialistas en formación

Introducción: Exponemos nuestra experiencia en la evaluación de tutores ligada a una pauta para incentivar la acción tutorial en el programa de formación de especialistas MIR y FIR. Material y Métodos: Se han diseñado dos cuestionarios de evaluación, uno para el jefe de la unidad docente y otro para la comisión de docencia, la suma de los resultados obtenidos en cada uno de ellos sirve para calcular el porcentaje global de objetivos alcanzado. Los cuestionarios se han aplicado a 38 tutores, anualmente, en los años 2000, 2001 y 2002. Se han utilizado las pruebas de Wilcoxon y de Spearman, aplicando la corrección de Bonferroni, para valorar las diferencias interanuales y la correlación intraanual de los resultados. Resultados: Los tutores han obtenido un porcentaje medio de objetivos del 92,6% en 2000, del 89,1% en 2001 y del 89,9% en 2002. El cuestionario evaluado por la comisión de docencia no muestra diferencias interanuales, mientras que el valorado por los jefes de unidad muestra diferencias entre los años 2000 y 2002 (P<0,01). Las evaluaciones de los jefes de unidad y de la comisión de docencia no mostraron correlación significativa. Discusión: La evaluación, dentro del sistema de formación MIR, es uno de los campos en los que se debe seguir avanzando. Evaluar y reconocer la labor tutorial puede ser un mecanismo de gran utilidad para mejorar el sistema de formación especializada. De acuerdo con la metodología utilizada, los resultados de nuestro estudio muestran que los tutores cumplen sus funciones adecuadamente. La herramienta evaluadora que se ha utilizado posee suficiente estabilidad en los resultados y poder de discriminación, durante el periodo estudiado

Impact of a Novel Strategy for Critical Values Communication for the Management of Patients Treated with Clozapine

Clozapine is an antipsychotic drug used to treat resistant schizophrenia and other disorders. Based on the actual Spanish legislation, patients treated with clozapine must undergo periodical haematological examinations and treatment should be reviewed when the haemogram shows either a leukocyte count of ≤ 3500/mm 3 or neutrophil count < 2000/mm 3. An automatic notification system has been developed to optimize patient management and it's utility was assessed following the implementation of the new system. When clozapine (CLO) laboratory test request was made, a reflex complete blood count test was also done. An automatic e-mail was sent by the laboratory information system to the physician when a CLO was ordered and low leukocyte or neutrophil counts were detected, or when a patient with an ordered CLO test did not attend the laboratory for blood drawing. For patients with haemogram alterations, the time to take clinical action was significantly decreased from 23 to 7 days (p = 0.02). Moreover, the adherence to Spanish Agency of Drugs and Sanitary Devices recommendations significantly increased from 45% to 76% (p = 0.02). For not attending patients, the days out of control decreased from 29 to 12 days, although it was not statistically significant (p = 0.06). This strategy has allowed the compliance of legal requirements, the improvement of patient safety, and the optimisation of clinical and laboratory procedure

Arterial stiffness in type 1 diabetes: the case for the arterial wall itself as a target organ

Arterial stiffness (AS) integrates the cumulative burden of known and unknown cardiovascular risk factors on the elastic wall of large arteries along the lifespan of an individual. As a marker of vascular aging, AS is an independent predictor of cardiovascular events and improves cardiovascular risk prediction when added to the Framingham Risk Score. In addition, AS may affect the microvasculature and promote the development of microvascular complications. Its impact on both the macro- and microvasculature has led to the concept that the arterial wall itself should be considered as a target organ. Here, we review the biological and clinical consequences of AS on the macro- and microvasculature and the measurement of AS in routine clinical practice. We also discuss the pathophysiological mechanisms underpinning AS development using diabetes and, in particular, type 1 diabetes, as a disease model with a high risk of cardiovascular events and microvascular complications that are accelerated by AS