Differences in intraoperative and surgical outcomes between normotensive pheochromocytomas and sympathetic paragangliomas (PPGLs) and hypertensive PPGLs: results from the PHEO-RISK STUDY.

PURPOSE: To compare the intraoperative and surgical outcomes of normotensive pheochromocytomas and sympathetic paragangliomas (PPGLs), hypertensive PPGLs and non-PPGL adrenal lesions. METHODS: This a retrospective multicenter cohort study of patients with PPGLs from 18 tertiary hospitals. A control group of histologically confirmed adrenocortical adenomas (non-PPGL group) was selected to compare intraoperative and surgical outcomes with of the normotensive PPGLs. RESULTS: Two hundred and ninety-six surgeries performed in 289 patients with PPGLs were included. Before surgery, 209 patients were classified as hypertensive PPGLs (70.6%) and 87 as normotensive PPGLs. A higher proportion of normotensive PPGLs than hypertensive PPGLs did not receive alpha presurgical blockade (P = 0.009). When we only considered those patients who received presurgical alpha blockers (200 hypertensive PPGLs and 76 normotensive PPGLs), hypertensive PPGLs had a threefold higher risk of intraoperative hypertensive crisis (OR 3.0 [95% 1.3-7.0]) and of hypotensive episodes (OR 2.9 [95% CI 1.2-6.7]) than normotensive PPGLs. When we compared normotensive PPGLs (n = 76) and non-PPGLs (n = 58), normotensive PPGLs had a fivefold higher risk of intraoperative complications (OR 5.3 [95% CI 1.9-14.9]) and a six times higher risk of postoperative complications (OR 6.1 [95% CI 1.7-21.6]) than non-PPGLs. CONCLUSION: Although the risk of intraoperative hypertensive and hypotensive episodes in normotensive PPGLs is significantly lower than in hypertensive PPGLs, normotensive PPGLs have a greater risk of intraoperative and postoperative complications than non-PPGL adrenal lesions. Therefore, it is recommended to follow the standard of care for presurgical and anesthetic management of PPGLs also in normotensive PPGLs.

Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss.

Objective: This study aimed to compare the efficacy and safety of ossein-hydroxyapatite complex (OHC) versus calcium carbonate (CC) for preventing bone loss during perimenopause in current clinical practice.Methods: The prospective, comparative, non-randomized, open-label study included 851 perimenopausal women with basal bone mineral density (BMD) T-score ≥-2 standard deviations (SDs). Participants received either OHC (712 mg calcium/day) or CC (1000 mg calcium/day) over 3 years. BMD was evaluated by dual-energy X-ray absorptiometry at the lumbar spine (L2-L4) at baseline and after 18 and 36 months of follow-up. Adverse drug reactions (ADRs) were also recorded.Results: In women receiving OHC, BMD at the L2-L4 site remained stable over the 3-year follow-up period (mean [SD] change 0.00 [0.11] g/cm2). BMD in the CC arm decreased -3.1% (mean [SD] - 0.03 [0.11] g/cm2). Between-group differences were statistically significant (p < 0.001) and favored OHC. ADRs were more frequent in the CC group (7.7% vs. 2.7% in the OHC group; p = 0.001), affecting primarily the gastrointestinal system.Conclusion: OHC showed greater efficacy and tolerability than CC for bone loss prevention in perimenopausal women in real-world practice. As the daily dose of calcium was higher in the CC group, the differences might be linked to the ossein compound in OHC.

Temporal expression of cytokines and signal transducer and activator of transcription factor 3 activation after neonatal hypoxia/ischemia in mice.

Hypoxia/ischemia (HI) is a prevalent reason for neonatal brain injury with inflammation being an inevitable phenomenon following such injury; but there is a scarcity of data regarding the signaling pathway involved and the effector molecules. The signal transducer and activator of transcription factor 3 (STAT3) is known to modulate injury following imbalance between pro- and anti-inflammatory cytokines in peripheral and central nervous system injury making it a potential molecule for study. The current study investigates the temporal expression of interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, IL-1ra, IL-4, IL-10, IL-13 and phosphorylated STAT3 (pSTAT3) after carotid occlusion and hypoxia (8% O2, 55 min) in postnatal day 7 C57BL/6 mice from 3 h to 21 days after hypoxia. Protein array illustrated notable changes in cytokines expressed in both hemispheres in a time-dependent manner. The major pro-inflammatory cytokines showing immediate changes between ipsi- and contralateral hemispheres were IL-6 and IL-1ß. The anti-inflammatory cytokines IL-4 and IL-13 demonstrated a delayed augmentation with no prominent differences between hemispheres, while IL-1ra showed two distinct peaks of expression spread over time. We also illustrate for the first time the spatiotemporal activation of pSTAT3 (Y705 phosphorylation) after a neonatal HI in mice brain. The main regions expressing pSTAT3 were the hippocampus and the corpus callosum. pSTAT3+ cells were mostly a subpopulation of activated astrocytes (GFAP+) and microglia/macrophages (F4/80+) seen only in the ipsilateral hemisphere at most time points studied (till 7 days after hypoxia). The highest expression of pSTAT3+ cells was observed to be around 24-48 h, where the presence of pSTAT3+ astrocytes and pSTAT3+ microglia/macrophages was seen by confocal micrographs. In conclusion, our study highlights a synchronized expression of some pro- and anti-inflammatory cytokines, especially in the long term not previously defined. It also points towards a significant role of STAT3 signaling following micro- and astrogliosis in the pathophysiology of neonatal HI-related brain injury. In the study, a shift from pro-inflammatory to anti-inflammatory cytokine profile was also noted as the injury progressed. We suggest that while designing efficient neuroprotective therapies using inflammatory molecules, the time of intervention and balance between the pro- and anti-inflammatory cytokines must be considered.

Usefulness of antimicrobial susceptibility in the eradication of Helicobacter pylori.

The rate of eradication of Helicobacter pylori with standard triple therapy using omeprazole, amoxicillin and clarithromycin (OAC) is unacceptable in populations with high rates of clarithromycin resistance (15-20%). The aim of this study was to compare the efficacy of 10-day OAC therapy as the first-line treatment in patients diagnosed by culture with antimicrobial susceptibility or diagnosed by a (13) C-labelled urea breath test (UBT) without antimicrobial susceptibility in an area where the clarithromycin resistance rate was 15-20%. This was a retrospective cohort study of 266 patients, recruited consecutively throughout 2008. A total of 247 H. pylori-infected patients received antibiotic therapy (221 received the 10-day OAC therapy and 26 received other regimens) of which 134 patients were diagnosed by culture of gastric samples followed by antimicrobial susceptibility testing and 113 were diagnosed by UBT. In all patients, the eradication of H. pylori was checked by UBT. The cost of eradication by 10-day OAC treatment was assessed in each patient. The success rate of 10-day OAC therapy in patients diagnosed by culture and by UBT was 88% (103/117) and 49% (51/104), respectively (p <0.0005). The treatment was also more cost-effective in the former of these two groups (€571 versus €666). To perform culture and antimicrobial susceptibility of the H. pylori isolates was a more successful and cost effective strategy than empirical 10-day OAC treatment in populations with high rates of resistance to clarithromycin.

Nutrición en la esclerosis sistémica / Nutrition in systemic sclerosis

La esclerosis sistémica es una enfermedad del tejido conectivo caracterizada por inflamación y fibrosis de múltiples órganos (piel, aparato digestivo, pulmón, riñón y corazón). Después de la piel, el órgano más afectado, con una frecuencia del 75 al 90%, es el tracto gastrointestinal. La afectación del tracto gastrointestinal se manifiesta por la aparición de disfagia orofaríngea, disfagia esofágica, reflujo gastroesofágico, gastroparesia, seudoobstrucción, sobrecrecimiento bacteriano y malabsorción intestinal, estreñimiento, diarrea y/o incontinencia fecal. Estas afectaciones condicionan la ingesta alimentaria y la absorción intestinal y conducen a la aparición progresiva de deficiencias nutricionales. Alrededor de un 30% de los pacientes con esclerosis sistémica presentan un riesgo de malnutrición. En el 5-10%, los trastornos gastrointestinales son la principal causa de muerte. Las estrategias terapéuticas existentes en la actualidad son limitadas y están dirigidas a reducir la sintomatología clínica. El manejo multidisciplinar de dichos pacientes, que incluya la intervención nutricional, contribuye a mejorar la sintomatología gastrointestinal, además de evitar la malnutrición, la morbilidad y aumentar la calidad de vida (AU)

Systemic sclerosis is a connective tissue disease characterized by inflammation and fibrosis of multiple organs (skin, gastrointestinal tract, lung, kidney and heart). After the skin, the organ most affected with a frequency of 75 to 90%, the gastrointestinal tract is more often involved. Gastrointestinal tract involvement is manifested by the appearance of oropharyngeal dysphagia, esophageal dysphagia, gastroesophageal reflux, gastroparesis, pseudo-obstruction, bacterial overgrowth and intestinal malabsorption, constipation, diarrhea and/or fecal incontinence. These effects influence food intake and intestinal absorption leading to the gradual emergence of nutritional deficiencies. About 30% of patients with systemic sclerosis are at risk of malnutrition. In 5-10%, gastrointestinal disorders are the leading cause of death. Therapeutic strategies currently available are limited and aimed at reducing clinical symptoms. The multidisciplinary management of these patients, including nutritional intervention, helps improve gastrointestinal symptoms, and avoid malnutrition, morbidity and improve quality of life (AU)

Nutrition in systemic sclerosis.

Systemic sclerosis is a connective tissue disease characterized by inflammation and fibrosis of multiple organs (skin, gastrointestinal tract, lung, kidney and heart). After the skin, the organ most affected with a frequency of 75 to 90%, the gastrointestinal tract is more often involved. Gastrointestinal tract involvement is manifested by the appearance of oropharyngeal dysphagia, esophageal dysphagia, gastroesophageal reflux, gastroparesis, pseudo-obstruction, bacterial overgrowth and intestinal malabsorption, constipation, diarrhea and/or fecal incontinence. These effects influence food intake and intestinal absorption leading to the gradual emergence of nutritional deficiencies. About 30% of patients with systemic sclerosis are at risk of malnutrition. In 5-10%, gastrointestinal disorders are the leading cause of death. Therapeutic strategies currently available are limited and aimed at reducing clinical symptoms. The multidisciplinary management of these patients, including nutritional intervention, helps improve gastrointestinal symptoms, and avoid malnutrition, morbidity and improve quality of life.

Síndrome de Cushing suprarrenal / No disponible

No disponible

Gran tumor suprarrenal / No disponible

No disponible

Metástasis adrenal de carcinoma pulmonar / No disponible

No disponible

Asymptomatic bilateral adrenal pheochromocytoma in a patient with a germline V804M mutation in the RET proto-oncogene.

UNLABELLED: A diagnosis of bilateral pheochromocytoma warrants exclusion of hereditary pheochromocytoma. OBJECTIVE: To describe the first case of a bilateral pheochromocytoma associated with V804M mutation in the RET proto-oncogene. PATIENTS: The index case was a 54-year-old man with bilateral adrenal masses discovered during a CT scan performed for other reasons. MEASUREMENTS: Genetic analysis included exons 8-11 and 13-17 in the RET proto-oncogene, all four exons and flanking intronic regions in the SDHD gene, all eight exons and flanking intronic regions in the SDHB, and all three exons in the VHL gene. RESULTS: Investigations revealed elevated urinary metanephrines (32.3 micromol/day), and laparoscopic bilateral adrenalectomy confirmed bilateral pheochromocytomas. A heterozygous V804M mutation in exon 14 of the RET was found in the index case and in four relatives. Total thyroidectomy, performed in four of five affected members in this kindred, disclosed a medullary thyroid carcinoma in the index case and in a 50-year-old woman, and nodular C-cell hyperplasia in the other two subjects. CONCLUSIONS: This clinical case suggests that individuals carrying the germline V804M mutation should be screened annually for the presence of pheochromocytoma.

Retraso mental de origen genético / Genetic mental retardation

Introducción. El retraso mental (RM) es la discapacidadmás frecuente y con mayor impacto en la vida de la persona afectada,su familia y la sociedad, con una incidencia estimada de un 1-3% en las poblaciones desarrolladas. Entre las causas que lo originan,un 30% parece ser de origen genético, un 15% de origenambiental, y el resto se desconoce. Objetivo. Dar una visión actualizadade las causas genéticas del RM y de cómo las recientesmetodologías permiten alcanzar un diagnóstico cada día en unnúmero mayor de casos para llegar a la prevención mediante elconsejo genético. Desarrollo. Las causas del RM son extremadamenteheterogéneas. Las causas genéticas podemos agruparlas en:alteraciones cromosómicas (aneuploidías, reordenamientos subteloméricos,síndromes microdelecionales o microduplicacionales),alteraciones monogénicas, metabólicas y multifactoriales. Graciasal desarrollo de nuevas técnicas de alta resolución –arrays dehibridación genómica comparada (CGH) y multiplex ligation probeamplification (MLPA)– se pueden detectar microduplicaciones ymicrodeleciones a lo largo de todo genoma, lo que está contribuyendoa la identificación de nuevos síndromes y genes asociados alRM. Conclusiones. Las bases genéticas del RM son muy variadas ycomplejas. Actualmente disponemos de tecnología para realizarmuchos tipos de estudios; no obstante, casi la mitad de los casos deRM quedan sin diagnosticar. Los antecedentes familiares, si sonpositivos, permitirán emitir un consejo genético aunque no tengamosun diagnóstico. Es necesario llegar a un diagnóstico exactopara poder ofrecer un diagnóstico prenatal o preimplantacional

Introduction. Mental retardation is a frequently occurring disorder with a major impact on the life of the affectedperson, the family and society, with an estimated incidence of 1-3% in developed countries. Among the etiologies that causemental retardation it would appear that 30% have a genetic origin, 15% have an environmental origin, and the rest have anunknown origin. Aim. To report the genetic causes of mental retardation and the new molecular techniques used in order toreach a diagnosis. The identification of the causes of mental retardation is of great interest due to the consequences it has inthe intervention, prognosis, estimation of risk of recurrence and its prevention. Development. Causes of mental retardationare extremely heterogeneous. Genetic causes can be classified as chromosomal alterations (aneuploidies, subtelomericrearrangements, microdeletion or microduplication syndrome), monogenic, metabolic, or multifactorial alterations. Thanksto the development of high-resolution new techniques –comparative genomic hybridization (CGH) arrays, and multiplexligation probe amplification (MLPA)– now we are able to detect microdeletions and microduplication all over the genome,which might be related with mental retardation. Conclusions. The genetic causes of mental retardation are highlyheterogeneous and complex. Nowadays and thanks to the new molecular techniques we are able to perform several studies,even though almost half of cases remain undiagnosed. In those undiagnosed cases with positive familial history a geneticcounseling can be provided. However, in order to perform a prenatal or a preimplantational study a genetic diagnosis isrequired

Diagnóstico del retraso mental de origen genético. Protocolo de estudio / Diagnosis of genetic mental retardation. Protocol of study

Introducción. El estudio del retraso mental (RM) es unode los campos más complejos en genética humana, debido a quepresenta una heterogeneidad clínica y genética muy elevada, conuna gran complejidad de las bases genéticas y ambientales queinfluyen sobre éstas. En estos momentos, casi la mitad de los RMquedan sin un diagnóstico. Objetivo. Presentar un protocolo de actuaciónen el laboratorio mediante la tecnología de que disponemosactualmente para llegar al diagnóstico del RM. Desarrollo. Elprimer paso es la evaluación del paciente con una exploración clínicaminuciosa y la obtención de datos sobre antecedentes personalesy familiares. Ante una sospecha diagnóstica de uno o variossíndromes que cursan con RM, ésta deberá confirmarse en el laboratorio,si es posible, con la técnica correspondiente. Ante casos deRM en los que no existe sospecha clínica para ningún síndromedeterminado se realizarán tres pruebas: cariotipo, estudio molecularde la expansión CGG del gen FMR1 y estudio de las regionessubteloméricas. Si el estudio es negativo y se trata de un caso familiarcon una estructura adecuada, realizaremos un estudio de ligamiento.En cuanto a los casos esporádicos es difícil avanzar de formarutinaria, aunque hay algunas pruebas que permiten realizardeterminaciones de varios genes a la vez. Existen otras técnicasencaminadas a profundizar más, como los cribados de genes responsablesde RM inespecífico ligado al cromosoma X o los arrays-CGH (arrays basados en la hibridación genómica comparada) paratodo el genoma o para un cromosoma determinado, pero por elmomento están limitados a proyectos de investigación o a casosmuy concretos. Conclusiones. Proponemos un protocolo de estudioy destacamos la importancia de su utilización con el fin de obtenerel máximo rendimiento para lograr un diagnóstico que nos permitadar el consejo genético y ofrecer un diagnóstico prenatal par futurasgeneraciones

Introduction. The study of mental retardation (MR) is one of the most complex fields in human genetics, due to thefact that it presents a very high degree of clinical and genetic heterogeneity, and both the genetic bases and the environmentalfactors that act upon them are extremely complex. At the present time almost half of the cases of MR remain undiagnosed. Aim.To present a protocol for laboratory work using the technology that is currently available to reach a diagnosis of MR.Development. The first step is to evaluate the patient with a thorough clinical examination and by obtaining information aboutthe personal and family history. A suspected diagnosis of one or several syndromes that involve MR must be confirmed, ifpossible, in the laboratory with the appropriate technique. In cases of MR with no clinical suspicion of any specific syndrome,three tests must be conducted: karyotype, molecular study of the expansion of CGG in the FMR1 gene, and study of the subtelomericregions. If the study is negative and we are dealing with a familial case with a suitable structure, a linkage study mustbe performed. As far as sporadic cases are concerned, it is difficult to advance in a routine manner although some tests allowscreening several genes determinations to be carried out on several genes at the same time. Other techniques permit toinvestigate in greater depth, such as screening for genes responsible for non-specific X-linked MR or CGH-arrays (arrays basedon compared genomic hybridisation) for the whole genome or for a particular chromosome. At the present time, however, suchtechniques are limited to research projects or very special cases. Conclusions. We propose a study protocol and highlight theimportance of its use to obtain maximum performance in order to reach a diagnosis that allows us to give genetic counsellingand offer a prenatal diagnosis for future generations

[Obesity and inflammation]. / Obesidad e inflamación.

The adipose tissue produces a vast number of molecules called adipokines such as leptin, tumoral necrosis factor (TNFalpha), interleukins and adiponectin. Many of the metabolic disturbances associated with obesity and the metabolic syndrome may be due to citokine production by adipocytes. The adipose tissue increases the soluble fractions of TNFalpha leading to a rise in its biological activity. The activation of TNFalpha system causes insulin resistance through different mechanisms such as defects in receptor fosforilation and reduction in insulin-sensitive glucose transporters. TNFalpha is also involved in the pathophysiology of hypertension and dyslipidaemia associated with obesity and insulin resistance. More than one third of interleukin-6 (IL-6) concentrations come from the adipocytes. It has been demonstrated a role for IL-6 in the development of hyperlipidemia, diabetes and hypertension. In contrast to the rest of adipokines, adiponectin is reduced in obesity, diabetes or cardiovascular disease. Adiponectin improves insulin resistance, dyslipidaemia and adhesion to endothelial cells protecting from atherosclerosis development. Thus, adipokines have an important role in the pathophysiology of metabolic syndrome by different mechanisms involving metabolic and vascular effects.

Management of osteoporosis in general practice: a cross-sectional survey of primary care practitioners in Spain.

A cross-sectional survey was conducted to determine the current situation in Spain regarding diagnosis and care of patients with osteoporosis in the primary care setting. A total of 2,500 primary care physicians who were homogeneously grouped in autonomous communities throughout the country received a postal 30-item anonymous self-administered questionnaire. The questionnaire covered demographics and personal characteristics of the physicians, conditions in everyday consultation, and degree of knowledge with regard to risk factors, diagnosis, treatment, and follow-up of the disease. The overall response was 850 (34%). The mean age of physicians surveyed was 43 years (range 23-66 years). The percentage of physicians specialized in community and family medicine was 46.7%. In 55.2% of cases, years of practice ranged between 11 and 20, and 55.7% of physicians visited between 31 and 50 patients per day. Age and years of practice were not associated with daily number of visits. Only 4% of physicians stated that there were specific programs for osteoporosis implemented in their primary care center. Diagnostic complementary investigations that could be ordered included plain radiographs in 96.2% of cases and bone densitometry in 27.8%. Laboratory tests included serum hormones in 61.6% of cases, PTH in 50.2%, and bone alkaline phosphatase in 33.4%. The diagnosis of osteoporosis was made always personally in 25.2% of cases. Personal diagnosis and follow-up, as well as actions directed to detection of osteoporosis were significantly higher among physicians working in centers with specific programs for osteoporosis. With regard to knowledge about osteoporosis, the mean percentage of correct responses was 63%. The percentage of correct responses was inversely associated with age and years of practice, and positively associated with speciality of community and family medicine. Primary care providers are in a good position to assess risk factors and recommend prevention strategies, as well as to play an active role in the diagnosis, care, and follow-up of patients with osteoporosis. Practitioners of younger age and relatively few years of practice were those with more up-to-date information regarding the disease, and the existence of a specific program for osteoporosis seems to improve the management of this condition.

[FMRP immunodetection on hair roots: application to the diagnosis of fragile X syndrome]. / Estudio de la proteína FMRP en la raíz de cabello: aplicación al diagnóstico del síndrome del cromosoma X frágil.

INTRODUCTION: Fragile X syndrome is the most common inherited form of mental retardation. The absence of FMRP protein, codified by the FMR1 gene, results in fragile X phenotype. DNA-based diagnostic methods determine the length of the CGG repeat within the FMR1 gene, the main mutation causing the syndrome. Immunohistochemical diagnostic tests detect all mutations leading to the absence of FMRP expression. Results of the antibody test on hair roots correlate with intellectual quotient in affected men and women. PATIENTS AND METHODS: Immunohistochemical techniques were used to study FMRP expression in hair roots in a control group to establish the correlation with the length of the CGG repeat. Subsequently, 65 girls and boys with mental retardation attending special schools were screened by using the FMRP test on hair roots. RESULTS: Males and females molecularly characterized as within the normal and premutated range expressed FMRP in more than 70 % of hair roots. Full mutation carriers expressed FMRP in less than 70 % of hair roots. Immunohistochemical studies in males and females with mental retardation led to the identification of one affected male. CONCLUSIONS: Fragile X syndrome detection by immunohistochemical testing of hair roots is a valid method of population screening because of the relative noninvasiveness of obtaining samples, and the ease and rapidness of the technique, which can be applied to routine clinical practice.