Fine-mapping butyrophilin family genes revealed several polymorphisms influencing viral genotype selection in hepatitis C infection.

Host-viral genetic interaction has a key role in hepatitis C infection (HCV) and maybe in the viral selection. In a preliminary GWAS analysis, we identified BTN3A2 rs9104 to be associated with HCV genotype 1. Therefore, our aim was to determine the influence of BTN family on the selection of HCV genotype. We performed a fine-mapping analysis of BTN gene region in a cohort of chronic HCV infection (N=841), validating significant results in another independent chronic HCV infection cohort (N=637), according to selection of viral genotype. BTN3A2 rs9104, BTN3A2 rs733528, BTN2A1 rs6929846, BTN2A1 rs7763910 and BTN3A3 rs13220495 were associated with viral genotype selection. Interestingly, BTN3A2 rs9104 GG genotype was closely related to genotype 1 infection (80.7% (394/488) compared with genotype 3 infection (53.5% (23/43); P=0.0001) in patients harboring IL28B-CT/TT genotype, although this effect was not observed in IL28B-CC genotype. Similarly, BTN3A3 rs13220495 CC genotype was linked to genotype 3 infection (100% (32/32)) compared to genotype 1 (87.3% (137/157); P=0.028) in patients harboring IL28B-CC genotype, but did not in IL28B-CT/TT genotype. Genetic variants in the butyrophilin family genes may alter susceptibility to infection, selecting HCV genotype and influencing disease progression. BTN3A2 rs9104 was strongly associated with genotype 1 infection and the haplotype BTN3A3 rs13220495 CC+IL28B genotype CC was universal in patients with hepatitis C genotype 3a.

Andalusian Registry for familial adenomatous polyposis. Analysis of patients included.

OBJECTIVE: To evaluate the phenotype and genotype characteristic of patients included in the Andalusian Registry for familial adenomatous polyposis, the genotype/phenotype correlation and the impact of Registry in the frequency of colorectal cancer of registered. MATERIAL AND METHODS: A descriptive study of 77 patients with FAP belonging to 33 families, included in a centralized database visited by the physicians of the hospitals taking part in the present study, on prior signing of confidentiality letters. All genetic studies were carried out in the Immunology Service of our institution. RESULTS: We have included in our study 77 patients of 33 families; 31 probands with a mean age of 32 years (13-51) and 46 relatives at risk with a mean age of 21.8 years (6-55). Genetic study informed in 68/77 with positive result in 92.6%. Ten probands showed colorectal cancer (CRC) at the time of diagnosis (32.2%). Only two affected relatives showed CRC at diagnosis (4.3%), a statistically significant difference (p < 0.05). Gastrointestinal involvement was observed in 30/61 (49%), desmoid tumors in 7/77 (9.1%) and congenital hypertrophy of the retinal pigment epithelium in 23/55 (65.7%). 86.7% of patients with this alteration showed mutations between codons 454 and 1019, with a statistically significant correlation ((p < 0.05). CONCLUSIONS: The registry has facilitated the genetic diagnosis for all affected families disregard their province of origin. It has also improved the screening of affected relatives and has made it possible to take preventive measures immediately, therefore diminishing the incidence of CRC at diagnosis in registered affected relatives. The correlation between congenital hypertrophy of the retinal pigment epithelium with some mutations is the only phenotypic-genotypic correlation with statistical significance.

Registro Andaluz de la Poliposis Adenomatosa Familiar. Análisis de los pacientes incluidos / No disponible

Objetivos: Valorar las características fenotípicas y genotípicas de los pacientes incluidos en el Registro Andaluz de la poliposis adenomatosa familiar, la relación genotipo/fenotipo y el impacto del Registro en la frecuencia de cáncer colorrectal de los familiares registrados. Material y métodos: Estudio descriptivo de 77 pacientes con PAF, pertenecientes a 33 familias, incluidos en una base de datos centralizada a la que tienen acceso los responsables de los hospitales participantes, previa firma de cartas de confidencialidad. Todos los estudios genéticos se realizan en el Servicio de Inmunología de nuestro Hospital. Resultados: 77 pacientes registrados (50,6% varones): 31 probandos, edad media: 32 años (13-51) y 46 familiares afectos, edad media 21,8 años (6-55). Estudio genético informado en 68/77 con resultado positivo en 92,6%. Cáncer colorrectal al diagnóstico en diez probandos (32,2%) y 2 familiares afectos (4,3%), diferencia estadísticamente significativa (p < 0,05). Se observó afectación de tramos altos en 30/61 (49%), tumor desmoides en 7/77 (9,1%) e hipertrofia del epitelio pigmentario de la retina en 23/35 (65,7%). El 86,7% de los pacientes con esta alteración mostraron mutaciones entre los codones 454 y 1.019, relación estadísticamente significativa (p < 0,05). Conclusiones: El Registro Andaluz ha permitido ofrecer el diagnóstico genético en todas las familias afectas independientemente de su provincia de origen, mejorar el cribado, iniciar medidas preventivas precozmente y disminuir la frecuencia de cáncer colorrectal al diagnóstico en los familiares afectos registrados. La relación de la hipertrofia congénita del epitelio pigmentario de la retina con determinadas mutaciones es la única relación feno-genotípica con significación estadística(AU)

Objective: To evaluate the phenotype and genotype characteristic of patients included in the Andalusian Registry for familial adenomatous polyposis, the genotype/phenotype correlation and the impact of Registry in the frequency of colorectal cancer of registered. Material and methods: A descriptive study of 77 patients with FAP belonging to 33 families, included in a centralized database visited by the physicians of the hospitals taking part in the present study, on prior signing of confidentiality letters. All genetic studies were carried out in the Immunology Service of our institution. Results: We have included in our study 77 patients of 33 families; 31 probands with a mean age of 32 years (13-51) and 46 relatives at risk with a mean age of 21.8 years (6-55). Genetic study informed in 68/77 with positive result in 92.6%. Ten probands showed colorectal cancer (CRC) at the time of diagnosis (32.2%). Only two affected relatives showed CRC at diagnosis (4.3%), a statistically significant difference (p < 0.05). Gastrointestinal involvement was observed in 30/61 (49%), desmoid tumors in 7/77 (9.1%) and congenital hypertrophy of the retinal pigment epithelium in 23/55 (65.7%). 86.7% of patients with this alteration showed mutations between codons 454 and 1019, with a statistically significant correlation ((p< 0.05). Conclusions: The registry has facilitated the genetic diagnosis for all affected families disregard their province of origin. It has also improved the screening of affected relatives and has made it possible to take preventive measures immediately, therefore diminishing the incidence of CRC at diagnosis in registered affected relatives. The correlation between congenital hypertrophy of the retinal pigment epithelium with some mutations is the only phenotypic- genotypic correlation with statistical significance(AU)

Temporary structures as a generator of waste in covered trade fairs.

Events like trade fairs are a complex service activity with a considerable economic, social and environmental impact due, among other factors, to their high level of waste generation. There are few studies of the environmental impact associated with waste generation and typology. An environmental analysis methodology has been developed to characterise the waste associated with the temporary structures used at trade fair events: stands and communal spaces. This methodology has been checked in a pilot test at 6 closed trade fairs in Barcelona, with a range of between 60 and 4400 exhibitors. The methodology developed has made possible to obtain a waste generation profile according to the size of the fair and the types of stands. The stages with the largest amount of temporary structure wastes generated are the assembly and the dismantling of the trade fair. The results indicate that the most common wastes generated are the protective plastic from carpets at the assembly stage and the carpet itself at the dismantling stage. The stand carpet is collected in bulk, while the carpet from the communal spaces is recycled. As the size of the fair increases, and with it the proportion of stands with customised design (or non-reusable stands), the quantity of wood and hazardous waste increases.

Alteraciones en el metabolismo mineral óseo en pacientes con urolitiasis de repetición y polimorfismos del gen del receptor de la vitamina D. Resultados preliminares / Alterations in bone mineral metabolism in patients with calcium kidney stone disease and polymorphism of vitamin D receptor, preliminary results

Existe controversia sobre la afectación ósea en la litiasis renal cálcica. Por otro lado, algunos estudios genéticos han encontrado asociación entre los polimorfismos del receptor de la vitamina D (VDR) y la urolitiasis.Objetivo principal: Relacionar la nefrolitiasis cálcica de repetición con el metabolismo óseo y los polimorfismos del gen del VDR. Material y métodos: Estudio de casos y controles, estando el grupo de casos formado por 51 pacientes con litiasis renal de repetición, que subdividimos enno hipercalciúricos (NHC, n = 27), hipercalciúricos absortivos (HCA, n = 10) e hipercalciúricosrenales (HCR, n = 14); el grupo control, formado por 21 sujetos sin historia de litiasis renal ni hipercalciuria. Se les determinaron parámetros del metabolismo fosfo-cálcico, marcadores de remodelado óseo, densidad mineral ósea (DMO) en columna lumbar y en cuello femoral, y polimorfismos del gen del VDRpara los loci b, a y t. Resultados: Los pacientes litiásicos presentaron frente a los controles una DMO inferior tanto en L2-L4 como en cuello femoral (Z-score, p = 0,045 y 0,031), niveles superiores de 1,25 (OH)2 vitamina D (p = 0,002) e inferiores de PTH (p = 0,049), y una menor ingesta cálcica (p < 0,001). Los HCA mostraron una mayor DMO frente a los NHC (sólo significativo en cuello femoral). Los pacientes con LRC no mostraron diferencias en las frecuencias genotípicas estudiadas frente a los controles. Al reagrupar los alelos, sólo se apreció una menor frecuencia del genotipo BB respecto al Bb-bb, y del tt frente al TT-Tt, en los pacientes litiásicos (p =0,098 y p = 0,051, respectivamente). Conclusiones: La litiasis renal cálcica pareceinfluir en la DMO de cuello femoral. Los pacientes litiásicos mostraron niveles elevados de 1,25 (OH)2 vitamina D, posiblemente relacionado con la baja dieta cálcica. Los genotipos homocigóticos BB y tt parecen ser menos frecuentes entre los pacientes con litiasis renal cálcica

Bone health, within calcium kidney stone disease is a matter of controversy. On the other hand, some genetic studies have shown an association between some Vitamin Dreceptor polymorphisms and calcium kidney stone disease. Main objective: To study the possible association between calcium kidney stone disease with bone metabolismand some Vitamin D receptor polymorphisms. Patients and methods: This is a casecontrol study, with seventy-two subjects of both genders divided into two groups: Group I: cases, composed by 51 patients suffering from calcium kidney stone disease. Twenty-four of them had no hypercalciuria, 16 had absortive hypercalciuria and 11 had renal hypercalciuria. Group II: controls, composed by 21 people, without either urolithiasis or hypercalciuria. We performed a complete study including biochemical markers of bone mineral remodelling, bone mineral density (BMD) was estimatedboth in the lumbar spine (L2-L4) and femoral neck, and also VDR polymorphism for the loci b, a and t. Results: Patients with urolithiasis had lower values of BMD both in the lumbar spine and femoral neck, compared to controls. Z-score were lower in the lumbar spine and femoral neck (p = 0.045 y 0.031, respectively). Those patients with absorptive hypercalciuria had higher BMD in the femoral neck than those with renal hypercalciuria and non-hypercalciuria. Because they had more weight and height all the statistical study was performed alter adjusting by these two variables and statisticalsignificance was then only stated between patients with hypercalciuria and without it. Patients with urolithiasis had higher values of 1.25 (OH)2 vitamin D (p = 0.002), and lower of PTH (p = 0.049), without any relationship to hypercalciuria and its subtypes.Seventy six percent of the patients had a daily calcium intake lower than 800 mg/day. The distribution of VDR alleles in patients with urolithiasis was similar to controls, although after grouping genotypes, a lower distribution of BB and tt polymorphisms wereobserved in patients suffering from urolithiasis. Conclusions: Calcium kidney stone diseaseby itself produces a decrease in BMD, more intense in femoral neck, independently the presence or absence of hypercalciuria. Patients suffering from urolitihiasishave higher values of 1.25 (OH)2 vitamin D than non-hypercalciuric patients and lower values of PTH probably due to a low dietary calcium intake. In our populationstudied there is no relationship between VDR polymorphisms and the presence of calcium kidney stone disease. Because the reduced number of patients of our study,more studies are needed to obtain definitely conclusions

[Follow-up after surgical treatment of patients with familial adenomatous polyposis: results in a southern Spanish population]. / Seguimiento posquirúrgico de los pacientes con poliposis adenomatosa familiar: resultados en una población del sur de España.

OBJECTIVE: The study was to assess changes in the rectal mucosa and pouch in a series of patients with familial adenomatous polyposis (FAP) who underwent either subtotal colectomy and ileorectal anastomosis (IRA) or proctocolectomy and ileal pouch-anal anastomosis (IPAA), and to evaluate the suitability of the follow-up interval and postoperative treatment employed to prevent the development of cancer. METHOD: This study involved 28 patients with FAP who underwent IRA (n=20) or IPAA (n=8), and were followed endoscopically over a mean period of 7.47 years. The number and both macroscopic and histological features of polyps before and after surgery, the treatment, and complications were all analyzed. The suitability of the follow-up interval was assessed. RESULTS: None of the 26 patients who complied with follow-up developed rectal cancer. Two patients developed rectal cancer at 21 and 36 months after withdrawing from the protocol. Except in two cases in which surgery was indicated, patients who developed adenomas during follow-up were treated by endoscopic polypectomy. CONCLUSIONS: In our series, the failure to comply with follow-up examinations was associated with cancer development.

Seguimiento posquirúrgico de los pacientes con poliposis adenomatosa familiar: resultados en una población del sur de España / Follow-up after surgical treatment of patients with familial adenomtous polyposis: Results in a Southern Spanish population

Objetivo: analizar la evolución de la mucosa rectal y del reservorioasí como idoneidad de los intervalos de seguimiento y deltratamiento realizado para evitar la aparición del cáncer, en unaserie de pacientes con poliposis adenomatosa familiar (PAF), intervenidos.Método: estudio prospectivo de 28 pacientes con PAF intervenidosmediante anastomosis íleo-rectal (20 pacientes) y anastomosisíleo-anal con reservorio (8 pacientes). A todos se les habíarealizado un control endoscópico dos veces al año y análisis delnúmero y características macroscópicas e histológicas de los póliposantes y después de la cirugía así como del tratamiento realizado,de sus complicaciones y de la adecuación del intervalo de seguimiento.El seguimiento medio fue de 6,47 años (DE = 4,59;rango = 0,72-16,75 años).Resultados: ninguno de los 26 pacientes que cumplimentaroncorrectamente el protocolo de seguimiento desarrolló cáncer.Sólo dos pacientes lo desarrollaron al 1,75 y los 3 años, respectivamentedel abandono del protocolo. Los pacientes que desarrollaronadenomas durante el seguimiento fueron tratados con éxitomediante polipectomía endoscópica, salvo en dos casos que se indicócirugía.Conclusiones: en nuestra serie, el incumplimiento de las revisionesha sido el factor que ha condicionado la aparición de cáncer

Objective: the study was to assess changes in the rectal mucosaand pouch in a series of patients with familial adenomatouspolyposis (FAP) who underwent either subtotal colectomy and ileorectalanastomosis (IRA) or proctocolectomy and ileal pouchanalanastomosis (IPAA), and to evaluate the suitability of the follow-up interval and postoperative treatment employed to preventthe development of cancer.Method: this study involved 28 patients with FAP who underwentIRA (n=20) or IPAA (n=8), and were followed endoscopicallyover a mean period of 7.47 years. The number and bothmacroscopic and histological features of polyps before and aftersurgery, the treatment, and complications were all analyzed. Thesuitability of the follow-up interval was assessed.Results: none of the 26 patients who complied with follow-updeveloped rectal cancer. Two patients developed rectal cancer at21 and 36 months after withdrawing from the protocol. Except intwo cases in which surgery was indicated, patients who developedadenomas during follow-up were treated by endoscopic polypectomy.Conclusions: in our series, the failure to comply with followupexaminations was associated with cancer development

[Alterations in bone mineral metabolism in patients with calcium kidney stone disease and polymorphism of vitamin D receptor. Preliminary results]. / Alteraciones en el metabolismo mineral óseo en pacientes con urolitiasis de repetición y polimorfismos del gen del receptor de la vitamina D. Resultados preliminares.

UNLABELLED: Bone health, within calcium kidney stone disease is a matter of controversy. On the other hand, some genetic studies have shown an association between some Vitamin D receptor polymorphisms and calcium kidney stone disease. MAIN OBJECTIVE: To study the possible association between calcium kidney stone disease with bone metabolism and some Vitamin D receptor polymorphisms. PATIENTS AND METHODS: This is a case-control study, with seventy-two subjects of both genders divided into two groups: Group I: cases, composed by 51 patients suffering from calcium kidney stone disease. Twenty-four of them had no hypercalciuria, 16 had absortive hypercalciuria and 11 had renal hypercalciuria. Group II: controls, composed by 21 people, without either urolithiasis or hypercalciuria. We performed a complete study including biochemical markers of bone mineral remodelling, bone mineral density (BMD) was estimated both in the lumbar spine (L2-L4) and femoral neck, and also VDR polymorphism for the loci b, a and t. RESULTS: Patients with urolithiasis had lower values of BMD both in the lumbar spine and femoral neck, compared to controls. Z-score were lower in the lumbar spine and femoral neck (p =0,045 y 0,031, respectively). Those patients with absorptive hypercalciuria had higher BMD in the femoral neck than those with renal hypercalciuria and non-hypercalciuria. Because they had more weight and height all the statistical study was performed alter adjusting by these two variables and statistical significance was then only stated between patients with hypercalciuria and without it. Patients with urolithiasis had higher values of 1,25 (OH)2 vitamin D (p=0,002), and lower of PTH (p=0,049), without any relationship to hypercalciuria and its subtypes. Seventy six percent of the patients had a daily calcium intake lower than 800 mg/day. The distribution of VDR alleles in patients with urolithiasis was similar to controls, although after grouping genotypes, a lower distribution of BB and tt polymorphisms were observed in patients suffering from urolithiasis. CONCLUSIONS: Calcium kidney stone disease by itself produces a decrease in BMD, more intense in femoral neck, independently the presence or absence of hypercalciuria. Patients suffering from urolitihiasis have higher values of 1,25 (OH)2 vitamin D than non-hypercalciuric patients and lower values of PTH probably due to a low dietary calcium intake. In our population studied there is no relationship between VDR polymorphisms and the presence of calcium kidney stone disease. Because the reduced number of patients of our study, more studies are needed to obtain definitely conclusions.

Clinical and ethical implications of genetic counselling in familial adenomatous polyposis.

The association of specific genetic disturbances with the development of hereditary cancer helps us to understand the risk of suffering from it, the possibility of an earlier diagnosis, and the treatment and prevention of this disease. Familial adenomatous polyposis (FAP) is a pre-neoplastic syndrome characterized by the presence of hundreds of adenomatous polyps in the colon, which develop into a carcinoma. FAP can be diagnosed using sequencing techniques to detect mutations in the germinal line of the APC (adenomatous polyposis coli) gene. The genetic diagnostic approach in families with FAP, previously followed up in the Gastrointestinal Clinic, has both advantages and disadvantages, and places us nearer the disease and patient. Disclosing the results of this genetic test entails relevant problems in clinical practice, which affect the health field and raise legal and ethical issues, along with the familial, occupational, and social implications that knowing the genetic status can have on the patient. Genetic analysis is rare in normal clinical practice, which involves errors in the interpretation of the results obtained, and during the process of genetic counselling. Specialized multidisciplinary units are necessary for the management of patients with FAP undergoing analysis and appropriate genetic counselling, thus providing an individualized service. The creation of FAP registers and protocols for this healthcare process should optimize the management of these patients and their families.

Pancreatitis idiopática fibrosante como causa de ictericia obstructiva / Idiopathic fibrosing pancreatitis as a rare cause of obstructive jaundice

No disponible

Implicaciones clínicas y éticas del consejo genético en la poliposis adenomatosa familiar / Clinical and ethical implications of genetic counselling in familial adenomatous polyposis

La asociación de determinadas alteraciones genéticas con laaparición de cáncer hereditario, nos permite conocer el riesgo depadecerlo, posibilitando el diagnóstico precoz, el tratamiento y laprevención de la enfermedad. La poliposis adenomatosa familiar(PAF) es un síndrome preneoplásico que se caracteriza por la presenciade cientos de pólipos adenomatosos en colon, que evolucionaránhacia carcinoma. La PAF puede ser diagnosticada mediantetécnicas de secuenciación que detectan mutaciones en lalínea germinal del gen APC (adenomatous poliposis coli).El abordaje del diagnóstico genético en familias con PAF seguidaspreviamente en la consulta de digestivo, ha permitido ponerde manifiesto tanto las ventajas como los inconvenientes de estaforma de acercarnos a la enfermedad y a los pacientes. La revelaciónde los resultados de la prueba genética comporta importantesproblemas en la práctica clínica, que afectan tanto al ámbito sanitario,como al ético y legal, además de las implicaciones familiares,laborales y sociales que el conocimiento del status genéticopuede tener para el paciente.El análisis genético es poco frecuente en la práctica clínica habitual,lo que conlleva errores tanto en la interpretación de los resultadosobtenidos como durante el proceso del consejo genético.Son necesarias unidades multidisciplinares especializadas en elmanejo de pacientes con PAF, en las cuales se realice un análisis yun consejo genético adecuado, permitiendo así una atención personalizada.La creación de registros de PAF y la protocolizaciónde este proceso sanitario debería optimizar el manejo de estos pacientesy sus familias

The association of specific genetic disturbances with the developmentof hereditary cancer helps us to understand the risk of sufferingfrom it, the possibility of an earlier diagnosis, and the treatmentand prevention of this disease. Familial adenomatouspolyposis (FAP) is a pre-neoplastic syndrome characterized by thepresence of hundreds of adenomatous polyps in the colon, whichdevelop into a carcinoma. FAP can be diagnosed using sequencingtechniques to detect mutations in the germinal line of the APC(adenomatous polyposis coli) gene.The genetic diagnostic approach in families with FAP, previouslyfollowed up in the Gastrointestinal Clinic, has both advantagesand disadvantages, and places us nearer the disease and patient.Disclosing the results of this genetic test entails relevantproblems in clinical practice, which affect the health field and raiselegal and ethical issues, along with the familial, occupational, andsocial implications that knowing the genetic status can have onthe patient.Genetic analysis is rare in normal clinical practice, which involveserrors in the interpretation of the results obtained, and duringthe process of genetic counselling. Specialized multidisciplinaryunits are necessary for the management of patients with FAPundergoing analysis and appropriate genetic counselling, thusproviding an individualized service. The creation of FAP registersand protocols for this healthcare process should optimize themanagement of these patients and their families

Transient topographical disorientation.

Transient topographical disorientation (TTD) is a short-lasting inability to find one's way in a familiar environment, while the patient remains conscious and is able to recall what happened. We report the study of 10 patients with episodes of TTD, studied on the days following the last episode. The episodes of TTD could be separated into two types: the patients either reported difficulties in spatial orientation with preserved abilities to recognize landmarks and objects, or the difficulties appeared with the recognition of landmarks. Tests exploring spatial orientation, as well as higher visuoperceptive capacities were altered in most of the patients and brain SPECT showed hypoperfusion of the right hemisphere in all patients, which could also be demonstrated 2 years later in some cases. Altogether, our findings suggest that TTD is frequently associated with a more persistent right hemisphere dysfunction of unknown cause. This chronic alteration could represent either a sequel of the acute episode or a preexisting right hemisphere deficit, which inclined the acute insult to be manifested as TTD.

Mitochondrial disease and stroke.

BACKGROUND AND PURPOSE: It is well known that some mitochondrial disorders are responsible for ischemic cerebral infarction in young patients. Our purpose was to determine, in this prospective ongoing study, whether ischemic stroke is the only manifestation of a mitochondrial disorder in young patients. METHODS: Patients aged

Apolipoprotein E gene polymorphism is related to metabolic abnormalities, but does not influence erythrocyte membrane lipid composition or sodium-lithium countertransport activity in essential hypertension.

The aim of this study was to analyze the influence of the apolipoprotein E (apoE) gene polymorphism on insulin resistance and plasma lipid composition of essential hypertensive patients. A secondary objective was to analyze if differences regarding plasma lipids had an effect on the erythrocyte membrane lipid composition and the activity of the erythrocyte membrane sodium-lithium countertransport. We studied 128 untreated nondiabetic essential hypertensive patients enrolled from our outpatient clinic. We considered as hyperinsulinemic all subjects having more than 80 mU/L of plasma insulin 120 minutes after a 75-g oral glucose intake. The number of hyperinsulinemic subjects among carriers of the epsilon4 allele was higher that in epsilon4 noncarrier subjects (13 of 19 v45 of 109, P < .05; odds ratio [OR], 3.08; confidence interval [CI], 0.99-10.57). Plasma insulin at baseline and plasma insulin and glucose at 120 minutes after overload was higher in carriers of the epsilon4 allele (respectively, 17.5 +/- 6.9 v 12.4 +/- 4.9 mU/L, P < .01; 111.9 +/- 39.9 v 88.7 +/- 48.2, P < .05; and 143.8 +/- 29.3 v 121.2 +/- 30.8 mg/dL, P < .005). Subjects with the epsilon4 allele had a plasma lipid profile more atherogenic than those without this allele. This profile was mainly characterized by higher levels of low-density lipoprotein (LDL) cholesterol (150.1 +/- 31.2 v 133.0 +/- 34.3 mg/dL, P < .05) and very-low-density lipoprotein (VLDL) triglycerides (134.7 +/- 85.5 v 99.2 +/- 68.8 mg/dL, P < .05) and by lower levels of high-density lipoprotein (HDL) cholesterol (41.8 +/- 10.7 v 50.0 +/- 14.7 mg/dL, P < .05). There were no differences between groups regarding erythrocyte membrane cholesterol or phospholipids composition and sodium-lithium countertransport (SLC) activity.

Genetic variation in the beta-3-adrenergic receptor in essential hypertension.

We investigated the role of the beta-3-adrenergic receptor polymorphism in membrane lipid composition and erythrocyte membrane sodium transport in essential hypertensive patients. We studied 87 essential hypertensive patients determining: The Trp64Arg mutation of the beta-3-adrenergic receptor by PCR, lipoprotein profile by standard laboratory methods, membrane lipid composition by IATROSCAN and erythrocyte sodium lithium countertransport by Canessa technique. Patients with the mutation as compared with those without it showed lower membrane cholesterol, membrane cholesterol phospholipids ratio and erythrocyte sodium lithium countertransport, however blood pressure and the other studied variables were similar in both groups of patients. After adjusting by sex sodium lithium countertransport activity remained significant. These data suggest that although the Trp64Arg mutation of the beta-3-adrenergic receptor is related with a different membrane lipid composition and erythrocyte sodium lithium countertransport values it does not contribute to blood pressure levels in essential hypertensive patients.

[Mitochondrial encephalomyopathy of late presentation with progressive ophthalmoplegia, tremor and diffuse leukoencephalopathy]. / Encefalomiopatía mitocondrial de presentación tardía, con oftalmoplejía externa progresiva, temblor y leucoencefalopatía difusa.

A 60-year-old woman had developed ptosis, progressive external ophthalmoplegia and action tremor over the last ten years. Physical examination also revealed short stature and retinal pigmentation. Anaerobic forearm exercise test showed increase of basal lactate and rise of lactate/piruvate index. Biceps biopsy displayed numerous ragged red fibers. Respiratory chain studies were consistent with complex I deficiency. Point mutations or deletions in mitochondrial DNA were not found. MR identified a diffuse leukoencephalopathy over both cerebral hemispheres, mesencephalon, pons and cerebellum. The late and sporadic onset of a progressive external ophthalmoplegia outlining a Kearns-Sayre syndrome is striking. A leukoencephalopathy associated with mitochondrial encephalomyopathy is an infrequent finding. The action tremor of this patient could be symptomatic of her mitochondrial disfunction.

[The effect of the angiotensinogen M235T and the angiotensin-converting enzyme I/D polymorphisms on arterial hypertension and other cardiovascular risk factors]. / Influencia de los polimorfismos M235T del angiotensinógeno e I/D de la enzima conversiva de la angiotensina sobre la hipertensión arterial y otros factores de riesgo cardiovascular.

BACKGROUND: It has been reported the association between M235T angiotensinogen (AGT) and I/D angiotensin converting enzyme (ACE) gene polymorphisms and hypertension and other cardiovascular risk factors. However there are few data about Spanish population. So that we have studied the relationship among the aforementioned polymorphisms and hypertension and the possibility of association between any polymorphism and a worse cardiovascular risk profile. PATIENTS AND METHODS: 251 hypertensive and 245 control normotensive subjects were studied. The M235T AGT and the I/D ACE gene polymorphisms were determined by polymerase chain reaction (PCR). Family and personal history of cardiovascular disease, lipoprotein profile, microalbuminuria and left ventricular hypertrophy (LVH) by Sokolow index were analyzed in hypertensive patients. RESULTS: The distribution of the different polymorphisms was similar among hypertensive and normotensive subjects. There was not any relationship among AGT nor ACE genotypes and target organ damage. The II ACE genotype was associated with higher lipoprotein (a) (Lp[a]) levels and greater cerebrovascular disease family history and the MT AGT genotype with lower total cholesterol (TC) and triglycerides (TG) levels. CONCLUSIONS: In our study there was not any relationship between arterial hypertension and M235T AGT or I/D ACE gene polymorphisms. None specific genotype was associated with worse cardiovascular risk profile. The II ACE genotype was a predictor of cerebrovascular disease risk through higher levels of Lp(a) and the MT AGT genotype was associated with a better lipid profile.

Presence of antibodies to replication protein A in some patients with systemic lupus erythematosus (SLE).

Presence of antibodies directed against replication protein A (RPA), a DNA binding protein complex composed of three subunits (RPA-70, RPA-32 and RPA-14) was investigated among patients with SLE and other autoimmune diseases using immunoblot analysis to RPA-70 and RPA-32 recombinant proteins. Anti-RPA antibodies were found in two out of 108 sera from SLE patients, one of them showing reactivity against RPA-32 and RPA-70 and the other reacting only against RPA-32. Sera from 108 patients with other autoimmune disorders as well as from 42 healthy control individuals were negative. Thus, the frequency of these antibodies in SLE is estimated to be 2-3%. The study demonstrates that RPA is one target more of the wide array of autoantigens that elicit an immune response in SLE. The presence of anti-RPA autoantibodies seems to be circumscribed to a small number of patients with SLE.