Matrix regulation of skeletal cell apoptosis II: role of Arg-Gly-Asp-containing peptides.

This investigation was based on the assumption that arg-gly-asp (RGD)-containing peptides are released from the extracellular matrix of bone and cartilage during the remodeling cycle. We asked the question: Can RGD peptides influence skeletal cell viability? Primary human osteoblasts, mouse MC-3T3-E1 cells, and chick chondrocytes were incubated with purified RGD-containing peptides and cell viability was determined. The RGD peptide did not kill osteoblasts, chondrocytes, or MC-3T3-E1 cells. In contrast, RGDS and GRGDSP peptides killed all three cell types. Osteoblast death was quite rapid, occurring within 6 h of treatment. transferase uridyl mediated nick end labeling (TUNEL) and transmission electron microscopy (TEM) analysis indicated that death was mediated by apoptosis. To learn if mitochondria transduced the death signal, cells were treated with RGDS and organelle function was evaluated using a voltage-sensitive fluorescent probe. It was observed that there was no net loss of fluorescence and, hence, it was concluded that mitochondria were not the primary effectors of the apoptotic response. Experiments were performed with enzyme inhibitors to determine the import of the caspase pathway on RGDS-mediated osteoblast apoptosis. Results of these studies, as well as a study conducted using a fluorescent substrate, pointed to caspase 3 mediating the effector stage of the apoptotic process. Finally, using a purified labeled-RGDS peptide, we showed that the molecule was not restricted by the plasma membrane because it was accumulated in the cytosolic compartment. Results of the investigation support the view that resorption of the extracellular matrix generates peptide products that can induce apoptosis of vicinal cells.     

Real-time movie imaging from a single cardiac cycle by NMR

Using a 1-m-bore superconductive magnet at 0.1 T, whole-body transverse images through adult humans have been obtained at repetition times of 57 ms. The techniques used were minor variations of echo-planar imaging (EPI) employing large pulsed gradients to provide complete coverage of the plane in phase space, and low-angle RF excitation sequences allowing rapid repetition of the experiment. In addition active magnetic screening of the gradient coils was implemented to protect the surrounding magnet from the eddy currents induced by the necessarily fast switching of the large gradient fields.     

Duodenal atresia and stenosis: Reassessment of treatment and outcome based on antenatal diagnosis,pathologic variance,and long-term follow-up

Duodenal atresia and stenosis was observed in 103 infants and children from 1972 to 1991. There were 59 girls and 44 boys. Atresia was noted in 79 instances and stenosis in 24. Maternal hydramnios was detected in 33 cases, 46 babies were premature, and 31 had Down's syndrome. Fifty-four infants had significant associated anomalies including 35 with cardiac defects. Diagnosis was achieved by prenatal ultrasound examination in 14 cases, observation of a double-bubble sign on abdominal radiograph in 73, and contrast studies in 30 infants including 24 with stenosis. At operation annular pancreas was noted in 37 cases, malrotation in 37 cases, anterior portal vein in 4, and a second web in 3. Surgical treatment included duodenoduodenostomy in 85, duodenotomy and web excision in 8, and duodenojejunostomy in 10. Operative survival was 95%. Deaths were related to complex cardiac defects. Despite antenatal diagnosis, prompt intervention, and apparent early surgical success (95% survival), late deaths (5%) and late complications including motility disorders, megaduodenum, gastroesophageal reflux, duodenal-gastric reflux, gastritis, peptic ulcer disease, blind loop syndrome, and biliary-pancreatic conditions may be observed months to years after management during the neonatal period. Modifications in surgical technique including early tapering duodenoplasty may be useful, and close long-term follow-up is an essential component of patient care.

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Resumen Se encontró atresia duodenal y estenosis en 103 niños, 59 de sexo femenino y 44 de sexo masculino, en el período 1972–91: atresia en 79 casos y estenosis en 24. Se registró hidramnios materna en 33 casos; 46 niños fueron prematuros y 31 presentaban síndrome de Down; 54 exhibían anomalías de significación, incluyendo 35 con defectos cardiacos. El diagnóstico fue establecido por ultrasonido prenatal en 14 casos, mediante la observación de burbuja doble en la radiografía abdominal en 73 y por estudio con medio de contraste en 30, entre los cuales había 24 con estenosis. En la operación se encontró páncreas anular en 37 casos, malrotación en 37, vena porta anterior en 4 y segunda membrana en 3. El tratamiento quirúrgico incluyó duodenostomía en 85 pacientes, duodenotomía y resección de membrana en 8 y duodenoyeyunostomía en 10. La tasa de sobrevida operatoria fue de 95%. Las muertes estuvieron asociadas con los defectos cardfacos complejos. A pesar de su diagnóstico prenatal, una intervención quirúrgica precoz y un aparente éxito operatorio (sobrevida de 95%), se observan muertes tardías (5%) y complicaciones a largo plazo tales como desórdenes de la motilidad intestinal, megaduodeno, reflujo gastroesofágico, reflujo duodeno-gástrico, gastritis, enfermedad ulcerosa péptica, síndrome de asa ciega y alteraciones biliopancreáticas, meses a años después del tratamiento y manejo neonatales. Algunas modificaciones en la técnica quirúrgica, tales como duodenoplastia, pueden ser de utilidad; el seguimiento cuidadoso a largo plazo constituye un componente esencial de la atención de estos pacientes.

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Résumé Entre 1972 et 1991, on a observé 79 cas d'atrésie duodénale et 24 cas de sténose duodénale chez un total de 103 enfants, 59 filles et 44 garçons. Une hydramnios a été retrouvée chez 33 des mères, 46 enfants étaient des prématurés et 31 avait un syndrome de Down. Chez 54 enfants, il y avait des malformations associées, dont 35 cardiaques. Le diagnostic avait été établi dans 14 cas par une échographie anténatale, par l'existence du signe de la double bulle sur les abdomens sans préparation chez 73 patients et par une étude du transit intestinal en double contraste chez 34 enfants, dont 24 avec une sténose. A l'opération, on a retrouvé un pancréas annulaire chez 37 enfants, une malrotation chez 37, une veine porte antérieure chez 4, et une membrane intraluminale chez 3. Le traitement a été une anastomose duodénoduodénale chez 85 enfants, une excision de membrane après duodénotomie chez 8 et une duodénojéjunostomie chez 10. La mortalité opératoire était de 5%, en rapport essentiellement avec des malformations cardiaques complexes. En dépit d'un diagnostic anténatal, une intervention précoce et un succès chirurgical apparent, la morbidité tardive est toujours possible et comprend essentiellement des anomalies de la motilité duodénale, le mégaduodénum, un reflux gastroesophagien, un reflux duodénogastrique, une gastrite, la maladie ulcéreuse, un syndrome de l'anse borgne, et d'autres anomalies biliopancréatiques qui peuvent se voir des mois ou des années après la période néonatale. Les modifications de la technique chirurgicale et notamment la duodénoplastie précoce ainsi qu'une meilleure surveillance à distance, peuvent en améliorer le pronostic.

     

Anterior ischemic optic neuropathy: Classification of field defects by Octopus™ automated static perimetry

Visual fields of patients with anterior ischemic optic neuropathy (AION) were classified according to quantitative criteria, using the Octopus perimeter. Although a significant altitudinal pattern of field loss was found in 55% of perimetric examinations, the "spared" hemifields routinely showed some loss of sensitivity. This finding, along with the diffuse loss of sensitivity in a high percentage of visual fields, indicates more extensive involvement of the circulation of the anterior optic nerve head than has previously been suggested. Furthermore, patients with diabetes mellitus alone were found to have a statistically separable pattern of visual field loss. The pathophysiologic implications of the visual fields in AION and their relationship to the clinical findings were investigated.     

“Reducing body”-like inclusions in skeletal muscle in childhood-onset acid maltase deficiency

Summary Unusual inclusions with some of the features of reducing bodies were encountered in the skeletal muscle biopsy of a 2.5-year-old boy with childhoodonset acid maltase deficiency. The biopsy revealed a vacuolar myopathy with lysosomal storage of glycogen and eosinophilic refractile inclusions in myofibers, which appeared dark blue with the menadione-nitroblue tetrazolium reaction. The significance of the association of inclusions with reducing properties in the setting of acid maltase deficiency is discussed.     

Current concepts in inguinal hernia in infants and children

Trends are changing in the management of infants and children with indirect inguinal hernias. Advances in neonatal intensive care have resulted in the survival of many small premature infants who have a high incidence of inguinal hernia. The rate of incarceration, strangulation, and gonadal infarction in these babies is twice that of the general pediatric age group. Respiratory immaturity, apnea, bradycardia, and associated neonatal conditions require special management at the time of hernia repair, usually performed just before discharge from the neonatal intensive care unit. New information concerning volume loss and depletion of germ cells beginning at 6 months of age in boys with undescended testes has stimulated the performance of orchiopexy when the patient is 1 year of age. More than 90% of boys with cryptorchid testes at the age of 1 year have an associated hernia that requires concomitant repair at the time of orchiopexy. The use of the peritoneal cavity for fluid absorptive purposes in hydrocephalus treated by venticuloperitoneal shunts or of peritoneal dialysis for renal failure and metabolic diseases such as hyperammonemia and lactic acidosis causes increased intraabdominal pressure and results in the appearance of a previously unrecognized hernia. Recognition of these and other conditions associated with a high incidence of hernial occurrence should allow early diagnosis and treatment before the development of complications. Most elective repairs of hernias are safely performed in the outpatient setting; however, some infants and children with concurrent illnesses are best managed in a morning admissions program, in which hospital admission occurs postoperatively.

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Resumen Este artículo se refiere a las tendencias en el manejo de lactantes y niños con hernias inguinales indirectas. Los avances logrados en el cuidado intensivo neonatal han resultado en la supervivencia de muchos pequeños prematuros, quienes exhiben una elevada incidencia de hernia inguinal. La tasa de incarceración, estrangulación, e infarto gonadal en estos pacientes es dos veces la de la población pediátrica general. La inmadurez respiratoria, apnea, bradicardia, y otras condiciones neonatales asociadas requieren un manejo especial con ocasión de la reparación herniaria, la cual generalmente se realiza inmediatamente antes de la salida de la unidad de cuidado intensivo neonatal. Nuevos conocimientos sobre pérdida de volumen y depleción de las células germinales, lo cual comienza a los 6 meses de edad en niños con testículos no descendidos, ha estimulado la realización de orquidopexia cuando el paciente llegue a la edad de un ano. Más del 90% de los niños con testículos criptorquídicos a la edad de un año tienen una hernia asociada que requiere reparación concomitante con la orquidopexia. El uso de la cavidad peritoneal para efectos de absorción de fluidos en el caso de hidrocéfalos tratados con la implantación de sistemas valvulares ventriculoperitoneales, o de diálisis peritoneal para falla renal y enfermedades metabólicas tales como hiperamonemia o acidosis láctica, causa un aumento en la presión intraabdominal y resulta en la aparición de una hernia previamente inaparente. La identificación de estas y otras condiciones asociadas con una elevada incidencia de hernia debe hacer posible el diagnóstico y tratamiento tempranos, antes de que se presenten complicaciones. La mayoría de las reparaciones herniarias pueden ser realizadas en forma adecuada como procedimientos ambulatorios. Sin embargo, algunos infantes y niños con enfermedades concurrentes pueden ser mejor manejados en un programa de admisión matinal, en el cual la hospitalización se produce en el postoperatorio.

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Résumé Le traitement des hernies inguinales obliques externes chez le bébé et l'enfant évolue. Les progrès accomplis dans les soins intensifs des nouveau-nés ont permis la survie d'un plus grand nombre d'enfants prématurés qui présentent une fréquence plus importante de hernies inguinales. Le taux d'engouement, d'étranglement, et d'ischémie gonadale chez cette population est deux fois celui de la population pédiatrique générale. Le développement respiratoire inachevé, l'apnée, la bradycardie, et d'autres conditions néonatales associées sont autant de facteurs qui nécessitent le travail d'une équipe spécialisée au moment du traitement de la hernie qui se situe juste avant la sortie de l'unité de soins intensifs. Certaines études ayant montré une perte de volume et une déplétion de cellules germinales à partir de l'âge de 6 mois chez le garçon avec une ectopie testiculaire, on préconise une orchidopexie tôt, à l'âge d'un an. Plus de 90% de ces enfants présentent une hernie associée qui doit être réparée en même temps. L'utilisation de la cavité péritonéale pour dériver l'hydrocéphalie par shunt ventriculopéritonéal ou pour dialyse péritonéale en cas d'insuffisance rénale ou autres maladies métaboliques comme l'hyperammonémie et l'acidose lactique sont des causes d'hyperpression intra-abdominale avec augmentation du nombre de cas de hernies jusqu'alors méconnues. Une meilleure connaissance de ces conditions propices à augmenter le nombre de hernies symptomatiques devrait permettre d'en faire le diagnostic plus tôt et de les traiter avant l'apparition des complications. La plupart des hernies non compliquées sont traitées sans hospitalisation. Cependant, quelques bébés et enfants ayant d'autres maladies concomitantes sont mieux traités avec un programme d'hospitalisation de jour, c'est-à-dire que l'enfant est hospitalisé pendant 24 heures après son opération.

     

Lung surfactant gelation induced by epithelial cells exposed to air pollution or oxidative stress

Lung surfactant lowers surface tension and adjusts interfacial rheology to facilitate breathing. A novel instrument, the interfacial stress rheometer (ISR), uses an oscillating magnetic needle to measure the shear viscosity and elasticity of a surfactant monolayer at the air-water interface. The ISR reveals that calf lung surfactant, Infasurf, exhibits remarkable fluidity, even when exposed to air pollution residual oil fly ash (ROFA), hydrogen peroxide (H2O2), or conditioned media from resting A549 alveolar epithelial cells (AEC). However, when Infasurf is exposed to a subphase of the soluble fraction of ROFA- or H2O2-treated AEC conditioned media, there is a prominent increase in surfactant elasticity and viscosity, representing two-dimensional gelation. Surfactant gelation is decreased when ROFA-AEC are pretreated with inhibitors of cellular reactive oxygen species (ROS), or with a mitochondrial anion channel inhibitor, as well as when A549-rho0 cells that lack mitochondrial DNA and functional electron transport are investigated. These results implicate both mitochondrial and nonmitochondrial ROS generation in ROFA-AEC-induced surfactant gelation. A549 cells treated with H2O2 demonstrate a dose-dependent increase in lung surfactant gelation. The ISR is a unique and sensitive instrument to characterize surfactant gelation induced by oxidatively stressed AEC.     

The CC chemokine receptor 5 delta32 mutation is not associated with inflammatory bowel disease (IBD) in NE England

Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract of unknown aetiology. Evidence of abnormalities in immune regulation and cytokine production in patients with IBD has led to investigations of various immuno-regulatory genes as potential candidate susceptibility loci. Studies using whole genome scanning have highlighted chromosomes 3, 7, 12 and 16. A 32 base-pair deletion in the CC-chemokine receptor-5 gene (CCR5-A32, chromosome 3p21.3) has been associated with susceptibility to IBD. We have investigated CCR5 as a candidate susceptibility gene in 350 patients (251 with ulcerative colitis and 99 with Crohn's disease) and 103 controls using polymerase chain reaction. There were no significant differences in the distribution of CCR5 genotypes or frequencies comparing patients and controls, or associations with extent of colitis. In contrast to preliminary data, these findings suggest no evidence for involvement of this mutation in susceptibility/resistance or disease progression in IBD.