Treatment with non-selective beta-blockers affects the systemic inflammatory response to bacterial DNA in patients with cirrhosis.

BACKGROUND & AIMS: The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating bacterial DNA. METHODS: Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites. Thirty of those patients were on beta-blockers. Blood samples were obtained after each patient had been in the supine position for at least 30 minutes in a quiet atmosphere. Bacterial DNA, serum cytokines, nitric oxide, and LPS were determined. Phagocytic and oxidative burst activities were determined in polymorphonuclear cells from the patients. RESULTS: The detection rate of bacterial DNA in the blood was the same (33%) for patients not treated and treated with non-selective beta-blockers. Patients naive to non-selective beta-blockers showed significantly higher serum levels of IL6, IFN-gamma and IL10 in response to the presence of bacterial DNA. Patients treated with non-selective beta-blockers showed higher basal inflammatory activity that did not change with the presence of bacterial DNA. Monocytes and granulocytes from patients treated with non-selective beta-blockers showed a significantly increased phagocytic capacity in the presence of bacterial DNA. CONCLUSIONS: In patients with cirrhosis, chronic treatment with beta-blockers is associated with a higher unstimulated production of serum cytokines and an increased phagocytic activity in the presence of bacterial DNA.

Reference ranges for serum and salivary testosterone in young men of Mediterranean region.

BACKGROUND AND AIMS: The interassay variability found in the measurement of testosterone (T) levels warrants the need for laboratories to validate their methods to establish trustworthy cut-off points for diagnosis of male hypogonadism. The aims of this study were to validate measurement of total T (TT) at our laboratory in order to obtain reference ranges for TT, calculated free T (CFT), calculated bioavailable T (CBT), and salivary T (ST) in healthy young men from the Mediterranean region, and to evaluate the potential clinical value of ST by establishing its correlation with serum T. METHODS: An observational, cross-sectional study with sequential sampling. INCLUSION CRITERIA: men aged 18-30 years with body mass index (BMI)<30. EXCLUSION CRITERIA: chronic diseases, hepatic insufficiency or use of drugs altering circulating T levels. Main outcome measures TT (chemiluminescent immunoassay UniCell DXI 800 [Access T Beckman Coulter]), CFT and CBT (Vermeulen's formula), and ST (radioimmunoassay for serum TT modified for saliva [Coat-A-Count, Siemens]). Descriptive statistical analyses and correlation by Spearman's rho (SPSS 19.0 Inc., Chicago) were used. RESULTS: One hundred and twenty-one subjects aged 24±3.6 years with BMI 24±2.5 kg/m(2) were enrolled. Hormone study: TT, 19±5.5 nmol/L (reference range [rr.] 9.7-33.3); CFT, 0.38 nmol/L (rr. 0.22-0.79); CBT, 9.7 nmol/L (rr. 4.9-19.2); and ST, 0.35 nmol/L (rr. 0.19-0.68). Correlation between ST and CFT was 0.46. CONCLUSIONS: In men from the Mediterranean region, values of TT>9.7 nmol/L, CFT>0.22 nmol/L, and/or CBT>4.9 nmol/L make the presence of biochemical hypogonadism unlikely. According to the correlation between serum and ST, the clinical value of ST remains to be established.

Pneumonia as comorbidity in chronic obstructive pulmonary disease (COPD). Differences between acute exacerbation of COPD and pneumonia in patients with COPD.

INTRODUCTION: Pneumonia is considered an independent entity in chronic obstructive pulmonary disease (COPD), to be distinguished from an infectious exacerbation of COPD. The aim of this study was to analyze the clinical characteristics and progress of the exacerbation of COPD (ECOPD) compared to pneumonia in COPD (PCOPD) patients requiring hospitalization. PATIENTS AND METHODS: Prospective, longitudinal, observational cohort study including 124 COPD patients requiring hospital admission for lower respiratory tract infection. Patients were categorized according to presence of ECOPD (n=104) or PCOPD (n=20), depending on presence of consolidation on X-ray. Demographic, clinical, laboratory, microbiological and progress variables were collected. RESULTS: Patients with ECOPD showed more severe respiratory disease according to the degree of obstruction (P<.01) and need for oxygen therapy (P<.05). PCOPD patients showed increased presence of fever (P<.05), lower blood pressure (P<.001), more laboratory abnormalities (P<.05; leukocytosis, elevated CRP, low serum albumin) and increased presence of crepitus (P<.01). Microbiological diagnosis was achieved in 30.8% of cases of ECOPD and 35% of PCOPD; sputum culture yielded the highest percentage of positive results, predominantly Pseudomonas aeruginosa. Regarding the progress of the episode, no differences were found in hospital stay, need for ICU or mechanical ventilation. CONCLUSIONS: Our data confirm clinical and analytical differences between ECOPD and PCOPD in patients who require hospital admission, while there were no differences in subsequent progress.

Identification of four novel mutations in the thyroid hormone receptor-ß gene in 164 Spanish and 2 Greek patients with resistance to thyroid hormone.

OBJECTIVE: The aim of the study was to describe the clinical, biochemical, and genetic features of a sample of Mediterranean patients with RTH (resistance to thyroid hormone) due to mutations in TRß (thyroid hormone receptor beta) referred to our institution during the last 15 years. DESIGN: 166 blood samples were received for RTH genetic testing between January 1997 and December 2011. Genetic testing was performed by PCR amplification followed by sequencing of exons 7, 8, 9, and 10. Clinical and biochemical features were obtained from available information sent by referring hospitals. RESULTS: Mutations were identified in 50 patients (29 probands and 21 relatives). 64% were women, and mean ± stdev age at diagnosis among probands was 33.2 ± 20.5 years. The following clinical features were recorded: goiter in 50%, hyperkinetic behavior in 32%, and tachycardia in 29%. Up to 19% of the probands had undergone some type of thyroidal ablative therapy before diagnosis. As for biochemical features, mean ± stdev TSH was 10.2 ± 21.4 mUI/L, and mean ± stdev fT4 was 35.5 ± 10.8 pmol/L. We found four new mutations: p.Phe451Leu, p.Pro452Arg, p.Glu457Gly, and p.Phe459Leu. CONCLUSIONS: The clinical and biochemical characteristics of our samples of Mediterranean populations with RTH were similar to those described in the published literature. Interestingly, in our populations we have identified four novel mutations in the TRß gene.

Circadian rhythm of salivary cortisol in Asian elephants (Elephas maximus): a factor to consider during welfare assessment.

Elevated glucocorticoid levels during an extended time period might be a stress indicator in nonhuman animals. Therefore, knowledge of the circadian pattern of cortisol secretion is very important to correctly interpret data obtained for welfare assessment of animals in captivity through salivary cortisol. In order to define the circadian rhythm of salivary cortisol secretion in the Asian elephant (Elephas maximus), morning and evening saliva samples of 3 Asian elephants were collected and analyzed by radioimmunoassay. Significantly higher salivary cortisol concentrations were found in the morning than in the evening in all individuals. These results show that salivary cortisol of Asian elephants follows a diurnal pattern of secretion, which could be taken into account when using this methodology to assess welfare in captive Asian elephants.

Microbiological study of patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and the usefulness of analytical and clinical parameters in its identification (VIRAE study).

PURPOSE: Respiratory infection is the most common cause for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The aim of this work was to study the etiology of the respiratory infection in order to assess the usefulness of the clinical and analytical parameters used for COPD identification. PATIENTS AND METHODS: We included 132 patients over a period of 2 years. The etiology of the respiratory infection was studied by conventional sputum, paired serology tests for atypical bacteria, and viral diagnostic techniques (immunochromatography, immunofluorescence, cell culture, and molecular biology techniques). We grouped the patients into four groups based on the pathogens isolated (bacterial versus. viral, known etiology versus unknown etiology) and compared the groups. RESULTS: A pathogen was identified in 48 patients. The pathogen was identified through sputum culture in 34 patients, seroconversion in three patients, and a positive result from viral techniques in 14 patients. No significant differences in identifying etiology were observed in the clinical and analytical parameters within the different groups. The most cost-effective tests were the sputum test and the polymerase chain reaction. CONCLUSION: Based on our experience, clinical and analytical parameters are not useful for the etiological identification of COPD exacerbations. Diagnosing COPD exacerbation is difficult, with the conventional sputum test for bacterial etiology and molecular biology techniques for viral etiology providing the most profitability. Further studies are necessary to identify respiratory syndromes or analytical parameters that can be used to identify the etiology of new AE-COPD cases without the laborious diagnostic techniques.

The determination of total testosterone and free testosterone (RIA) are not applicable to the evaluation of gonadal function in HIV-infected males.

INTRODUCTION: Hypogonadism is common in human immunodeficiency virus (HIV)-infected men; the high concentration of sex hormone binding globulin (SHBG) in this population, induces a "false increase" in total testosterone (TT) values. AIMS: To validate the determination of TT and measured free testosterone (FT [radioimmunoassay {RIA}]) for hypogonadism diagnosis in an HIV-infected population using calculated free testosterone (CFT) as reference method; and also to determine the prevalence and identify the risks factors of hypogonadism. METHODS: Cross-sectional, observational study. Ninety HIV-infected males (42 ± 8.2 years), not HCV coinfected, antiretroviral therapy (ART)-naive (14 patients), on current ART with enhanced protease inhibitor (PI) (39 patients), or patients on PI-naive ART (NN) (37 patients). MAIN OUTCOME MEASURES: CFT was calculated by determining TT, SHBG, and albumin (Vermeulen's formula); hypogonadism was defined as CFT <0.22 nmol/L (reference range for young healthy males in our laboratory); sensitivity of TT and FT (RIA) for hypogonadism diagnosis was calculated. RESULTS: Twelve patients (13.3%, 95% confidence interval [CI] 7.8-21.9) by CFT presented hypogonadism. TT and FT (RIA) presented a sensitivity of less than 30% in the diagnosis of hypogonadism. Logistic regression multivariate analysis confirmed an independent association between hypogonadism, the patient's age per decade, odds ratio (OR) 6.9 (CI 1.9-24.8; P = 0.003), and longer duration of HIV infection per decade, OR 13.1 (CI 1.3-130.6; P = 0.02). Hypogonadism was associated with erectile dysfunction. CONCLUSIONS: TT and FT (RIA) are not useful in the differential diagnosis of hypogonadism in HIV-infected males. There is a significant prevalence of hypogonadism in HIV-infected males, with the patient's age and duration of the disease being the only identifiable risk factors.

Algunos aspectos que el endocrinólogo debe conocer sobre los métodos de determinaciones hormonales / Hormone assays: some aspects that endocrinologists should know

Desde los trabajos pioneros de Yalow y Berson, que introdujeron el radioinmunoanálisis (RIA), los métodos de análisis de hormonas han evolucionado gradualmente con mejoras en todos los aspectos de su diseño, desde los análisis inmunorradiométricos a la automatización. Un ejemplo de esta evolución son los análisis de tirotropina y paratirina. A pesar de la gran precisión y la fiabilidad de los métodos hormonales utilizados en la actualidad, es importante revisar algunas limitaciones, como la interferencia por autoanticuerpos, anticuerpos heterofílicos o macroprolactina o el efecto gancho Objetivo: Conocer el proceso de adaptación a la diabetes mellitus tipo 1 (DM1) y analizar su correspondencia con las etapas del proceso de duelo descritas por Kübler-Ross. Sujetos y método: Estudio etnográfico mediante entrevistas en profundidad a 20 pacientes, 10 familiares y 12 profesionales (6 médicos y 6 enfermeras). Para el análisis se siguió el esquema de análisis de datos cualitativos de Miles y Huberman. Resultados: El paciente diagnosticado de DM1 y su familia afrontan la pérdida del estilo de vida y los objetos reales o imaginarios de su vida pasada. Enfermos y familiares experimentan reacciones emocionales que, en algún caso, pueden asemejarse a las etapas de duelo descritas por Kübler-Ross en una enfermedad terminal (negación, rebeldía, negociación, depresión y aceptación), pero hay diferencias que dependen de factores personales y psicosociales. Los profesionales tienden a relacionar la mala adherencia con la negación de la enfermedad, pero algunos pacientes se sienten amenazados por las exigencias de tratamiento y control y por sus consecuencias en su calidad de vida, y conscientemente optan por no seguir las recomendaciones. Es más realista hablar de adaptación a la enfermedad que de aceptación, puesto que los procesos de pérdida son constantes y el enfermo debe reconstruir nuevas identidades según su estado. El proceso de duelo afecta también a la familia y puede ser diferente que el del enfermo en tiempo, intensidad y valoración de los problemas. Conclusiones: La adaptación es un proceso complejo en el que intervienen muchas variables. Se observan diferencias en los mecanismos que utiliza cada sujeto en particular. Los profesionales sanitarios y, particularmente la enfermera, deben considerar las múltiples dimensiones psicosociales de la enfermedad crónica (AU)

Since the pioneering works of Yalow and Berson that introduced radioimmunoassays (RIA), hormone assays have been developed gradually, with improvements in all aspects of their design, from immunoradiometric assays to automatization. Examples of this evolution are the thyrotropin (TSH) and parathyroid (PTH) assays. Despite the strong accuracy and reliability of currently used hormone assays, some limitations should be reviewed, such as interference by autoantibodies, heterophile antibodies or macroprolactin and the hook effect (AU)

Hormone assays: some aspects that endocrinologists should know.

Since the pioneering works of Yalow and Berson that introduced radioimmunoassays (RIA), hormone assays have been developed gradually, with improvements in all aspects of their design, from immunoradiometric assays to automatization. Examples of this evolution are the thyrotropin (TSH) and parathyroid (PTH) assays. Despite the strong accuracy and reliability of currently used hormone assays, some limitations should be reviewed, such as interference by autoantibodies, heterophile antibodies or macroprolactin and the hook effect.

Diagnóstico bioquímico de la deficiencia de hormona de crecimiento / Biochemical diagnosis of growth hormone deficiency

El diagnóstico bioquímico de la deficiencia de hormona de crecimiento (GH) es un tema controvertido. Los avances tecnológicos no han contribuido a su esclarecimiento debido a muchos factores inherentes a la fisiología de la secreción de GH y a la falta de consenso en muchos aspectos metodológicos. Los resultados obtenidos con los distintos inmunoanálisis presentan una gran variabilidad por los distintos anticuerpos utilizados y los diferentes calibradores. A pesar de sus limitaciones, se sigue utilizando pruebas farmacológicas de estímulo. Sin embargo, no existe en la actualidad ninguna prueba bioquímica ni clínica definitiva para el diagnóstico del déficit de GH. El endocrinólogo debe conocer la especificidad y las limitaciones de los métodos de laboratorio. Los datos bioquímicos deben interpretarse en el contexto clínico y no deben ser utilizados como único criterio para establecer un diagnóstico (AU)

Biochemical diagnosis of growth hormone (GH) deficiency is controversial. Despite advances in assay design, many factors inherent to the physiology of GH secretion and the lack of consensus on methodological issues hamper resolution of these controversies. The results obtained with various assays show wide variability due to differences in the antibodies used and the distinct reference preparations employed for the calibration of assay kits. Despite its limitations, provocation testing continues to be performed. However, there is no definitive clinical or biochemical test for the diagnosis of GH deficiency. Endocrinologist should be familiar with the specificity and limitations of biochemical tests. Biochemical data should be interpreted in the clinical context and should not be the only criterion used to establish the diagnosis (AU)

[Hypoglycemia insulin test in the assessment of the hypothalamic-pituitary-adrenal function]. / Prueba de hipoglucemia insulínica en la exploración del eje hipotálamo-hipófisis-suprarrenal.

BACKGROUND: Recent advances in sensitivity and specificity of hormone immunoanalysis and their automatization have brought about changes in clinical laboratories that led us to review the need for some endocrine dynamic tests. The specific aim of this study was to determine the basal cortisol values predicting a normal or impaired response to the insulin hypoglycemia test (ITT). SUBJECTS AND METHOD: We retrospectively analysed cortisol responses to ITT in 320 subjects. Moreover, we studied the impact the use of a new strategy has on economic cost, by means of a relative value unit (RVU) calculation. RESULTS: No patient with a basal cortisol < 6 g/dl (13%) responded to the test whereas all those with a basal cortisol > 18 g/dl responded in full. The rest of patients exhibited a basal cortisol level between 6-18 g/dl, 39% of them responding and 16% showing an inadequate response. Baseline and peak cortisol concentrations were strongly correlated (r = 0.74; p < 0.0001). The cost of ITT was 131.6 RVU as compared to 17.8 RVU for cortisol. CONCLUSIONS: Basal cortisol levels below 6 g/dl or above 18 g/dl make the test unnecessary. Cortisol measurement by automated methods, along with subsequent reduced assay times, allows us to apply new diagnosis strategies. Considering that the cost of ITT is 15 fold higher than that of single cortisol measurement, the potentially generated saving is significant.

Prueba de hipoglucemia insulínica en la exploración del eje hipotálamo-hipófisis-suprarrenal / Hypoglycemia insulin test in the assessment of the hypothalamic-pituitary-adrenal function

FUNDAMENTO: Los recientes avances en la sensibilidad y especificidad de los inmunoanálisis hormonales y su progresiva automatización han introducido cambios en los laboratorios clínicos que obligan a replantear la necesidad de algunas pruebas funcionales endocrinas. El objetivo de este trabajo es determinar las concentraciones basales de cortisol que predicen una respuesta normal o patológica a la prueba de hipoglucemia insulínica (ITT).SUJETOS Y MÉTODO: En un estudio retrospectivo hemos analizado la respuesta de cortisol a la ITT en 320 pacientes. Asimismo se ha analizado, mediante cálculo de unidades relativas de valor (URV), el impacto en el coste económico del uso de una nueva estrategia. RESULTADOS: Ningún paciente con cortisol basal inferior a 6 µg/dl (13 por ciento) respondió a la prueba y aquellos con un cortisol basal mayor de 18 µg/dl respondieron en su totalidad (30 por ciento). Los restantes pacientes presentaron cortisol basal entre 6-18 µg/dl, de ellos el 39 por ciento respondió y el 16 por ciento no lo hizo. Se observó una buena correlación entre el cortisol basal y el pico de respuesta (r = 0,74; p < 0,0001). El coste de una ITT es de 131,6 URV frente a 17,8 URV del de cortisol. CONCLUSIONES: Las concentraciones de cortisol basal inferiores a 6 µg/dl o superiores a 18 µg/dl hacen innecesaria la prueba de hipoglucemia insulínica. La medida de cortisol mediante métodos automatizados, con la consiguiente disminución del tiempo de respuesta, permite aplicar nuevas estrategias diagnósticas. Considerando que el coste económico de una ITT es 15 veces superior al de una determinación de cortisol, el ahorro que se puede generar es elevado. (AU)