Familial hypobetalipoproteinemia: analysis of three Spanish cases with two new mutations in the APOB gene.

Extremely low LDL-cholesterol concentrations are very unusual and generally related with comorbidities accompanying malnutrition. Less frequently low LDL-cholesterol levels result from mutations in the APOB, PCSK9, ANGPTL3, SAR1B and MTTP genes (primary hypobetalipoproteinemia). We investigated three patients with plasma LDL-cholesterol levels below the fifth percentile of the Spanish population. We recorded data on demographic and anthropometric characteristics, life style habits, physical examination, liver ultrasound and lipid and lipoprotein levels, in the probands and their first-degree relatives. Secondary causes of hypocholesterolemia were ruled out by clinical study, complementary tests and follow-up. The APOB, MTTP and SAR1B genes were sequenced. Patients were found to be heterozygotes for point mutations located in the exon 26 of the APOB gene. One patient, with fatty liver, carried a previously described mutation (c.7600C>T) (Arg2507X), causing the formation of truncated Apo B-55.25. The other two mutations producing truncations are new. One asymptomatic patient carried the Arg3672X (Apo B-80.93) and the other with fatty liver and steatorrhea carried the Ser2184fsVal2193X (Apo B-48.32). Our study reinforces the concept that in the heterozygous carriers of truncated Apo Bs, the clinical manifestations of FHBL are dependent on the size of the truncations.

Clinical utility of a combination of tumour markers in the diagnosis of malignant pleural effusions.

BACKGROUND: The aim of the present study was to evaluate the diagnostic value of the tumour markers carcinoembryonic antigen (CEA), carbohydrate antigens CA 125, CA 15.3, CA 19.9 and tumor-associated glycoprotein 72 (TAG 72) in the pleural fluid (PF) of patients with pleural effusions of different etiologies. PATIENTS AND METHODS: One hundred and fifty-five patients with pleural effusions (40 malignant, 84 benign and 31 paraneoplastic) were studied prospectively. The concentration of the tumour markers in serum and PF were measured by magnetic particle enzyme immunoassay. The PF to serum (PF/S) concentration ratios were calculated. RESULTS: The concentrations of CEA, CA 15.3, CA 19.9 and TAG 72 in PF and the PF/serum ratios were significantly higher in effusions of malignant and paraneoplastic origin than in those of benign origin. The receiver operating characteristic (ROC) curves were calculated for each marker and the diagnostic cut-off point was selected as the value that offered a specificity of 100% (CEA: 6.5 ng/ml; CA 15.3:62.4 IU/l; TAG 72:10.9 IU/l). CEA presented the greatest sensitivity [45% in the malignant group, 38.7% in the paraneoplastic group, and 41.4% in the pooled group (combined malignant and paraneoplastic)]. TAG 72 presented the largest area under the curve (0.89 in the malignant group and 0.80 in the pooled group). The diagnostic efficacy of the PF/S ratios was not better than measurement of the tumour markers in pleural fluid. The highest diagnostic accuracy for the diagnosis of malignant pleural effusions was achieved by grouping the markers in a panel comprising CEA, CA 15.3 and TAG 72; this showed a sensitivity of 75% and a negative predictive value of 79.1% . In the subgroup of patients with negative cytology, the sensitivity was 41.2% for CEA, 35.5% for CA 15.3 and 33.3% for TAG 72. The combination of these three markers achieved a sensitivity of 84.6%. CONCLUSION: The combined measurement of CEA, CA 15.3 and TAG 72 in pleural fluid is a useful complementary test in the differential diagnosis of pleural effusions of malignant origin.

Phosphocalcic metabolism after biliopancreatic diversion.

BACKGROUND: Malabsorptive techniques to treat morbid obesity have been followed by alterations in phosphocalcic metabolism. Knowledge of the preoperative situation is important to assess the influence of these techniques on phosphocalcic metabolism and to consider treatments for these alterations. METHODS: 61 consecutive morbidly obese patients (50 women, 11 men, age 19 to 63 years) having had biliopancreatic diversion (BPD) were studied in a prospective manner. Preoperative and postoperative levels of calcium, phosphorus, 25-hydroxyvitamin D, tartrate resistant acid phosphate, plasma parathormone (PTH), tubular absorption of phosphate, and urinary calcium and pyridinolines were analyzed, as well as the potential risk factors for their alterations. Follow-up of all patients was a minimum of 4 years. RESULTS: Before BPD, 42.3% of patients presented an increase in PTH and 54% a decrease in the 25-OH vitamin D, but the values of calcium and plasma phosphorus maintained at normal level. 81.8% of the patients with an increase in the PTH maintained high levels after BPD, while 60% of those with a normal preoperative PTH also presented hyperparathyroidism 4 years after the intervention. A correlation between the levels of plasma PTH and body mass index was not found. CONCLUSION: Morbid obesity is accompanied by a high percentage of hyperparathyroidism. BPD produces malabsorption of vitamin D during the first years, favoring the persistence or appearance of hyperparathyroidism. It is important to recognize and treat the secondary hyperparathyroidism. The postoperative period could necessitate more energetic interventions to get more efficient control of the phosphocalcic metabolism.

[Diagnostic efficacy of fine needle aspiration biopsy in patients with thyroid nodular disease. Analysis of 510 cases]. / Eficacia diagnóstica de la punción-aspiración con aguja fina en pacientes con patología nodular tiroidea. Análisis de 510 casos.

INTRODUCTION: The prevalence of palpable thyroid nodules in the general population is 4%-7%. Although most are benign, 5% are carcinomas. This study aimed to assess the efficacy of fine needle aspiration biopsy (FNAB) of thyroid nodules to diagnose malignancy and know the benefit of repeating the FNAB in the same nodule. PATIENTS AND METHODS: A total of 510 patients (431 women and 79 men; mean age [standard deviation]: 47.6 [14.3] years) with surgery due to thyroid nodular condition between 1989 and 2002 and who had at least one FNAB prior to the surgery were studied. RESULTS: The first FNAB was benign in 312 patients (61.2%), malignant in 38 (7.5%), suspicious or indeterminate in 97 (19%) and insufficient in 63 (12.4%). Sensitivity and specificity in the first FNAB for malignancy diagnosis was 76% and 84%, respectively. Successive FNABs had a moderate concordance and significance. However, repeating the puncture did not improve diagnostic performance, since sensitive increased (84%), but specificity worsened (79%) and the area under the ROC curve was similar. In the group with suspicious or indeterminate FNAB, histology was benign in 70% and malignant in 30%. CONCLUSIONS: FNAB sensitivity and specificity for diagnosis of malignancy in thyroid nodules are high. Repetition of puncture on the same nodule does not improve diagnostic performance of the cytology. Among patients with suspicious FNAB, there is a high proportion of malignancy, which makes surgery necessary in these cases.

Eficacia diagnóstica de la punción-aspiración con aguja fina en pacientes con patología nodular tiroidea. Análisis de 510 casos / Diagnostic efficacy of fine needle aspiration biopsy in patients with thyroid nodular disease. Analysis of 510 cases

Introducción. La prevalencia de nódulos tiroideos palpables en la población general es del 4%-7%. Aunque la mayoría son benignos, un 5% son carcinomas. El objetivo de este estudio fue valorar la eficacia de la punción-aspiración con aguja fina (PAAF) de los nódulos tiroideos para diagnosticar malignidad y conocer el rendimiento de repetir la PAAF en el mismo nódulo. Pacientes y métodos. Se estudiaron 510 pacientes (431 mujeres y 79 varones; edad media [desviación estándar]: 47,6 [14,3] años) intervenidos quirúrgicamente por patología nodular tiroidea entre 1989 y 2002 y que tenían, al menos, una PAAF previa a la cirugía. Resultados. La primera PAAF fue benigna en 312 pacientes (61,2%), maligna en 38 (7,5%), sospechosa o indeterminada en 97 (19%) e insuficiente en 63 (12,4%). La sensibilidad y especificidad de la primera PAAF para el diagnóstico de malignidad fue del 76% y 84%, respectivamente. Las PAAF sucesivas tuvieron una concordancia moderada y significativa; sin embargo, la repetición de la punción no mejoró el rendimiento diagnóstico, ya que aumentó la sensibilidad (84%), pero empeoró la especificidad (79%) y el área bajo la curva ROC fue similar. En el grupo con PAAF sospechosa o indeterminada la histología fue benigna en el 70% y maligna en el 30%. Conclusiones. La sensibilidad y especificidad de la PAAF para el diagnóstico de malignidad en los nódulos tiroideos son elevadas. La repetición de la punción sobre el mismo nódulo no mejora el rendimiento diagnóstico de la citología. Entre los pacientes con PAAF sospechosa existe una proporción elevada de malignidad, lo que obliga a la intervención quirúrgica en estos casos

Introduction. The prevalence of palpable thyroid nodules in the general population is 4%-7%. Although most are benign, 5% are carcinomas. This study aimed to assess the efficacy of fine needle aspiration biopsy (FNAB) of thyroid nodules to diagnose malignancy and know the benefit of repeating the FNAB in the same nodule. Patients and methods. A total of 510 patients (431 women and 79 men; mean age [standard deviation]: 47.6 [14.3] years) with surgery due to thyroid nodular condition between 1989 and 2002 and who had at least one FNAB prior to the surgery were studied. Results. The first FNAB was benign in 312 patients (61.2%), malignant in 38 (7.5%), suspicious or indeterminate in 97 (19%) and insufficient in 63 (12.4%). Sensitivity and specificity in the first FNAB for malignancy diagnosis was 76% and 84%, respectively. Successive FNABs had a moderate concordance and significance. However, repeating the puncture did not improve diagnostic performance, since sensitive increased (84%), but specificity worsened (79%) and the area under the ROC curve was similar. In the group with suspicious or indeterminate FNAB, histology was benign in 70% and malignant in 30%. Conclusions. FNAB sensitivity and specificity for diagnosis of malignancy in thyroid nodules are high. Repetition of puncture on the same nodule does not improve diagnostic performance of the cytology. Among patients with suspicious FNAB, there is a high proportion of malignancy, which makes surgery necessary in these cases

[Epidemiological and clinicopathological study of thyroid cancer in east Madrid]. / Estudio epidemiológico y clinicopatológico del cáncer de tiroides en la zona este de Madrid.

OBJECTIVES: To analyze the incidence, clinical and histopathological manifestations, surgical complications, and prognostic factors of thyroid cancer in the east Madrid population. PATIENTS AND METHODS: Retrospective analysis of 141 consecutive diagnosed of thyroid cancer in our area between 1985 and 2001. Median follow-up was 4,5 years. RESULTS: The annual incidence rate was 4.74/100,000 inhabitants and the female:male proportion 3.5:1. The average age of patients at diagnosis was 44.5 years and nodular goiter was the principal type of clinical presentation (74.5%). The most frequent histological variant was papillary thyroid carcinoma (69%). Total thyroidectomy was carried out in 86% patients. 9.6% patients suffered permanent hypoparathyroidism and 3.3% paralysis of recurrent laryngeal nerve. Radioactive iodine ablation of remaining thyroid was carried out in 91 patients. Residual disease or local recurrence was observed on follow-up in 21% of patients, and metastasis at a distant site in 9%. 7.9% died along follow-up. The principal prognostic factors for metastasis or death were age, histological type, tumor size, local invasion and existence of metastasis at the time of diagnosis. CONCLUSIONS: The incidence of thyroid cancer in our population was high, especially in women. Although the proportion of postsurgical complications was elevated, global prognosis is good and some factors related to it have been identified. Increase of thyroglobulin plasma level at follow-up is a good recurrence indicator of the disease, especially with regard to distant metastases.

Estudio epidemiológico y clinicopatológico del cáncer de tiroides en la zona este de Madrid / Epidemiological and clinicopathological study of thyroid cancer in east Madrid

Objetivos. Analizar la incidencia, características clínicas e histopatológicas, complicaciones quirúrgicas y factores pronósticos del cáncer tiroideo en la población este de Madrid.Pacientes y métodos. Estudio descriptivo retrospectivo de 141 pacientes consecutivos diagnosticados de cáncer tiroideo en nuestra área entre 1985-2001. La mediana de seguimiento fue de 4,5 años. Resultados. La tasa de incidencia anual fue de 4,74/100.000 habitantes y la relación por sexos mujer:varón 3,5:1. La edad media al diagnóstico fue de 44,5 años y el bocio nodular supuso la principal forma de presentación (74,5%). La variante histológica más frecuente fue la papilar (69%). Se realizó tiroidectomía total en el 86% de los casos. El 9,6% de los casos tuvo hipoparatiroidismo permanente y el 3,3% parálisis del nervio laríngeo recurrente. En 91 pacientes se realizó ablación de restos tiroideos con radioyodo. Durante la evolución se observó enfermedad residual o recurrencia local en el 21% de los casos y metástasis a distancia en el 9%. El 7,9% fallecieron durante el seguimiento. Los principales factores pronósticos de metástasis o fallecimiento fueron la edad, el tipo histológico, el tamaño tumoral, la invasión local y la existencia de metástasis en el momento del diagnóstico. Conclusiones. La tasa de incidencia de cáncer tiroideo en nuestra población fue alta, especialmente en mujeres. Aunque la proporción de complicaciones postquirúrgicas fue elevada, el pronóstico global es bueno y se han identificado algunos factores relacionados con el mismo. La elevación de la tiroglobulina plasmática durante el seguimiento es un buen indicador de recurrencia de la enfermedad, especialmente de metástasis a distancia

Objectives. To analyze the incidence, clinical and histopathological manifestations, surgical complications, and prognostic factors of thyroid cancer in the east Madrid population. Patients and methods. Retrospective analysis of 141 consecutive diagnosed of thyroid cancer in our area between 1985 and 2001. Median follow-up was 4,5 years. Results. The annual incidence rate was 4.74/100,000 inhabitants and the female:male proportion 3.5:1. The average age of patients at diagnosis was 44.5 years and nodular goiter was the principal type of clinical presentation (74.5%). The most frequent histological variant was papillary thyroid carcinoma (69%). Total thyroidectomy was carried out in 86% patients. 9.6% patients suffered permanent hypoparathyroidism and 3.3% paralysis of recurrent laryngeal nerve. Radioactive iodine ablation of remaining thyroid was carried out in 91 patients. Residual disease or local recurrence was observed on follow-up in 21% of patients, and metastasis at a distant site in 9%. 7.9% died along follow-up. The principal prognostic factors for metastasis or death were age, histological type, tumor size, local invasion and existence of metastasis at the time of diagnosis. Conclusions. The incidence of thyroid cancer in our population was high, especially in women. Although the proportion of postsurgical complications was elevated, global prognosis is good and some factors related to it have been identified. Increase of thyroglobulin plasma level at follow-up is a good recurrence indicator of the disease, especially with regard to distant metastases

Paresia oculomotora compleja: una suma de quebrados / Complex oculomotor paresis: a sum of fractions

No disponible

[Effect of lipoprotein (a) on the risk of coronary heart disease in adults aged less than 65 years in function of gender differences]. / Efecto de la lipoproteína (a) en el riesgo de enfermedad coronaria en adultos menores de 65 años en función del sexo.

BACKGROUND: Lipoprotein (a) is an independent risk factor for coronary heart disease, particularly the premature form. However, differences in its effect have been observed between men and women and in different populations. SUBJECTS AND METHODS: Lipid and non-lipid risk factors were compared (univariate and multivariate analyses) between a group of patients with myocardial infarction aged less than 65 years (n = 33) and those in their siblings (n = 32) and an unrelated healthy control group (n = 45) of the same gender. RESULTS: No differences were observed between male patients and their siblings. Differences were indeed observed when patients when compared with controls regarding HDL cholesterol (p = 0.001) and lipoprotein(a) (p = 0.002) serum concentrations. Female patients also had lower serum concentrations of HDL cholesterol than their siblings and controls, but non significant differences were observed for lipoprotein (a). The analysis of lipoprotein (a), categorized with respect to the 90th percentile of controls for each gender, showed a significant association with coronary heart disease only for males: crude odds ratio (OR) compared with controls 10.7 (95% CI: 2.1-54.9) and adjusted of 9.9 (95% CI: 1.6-60.7). The strength of this association was smaller and non-significant in women: crude OR 6,4 (95% CI: 0.8-51.8) and adjusted of 3.09 (95% CI: 0.3-47.2). CONCLUSIONS: Lipoprotein (a) concentrations are similar in siblings and increased concentrations in our population are more strongly and clearly association with coronary heart disease in men.

Efecto de la lipoproteína (a) en el riesgo de enfermedad coronaria en adultos menores de 65 años en función del sexo / Effect of lipoprotein (a) on the risk of coronary heart disease in adults aged less than 65 years. Gender differences

Fundamento. La lipoproteína (a) es un factor de riesgo independiente de enfermedad coronaria, sobre todo prematura; sin embargo, se han encontrado diferencias en su efecto entre varones y mujeres y en distintas poblaciones. Sujetos y métodos. Se comparan (análisis univariante y multivariante) los factores de riesgo lipídicos y no lipídicos de un grupo de pacientes con infarto de miocardio menores de 65 años (n = 33) con los de sus hermanos (n = 32) y un grupo de controles sanos no relacionados (n = 45) del mismo sexo. Resultados. No se han encontrado diferencias entre los pacientes varones y sus hermanos, pero sí al compararlos con los controles en cuanto a las concentraciones de colesterol HDL (p = 0,001) y las de lipoproteína (a) (p = 0,002). Las mujeres enfermas tuvieron también el colesterol HDL más bajo que sus hermanas y las controles, pero no mostraron diferencias significativas en la lipoproteína (a). El análisis de esta última, categorizada respecto al percentil 90 de los controles de su sexo, mostró una asociación significativa de su elevación con la enfermedad coronaria sólo en los varones: odds ratio (OR) crudo frente a los controles de 10,7 (IC 95 por ciento: 2,1-54,9) y ajustado de 9,9 (IC 95 por ciento: 1,6-60,7). En las mujeres la magnitud de esta asociación fue menor y no significativa: OR crudo de 6,4 (IC 95 por ciento: 0,8-51,8) y ajustado de 3,09 (IC 95 por ciento: 0,3-47,2). Conclusiones. Los valores de lipoproteína (a) son similares entre hermanos y en nuestra población su elevación se asocia con la enfermedad coronaria de una forma más clara e intensa en los varones (AU)

[Hyperimmunoglobulinemia D and periodic fever syndrome. A phenotypical analysis of a Spanish family]. / Hiperinmunoglobulinemia D y fiebre periódica. Análisis fenotípico de una familia española.

BACKGROUND: Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) is a disorder diagnosed with low frequency, that produces a very prolonged and recurrent fever with other symptoms and analytical markers of inflammation. Its origin seems to be hereditary with a recessive autosomic pattern, but its pathogenic mechanisms are unclear. The aim of this study is to analyse the clinical characteristics and serum levels of immunoglobulins a Spanish family with HIDS. METHODS: We describe a young woman diagnosed with HIDS and investigate the other memberships of her family (parents and 5 brothers) by clinical interview, physical examination, hematological and biochemical analyses and measurements of IgG, IgA, IgM, IgE, IgD and the kappa/lambda ratio of light chains. Moreover, we also determine the IgD in a control group of 35 healthy blood donors. RESULTS: One male brother of the index case also showed a clinical picture of HIDS. The serum IgD levels were increased (above 100 U/ml) in both and in other two sisters without symptoms and were normal in the rest of the family. With only one exception, all individuals of the control group showed a normal IgD level and this was not associated with sex or age. The other immunoglobulins were normal in the family. In spite of the different treatments tested in the index case, only glucocorticoids aborted her fever attacks. CONCLUSIONS: In HIDS the clinical picture and the high IgD levels are both transmitted with a recessive autosomic pattern, but these are not necessarily associated in the same memberships of the family. Its diagnosis is difficult and there is not effective and long-term safe treatment.

[Surgery of the laryngeal framework: type I thyroplasty]. / Cirugía del esqueleto laríngeo: tiroplastias tipo I.

Eight type I thyroplasties were performed. All the patients had a breathy voice related with unilateral vocal cord paralysis. Several causes were involved. All 8 patients achieved good glottic closure and the free edges of the vocal cords mi closed uniformly. Acoustic parameters were studied using Dr. Speech version 2.0 for Windows. The SPSS program was used for statistical analysis. The study showed significant improvement in maximum phonation time, shimmer, and normalized noise energy. Modifications in the surgical technique are discussed.