Úlcera marginal perforada post bypass gástrico laparoscópico / Perforated marginal ulcer after laparoscopic gastric bypass

Introduction: Perforated marginal ulcer is a serious event that usually requires reoperation and is associated with morbidity and mortality. Characterization and management of these patients is still debated. Objective: To describe a series of patients subjected to a laparoscopic gastric bypass (LGBP) that evolved with a perforated marginal ulcer. Material and Methods: Records of patients undergoing a LGBP the last 10 years and evolved with a perforated marginal ulcer were retrospectively reviewed. Clinical features, treatment and perioperative morbidity and mortality were analyzed. Results: During this period 2,095 patients were subjected to a LGBP, 12 of them presented a perforated marginal ulcer, corresponding to 10 women and 2 men. Mean age was 39 (21-60) and mean body mass index at the time of initial surgery was 34 (29.3 to 38.6). Ten patients were smoker at the moment of perforation. The occurrence of this happened at a mean of 27 months (range 3-54, median 23.5) after surgery. Eleven cases had a surgical resolution, with a laparoscopic approach in 9 of them and laparotomy on 2. In all cases, a perforated ulcer in the jejunal side of the gastro-jejunal anastomosis was found. There was no mortality or morbidity associated with surgery. Conclusions: In our experience the occurrence of perforated marginal ulcer after a LGBP develops in a small percentage of patients. The laparoscopic approach is of choice, presenting a low morbidity and mortality. Smoking was present in most patients.

Introducción: La perforación de una úlcera marginal es un evento grave que suele requerir una reoperación y se asocia a morbimortalidad. El manejo de estos pacientes es debatido y complejo. Objetivo: Describir una serie de pacientes operados de bypass gástrico laparoscópico (BPGLP) que evolucionaron con una úlcera marginal perforada. Material y Método: Se revisaron retrospectivamente las fichas de pacientes operados de BPGL los últimos 10 años y que evolucionaron con una úlcera marginal perforada. Se analizaron las características clínicas, de tratamiento y morbimortalidad perioperatoria. Resultados: Durante este período se operaron 2.095 pacientes de BPGLP, 12 de los cuales presentaron una úlcera marginal perforada, correspondientes a 10 mujeres y 2 hombres. El promedio de edad fue 39 años (21-60) y el índice de masa corporal (IMC) promedio al momento de la primera cirugía fue 34 (29,3-38,6). Diez pacientes tenían hábito tabáquico activo al momento de la perforación. La ocurrencia de esta sucedió en promedio a los 27 meses (rango 3-54, mediana 23,5) de la cirugía. En 11 casos la resolución fue quirúrgica, mediante abordaje laparoscópico en 9 y laparotomía en 2. En todos los casos se encontró una úlcera perforada en la vertiente yeyunal de la gastro-yeyuno anastomosis. No hubo mortalidad ni morbilidad asociada a la cirugía. Conclusiones: En nuestra experiencia la ocurrencia de úlcera marginal perforada post BPGLP se desarrolla en un bajo porcentaje de pacientes. El abordaje laparoscópico es de elección, presentando una baja morbimortalidad. El hábito tabáquico estuvo presente en la mayoría de los pacientes.

Hernioplastía ventral laparoscópica / Laparoscopic repair of ventral hernias

Background: Ventral hernias are defects of the anterior abdominal wall, the laparoscopic repair has shown some advantages compared to open repair. Aim: To evaluate perioperative outcomes of the laparoscopic ventral hernia repair and to describe risk factors associated to recurrence. Methods: Non-concurrent prospective cohort study, clinical data of all patients who underwent laparoscopic ventral hernia repair between June 2006 and May 2013 were reviewed. Univariate analyses were performed using chi-square for categorical variables and U Mann-Whitney test for continuous variables. Multivariate analysis was performed using a logistic regression model. Results: 127 patients underwent laparoscopic ventral hernia, 52 percent female, age of 58.1 +/- 1.2 years old. Mean Body Mass Index (BMI) was 31 +/- 0.5 kg/m² and 67.7 percent were incisional hernias. Median operative time was 80 minutes (ranging from 30-350) and the median defect size was 6 cm (ranging from 2-20). Conversion to open surgery was necessary in 4 cases (3.9 percent). Median of hospital stay was 2 days (ranging from 1-15). Recurrence rate was 14.2 percent and the median to recurrence was 9 months. Recurrence rate was associated positively to defect size > 10 cm (p = 0.002), previous recurrence (p = 0.029) and operative time > 90 minutes (p = 0.017) in the univariate analyses. However, it was only associated to the first two in the multivariate analysis (OR 3.906; IC 1.734-13.058 y OR 5.93; IC 1.546-22.976, respectively). Conclusions: Laparoscopic repair of ventral hernia is a safe procedure with acceptable perioperative complication rates. Defect size and previous recurrence are associated to a higher recurrence rate.

Introducción: Las hernias ventrales son defectos de la pared abdominal, su reparación laparoscópica ha demostrado ventajas frente a la cirugía abierta. Objetivo: Mostrar nuestra experiencia en reparación laparoscópica de hernias ventrales y describir factores asociados a recidiva. Material y Método: Estudio prospectivo de cohorte no concurrente, revisión de registros clínicos de pacientes sometidos a hernioplastía ventral laparoscópica entre junio de 2006 y mayo de 2013. Registro de variables demográficas, perioperatorias y recidiva. Búsqueda de asociaciones entre variables y recidiva mediante análisis univariado, las que se ajustan usando un modelo de regresión logística. Resultados: Se analizan 127 pacientes, 52 por ciento mujeres, promedio de edad de 58,1 +/- 1,2 años e índice de masa corporal (IMC) de 31 +/- 0,5 kg/m². 67,7 por ciento fueron hernias incisionales, con una mediana de diámetro del defecto reparado de 6 cm (rango 2-20) y de tiempo operatorio de 80 min (rango 30-350). 4 casos (3,9 por ciento) fueron convertidos a cirugía abierta. La mediana de tiempo de hospitalización fue 2 días (rango 1-15). 14,2 por ciento de los casos presentaron recidiva. En el análisis univariado, el diámetro de defecto mayor a 10 cm (p = 0,002), antecedentes de recidiva herniaria (p = 0,029) y un tiempo quirúrgico mayor a 90 min (p = 0,017) se asociaron a recidiva. Posterior al análisis multivariado sólo los dos primeros mantuvieron su asociación (p = 0,01 y p = 0,03 respectivamente). Conclusión: La hernioplastía ventral laparoscópica es una técnica segura, con baja morbilidad. En esta serie inicial, el antecedente de recidiva y defectos mayores a 10 cm se asocian a mayor recidiva herniaria.

Tratamiento laparoscópico de la obstrucción intestinal por bridas / Laparoscopic treatment of adhesive small bowel obstruction

Background: Treatment options for adhesive small bowel obstruction (ASBO) involve conservative and surgical management, traditionally through open adhesiolysis. Laparoscopic approach has been performed in recent years; however, limited data exist on its safety and results vary considerably. Our aim is to report our experience of laparoscopic treatment for ASBO. Methods: Retrospective study including patients admitted with the diagnosis of adhesive small bowel obstruction and that were submitted to laparoscopic exploration, between June 2003 and April 2013. We analyzed demographic, surgical variables and outcomes in terms of conversion rate, operative time, re-feeding time and length of stay. Non-parametric tests were used for statistical analysis. Results: Series of 38 patients submitted to laparoscopic exploration, mean age: 51 +/- 16 years, 47 percent male. 53 percent had prior intra-abdominal surgeries. Laparoscopic resolution of bowel obstruction was possible in 31 patients (82 percent), with 7 conversions to open surgery. Median operative time was 60 (25-180) minutes, median re-feeding time was 24 (24-192) hours and median length of stay was 4 (2-52) days. Two patients required re-intervention during their hospital stay, one due to persistent bowel obstruction and one due to ischemic colitis. There were no other complications or mortality. Conclusions: Laparoscopy in adhesive small bowel obstruction was a feasible approach in this series, with good results when laparoscopic resolution is achieved. Patients with no prior surgeries seem to be good candidates for this approach.

Introducción: El tratamiento de la Obstrucción Intestinal por Bridas (OIB) incluye alternativas conservadoras y quirúrgicas, esta última tradicionalmente a través de cirugía abierta. El abordaje laparoscópico ha sido incorporado recientemente, sin embargo, existe información limitada sobre su seguridad y sus resultados varían considerablemente. Nuestro objetivo es presentar la experiencia de nuestro centro en el tratamiento laparoscópico de la OIB. Material y Métodos: Estudio retrospectivo incluyendo pacientes con el diagnóstico de OIB que fueron sometidos a cirugía laparoscópica en nuestro centro, entre junio de 2003 y abril de 2013. Análisis de variables demográficas, quirúrgicas y resultados obtenidos en términos de tasa de conversión, tiempo operatorio, tiempo de realimentación y estadía hospitalaria. Análisis estadístico con pruebas no paramétricas. Resultados: Serie de 38 pacientes, edad promedio: 51 +/- 16 años, 47 por ciento sexo masculino. 53 por ciento con antecedente de cirugía abdominal previa. Resolución completa por laparoscopía fue posible en 31 pacientes (82 por ciento), con 7 conversiones a cirugía abierta. La mediana de tiempo operatorio fue de 60 m (25-180), la mediana de tiempo a la realimentación fue de 24 h (24-192) y la mediana de estadía hospitalaria de 4 (2-52) días. Dos pacientes requirieron reoperaciones durante su hospitalización; uno debido a obstrucción intestinal persistente y otro debido a colitis isquémica. No se presentaron otras complicaciones ni mortalidad en esta serie. Conclusiones: El abordaje laparoscópico en OIB es factible de realizar en pacientes seleccionados, logrando buenos resultados en caso de resolución completa por laparoscopía. Pacientes sin cirugías abdominales previas son buenos candidatos para un abordaje laparoscópico inicial.

Gastrectomía laparoscópica en carcinoide gástrico / Laparoscopic gastrectomy in gastric carcinoid

Introduction: gastric carcinoid is a very low frequency tumor. A proportion of them require surgery to control the disease. The ideal surgical treatment is controversial. Aim: to describe the perioperative and follow-up course of patients with gastric carcinoid subjected to laparoscopic gastrectomy. Materials and Methods: retrospective study of patients undergoing some type of laparoscopic gastrectomy for gastric carcinoid the last 10 years. We collected demographic background, preoperative evaluation, type of surgery, complications and follow-up. Results: during the study period were operated 7 patients, 5 were men. The average age was 54 years. In three patients the diagnosis was a finding, while the rest had abdominal pain associated with nonspecific symptoms. Four patients had a type I gastric carcinoid associated with chronic gastritis and hypergastrinemia, and the others had a type III gastric carcinoid. Six patients underwent lapa-roscopic total gastrectomy while in the remaining patient (type III) was subtotal. There were no postoperative complications. During follow-up one patient required a reoperation for mechanical ileus secondary to adhesions and one patient required endoscopic dilatation because esophagoyeyunostomy stenosis. At 32 months of median follow-up (1-52) no patient has relapsed. Conclusion: laparoscopic gastrectomy is an alternative in the surgical treatment of patients with gastric carcinoid. It's safe and represent adequate oncological results in the short and medium term.

Introducción: el carcinoide gástrico es un tumor de muy baja frecuencia. Una proporción de ellos requiere de cirugía para controlar la enfermedad. El tratamiento quirúrgico ideal es controversial. Objetivo: describir los resultados perioperatorios y de seguimiento de pacientes con carcinoide gástrico de indicación quirúrgica, sometidos a gastrectomía laparoscópica. Materiales y Métodos: estudio retrospectivo de pacientes sometidos a algún tipo de gastrectomía por vía laparoscópica por carcinoide gástrico en los últimos 10 años. Se recopilaron antecedentes demográficos, estudio preoperatorio, tipo de cirugía, complicaciones y seguimiento. Resultados: durante el período de estudio se operaron 7 pacientes, 5 eran hombres. El promedio de edad fue 54 años. En tres pacientes el diagnóstico fue por hallazgo mientras que en el resto la presentación fue dolor abdominal asociado a síntomas inespecíficos. Cuatro pacientes presentaban un carcinoide tipo I asociado a gastritis crónica e hipergastrinemia, mientras el resto presentaba un carcinoide tipo III. En 6 pacientes se realizó una gastrectomía total por vía laparoscópica mientras que en el paciente restante (tipo III) fue subtotal. No hubo complicaciones postoperatorias. Durante el seguimiento un paciente requirió una re-exploración quirúrgica por un íleo mecánico secundario a bridas y otro paciente requirió dilatación endoscópica por estenosis de la esófago-yeyuno anastomosis. A los 32 meses de seguimiento promedio (1-52) ningún paciente ha recidivado. Conclusión: la gastrectomía laparoscópica constituye una alternativa quirúrgica en el tratamiento de los pacientes con carcinoide gástrico. Es una cirugía segura y de resultados oncológicos adecuados en el seguimiento a corto y mediano plazo de este tipo de pacientes.

Heterozygosity for lysosomal acid lipase E8SJM mutation and serum lipid concentrations.

BACKGROUND AND AIM: The complete absence of the lysosomal acid lipase (LAL) enzyme function causes Wolman's Disease that is fatal within the first six months of life. Subtotal defects cause Cholesteryl ester storage disease (CESD), an autosomal recessive disorder leading to hepatic steatosis, fibrosis, micronodular cirrhosis, combined hyperlipidemia with low HDL-cholesterol, increased risk for atherosclerosis, premature death. Since the frequency of the Exon 8 splice junction mutation (c.894 G > A, E8SJM), the CESD leading mutation, is not rare in the general population (allele frequency 0.0025), we investigated the impact of this mutation on serum lipid profile in E8SJM carriers. METHODS AND RESULTS: We collected E8SJM carriers both form genetic study-population analysis and from Outpatient Lipid Clinics and then we assessed their serum lipid profile. We found thirteen individuals heterozygote for E8SJM. Most of them were Germans, three Spanish and two Italian. We found a significant increase in total cholesterol levels in both sexes with E8SJM mutation, leading to a significant increase in LDL cholesterol in males. CONCLUSIONS: Our results show that LAL E8SJM carriers have an alteration in lipid profile with a Polygenic Hypercholesterolemia phenotype, leading to an increase in cardiovascular risk profile.

Necrosectomía laparoscópica en pancreatitis aguda / Laparoscopic necrosectomy in severe pancreatitis: retrospective analysis of 11 patients

Background: Laparoscopic surgery can be used in the treatment of severe acute pancreatitis. Aim: To report the experience with laparoscopic necrosectomy and abscess drainage in severe acute pancreatitis. Material and Methods: Retrospective analysis of medical records of 11 patients aged 13 to 78 years (10 males), with severe pancreatitis, subjected to laparoscopic necrosectomy or abscess drainage between 2006 and 2009. Results: Operative time ranged from 110 to 205 min. In all cases, a satisfactory necrosectomy and collection drainage were performed. No complications were recorded and no patient required to be converted to open surgery. Five patients were reoperated. In three of these, the laparoscopic approach was used again. Conclusions: Laparoscopic necrosectomy is safe and useful for patients with severe pancreatitis.

Introducción: La pancreatitis aguda grave, asociada a necrosis pancreática infectada, tiene una elevada mortalidad. En la mayoría de los casos, el tratamiento es quirúrgico, sin embargo, este se asocia a una alta morbilidad. El desarrollo de la cirugía mínimamente invasiva ha permitido incorporar la técnica laparoscópica al tratamiento de esta enfermedad. Objetivo: Presentar nuestra experiencia en necrosectomía y drenaje de abscesos por vía laparoscópica en pacientes con pancreatitis aguda grave. Pacientes y Métodos: Análisis retrospectivo de todos los pacientes con diagnóstico de pancreatitis aguda grave con necrosis infectada y/o abscesos sometidos a necrosectomía y drenaje de abscesos por vía laparoscópica. Se describen los datos demográficos, etiología de la pancreatitis aguda, imágenes pre y post-operatorias, así como los detalles de cada cirugía, la indicación quirúrgica, complicaciones, necesidad de re-operaciones y evolución tardía. Resultados: La serie está compuesta por 11 pacientes, todos con diagnóstico de pancreatitis aguda grave, operados entre abril de 2006 y junio de 2009. El tiempo operatorio promedio fue 138 min (110-205 min). En todos los casos, se realizó una necrosectomía satisfactoria y drenaje de colecciones. No hubo complicaciones derivadas de la técnica laparoscópica ni conversión a cirugía abierta en ningún paciente durante la primera cirugía. Cinco pacientes fueron re-operados, 3 de ellos por vía laparoscópica. Conclusiones: La necrosectomía laparoscópica es una alternativa válida y disponible en nuestro centro, con resultados comparables y probablemente superiores a la cirugía abierta, y con resultados satisfactorios en cuanto a morbilidad, protección de la pared abdominal y mortalidad postoperatoria.

Reparación de hernia incisional por vía laparoscópica: resultados iniciales / Laparoscopic repair of incisional hernias: experience in 21 patients

Background: Ventral hernias are one of the most common complications of open abdominal surgery and can be repaired laparoscopically. Aim: To assess the feasibility, safety and efficacy of the laparoscopic repair of incisional hernias. Patients and Methods: Retrospective study of the patients undergoing laparoscopic ventral hernia repair from march 2006 to october 2008 at a surgical department of a clinical hospital. We analyzed patient's characteristics, surgical variables, perioperative results, complications and short term follow up. Results: Twenty-one patients aged 54 +/- 14 years (16 females) underwent laparoscopic ventral hernia repair during this period. Their mean body mass index was 32.2 +/-6.5 kg/m². One patient was converted to open surgery. The mean hernia ring diameter was 8.4 +/- 3.9 cm (range 3-17). Median operative time was 92 minutes (range 45-300). Mean hospital stay was 3.0 +/-1.6 days. During the procedure, two patients were simultaneously subjected to a sleeve gastrectomy and cholecystectomy, respectively. Apulmonary atelectasis and a seroma occurred in two patients (10 percent) as early minor complications. As late complications, two patients (10 percent) experienced continuing pain in the area in both operations. No patient died. Follow up was 100 percent with a mean of 14 months (range 4-36), without hernia recurrence during this period. Conclusions: Laparoscopic incisional hernia repair is a feasible technique to perform, without serious complications.

Introducción: La hernia incisional (HI) es una de las complicaciones más frecuentes en cirugía abdominal abierta, siendo una alternativa para su corrección la hernioplastía por vía laparoscópica. El objetivo de este trabajo fue evaluar la factibilidad y eficacia de la reparación laparoscópica de la HI con seguimiento a corto plazo, dando a conocer nuestra experiencia inicial. Material y Método: Estudio retrospectivo de pacientes sometidos a hernioplastía incisional laparoscópica entre marzo de 2006 y octubre de 2008 en el Hospital Clínico de la Pontificia Universidad Católica de Chile. Se evaluó variables demográficas, perioperatorias, morbilidad y recidiva. Resultados: Fueron operados 21 pacientes en este período, 16 de género femenino, con un promedio de edad e índice de masa corporal de 54 +/- 13 años y 32,2 +/- 6,5 kg/m², respectivamente. Uno de ellos se convirtió a cirugía abierta. El diámetro mayor del anillo hemiario fue en promedio 8,4 +/-3,9 cm (rango 3-17) y la mediana de tiempo operatorio fue de 92 minutos (rango 45-300). La estadía hospitalaria fue 3,0 +/-1,6 días, en promedio. Durante la misma cirugía se realizó en dos pacientes gastrectomía en manga y colecistectomía. Se presentaron complicaciones precoces menores en dos pacientes (10 por ciento), una atelectasia pulmonar y un seroma, y complicaciones tardías menores en otros dos pacientes (10 por ciento), que correspondió a dolor prolongado en la zona operatoria en ambos. No hubo mortalidad en la serie. El seguimiento fue 100 por ciento, con un promedio de 14 meses (rango 4-36), sin recidiva en este período. Conclusiones: La hernioplastía incisional laparoscópica es una técnica factible de realizar en nuestro medio, sin complicaciones mayores en esta serie y buenos resultados a un a±o de seguimiento.

Pancreatoduodenectomía totalmente laparoscópica: técnica quirúrgica y experiencia inicial / Totally laparoscopic pancreaticoduodenectomy: surgical technique and initial experience

Introduction: Nowadays the utility of laparoscopic pancreatic surgery is accepted for a wide variety of indications. However pancreaticoduodenectomy has been considered beyond the possibilities of laparoscopy by the majority of surgeons. The objective of this report is to show our surgical technique and initial experience with totally laparoscopic pancreaticoduodenectomy. Material and Methods: Between November of 2007 and June of 2008, a laparoscopic technique was offered to patients with indication of pancreaticoduodenectomy for different pathologies. We describe the surgical technique, perioperative care, intraoperative complications, need for conversion to open technique, mortality, and early postoperative complications. Results: A total of three patients were subjected to laparoscopic pancreaticoduodenectomy. The surgical indication was an ampullar adenocarcinoma in a 52 years old woman, a pseudopapilar tumor of the pancreatic head in a 17 years oíd woman, and a duodenal gastrointestinal stromal tumor in a 63 years oíd man. There was no need for conversion to open technique. There was no mortality. The operative time ranged from 300 to 360 min. The first patient presented an upper gastrointestinal bleeding, from pancreatic anastomoses requiring surgical hemostasis. The last patient developed a self-limited biliary fistula, managed successfully with drains. The hospital stay varied from 8 to 25 days. Discussion: Totally laparoscopic pancreaticoduodenectomy is a feasible procedure, replicating the same steps of open surgery in a reasonable operative time, and with surgical results comparable with open technique.

Introducción: Actualmente la utilidad de la laparoscopía en la cirugía pancreática es ampliamente aceptada en diversas áreas; sin embargo, la pancreatoduodenectomía había sido considerada un procedimiento fuera de las posibilidades de laparoscopía por la mayoría de los cirujanos. El objetivo de este trabajo es dar a conocer la técnica quirúrgica y nuestra experiencia inicial con la pancreatoduodenectomía totalmente laparoscópica. Material y Métodos: Desde noviembre del 2007 hasta junio del 2008, se ofreció la vía de abordaje laparoscópica a pacientes con indicación de pancreatoduodenectomía curativa por diversas patologías. Se describe la técnica quirúrgica utilizada, el manejo perioperatorio, complicaciones intraoperatorias, necesidad de conversión a técnica abierta, mortalidad y complicaciones precoces. Resultados: Total = 3 pacientes. La indicación de cirugía fue por un adenoma ampular en una mujer de 52 años, un tumor pseudopapilar de cabeza de páncreas en una mujer de 17 años y un tumor estromal gastrointestinal duodenal en un hombre de 63 años. No se requirió de conversión a técnica abierta en ningún caso. No hubo mortalidad postoperatoria. Los tiempos operatorios variaron entre 300-360 min. La primera paciente presentó una hemorragia digestiva alta por sangrado del muñón pancreático, requiriendo reoperación. El último paciente presentó una fístula biliar autolimitada, manejada con drenajes. La estadía hospitalaria varió entre 8 y 25 días. Discusión: La pancreatoduodenectomía totalmente laparoscópica es técnicamente factible de realizar, replicando los mismos pasos de la técnica abierta, en un tiempo operatorio razonable, y obteniendo resultados quirúrgicos comparables a la técnica abierta.

Evaluation of single nucleotide polymorphisms in the phosphodiesterase 4D gene (PDE4D) and their association with ischaemic stroke in a large German cohort.

Genetic fine mapping of the first locus identified for genetically complex forms of stroke, STRK1 (which has been mapped to chromosome 5q12 in Icelandic families), has identified the phosphodiesterase 4D gene (PDE4D) gene as a good candidate gene. Association analysis of single nucleotide polymorphisms (SNPs) in the PDE4D gene in an Icelandic stroke cohort demonstrated genetic association between six SNPs in the 5' region of PDE4D and ischaemic stroke. The present study aimed to test whether the same six SNPs in PDE4D were also associated with stroke in a large stroke cohort from northern Germany (stroke patients with acute completed ischaemic stroke: n = 1181; population based controls: n = 1569). None of the six SNPs showed significant association with ischaemic stroke in the whole stroke sample before and after adjustment for conventional stroke risk factors (age, sex, hypertension, diabetes, and hypercholesterolaemia). Haplotype analysis did also not reveal any significant association. Marginally positive statistical measures of association in the subgroup with cardioembolic stroke did not remain significant after correction for multiple testing. In conclusion, this study was unable to demonstrate an association between the six SNPs which had showed significant single marker association with stroke in the Icelandic stroke cohort and ischaemic stroke in a large German cohort.

Resultados y utilidad de la biopsia pulmonar quirúrgica / Chirurgical pulmonary biopsy

Introducción: La biopsia pulmonar quirúrgica (BPQ) es útil en el diagnóstico de un grupo heterogéneo de enfermedades pulmonares, representando un potencial impacto terapéutico. Objetivo: Describir resultados y evaluar aporte práctico de la BPQ. Material y método: Estudio descriptivo-retrospectivo. Período Enero 1993-Junio 2004. Información de base de datos equipo cirugía cardiotorácica y fichas clínicas. Serie 63 pacientes, 37 de sexo femenino, promedio edad 54,4 ± 13,8 años. Todos referidos por especialista broncopulmonar con indicación de BPQ. En 56 casos se realizó minitoracotomía, en 7 videotoracoscopía. En 8 pacientes se realizó otro procedimiento. El diagnóstico preoperatorio más frecuente fue fibrosis pulmonar idiopática en 39. La muestra fue de pulmón izquierdo en 47, y en 36 de língula. Se describen complicaciones intraoperatorias, morbimortalidad, estadía postoperatoria, diagnóstico histopatológico. Para evaluar impacto en tratamiento, con especialista broncopulmonar se determinan criterios de cambio de tratamiento. Para análisis estadístico se utilizaron los test chi-cuadrado y exacto de Fisher. Resultados: No hubo complicaciones intraoperatorias. Presentaron complicaciones postoperatorias...

[Genetics of coronary heart disease]. / Genetik der koronaren Herzkrankheit.

Coronary heart disease (CHD) is among the leading causes for invalidity and death in industrialized countries. A prominent role of genetic factors in the onset of this disease has been documented in twin and family studies, by the use of experimental animal models, and by unravelling the genetic basis of monogenic disorders closely associated with CHD. Notwithstanding this knowledge attempts have failed to significantly improve prediction, early diagnosis and treatment of the common disorder CHD. The following will discuss the reasons for this lack of success but argue for positive perspectives that are ahead of us.

[Clinical aspects and molecular genetics of the Jervell- and Lange-Nielsen Syndrome]. / Klinik und Molekulargenetik des Jervell- und Lange-Nielsen-Syndroms.

In contrast to the Romano-Ward (R-W) syndrome, the Jervell and Lange-Nielsen (J-LN) syndrome is an autosomal recessive inherited disease characterized by QT-prolongation in the electrocardiogram (ECG) and recurrent syncopal attacks which are also typical for the R-W syndrome, but also by congenital deafness. Recently, defect alleles in the genes for KCNQ1 and KCNE1 have been identified in patients with the J-LN syndrome. These genes may be causative for the R-W syndrome as well but in J-LN patients, they are only present in the homozygote or compound heterozygote form. In the present paper, we review the clinical and genetic similarities and differences of the J-LN and the R-W syndrome as well as the diagnostic and therapeutic management of these patients and their family members.

Two newly identified SNPs in the APO AI-CIII intergenic region are strongly associated with familial combined hyperlipidaemia.

BACKGROUND: We previously reported linkage and association of the apoAI-CIII-AIV gene region on chromosome 11 with familial combined hyperlipidaemia (FCHL). However, the observed epistasis resulting in an increased susceptibility to FCHL still remains unexplained. We hypothesize that the region between the apo AI and apo CIII genes may harbour functional mutations that might be in linkage disequilibrium with the already identified SstI and MspI polymorphisms, and provide an alternative explanation for the observed relationship. METHODS: Using sequence analysis, we identified four new single nucleotide polymorphisms (SNPs) in the apo AI-CIII intergenic region. These four variants, T(3213)C, A(3235)C, T(3287)C and A(5132)C, were studied in 30 FCHL probands, 159 hyperlipidaemic relatives, 327 normolipidaemic relatives, and 218 spouses from the same families in which the original results were obtained. RESULTS: The allele frequencies were significantly different between probands and spouses (P < 0.05). Transmission/disequilibrium test (TDT) analyses revealed more frequent transmission of the minor alleles to the affected offspring. The minor genotype was associated with elevated plasma cholesterol and triglyceride levels. The T(3213)C and MspI, and the A(3235)C and SstI SNPs were in complete linkage disequilibrium, resulting in two different major haplotypes 2-2-1-2-2-1 and 1-1-2-2-2-2 (MspI-T(3213)C-A(3235)C-T(3287)C-A(5132)C-SstI). Both haplotypes appear to predispose to FCHL independently, and account, together with the wild-type, for almost 90% of those occurring in these FCHL families, extending the high-risk combination of haplotypes that were reported previously. CONCLUSION: These newly identified additional intergenic SNPs therefore provide an alternative explanation for the observed association of the SstI and MspI polymorphisms to the increased susceptibility for FCHL.

A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype.

Mutations in the human minK gene KCNE1 have been linked to autosomal dominant and autosomal recessive long-QT (LQT) syndrome, a cardiac condition predisposing to ventricular arrhythmias. minK and KvLQT1, the LQT1 gene product, form a native cardiac K+ channel that regulates the slowly delayed rectifier potassium current I(Ks). We used single-strand conformation polymorphism and sequencing techniques to identify novel KCNE1 mutations in patients with a congenital LQT syndrome of unknown genetic origin. In 150 unrelated index patients a missense mutation (V109I) was identified that significantly reduced the wild-type I(Ks) current amplitude (by 36%) when coexpressed with KvLQT1 in Xenopus oocytes. Other biophysical properties of the I(Ks) channel were not altered. Since we observed incomplete penetrance (only one of two mutation carriers could be diagnosed by clinical criteria), and the family's history was unremarkable for sudden cardiac death, the 109I allele most likely causes a mild phenotype. This finding may have implications for the occurrence of "acquired" conditions for ventricular arrhythmias and thereby the potential cardiac risk for asymptomatic mutation carriers still remains to be determined.

De novo mutation in the SCN5A gene associated with early onset of sudden infant death.

BACKGROUND: Congenital long QT syndrome (LQTS), a cardiac ion channel disease, is an important cause of sudden cardiac death. Prolongation of the QT interval has recently been associated with sudden infant death syndrome, which is the leading cause of death among infants between 1 week and 1 year of age. Available data suggest that early onset of congenital LQTS may contribute to premature sudden cardiac death in otherwise healthy infants. METHODS AND RESULTS: In an infant who died suddenly at the age of 9 weeks, we performed mutation screening in all known LQTS genes. In the surface ECG soon after birth, a prolonged QTc interval (600 ms(1/2)) and polymorphic ventricular tachyarrhythmias were documented. Mutational analysis identified a missense mutation (Ala1330Pro) in the cardiac sodium channel gene SCN5A, which was absent in both parents. Subsequent genetic testing confirmed paternity, thus suggesting a de novo origin. Voltage-clamp recordings of recombinant A1330P mutant channel expressed in HEK-293 cells showed a positive shift in voltage dependence of inactivation, a slowing of the time course of inactivation, and a faster recovery from inactivation. CONCLUSIONS: In this study, we report a de novo mutation in the sodium channel gene SCN5A, which is associated with sudden infant death. The altered functional characteristics of the mutant channel was different from previously reported LQTS3 mutants and caused a delay in final repolarization. Even in families without a history of LQTS, de novo mutations in cardiac ion channel genes may lead to sudden cardiac death in very young infants.

EXAFS as a tool for bond-length determination in the environment of heavy atoms.

Single crystal X-ray diffraction measurements are complicated in the presence of heavy atoms. In these cases the structure factors are mainly influenced by the heavy scatterers and the error in determination of atomic coordinates increases for light atoms. The difficulties grow if the unit cell dimensions or the space group symmetry remain uncertain. If the structure model is similar to the correct structure, it is difficult to find an independent criterion for the accuracy of the bond-length determination. We demonstrate that extended X-ray absorption fine structure (EXAFS) spectroscopy is a useful tool for the investigation of local bond lengths in the environment of heavy atoms.

Mutation analysis in Chariot-Marie Tooth disease type 1: point mutations in the MPZ gene and the GJB1 gene cause comparable phenotypic heterogeneity.

Charcot-Marie-Tooth disease type 1 (CMT1) is a demyelinating peripheral neuropathy most commonly caused by a DNA duplication on chromosome 17p11.2 including the peripheral myelin protein 22 (PMP22). Point mutations in the myelin protein zero gene (MPZ) and gap junction protein, beta-1 gene (GJB1) are also found in association with CMT1 or the subclass of CMT type X (CMTX), respectively. Recently point mutations in these genes have been found in patients showing the axonal variant of CMT, CMT type 2 (CMT2). We here describe the clinical and electro-physiological findings caused by two novel and two recently described MPZ mutations and six GJB1 mutations. Different MPZ and GJB1 mutations were associated with different grades of severity in CMT1 and CMTX. The novel MPZ Glu141st op mutation was associated with the axonal CMT2. We conclude that the clinical and electrophysiological heterogeneity among CMT patients carrying point mutations in MPZ and GJB1 is similar. Thus for clinical purposes CMT1 and CMT2 patients should be screened for mutations in these two genes after duplication on chromosome 17p11.2 has been excluded as the disease causing mutation.

Clinical value of electrocardiographic parameters in genotyped individuals with familial long QT syndrome.

Rate corrected QT interval (QTc) and QT dispersion (QTd) have been suggested as markers of an increased propensity to arrhythmic events and efficacy of therapy in patients with long QT syndrome (LQTS). To evaluate whether QTc and QTd correlate to genetic status and clinical symptoms in LQTS patients and their relatives, ECGs of 116 genotyped individuals were analyzed. JTc and QTc were longest in symptomatic patients (n = 28). Both QTd and JTd were significantly higher in symptomatic patients than in asymptomatic (n = 29) or unaffected family members (n = 59). The product of QTd/JTd and QTc/JTc was significantly different among all three groups. Both dispersion and product put additional and independent power on identification of mutation carriers when adjusted for sex and age in a logistic regression analysis. Thus, symptomatic patients with LQTS show marked inhomogenity of repolarization in the surface ECG. QT dispersion and QT product might be helpful in finding LQTS mutation carriers and might serve as additional ECG tools to identify asymptomatic LQTS patients.

Implications of the human genome project for the identification of genetic risk of coronary heart disease and its prevention in children.

Most male citizens of Western countries already have some degree of atherosclerosis by the age of 18, indicating that initiation of atherosclerosis in childhood is a virtually ubiquitous process. This process has a strong genetic component. However, identifying the exact nature of that component is not an easy task, because in the overwhelming majority of cases atherosclerosis is due not to disorders in single genes but to the effects of many genes operating together against a variable environmental background. The preliminary results of the sequencing of the human genome indicate fewer genes, but more complexity in the regulation of the expression of these genes, than was previously thought. For these reasons it is likely that prediction and management of atherosclerotic risk in children in the next years will depend not on the results of genetic testing, but on the differentiated analysis of classical risk factors. These issues are discussed in detail in this review.