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1.
Med Clin (Barc) ; 134(9): 381-5, 2010 Apr 03.
Article in Spanish | MEDLINE | ID: mdl-20138312

ABSTRACT

BACKGROUND AND OBJECTIVE: Our hypothesis is that there is a relationship between the short term outcomes of pediatric patients with type I diabetes mellitus and their HLA-DQ genotypes. PATIENTS AND METHOD: We performed a descriptive epidemiologic study of 129 children and adolescents under 16 years old with type 1 diabetes mellitus. We studied their HLA DQ genotypes and classified them into groups of diabetogenic risk. We studied general clinic and analytic parameters at onset of the disease and during a period of 3 years, and the development of associated chronic complications. RESULTS: In total, 93.8% of our patients had diabetes-risk HLA-DQ genotypes. Onset of the disease occurred earlier in patients who belonged to risk group III, and they had less pancreatic reserve. During the follow-up period, significant differences in systolic and diastolic blood pressure were found in patients in risk group III, and in diastolic blood pressure in patients in risk group I. CONCLUSIONS: Patients in risk group III have an onset at a lower age and present significant differences in systolic and diastolic blood pressure during the follow up period.


Subject(s)
Diabetes Mellitus, Type 1/genetics , HLA-DQ Antigens/genetics , Adolescent , Child , Child, Preschool , Diabetes Mellitus, Type 1/epidemiology , Female , Genotype , Humans , Infant , Infant, Newborn , Male , Treatment Outcome
2.
J Clin Endocrinol Metab ; 93(6): 2269-76, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18349058

ABSTRACT

CONTEXT: Rab proteins regulate the sequential steps of intracellular membrane transport. Alterations of these GTPases and their associated proteins are emerging as the underlying cause for several human diseases involving dysregulated secretory activities. OBJECTIVE: Herein we investigated the role of Rab18, which negatively regulates hormone secretion by interacting with secretory granules, in relation to the altered functioning of tumoral pituitary somatotropes causing acromegaly. PATIENTS: A total of 18 patients diagnosed with pituitary tumors causing acromegaly (nine patients) or nonfunctioning adenomas (nine patients) underwent endoscopic transsphenoidal surgery. Adenomas were subsequently processed to evaluate Rab18 production in relation to GH secretion. RESULTS: We found that somatotropinoma cells are characterized by a high secretory activity concomitantly with a remarkably reduced Rab18 expression (15%) and protein content levels (30%), as compared with cells from nonfunctioning pituitary adenomas derived from patients with normal or reduced GH plasma levels (100%). Furthermore, immunoelectron microscopy revealed that Rab18 association with the surface of GH-containing secretory granules was significantly lower in somatotropes from acromegalies than nonfunctioning pituitary adenomas. Finally, we provide evidence that modulation of Rab18 gene expression can revert substantially the hypersecretory activity of cells because Rab18 overexpression reduced by 40% the capacity of cells from acromegalies to respond to GHRH stimulation. CONCLUSION: These results suggest that molecular alterations affecting individual components of the secretory granule traffic machinery can contribute to maintain a high level of GH in plasma. Accordingly, Rab18 constitutes a valuable target as a diagnostic, prognostic, and/or therapeutic tool for human acromegaly.


Subject(s)
Acromegaly/genetics , Adenoma/genetics , Growth Hormone-Secreting Pituitary Adenoma/genetics , Human Growth Hormone/metabolism , rab GTP-Binding Proteins/genetics , Acromegaly/etiology , Adenoma/metabolism , Cell Membrane/metabolism , Gene Expression Regulation, Neoplastic/physiology , Growth Hormone-Secreting Pituitary Adenoma/metabolism , Humans , RNA, Messenger/metabolism , Secretory Vesicles/metabolism , Somatotrophs/metabolism , Tissue Distribution , Transfection , Tumor Cells, Cultured , rab GTP-Binding Proteins/metabolism , rab GTP-Binding Proteins/physiology
3.
J Clin Endocrinol Metab ; 91(6): 2225-31, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16551736

ABSTRACT

CONTEXT: In Cushing's disease, ACTH hypersecretion by pituitary corticotrope adenoma cells and resulting hypercortisolism is accompanied by a severely blunted GH secretory response. Interestingly, in Cushing's disease, ghrelin markedly increases plasma ACTH, whereas its stimulatory action on GH secretion is reduced. Although the reported expression of ghrelin receptors (GHS-R) in corticotrope tumors offers a potential mechanism for ghrelin-induced ACTH hypersecretion, studies on the direct effects of synthetic GH secretagogues on corticotropinoma cells offered contradictory results. OBJECTIVE AND DESIGN: To evaluate the direct action of ghrelin on corticotropinoma cells from two patients with Cushing's disease, we measured its effect on free cytosolic calcium concentration ([Ca(2+)](i)). Additionally, expression of GHS-R and its ligand ghrelin was examined in these cells and in five additional corticotropinomas. RESULTS: Ghrelin (10(-6) m) induced a marked [Ca(2+)](i) increase in 89.5% (case 1; n = 19 cells) and 85% (case 2; n = 13 cells) of corticotropinoma cells. Moreover, RT-PCR showed that expression of GHS-R isoforms is accompanied by that of ghrelin in all seven corticotrope adenomas examined. Importantly, double immunogold electron microscopy revealed that ghrelin is costored within ACTH secretory vesicles in densely granulated adenomatous corticotropes. CONCLUSIONS: These results constitute the first demonstration that ghrelin acts directly on corticotrope tumor cells derived from patients with Cushing's disease. The presence of ghrelin and GHS-R suggests that pituitary ghrelin may play an autocrine/paracrine role in regulating ACTH release in Cushing's disease. Our findings provide a plausible cellular basis for the exaggerated ACTH response to ghrelin in Cushing's disease and suggest novel research strategies to develop medical treatments for this disease.


Subject(s)
Adenoma/metabolism , Adrenocorticotropic Hormone/metabolism , Peptide Hormones/physiology , Pituitary Neoplasms/metabolism , Adult , Calcium/metabolism , Female , Fluorescent Antibody Technique , Ghrelin , Humans , Immunohistochemistry , Pro-Opiomelanocortin/genetics , RNA, Messenger/analysis , Receptors, G-Protein-Coupled/genetics , Receptors, Ghrelin
4.
Med Clin (Barc) ; 120(1): 6-9, 2003 Jan 18.
Article in Spanish | MEDLINE | ID: mdl-12525297

ABSTRACT

BACKGROUND AND OBJECTIVE: The hypothesis that diabetes mellitus presentation partially depends on the genetic characteristics of the patient has been proposed. Up to date this kind of studies have been made by serology, so there are no data about the role played by DQ haplotypes in the presentation and clinical importance of DM1. This fact is analysed in the present study. PATIENTS AND METHOD: We studied DQ haplotypes (molecular biology) in 86 patients affected by DM1. Their relationship with several parameters found on illness debut, such as age, sex, C peptid and clinical importance are analysed. RESULTS: 89% of the patients showed a DQ that increases the risk of diabetes. Average age on onset was 16 years and the median age 9 years. No differences in relation to sex were observed. DQA1*0501, 0301/DQB1*0201, 0302 heterocygotes show an earlier onset (9 years, opposite to 17 in the rest) and the youngest (smaller than 16 years) they have to the onset a smaller pancreatic reservation (peptid C of 0.37 ng/dl in front of 1.4 of those bigger than this age). CONCLUSIONS: DQA1*0501, 0301/DQB1*0201 heterocygocity increases the probability of an earlier and more aggressive debut of the illness, being related this characteristic younger debut to a smaller pancreatic reservation.


Subject(s)
Diabetes Mellitus, Type 1/genetics , HLA-DQ Antigens/genetics , Adolescent , Adult , Age of Onset , C-Peptide/blood , C-Peptide/genetics , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/epidemiology , Female , Gene Frequency , Genetic Markers , Genetic Predisposition to Disease/genetics , Genetic Testing/methods , Haplotypes/genetics , Humans , Male , Middle Aged
5.
PLoS One ; 8(4): e60041, 2013.
Article in English | MEDLINE | ID: mdl-23593161

ABSTRACT

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions.


Subject(s)
Acromegaly/diagnosis , Acromegaly/physiopathology , Cognition Disorders/physiopathology , Human Growth Hormone/metabolism , Pituitary Neoplasms/metabolism , Acromegaly/etiology , Acromegaly/surgery , Adult , Cognition Disorders/etiology , Diagnosis, Differential , Electroencephalography , Humans , Middle Aged , Neuropsychological Tests , Pituitary Neoplasms/complications , Pituitary Neoplasms/surgery , Quality of Life
6.
Endocrinol Nutr ; 60(1): 10-4, 2013 Jan.
Article in English, Spanish | MEDLINE | ID: mdl-23177093

ABSTRACT

OBJECTIVE: To assess the efficacy of intermittent, high-dose treatment with intravenous glucocorticoids (IV GCs) in moderate to severe Graves' ophthalmopathy (GO). MATERIALS AND METHODS: Patients with GO treated with IV GCs from August 2007 to August 2011 at the Endocrinology Department of Reina Sofía Hospital were enrolled into the study. IV pulse prednisolone (7.5 mg/kg/day) was administered twice weekly every two weeks for 6 weeks, and at half the dose for 6 additional weeks. RESULTS: Eighteen patients (mean age, 43 ± 11 years) with moderate to severe GO were analyzed (83.3% females). Four were active smokers, five former smokers, and the rest had never smoked. Hyperthyroidism due to Graves' disease was found in 66.7% of patients, 41.6% of whom had received radioiodine therapy. Response to treatment was satisfactory in 72.2%, partial in 11.1%, and poor in 16.7%. Mild side effects were reported by 5 patients. Before treatment, 83.3% had diplopia, 33.3% eyelid retraction, 72.2% eye pain, and 44.4% exophthalmos. After treatment, only 33.3% had diplopia (P=.004), 5.6% eyelid retraction (P=.063), 16.7% eye pain (P=.002), and 11.1% exophthalmos (P=.031). Response to treatment was not related to the underlying disease (P=.866), prior radioiodine treatment (P=.447), or smoking status (P=.368). CONCLUSIONS: Intravenous glucocorticoid therapy decreased activity in patients with moderate to severe active GO, with major improvement occurring in diplopia, eye pain, and exophthalmos. Side effects were mild and uncommon. Treatment response was independent from the underlying disease, prior radioiodine treatment, or smoking status.


Subject(s)
Glucocorticoids/administration & dosage , Graves Ophthalmopathy/drug therapy , Administration, Intravenous , Adult , Female , Humans , Male , Retrospective Studies , Severity of Illness Index
7.
Nutr Hosp ; 28(3): 958-60, 2013.
Article in Spanish | MEDLINE | ID: mdl-23848125

ABSTRACT

Inflammatory bowel disease (IBD) is rarely associated with obesity, as malabsorption is a common feature of these diseases (1). However, some patients may experience morbid obesity and associated complications refractory to dietary treatment and benefit from bariatric surgery. It has even been postulated that surgery may result in improvement of IBD by reducing inflammatory markers (2). However, patients may experience a higher incidence of complications following surgery in the context of immunosuppressive therapy and prior malabsorption. Therefore, if surgery is performed, careful patient selection and individualization of technique are essential. We present a patient diagnosed with ulcerative colitis who presented severe protein malnutrition after bariatric surgery type bilio-pancreatic diversion and review the available literature.


La Enfermedad Inflamatoria Intestinal (EII) raramente se asocia a obesidad, ya que la malabsorción es una característica frecuente de este grupo de patologías (1). Sin embargo, algunos pacientes pueden padecer obesidad mórbida asociada a complicaciones y refractaria a tratamiento dietético y beneficiarse de la cirugía bariátrica. Incluso se ha postulado que podría producirse una mejoría de la EII al disminuir los marcadores inflamatorios tras la cirugía (2). No obstante, los pacientes pueden experimentar mayor incidencia de complicaciones tras la cirugía en el contexto de terapias inmunosupresoras y agravamiento de la malabsorción previa. Por ello, si se realiza la cirugía, la cuidadosa selección de los pacientes y la individualización de la técnica a realizar son imprescindibles. Presentamos una paciente diagnosticada de Colitis Ulcerosa que presenta desnutrición proteica severa tras cirugía bariátrica tipo derivación bilio-pancreática y realizamos una revisión de la literatura disponible.


Subject(s)
Bariatric Surgery/adverse effects , Colitis, Ulcerative/complications , Obesity, Morbid/complications , Obesity, Morbid/surgery , Protein-Energy Malnutrition/etiology , Adult , Female , Humans
8.
Endocrinol Nutr ; 58(10): 510-5, 2011 Dec.
Article in Spanish | MEDLINE | ID: mdl-22056421

ABSTRACT

BACKGROUND AND OBJECTIVE: The current training program for resident physicians in endocrinology and nutrition (EN) organizes their medical learning. Program evaluation by physicians was assessed using a survey. MATERIAL AND METHOD: The survey asked about demographic variables, EN training methods, working time and center, and opinion on training program contents. RESULTS: Fifty-one members of Sociedad Castellano-Manchega de Endocrinología, Nutrición y Diabetes, and Sociedad Andaluza de Endocrinología y Nutrición completed the survey. Forty-percent of them disagreed with the compulsory nature of internal medicine, cardiology, nephrology and, especially, neurology rotations (60%); a majority (>50%) were against several recommended rotations included in the program. The fourth year of residence was considered by 37.8% of respondents as the optimum time for outpatient and inpatient control and monitoring without direct supervision. The recommended monthly number of on-call duties was 3.8±1.2. We detected a positive opinion about extension of residence duration to 4.4±0.5 years. Doctoral thesis development during the residence period was not considered convenient by 66.7% of physicians. Finally, 97.8% of resident physicians would recommend residency in EN to other colleagues. CONCLUSIONS: Endocrinologists surveyed disagreed with different training program aspects such as the rotation system, skill acquisition timing, and on-call duties. Therefore, an adaptation of the current training program in EN would be required.


Subject(s)
Endocrinology/education , Internship and Residency/standards , Nutritional Sciences/education , Physicians , Spain , Surveys and Questionnaires
9.
Endocrinol Nutr ; 58(10): 516-20, 2011 Dec.
Article in Spanish | MEDLINE | ID: mdl-22075130

ABSTRACT

INTRODUCTION: In 2006, a new training program was approved for resident physicians in endocrinology and nutrition (EN). A survey was conducted to EN residents to assess their training, their depth of knowledge, and compliance with the new program, as well as potential changes in training, and the results obtained were compared to those from previous surveys. MATERIAL AND METHODS: A survey previously conducted in 2000 and 2005 was used for this study. The survey included demographic factors, questions about the different rotations, scientific and practical training, assessment of their training departments and other aspects. Results of the current survey were compared to those of the 2005 survey. RESULTS: The survey was completed by 40 residents. Mandatory rotations are mainly fulfilled, except for neurology. Some rotations removed from the program, such as radiology and nuclear medicine, still are frequently performed and popular among residents, who would include them back into the program. There was a low compliance with practical training in the endocrinology area. Forty percent of residents were not aware of the new program, but 60% thought that it was fulfilled. A total of 82.5% of residents thought that their departments fulfilled the training objectives. CONCLUSIONS: Few differences were found in rotations as compared to the data collected in 2005 despite changes in the training program, and there was still a lack of practical training. By contrast, rating of training received from departments and senior physicians was improved as compared to prior surveys.


Subject(s)
Endocrinology/education , Internship and Residency/standards , Nutritional Sciences/education , Adult , Female , Humans , Male , Surveys and Questionnaires
10.
Eur J Endocrinol ; 164(3): 355-62, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21169415

ABSTRACT

CONTEXT: KISS1 was originally identified as a metastasis-suppressor gene able to inhibit tumor progression. KISS1 gene products, the kisspeptins, bind to a G-protein-coupled receptor (KISS1R, formerly GPR54), which is highly expressed in placenta, pituitary, and pancreas, whereas KISS1 mRNA is mainly expressed in placenta, hypothalamus, striatum, and pituitary. OBJECTIVE AND DESIGN: KISS1/KISS1R pituitary expression profile, coupled to their anti-tumoral capacities, led us to hypothesize that this system may be involved in the biology of pituitary tumors. To explore this notion, expression levels of KISS1R and KISS1 were evaluated in normal and adenomatous pituitaries. Additionally, functionality of this system was assessed by treating dispersed pituitary adenoma cells in primary culture with kisspeptin-10 and evaluating intracellular calcium kinetics and apoptotic rate. RESULTS: Both KISS1 and KISS1R were expressed in normal pituitary, whereas this simultaneous expression was frequently lost in pituitary tumors, where diverse patterns of KISS1/KISS1R expression were observed that differed among distinct types of pituitary adenomas. Measurement of calcium kinetics revealed that kisspeptin-10 elicits a remarkable increase in [Ca(2+)](i) in individual cells from four out of the five GH-producing adenomas studied, whereas cells derived from non-functioning pituitary adenomas (NFPA, n=45) did not respond. In contrast, kisspeptin-10 treatment increased the apoptotic rate in cells derived from both GH-producing and NFPA. CONCLUSIONS: These results provide primary evidence that KISS1 and KISS1R expression can be differentially lost in pituitary tumor subtypes, where this system can exert functional, proapoptotic actions, and thereby offer novel insights to investigate the biology and therapeutic options to treat these tumors.


Subject(s)
Apoptosis , Gene Expression Regulation, Neoplastic , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/physiopathology , Receptors, G-Protein-Coupled/metabolism , Tumor Suppressor Proteins/metabolism , Apoptosis/genetics , Apoptosis/physiology , Calcium/metabolism , Cells, Cultured , Fluorescent Antibody Technique , Humans , In Vitro Techniques , Kisspeptins , Pituitary Gland/metabolism , Pituitary Gland/pathology , Pituitary Neoplasms/pathology , Receptors, G-Protein-Coupled/genetics , Receptors, Kisspeptin-1 , Reverse Transcriptase Polymerase Chain Reaction , Temperature , Tumor Suppressor Proteins/genetics
11.
J Clin Endocrinol Metab ; 95(9): 4367-79, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20554710

ABSTRACT

CONTEXT: Recent studies have suggested that long-term exposure to high levels of GH and IGF-I affect brain and cognitive functions. However, very few human studies have challenged this hypothesis. OBJECTIVE: The aim of this study is to explore whether GH/IGF-I excess in naive patients with acromegaly alters cognitive functions, particularly memory, and whether these alterations are accompanied by neurophysiological correlates. DESIGN: We conducted a comprehensive neuropsychological and neurophysiological exam on 16 naive acromegaly patients and 16 strictly matched healthy controls. Comparative analyses were carried out on major neurocognitive domains (executive functions, visual/verbal memory, attention, visuoconstructive abilities, and verbal fluency) and on quantitative electroencephalogram and low-resolution brain electromagnetic tomography sources. Results were correlated with GH and IGF-I hormone concentrations. RESULTS: Short- and long-term memory were the most severely impaired cognitive functions. Moreover, memory performance correlated negatively with GH and IGF-I concentrations. No association was detected between depression and memory impairment, and only a marginal association was found with quality of life. Finally, acromegaly patients showed power attenuation in fast frequency electroencephalogram bands, as well as decreased activity in prefrontal and middle temporal cortices, that was associated to cognitive performance. CONCLUSIONS: Results provide evidence of cognitive and neurophysiological impairment, characterized by moderate-to-severe memory impairment and decreased neural activity in specific brain areas. High levels of GH and IGF-I in acromegaly patients could be the basis for these findings.


Subject(s)
Acromegaly/complications , Brain Diseases/etiology , Cognition Disorders/etiology , Acromegaly/epidemiology , Adult , Attention/physiology , Brain Diseases/diagnosis , Brain Diseases/epidemiology , Cognition/physiology , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Female , Humans , Male , Memory/physiology , Memory Disorders/diagnosis , Memory Disorders/epidemiology , Memory Disorders/etiology , Middle Aged , Neurophysiology/methods , Neuropsychological Tests , Task Performance and Analysis , Young Adult
12.
Endocrinol Nutr ; 57(3): 95-9, 2010 Mar.
Article in Spanish | MEDLINE | ID: mdl-20207206

ABSTRACT

BACKGROUND AND OBJECTIVE: The aim of this study was to assess the utility of arterial calcium stimulation with hepatic venous sampling (ASVS) in the localization of tumors in patients with endogenous hyperinsulinism not detected with other methods. PATIENTS AND METHODS: We performed a retrospective study of 26 patients admitted to our hospital for hypoglycemia who underwent ASVS because the source of hyperinsulinism was not clearly identified by other imaging techniques. The histopathological result in patients who underwent a surgical procedure was considered the reference for statistical study of the accuracy of this technique. Statistical analysis was performed by comparing proportions with the chi-squared test with Yates' correction for contingency tables, and Cohen's kappa coefficient as a measure of interrater agreement between two observations. RESULTS: Surgery was performed in 17 patients, 13 with positive ASVS and the remaining four with negative results. An insulinoma was removed in 12 patients, and 10 of these were detected in the ASVS. A total of 76.9 % of positive ASVS tests corresponded to a histological diagnosis of insulinoma, and 83% of these insulinomas were positive in ASVS. This association was statistically significant (chi cuadrado=7.340; p=0.012). Two of three patients with nesidioblastosis had a positive response in the ASVS. A good and statistically significant agreement was obtained between histopathologic diagnosis and ASVS results (kappa=0.556, p = 0.007). CONCLUSIONS: ASVS is a useful procedure in the localization diagnosis of endogenous hyperinsulinism not detected by other imaging tests. This technique allows tumors in the pancreatic gland to be identified and may be useful in the choice of the surgical technique to be used.


Subject(s)
Calcium , Hyperinsulinism/blood , Hyperinsulinism/diagnosis , Adult , Female , Hepatic Veins , Humans , Hyperinsulinism/etiology , Insulinoma/complications , Insulinoma/surgery , Male , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/surgery , Retrospective Studies
13.
J Clin Endocrinol Metab ; 94(7): 2634-43, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19401364

ABSTRACT

CONTEXT: Somatostatin and its related peptide cortistatin exert multiple actions on normal and tumoral tissue targets through a family of receptors termed somatostatin receptor (sst)1-5. Despite the considerable advances in the knowledge on these receptors and their (patho)physiological roles, there is still evidence that additional receptors for these peptides should exist to fully explain their actions. OBJECTIVE: The growing number of spliced variants found in similar receptor families, often present in tumors, and results from our group obtained on sst5 from other species (pig) led us to explore the existence of new human sst5 isoforms. DESIGN AND RESULTS: A rapid amplification of cDNA ends PCR approach on samples from a human pituitary tumor and a cell line enabled identification of two novel alternatively spliced sst5 receptor variants. The sequences obtained encode putative proteins that correspond to truncated isoforms of five and four transmembrane domains (TMDs), accordingly named sst5TMD5 and sst5TMD4, respectively. Both novel receptors show a differential expression pattern in normal tissues and are also present in pituitary tumors of diverse etiology including nonfunctioning adenomas, corticotropinomas, somatotropinomas, and a prolactinoma. In contrast to the predominant plasma membrane localization of full-length sst5, both sst5TMD5 and sst5TMD4 show a preferentially intracellular localization. Despite their truncated nature, both receptors are functional, as shown by their ability to mediate selective, ligand-induced rises in free cytosolic calcium concentration. Specifically, whereas sst5TMD5 is selectivity activated by somatostatin compared with cortistatin, cells transfected with sst5TMD4 almost exclusively respond to cortistatin and not to somatostatin. CONCLUSIONS: Our results demonstrate the existence of two previously unidentified sst5 spliced variants with distinct distribution in normal tissues and pituitary tumors, unique ligand-selective signaling properties, and subcellular distribution, which could contribute to somatostatin and cortistatin signaling in normal and tumoral cells.


Subject(s)
Adenoma/genetics , Pituitary Neoplasms/genetics , Receptors, Somatostatin/genetics , Adenoma/metabolism , Adenoma/pathology , Amino Acid Sequence , Animals , Base Sequence , CHO Cells , Cloning, Molecular , Cricetinae , Cricetulus , Gene Expression Regulation, Neoplastic , HeLa Cells , Humans , Molecular Sequence Data , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Protein Isoforms/genetics , Protein Isoforms/isolation & purification , Receptors, Somatostatin/isolation & purification , Receptors, Somatostatin/physiology , Sequence Homology, Amino Acid , Tissue Distribution
14.
Endocrinol. nutr. (Ed. impr.) ; 60(1): 10-14, ene. 2013. ilus, tab
Article in Spanish | IBECS (Spain) | ID: ibc-108889

ABSTRACT

Objetivo: Evaluar la efectividad del protocolo de tratamiento intermitente con glucocorticoides a altas dosis por vía intravenosa (i.v.) en la oftalmopatía de Graves (OG) moderada-grave del Hospital Reina Sofía. Material y métodos Se incluyeron los pacientes con OG tratados con glucocorticoides i.v. en nuestro servicio desde agosto de 2007 a agosto de 2011. Se administró prednisolona i.v. en dosis de 7,5mg/kg/d 2d alternos durante 6 semanas alternas y mitad de la dosis durante 6 semanas más. Resultados Analizamos 18 pacientes (83,3% mujeres) con una edad media de 43±11 años. Cuatro eran fumadores, 5 habían dejado el hábito y el resto nunca habían fumado. El 66,7% presentaban hipertiroidismo por enfermedad de Graves, de los cuales el 41,6% habían recibido radioyodo. La respuesta al tratamiento fue buena en el 72,2%, parcial en 11,1% y mala en 16,7%. En 5 aparecieron efectos secundarios leves. Antes del tratamiento el 83,3% presentaron diplopía, el 33,3% retracción palpebral, el 72,2% dolor ocular y el 44,4% exoftalmos. Después del tratamiento solo el 33,3% continuaron con diplopía (p=0,004), el 5,6% con retracción palpebral (p=0,063), el 16,7% con dolor ocular (p=0,002) y el 11,1% con exoftalmos (p=0,031). El 22,2% precisaron radioterapia. La respuesta al tratamiento no se asoció a la enfermedad de base (p=0,866) al haber recibido radioyodo previo como tratamiento del hipertiroidismo (p=0,447) o al ser fumador (p=0,368).Conclusiones El tratamiento con glucocorticoides i.v. en la oftalmopatía tiroidea reduce significativamente la diplopía, el dolor ocular y el exoftalmos. Los efectos secundarios son leves y poco frecuentes. La respuesta al tratamiento es independiente de la enfermedad de base, de haber recibido radioyodo y de ser fumador (AU)


Objective: To assess the efficacy of intermittent, high-dose treatment with intravenous glucocorticoids (IV GCs) in moderate to severe Graves’ ophthalmopathy (GO).Materials and methods: Patients with GO treated with IV GCs from August 2007 to August 2011at the Endocrinology Department of Reina Sofía Hospital were enrolled into the study. IV pulseprednisol one (7.5 mg/kg/day) was administered twice weekly every two weeks for 6 weeks, and at half the dose for 6 additional weeks. Results: Eighteen patients (mean age, 43+/-11 years) with moderate to severe GO were analyzed (83.3% females). Four were active smokers, five former smokers, and the rest had never smoked. Hyperthyroidism due to Graves’ disease was found in 66.7% of patients, 41.6% of whom had received radioiodine therapy. Response to treatment was satisfactory in 72.2%, partial in11.1%, and poor in 16.7%. Mild side effects were reported by 5 patients. Before treatment,83.3% had diplopia, 33.3% eyelid retraction, 72.2% eye pain, and 44.4% exophthalmos. After treatment, only 33.3% had diplopia (P = .004), 5.6% eyelid retraction (P = .063), 16.7% eye pain(P = .002), and 11.1% exophthalmos (P = .031). Response to treatment was not related to the underlying disease (P = .866), prior radioiodine treatment (P = .447), or smoking status (P = .368).Conclusions: Intravenous glucocorticoid therapy decreased activity in patients with moderate to severe active GO, with major improvement occurring in diplopia, eye pain, and exophthalmos. Side effects were mild and uncommon. Treatment response was independent from the underlying disease, prior radioiodine treatment, or smoking status (AU)


Subject(s)
Humans , Graves Ophthalmopathy/drug therapy , Glucocorticoids/therapeutic use , Injections, Intravenous , Diplopia/drug therapy , Exophthalmos/drug therapy , Eye Pain/drug therapy
15.
Endocrinol. nutr. (Ed. impr.) ; 58(10): 510-515, dic. 2011. ilus, tab
Article in Spanish | IBECS (Spain) | ID: ibc-96975

ABSTRACT

Background and objective The current training program for resident physicians in endocrinology and nutrition (EN) organizes their medical learning. Program evaluation by physicians was assessed using a survey. Material and method The survey asked about demographic variables, EN training methods, working time and center, and opinion on training program contents. Results Fifty-one members of Sociedad Castellano-Manchega de Endocrinología, Nutrición y Diabetes, and Sociedad Andaluza de Endocrinología y Nutrición completed the survey. Forty-percent of them disagreed with the compulsory nature of internal medicine, cardiology, nephrology and, especially, neurology rotations (60%); a majority (>50%) were against several recommended rotations included in the program. The fourth year of residence was considered by 37.8% of respondents as the optimum time for outpatient and inpatient control and monitoring without direct supervision. The recommended monthly number of on-call duties was 3.8±1.2. We detected a positive opinion about extension of residence duration to 4.4±0.5 years. Doctoral thesis development during the residence period was not considered convenient by 66.7% of physicians. Finally, 97.8% of resident physicians would recommend residency in EN to other colleagues. Conclusions Endocrinologists surveyed disagreed with different training program aspects such as the rotation system, skill acquisition timing, and on-call duties. Therefore, an adaptation of the current training program in EN would be required( AU)


Antecedentes y objetivos El programa de formación MIR regula el aprendizaje de los médicos residentes en Endocrinología y Nutrición (EYN). Evaluamos la valoración que realizan los facultativos en EYN sobre dicho programa mediante una encuesta. Material y método La encuesta incluía: variables demográficas, vía y hospital de formación, tiempo trabajado, centro de trabajo actual, y la opinión sobre el contenido del programa de formación: sistema de rotaciones, competencias, guardias, y otras preguntas. Resultados Se encuestó a 51 endocrinólogos asistentes a las Jornadas de Casos Clínicos de las Sociedades Castellano-Manchega y Andaluza de EYN (SCAMEND, SAEN). Los entrevistados mostraron su desacuerdo con las rotaciones obligatorias durante el primer año de residencia en Neurología y Protección Radiológica, y con las recomendables por Digestivo, Neumología, Hematología y Unidad de Cuidados Intensivos. Sin embargo, creyeron convenientes las obligatorias a partir del segundo año de residencia dentro del propio Servicio de EYN (Hospital de Día, Consultas Externas y Nutrición). El 37,8% de los encuestados consideraron el cuarto año de residencia como el momento en que el residente puede realizar sin tutorización el control y seguimiento de pacientes ambulatorios y hospitalizados (nivel 1 de responsabilidad). La mayoría de los (..) (AU)


Subject(s)
Humans , Internship and Residency/trends , Endocrinology/education , Nutritional Sciences/education , Education, Medical/trends , 24419 , Teaching Care Integration Services/trends
16.
Endocrinol. nutr. (Ed. impr.) ; 58(10): 516-520, dic. 2011. tab
Article in Spanish | IBECS (Spain) | ID: ibc-96976

ABSTRACT

Introducción En 2006 se aprobó un nuevo programa formativo para la especialidad endocrinología y nutrición (EYN). Con la realización de una encuesta a los residentes de la especialidad tratamos de evaluar cómo es la formación de nuestros residentes, el grado de conocimiento y cumplimiento del nuevo programa y posibles cambios en la formación de especialistas de EYN derivados de ello comparando los resultados con los de encuestas previas. Material y métodos Se utilizó la misma encuesta ya distribuida en 2000 y 2005. La encuesta incluye variables demográficas, y preguntas sobre las distintas rotaciones, formación práctica y científica, evaluación de los distintos servicios de origen y otros aspectos. Se compararon los resultados con los de 2005.Resultados La encuesta fue completada por 40 residentes. Las rotaciones obligatorias se cumplen en su mayoría a excepción de neurología. Existen rotaciones que han quedado fuera del programa como radiología y medicina nuclear que aún son frecuentes y que los residentes incluirían de nuevo. Existe poco cumplimiento en los aspectos de formación práctica del área de endocrinología. Un 40% de los residentes desconoce aún el programa, aunque un 60% considera que se cumple. El 82,5% considera que sus servicios consiguen los objetivos formativos. Conclusiones Existen pocas diferencias respecto a las rotaciones respecto a los datos obtenidos en 2005 a pesar del cambio de programa y sigue habiendo carencias en aspectos prácticos de la especialidad. Por el contrario, se percibe una mejoría de la valoración de los residentes de la formación recibida por sus servicios y facultativos adjuntos con respecto a encuestas previas(AU)


Introduction In 2006, a new training program was approved for resident physicians in endocrinology and nutrition (EN). A survey was conducted to EN residents to assess their training, their depth of knowledge, and compliance with the new program, as well as potential changes in training, and the results obtained were compared to those from previous surveys. Material and methods A survey previously conducted in 2000 and 2005 was used for this study. The survey included demographic factors, questions about the different rotations, scientific and practical training, assessment of their training departments and other aspects. Results of the current survey were compared to those of the 2005 survey. Results The survey was completed by 40 residents. Mandatory rotations are mainly fulfilled, except for neurology. Some rotations removed from the program, such as radiology and nuclear medicine, still are frequently performed and popular among residents, who would include them back into the program. There was a low compliance with practical training in the endocrinology area. Forty percent of residents were not aware of the new program, but 60% thought that it was fulfilled. A total of 82.5% of residents thought that their departments fulfilled the training objectives. Conclusions Few differences were found in rotations as compared to the data collected in 2005 despite changes in the training program, and there was still a lack of practical training. By contrast, rating of training received from departments and senior physicians was improved as compared to prior surveys (AU)


Subject(s)
Humans , Education, Medical/trends , Internship and Residency/trends , Endocrinology/education , Nutritional Sciences/education , 24419 , Teaching Care Integration Services/trends
17.
Av. diabetol ; 27(2): 42-46, mar.-abr. 2011.
Article in Spanish | IBECS (Spain) | ID: ibc-90415

ABSTRACT

Introducción. Paradigm Real Time 722® (PRT-722) permite la infusión subcutánea continua de insulina (ISCI) y la monitorización continua de glucosa intersticial en tiempo real (MCG-TR). Aparte de ensayos clínicos, no hay información sobre sus beneficios en la clínica habitual. Objetivos. Analizar los cambios en el control glucémico y en la calidad de vida relacionada con la diabetes (CVRD) en pacientes con diabetes mellitus tipo 1 (DM1) tratados con sistema PRT-722 a 3 y 12 meses. Material y métodos. Seguimiento durante 12 meses de 24 pacientes que iniciaron tratamiento con el sistema PRT-722. Variables: tratamiento insulínico, CVRD (cuestionario EsQOL), hipoglucemias graves (encuesta retrospectiva), MCG y hemoglobina glucosilada (HbA1C). Resultados. Duración media de DM1, 15,5 ± 9,5 años. Las hipoglucemias graves durante el año anterior fue de 1,54 ± 4. La puntuación EsQOL basal, 92,79 ± 18,42. La frecuencia de uso de MCG-TR fue 3 meses, 20 ± 10,7%; 12 meses, 20,2 ± 13,1%. Detectamos un descenso de HbA1C de 0,6 ± 0,2% y 0,49 ± 0,19% a los 3 y los 12 meses, respectivamente, y menos hipoglucemias graves (1,08 ± 0,53; p < 0,05) durante el seguimiento. Además observamos una mejoría en la puntuación EsQOL a 3 (83,8 ± 21,6; p < 0,05) y 12 meses (79,41 ± 13,81; p < 0,05). Conclusiones. La utilización de PRT-722, con una frecuencia de uso de MCG-TR del 20%, se asoció con un descenso de HbA1C, menos hipoglucemias graves y una mejoría de la CVRD(AU)


Background and objectives. Paradigm Real Time 722® (PRT-722) is a dual electronic device, which allows both continuous subcutaneous insulin infusion and real-time continuous glucose monitoring (RT-CGM). There is no information available from controlled trials on their benefits during normal clinical practice. Our objective was to determine blood glucose and quality of life improvement at three and twelve months in PRT-722 treated type 1 diabetes mellitus (T1DM) patients. Patients and methods. One-year follow-up was conducted on 24 patients who started PRT-722. Insulin treatment, diabetes quality of life (DQOL), severe hypoglycaemic events, capillary glucose, HbA1C and continuous glucose information, were all recorded. Results. T1DM medium duration, 15.5±9.5 years. Severe hypoglycaemic events during 1 year before PRT-722, 1.54±4. DQOL pre-PRT 722 score, 92.79±18.42. CGM system frequency use: 3-months, 20±10.7%; 12-months, 20.2±13.1%. We detected a significant reduction in HbA1C levels at 3 and 12 months (0.6±0.2% and 0.49±0.19%, respectively), as well as in severe hypoglycaemic events during follow-up, 1.08±0.53 (p < .05). We also observed a significant improvement in DQOL score at 3 months (83.8±21.6, p < .05) and 12 months (79.41±13.81, p < .05). Conclusions. RT-CGM use close to 20 per cent with PRT-722 dual system was associated with a reduction of HbA1C levels, less severe hypoglycaemias and improvement of DQOL in T1DM patients at 3 and 12 months(AU)


Subject(s)
Humans , Diabetes Mellitus, Type 1/drug therapy , Insulin Infusion Systems , Glycated Hemoglobin/analysis , Hypoglycemia/prevention & control , Hyperglycemia/prevention & control
18.
Med. clín (Ed. impr.) ; 134(9): 381-385, abr. 2010. graf
Article in Spanish | IBECS (Spain) | ID: ibc-82749

ABSTRACT

Fundamento y objetivo: En nuestro estudio se plantea la hipótesis de que existe relación entre la evolución a corto plazo de los pacientes pediátricos con diabetes mellitus de tipo 1 y el grupo genético HLA-DQ. Pacientes y método: Se realizó un estudio epidemiológico descriptivo sobre 129 niños y adolescentes menores de 16 años con diabetes mellitus de tipo 1. Se estudió el grupo genético HLA-DQ y se clasificaron por grupos de riesgo diabetógeno. Se estudiaron parámetros generales, clínicos y analíticos al inicio, y su evolución durante el período de seguimiento de 3 años, además de la búsqueda de aparición de complicaciones crónicas asociadas. Resultados: El 93,8% de nuestros pacientes presenta un grupo de riesgo genético HLA-DQ. Cuando se produce el inicio de la enfermedad, los pacientes heterocigóticos del grupo de riesgo iii inician con una edad más precoz y presentan una menor reserva pancreática. Durante el seguimiento, los pacientes del grupo de riesgo iii presentan diferencias significativas en las medidas de presión arterial sistólica y diastólica, también los pacientes del grupo de riesgo i en las medidas de presión arterial diastólica. Conclusiones: Los pacientes del grupo de riesgo iii inician con menor edad y presentan diferencias significativas en las cifras de presión arterial sistólica y diastólica durante su seguimiento (AU)


Background and Objetive: Our hypothesis is that there is a relationship between the short term outcomes of pediatric patients with type I diabetes mellitus and their HLA-DQ genotypes. Patients and Method: We performed a descriptive epidemiologic study of 129 children and adolescents under 16 years old with type 1 diabetes mellitus. We studied their HLA DQ genotypes and classified them into groups of diabetogenic risk. We studied general clinic and analytic parameters at onset of the disease and during a period of 3 years, and the development of associated chronic complications. Results: In total, 93.8% of our patients had diabetes-risk HLA-DQ genotypes. Onset of the disease occurred earlier in patients who belonged to risk group III, and they had less pancreatic reserve. During the follow-up period, significant differences in systolic and diastolic blood pressure were found in patients in risk group III, and in diastolic blood pressure in patients in risk group I. Conclusions: Patients in risk group III have an onset at a lower age and present significant differences in systolic and diastolic blood pressure during the follow up period (AU)


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Diabetes Mellitus, Type 1/genetics , HLA-DQ Antigens/genetics , Diabetes Mellitus, Type 1/epidemiology , Clinical Evolution , Treatment Outcome , Genotype , Epidemiology, Descriptive , Blood Pressure/genetics
20.
Med. clín (Ed. impr.) ; 120(1): 4-9, ene. 2003. tab, graf
Article in Es | IBECS (Spain) | ID: ibc-16023

ABSTRACT

FUNDAMENTO Y OBJETIVO: Se plantea la hipótesis de que la presentación de la diabetes mellitus tipo 1A (DM1) depende en parte de las características genéticas del paciente, ya que determinan la forma de inicio. Analizamos si los haplotipos HLA DQA-DQB son determinantes en la aparición de DM1 y su gravedad, ya que hasta el momento no hay una definición clara en este sentido. PACIENTES Y MÉTODO: Se realizó el estudio de los haplotipos HLA DQA-DQB por técnicas de biología molecular a 86 pacientes con DM1 y se relacionó con distintos parámetros hallados en el inicio de la enfermedad, como edad, sexo, péptido C y gravedad clínica. RESULTADOS: El 89 per cent de los pacientes presentó al menos un haplotipo DQ de riesgo diabetogénico. La edad media de inicio de la enfermedad fue de 16 años, aunque la edad de máxima frecuencia está en los 9 años. No se apreciaron diferencias en función del sexo. Los pacientes heterocigotos DQA1*0501,0301/DQB1*0201,0302 presentaron una mayor precocidad en la aparición de la diabetes (9, frente a los 17 años en el resto), y los más jóvenes (los menores de 16 años) presentaron al inicio una menor reserva pancreática (péptido C de 0,37 frente a 1,4 ng/dl de los mayores de dicha edad). CONCLUSIONES: La heterocigosis HLA DQA1*0501,0301/DQB1*0201,0302 se asocia a una presentación temprana de la DM1, que se relaciona con una menor reserva pancreática (AU)


Subject(s)
Adolescent , Adult , Female , Child, Preschool , Infant , Male , Middle Aged , Child , Humans , Diabetes Mellitus, Type 1/genetics , HLA-DQ Antigens/genetics , Genetic Markers , Haplotypes/genetics , Age of Onset , C-Peptide/genetics , Gene Frequency , Genetic Testing , Genetic Predisposition to Disease/genetics , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/epidemiology , C-Peptide/blood
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