Presence of an extra chromosome alters meiotic double-stranded break repair dynamics and MLH1 foci distribution in human oocytes.

Studies performed on human trisomic 21 oocytes have revealed that during meiosis, the three homologues 21 synapse and, in some cases, achieve what looks like a trivalent. This implies that meiotic recombination takes place among the three homologous chromosomes 21, and to some extent, crossovers form between them. To see how meiotic recombination is in the presence of an extra chromosome 21, we analyzed the distribution of three recombination markers (γH2AX, RPA, and MLH1) on trisomic 21 oocytes at pachynema and, in particular, on chromosomes 21. Results clearly show how the presence of an extra chromosome 21 alters meiotic recombination progression, leading to the presence of a higher number of early recombination markers at pachynema. Moreover, the distribution on these chromosomes 21 of some of these markers is different in aneuploid oocytes. Finally, there is a substantial increase in the number of MLH1 foci, a marker of most crossovers in mammals, which is related to the number of synapsed chromosomes in pachynema. Thus, bivalents 21 had fewer MLH1 foci than partial or total trivalents, suggesting a close relationship between synapsis and crossover designation. All of the data presented suggest that the presence of an extra chromosome alters meiotic recombination globally in aneuploid human oocytes.

Notch-mediated induction of N-cadherin and α9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells.

BACKGROUND: Rhabdomyosarcoma (RMS) is the commonest type of soft-tissue sarcoma in children. Patients with metastatic RMS continue to have very poor prognosis. Recently, several works have demonstrated a connection between Notch pathway activation and the regulation of cell motility and invasiveness. However, the molecular mechanisms of this possible relationship remain unclear. METHODS: The Notch pathway was manipulated pharmacologically and genetically. The mRNA changes were analysed by quantitative PCR and protein variations by western blot and immunofluorescence. Finally, the capabilities of RMS cells to adhere, heal a wound and invade were assessed in the presence of neuronal cadherin (N-cadherin)- and α9-integrin-blocking antibodies. RESULTS: Cells treated with γ-secretase inhibitor showed lower adhesion capability and downregulation of N-cadherin and α9-integrin. Genetic manipulation of the Notch pathway led to concomitant variations in N-cadherin and α9-integrin. Treatment with anti-N-cadherin-blocking antibody rendered marked inhibition of cell adhesion and motility, while anti-α9-integrin-blocking antibody exerted a remarkable effect on cell adhesion and invasiveness. CONCLUSION: Neuronal cadherin and α9-integrin are postulated as leading actors in the association between the Notch pathway and promotion of cell adhesion, motility and invasion, pointing to these proteins and the Notch pathway itself as interesting putative targets for new molecular therapies against metastases in RMS.

Ten novel mutations in the NR5A1 gene cause disordered sex development in 46,XY and ovarian insufficiency in 46,XX individuals.

CONTEXT: Steroidogenic factor-1 (SF-1/NR5A1) is a nuclear receptor that regulates adrenal and reproductive development and function. NR5A1 mutations have been detected in 46,XY individuals with disorders of sexual development (DSD) but apparently normal adrenal function and in 46,XX women with normal sexual development yet primary ovarian insufficiency (POI). OBJECTIVE: A group of 100 46,XY DSD and two POI was studied for NR5A1 mutations and their impact. DESIGN: Clinical, biochemical, histological, genetic, and functional characteristics of the patients with NR5A1 mutations are reported. SETTING: Patients were referred from different centers in Spain, Switzerland, and Turkey. Histological and genetic studies were performed in Barcelona, Spain. In vitro studies were performed in Bern, Switzerland. PATIENTS: A total of 65 Spanish and 35 Turkish patients with 46,XY DSD and two Swiss 46,XX patients with POI were investigated. MAIN OUTCOME: Ten novel heterozygote NR5A1 mutations were detected and characterized (five missense, one nonsense, three frameshift mutations, and one duplication). RESULTS: The novel NR5A1 mutations were tested in vitro by promoter transactivation assays showing grossly reduced activity for mutations in the DNA binding domain and variably reduced activity for other mutations. Dominant negative effect of the mutations was excluded. We found high variability and thus no apparent genotype-structure-function-phenotype correlation. Histological studies of testes revealed vacuolization of Leydig cells due to fat accumulation. CONCLUSIONS: SF-1/NR5A1 mutations are frequently found in 46,XY DSD individuals (9%) and manifest with a broad phenotype. Testes histology is characteristic for fat accumulation and degeneration over time, similar to findings observed in patients with lipoid congenital adrenal hyperplasia (due to StAR mutations). Genotype-structure-function-phenotype correlation remains elusive.

Gene expression is altered after bisphenol A exposure in human fetal oocytes in vitro.

Bisphenol A (BPA) is a 'weak' endocrine disruptor. The effect of BPA on human reproduction is controversial but has been related to meiotic anomalies, recurrent spontaneous abortion, abnormal karyotypes, the diminishing of oocyte survival, delay in meiotic progression and an elevated rate of MLH1 foci in vitro. The aim of this study is to characterize the gene expression of human fetal oocytes in culture as well as to evaluate the effect of BPA in cultured human oocytes. To accomplish our objective, 12 ovaries from 6 euploid fetuses were used. The ovarian fetal tissue was cultivated in two groups: control group and BPA group (BPA30 µM). The cultures were analyzed at T0 and after 7 (T7), 14 (T14) and 21 (T21) days of culture. Evaluation of gene expression was performed by real-time PCR (RT-PCR), with the evaluated genes being: Smc1ß, Sycp1 (pairing-synapsis), Spo11, Rpa, H2ax, Mlh1 and Blm [double-strand break (DSBs) generation, signaling and repair], Erα, Erß and Errγ (estrogen receptors), Stra8 and Nalp5 (markers of meiotic progression). Oocytes from ovaries cultured and treated with BPA show changes in the expression of Spo11, H2ax and Blm genes, with a significant increase from 3- to 5-fold (P≤ 0.05). Finally, Rpa, showed a 100-fold increment (P≤ 0.01). Erα, Erß and Errγ genes showed a BPA up-regulation of 2-4-fold in all of the culture times (P≤ 0.05). Oocytes exposed to BPA showed an up-regulation of genes involved in DSB generation, signaling and repair except by Mlh1. Thus, BPA can modify the gene expression pattern, which may explain the effects of BPA on female germ cells.

SRD5A2 gene mutations and polymorphisms in Spanish 46,XY patients with a disorder of sex differentiation.

One hundred and forty-six index patients with 46,XY DSD in whom gonads were confirmed as testes were consecutively studied for a molecular diagnosis during the period 2002-2010. AR gene was analysed in all patients as the first candidate gene, yielding a mutation in 42.5% of cases and SRD5A2 gene was analysed as the second candidate gene, resulting in the characterization of 10 different mutations (p.Y91D, p.G115D, p.Q126R, p.R171S, p.Y188CfsX9, p.N193S, p.A207D, p.F219SfsX60, p.R227Q and p.R246W) in nine index patients (6.2% of the total number of 46,XY DSD patients). One of the mutations (p.Y188CfsX9) has never been reported. In addition, we genotyped SRD5A2 gene p.V89L and c.281+15T>C polymorphisms in 46,XY DSD and in 156 normal adult males and found that patients with SRD5A2 mutations or without a known molecular diagnosis presented a higher frequency of homozygous p.L89, homozygous TT and combined CCTT genotypes compared with controls. This result suggests that 46,XY DSD patient phenotypes may be influenced by SRD5A2 polymorphism genotypes. SRD5A2 gene mutations may not be as infrequent as previously considered in 46,XY DSD patients with variable degrees of external genitalia virilization at birth and normal T production and appears to be the second aetiology in our series.

Hamartoma condromesenquimal endobronquial / Endobronchial chondromesenchymal hamartoma

Los tumores pulmonares primarios son poco frecuentes en la infancia. Dentro de estos, los endobronquiales son todavía menos frecuentes y entre los benignos, los pseudotumores inflamatorios y los hamartomas son los de mayor incidencia. Se presenta el caso de una niña de 2 años y medio de edad afecta de un hamartoma condromesenquimal endobronquial izquierdo con obstrucción del 90% de la luz bronquial. Se realizó resección completa de la masa endobronquial mediante broncoscopio rígido y aplicación de mitomicina C tópica. Desde la resección del tumor y tras un periodo de seguimiento de 12 meses, la paciente ha presentado una evolución favorable con desaparición inmediata de la clínica respiratoria y con fibrobroncoscopias sucesivas sin objetivar tumor residual (AU)

Primary lung tumours are uncommon in childhood. Among these tumours, endobronchial masses are even less common and, among benign tumours, inflammatory pseudotumours and hamartomas have the highest incidence in children. We present the case of a 2.5-year-old girl with a left endobronchial chondromesenchymal hamartoma with obstruction of 90% of the bronchial lumen. Complete resection of the endobronchial mass was performed by rigid bronchoscopy and application of topical mitomycin C. After tumour resection and a 12-month follow-up, the patient has shown a favourable outcome with immediate disappearance of respiratory symptoms. Successive fibreoptic bronchoscopies have shown no residual tumour (AU)

[Endobronchial chondromesenchymal hamartoma]. / Hamartoma condromesenquimal endobronquial.

Primary lung tumours are uncommon in childhood. Among these tumours, endobronchial masses are even less common and, among benign tumours, inflammatory pseudotumours and hamartomas have the highest incidence in children. We present the case of a 2.5-year-old girl with a left endobronchial chondromesenchymal hamartoma with obstruction of 90% of the bronchial lumen. Complete resection of the endobronchial mass was performed by rigid bronchoscopy and application of topical mitomycin C. After tumour resection and a 12-month follow-up, the patient has shown a favourable outcome with immediate disappearance of respiratory symptoms. Successive fibreoptic bronchoscopies have shown no residual tumour.

Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

BACKGROUND: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). OBJECTIVE: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. SETTING: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. METHODS: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. RESULTS: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. CONCLUSIONS: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.

Vitamin D and growth hormone regulate growth hormone/insulin-like growth factor (GH-IGF) axis gene expression in human fetal epiphyseal chondrocytes.

OBJECTIVE: Cell proliferation and gene expression regulation were studied in human fetal epiphyseal chondrocytes to ascertain the involvement of GH-IGF axis components in human fetal growth regulation by 1,25-dihydroxyvitamin D(3) (VitD) and growth hormone (GH). DESIGN: Chondrocytes from primary cultures were plated in serum-free medium for 48 h and incubated for a further 48 h with VitD (10(-11) to 10(-6)M) and/or IGF-I (100 ng/ml) and/or GH (500 ng/ml). We analyzed (3)H-thymidine incorporation into DNA and IGF-I, IGFBP-3, GHR, SOX9, COL2A1, aggrecan and COMP gene expression by real-time quantitative PCR. RESULTS: VitD dose-dependently and significantly inhibited (3)H-thymidine incorporation whereas GH had no effect on proliferation and, when combined with VitD, the same inhibition was observed as with VitD alone. IGF-I (100 ng/ml) significantly stimulated proliferation and opposed inhibition by VitD. VitD dose-dependently stimulated IGF-I (11.1+/-19.8 at VitD10(-6)M), IGFBP-3 (2.6+/-0.9), GHR (3.8+/-2.8) and COMP (1.5+/-0.6) expression whereas it inhibited SOX9 (0.7+/-0.2), COL2A1 (0.6+/-0.3) and aggrecan (0.6+/-0.2) expression and had no significant effect on IGF-II. IGF-I stimulated IGF-I, IGFBP-3, SOX9, COL2A1 and aggrecan expression and opposed COL2A1 and aggrecan gene expression inhibition by VitD. GH alone had no effect on gene expression whereas, in the presence of VitD, significantly-increased IGF-I expression stimulation was observed above values obtained with VitD alone (17.5+/-7.4). CONCLUSIONS: Our results suggest that VitD regulation of fetal growth cartilage could have consisted of parallel enhancing of cell differentiation and conditioning to a phenotype more sensitive to regulation by other hormones such as GH as shown by increased GHR and IGF-I expression, but not by IGF-II expression which was not regulated.

IGF-I and not IGF-II expression is regulated by glucocorticoids in human fetal epiphyseal chondrocytes.

OBJECTIVE: To elucidate the involvement of IGF axis components and the potential effects of glucocorticoids (GCs) in human fetal growth regulation. DESIGN: We studied the regulation by dexamethasone (Dx) and IGF-I of proliferation and IGF axis components and matrix protein gene expression in human fetal epiphyseal chondrocytes. RESULTS: High Dx concentration (10(-7)-10(-6)M) inhibited (3)H-thymidine incorporation, mifepristone (MF) 10(-6)M limited inhibition by Dx, and IGF-I (100 ng/ml) significantly stimulated proliferation and completely opposed inhibition by Dx. Dx dose-dependently (10(-9)-10(-6)M) inhibited IGF-I, IGFBP3 and SOX9 gene expression and expression of GHR, COL2A1 and aggrecan from 10(-7)M to 10(-6)M whereas it stimulated IGF-IR expression. By contrast, Dx had no significant effect on IGF-II expression. IGF-I stimulated IGF-I, IGFBP3, SOX9, COL2A1 and aggrecan expression whereas it inhibited IGF-IR expression. IGF-I could oppose COL2A1 and aggrecan gene expression inhibition by Dx. CONCLUSIONS: We demonstrated for the first time by real-time quantitative PCR that human fetal epiphyseal chondrocytes expressed IGF axis components, such as IGF-I, IGF-II, IGFBP3, IGF-IR and GHR and SOX9, COL2A1 and aggrecan, and that their expression was regulated by Dx and IGF-I. Among IGFs, IGF-I and not IGF-II expression was demonstrated to be down-regulated by GCs whereas IGF-I expression was up-regulated by itself.

Crecimiento pulmonar fetal tras oclusión traqueal en el feto humano con hernia diafragmática congénita / Fetal pulmonary growth after tracheal occlusion in the human fetus with congenital diaphragmatic hernia

No disponible

A histological study of fetoscopic membrane defects to document membrane healing.

OBJECTIVE: To evaluate the rate of spontaneous healing in human fetal membranes after fetoscopy. STUDY DESIGN: Membranes from patients that had undergone fetoscopic interventions and delivered in one of the two treatment centers were included in the study. The membranes were examined macroscopically for any remaining defects and if present, the size of the defect in chorion and amnion was measured. Subsequently, the defect was excised and stained with HE for histological evaluation. Additional immunohistochemical staining was performed with Ki-67, cytokeratin and vimentin. The proliferation index (percentage of proliferating cells) was calculated in amnion and chorion. RESULTS: Nineteen membrane defects were included in the study. The median time interval between invasive procedures and delivery was 60 days (range 3-112). All fetoscopic defects (n=19) could be identified in the gestational sac and in none spontaneous closure had occurred. Proliferation indices as measured by inmunohistochemistry were very low (median 2.8%, range 0-7%) in the chorion and 0% in the amnion. CONCLUSION: No evidence of spontaneous membrane healing was found after fetoscopic procedures, suggesting that the membrane defect normally persists until delivery. Absence of amniotic fluid leakage after invasive procedures may be based on mechanisms other than histologic membrane repair.

Nueva estrategia quirúrgica en la gastrosquisis: simplificación del tratamiento atendiendo a su fisiopatología / New surgical strategy in gastroschisis: treatment simplification according to its physiopathology

Introducción. La gastrosquisis (GQS) es un defecto congénito de la pared abdominal que se caracteriza por la exposición de las asas intestinales al líquido amniótico a través de un orificio paraumbilical derecho. Tras el nacimiento a término, observamos gran edema e inflamación del intestino expuesto. En la corrección quirúrgica, éste ofrece una difícil reubicación abdominal, precisando en ocasiones un silo y cierre diferido. En el postoperatorio observamos un período prolongado de hipomotilidad intestinal que obliga a una nutrición parenteral (NPT) y a una larga estancia hospitalaria. Objetivo. El objetivo de este estudio es evaluar los beneficios de adelantar el parto para evitar la inflamación de las asas y evitar sus consecuencias neonatales. Pacientes y métodos. Desde Julio 2002 hemos tratado 6 casos de GQS con diagnóstico prenatal, siguiendo una nueva estrategia que consiste en adelantar el parto por cesárea programada a las 34-35 semanas de edad gestacional (EG) y realizar una reducción intestinal en la propia incubadora bajo anestesia general. Hemos comparado este grupo pretérmino (PT) con los 6 casos previos, operados desde Enero 1999, en que se dejó la gestación a término (AT). Se analizan el aspecto de las asas, la técnica quirúrgica, necesidad de silo, existencia de atresias, evolución postoperatoria, necesidad de NPT y estancia hospitalaria. Resultados. Todos los casos AT (EG media: 36,3 semanas) presentaron importante edema intestinal con engrosamiento de la pared. Se practicó cierre primario mediante laparotomía en 2 casos y cierre diferido con silo de silástic en 4 casos. En un caso existía atresia intestinal, un caso falleció por sepsis de origen intestinal. Necesitaron NPT durante una media de 41,2 días y la estancia hospitalaria fue de 69,8 días. El grupo PT se controló mediante ecografía prenatal. Tras el parto por cesárea electiva (EG media: 34,8 semanas), se observaron asas intestinales herniadas de aspecto normal, sin signos inflamatorios ni edema, excepto en un caso, que mostraba sonoluscencia intestinal en la ecografía antes de las 34 semanas. Ningún caso presentó dificultad respiratoria. Se realizó reducción intestinal sin dificultad en todos los casos. Un caso requirió revisión por una adherencia oclusiva, que alargó su estancia. La NPT se precisó en una media de 13,4 días y la alimentación enteral se inició a los 6 días. La estancia hospitalaria media fue de 28,6 días, si incluimos el caso que mostraba asas edematizadas. Conclusiones. Esta nueva estrategia de tratamiento de la GQS, adelantando el parto, evita la inflamación de las asas intestinales, facilitando su reducción a la cavidad abdominal, minimiza la aparición de atresias, reduce el período de hipoperistalsis intestinal, con introducción precoz de la alimentación oral y reducción de los días de NPT y estancia hospitalaria. Requiere una buena cooperación multidisciplinar entre los equipos de obstetricia, neonatología y cirugía pediátrica (AU)

Introduction. Gastroschisis (GS) is a congenital abdominal wall defect that permits bowel exposure to amniotic fluid (AF). Intestinal damage is related to the chemical action of AF and constriction. After birth at term, a thickened intestinal wall with inflammation and, in some cases, intestinal atresias were observed. Surgical repair and intestinal reubication may be difficult, and thus staged silo repair could be necessary. These patients require a long hospital stay owing to bowel damage causing severe intestinal hypoperistalsis and poor absorptive capacity. Total parenteral nutrition (TPN) is required for a long period. Objective. The aim of this prospective study is to evaluate the benefits of a preterm delivery to avoid bowel damage and its post-natal consequences. Patients and methods. Six cases of prenatally-diagnosed GS have been treated following a new strategy since July 2002. A preterm Cesarean section (c-section) delivery was programmed at 34-35 weeks of gestational age (GA). Some hours after birth, at bedside in the NICU, bowel reduction through the defect hole was performed under general anesthesia. This preterm group (PT) was compared the past 6 cases at term (AT) from January 1998 to July 2002. Macroscopic appearance, atresia existence, surgical technique, silo requirement, neonatal outcome, TPN and hospital stay were analyzed. Results. All six cases AT (mean GA: 36.3 weeks) presented bowel inflammation and thickened wall. Only 2/6 cases allowed the intestine to be housed in a primary closure after laparotomy. 4/6 cases required staged silo repair. 1 patient presented intestinal atresia and other had perforations who died at 17 days of life from intestinal sepsis. Mean postoperative intubation period was 16.2 days. Mean TPN was 41.2 days and mean hospital stay 69.8 days. PT group was monitored by prenatal sonography seeking bowel sonolucency. After programmed PT c-section delivery (mean GA: 34.8 weeks) in all 6 cases, bowel loops presented normal appearance and intestinal thickening was absent, except in one case. No prematurity-related respiratory complications were observed. Easy bowel reduction without abdominal compression was performed in all cases. 1/6 cases required surgical release of occlusive intestinal adherence. Mean postoperative intubation period was 0.4 days (9.6 hours). Oral feeding was started at 6 days. Mean TPN was 13.4 days and mean hospital stay 28.6 days. Conclusions. The third trimester is a critical period for fetal bowel development. Intestinal damage rises with increasing exposure time to amniotic fluid. This strategy of preterm delivery for the treatment of GS avoids intestinal damage, prevents «peel» and intestinal atresia, renders surgical reduction easier, reduces the hypoperistalsis, need for TPN and hospital stay. Multidisciplinary coordination between obstetricians, neonatologists and pediatric surgeons is required (AU)

[New surgical strategy in gastroschisis: treatment simplification according to its physiopathology]. / Nueva estrategia quirúrgica en la gastrosquisis: simplificación del tratamiento atendiendo a su fisiopatología.

INTRODUCTION: Gastroschisis (GS) is a congenital abdominal wall defect that permits bowel exposure to amniotic fluid (AF). Intestinal damage is related to the chemical action of AF and constriction. After birth at term, a thickened intestinal wall with inflammation and, in some cases, intestinal atresias were observed. Surgical repair and intestinal reubication may be difficult, and thus staged silo repair could be necessary. These patients require a long hospital stay owing to bowel damage causing severe intestinal hypoperistalsis and poor absorptive capacity. Total parenteral nutrition (TPN) is required for a long period. OBJECTIVE: The aim of this prospective study is to evaluate the benefits of a preterm delivery to avoid bowel damage and its post-natal consequences. PATIENTS AND METHODS: Six cases of prenatally-diagnosed GS have been treated following a new strategy since July 2002. A preterm Cesarean section (c-section) delivery was programmed at 34-35 weeks of gestational age (GA). Some hours after birth, at bedside in the NICU, bowel reduction through the defect hole was performed under general anesthesia. This preterm group (PT) was compared the past 6 cases at term (AT) from January 1998 to July 2002. Macroscopic appearance, atresia existence, surgical technique, silo requirement, neonatal outcome, TPN and hospital stay were analyzed. RESULTS: All six cases AT (mean GA: 36.3 weeks) presented bowel inflammation and thickened wall. Only 2/6 cases allowed the intestine to be housed in a primary closure after laparotomy. 4/6 cases required staged silo repair. 1 patient presented intestinal atresia and other had perforations who died at 17 days of life from intestinal sepsis. Mean postoperative intubation period was 16.2 days. Mean TPN was 41.2 days and mean hospital stay 69.8 days. PT group was monitored by prenatal sonography seeking bowel sonolucency. After programmed PT c-section delivery (mean GA: 34.8 weeks) in all 6 cases, bowel loops presented normal appearance and intestinal thickening was absent, except in one case. No prematurity-related respiratory complications were observed. Easy bowel reduction without abdominal compression was performed in all cases. 1/6 cases required surgical release of occlusive intestinal adherence. Mean postoperative intubation period was 0.4 days (9.6 hours). Oral feeding was started at 6 days. Mean TPN was 13.4 days and mean hospital stay 28.6 days. CONCLUSIONS: The third trimester is a critical period for fetal bowel development. Intestinal damage rises with increasing exposure time to amniotic fluid. This strategy of preterm delivery for the treatment of GS avoids intestinal damage, prevents "peel" and intestinal atresia, renders surgical reduction easier, reduces the hypoperistalsis, need for TPN and hospital stay. Multidisciplinary coordination between obstetricians, neonatologists and pediatric surgeons is required.

[Pancreatectomy level in the persistent hyperinsulinic hypoglycemia]. / Extensión de la pancreatectomía en la hipoglucemia hiperinsulínica persistente: nueva estrategia.

INTRODUCTION: Persistent neonatal and infantile hyperinsulinemic hypoglycemia (PNHH) is a rare entity which remains to be elucidated but associated with severe lesions in pediatric patients. The aim of this study is to present our current surgical strategy face to this disease, based on our pathology findings and clinical experience. MATERIAL AND METHODS: It is a retrospective study of 29 patients treated at our centre, medically and surgically. In 15 surgical patients, morphologic, morphometric and immunohistochemical studies for insulin, somatostatin and glucagon were performed and consequently it has been possible to establish a focal and different forms of a diffuse type. RESULTS: Out of 29 patients studied, 25 were diagnosed before their first year old and 4 patients between the first and second infancy. Of the 25 first patients, one died at 7 hours postpartum. Twelve patients only received medical treatment, one of them died at 45 days of life and the remaining 11 patients had good outcome. Another 12 patients received in addition surgical treatment. In 2 of them we observed adenoma which was removed and patients cured. In the remaining 10 patients a subtotal pancreatectomy was performed. (One case was informed as normal and cured and the other 9 had the diffuse type). Of these 9 patients with diffuse type, 4 died, 3 cured and 2 underwent second surgery. Out of the 4 patients diagnosed in infancy, 3 underwent surgery (2 adenomas and 1 diffuse type) and the other one received only medical treatment. CONCLUSIONS: Currently, we give medical treatment in all types and forms of PNHH. If the patient is resistant, we dismiss adenoma. If this is diagnosis we remove it. If the type is diffuse, near-total pancreatectomy is performed with a peroperatory biopsy. In cases of hyperplasia or mixed form we recommend a total pancreatectomy and in case of nesidioblastosis we recommend a partial pancreatectomy.

Pancreatectomy extension in persistent hyperinsulinaemic hypoglycaemia: a new strategy.

INTRODUCTION: Persistent neonatal and infantile hyperinsulinaemic hypoglycaemia (PNHH) is a rare entity which remains to be elucidated but is associated with severe lesions in paediatric patients. The aim of this study was to present our current surgical strategy with this disease, based on our pathologic findings and clinical experience. MATERIALS AND METHODS: This is a retrospective study of 29 patients treated, medically and surgically, at our centre. In 15 surgical patients, morphologic, morphometric and immunohistochemical studies for insulin, somatostatin and glucagon were performed and consequently it was possible to establish a focal and different forms of a diffuse type. RESULTS: Of 29 patients studied, 25 were diagnosed before one year of age and 4 between the first and second year of infancy. Of the first 25 patients, one died 7 hours post partum. Twelve patients received medical treatment alone: one died at 45 days of life and the remaining 11 had a good outcome. Another 12 patients additionally received surgical treatment. In 2 of these, adenoma were observed and removed and the patients cured. Subtotal pancreatectomy was performed in the remaining 10. (One case was normal and cured and the other 9 had the diffuse type.) Of these 9 patients with diffuse type, 4 died, 3 were cured and 2 underwent repeat surgery. Of the 4 patients diagnosed later, 3 underwent surgery (2 with adenomas and 1 diffuse type) and the other received medical treatment alone. CONCLUSIONS: We currently give medical treatment for all types and forms of PNHH. If the patient is resistant to therapy, adenoma is ruled out. If adenoma is diagnosed, it is removed. If the type is diffuse, near-total pancreatectomy is performed with a perioperative biopsy. In cases of hyperplasia or mixed forms we recommend total pancreatectomy and in cases of nesidioblastosis, partial pancreatectomy.

Resonancia magnética en el diagnóstico prenatal de malformaciones congénitas / Role of prenatal magnetic resonance in congenital malformations diagnosis

Introducción: La ecografía sigue siendo el método de estudio inicial de las malformaciones fetales, sin embargo, existen condiciones especiales y limitaciones que hacen de la resonancia magnética el método útil en estas circunstancias proporcionando un gran detalle de la anatomía y patología fetal. Objetivos: Determinar el valor de la resonancia magnética en el estudio de la patología fetal. Material y métodos: Se estudiaron en nuestro Centro mediante resonancia magnética 26 gestantes con la sospecha de malformaciones fetales mediante ecografía: 15 presentaban anomalías intracraneales, 1 pulmonar,1 diafragmática, 5 renales, 2 pélvicas 1 anomalía de columna vertebral y un embarazo gemelar siamés. Resultados: En nuestra experiencia, la resonancia magnética aportó información adicional en 6 de las 26 pacientes (23,07 por ciento) modificando la actitud terapéutica en 3 de ellas (11,03 por ciento); en 2 pacientes (7,6 por ciento) no identificó las alteraciones detectadas mediante ecografía. Conclusiones: La ecografía sigue siendo el método de estudio inicial de las malformaciones fetales. En los últimos años la aparición de nuevas secuencias rápidas y poco sensibles al movimiento han permitido el estudio del feto por resonancia magnética. Existen condiciones en las cuales la ecografía presenta limitaciones siendo en estas situaciones la resonancia magnética de gran utilidad pudiendo aportar información adicional que en ocasiones influye en el manejo de estos pacientes (AU)