Brain activation associated with visual motion studied by functional magnetic resonance imaging in humans

Localized brain activation in response to moving visual stimuli was studied by functional magnetic resonance imaging (fMRI). Stimuli were 100 small white dots randomly arranged on a visual display. During the Motion condition, the dots moved along random, noncoherent linear trajectories at different velocities. During the Blink condition, the dots remained stationary but blinked on and off every 500 ms. The Motion and Blink conditions continuously alternated with 10 cycles per run and 6–8 runs per experiment. In half of the runs, the starting stimulus condition was Motion, while in the remaining runs it was Blink. A series of 128 gradient echo echoplanar images were acquired from 5–7 slices during each run using a 1.5 T GE Signa with an Advanced NMR echoplanar subsystem. The time series for each voxel were analyzed in the frequency domain. Voxels which demonstrated a significant spectral peak at the alternation frequency and whose phase changed in response to stimulus order were considered activated. These activated voxels were displayed upon high resolution anatomical images to determine the sites of activation and were also transformed into the coordinates of Talairach and Tournoux ([1988] Co-planar Stereotaxic Atlas of the Human Brain, New York: Thieme) for comparison to prior neuroimaging studies. Seven of ten subjects showed clusters of activation bilaterally at the junction of the temporal and occipital lobes (area 37) in response to moving stimuli. Most activated voxels were located within or adjacent to a region designated the parietal-temporal-occipital fossa, or PTOF. Five subjects also showed activation to moving stimuli in midline occipital cortex. The activated voxels in midline cortex had a significantly shorter phase delay in their MR signal change relative to voxels in PTOF. © 1995 Wiley-Liss, Inc. 1

1 This article is a US Government work and, as such, is in the public domain in the United States of America

     

Motility Disorders after Roux-en-Y Gastrojejunostomy

About 30% of patients who have a Roux-en-Y gastrojejunostomy after gastrectomy suffer from abdominal pain, nausea, vomiting of food and bloating made worse by eating. This syndrome, called the Roux stasis syndrome, is caused, in part, by a motility disorder of the Roux limb. Transection of the jejunum during the construction of the limb separates the limb from the natural small intestinal pacemaker located in the duodenum. Ectopic pacemakers then appear in the limb and trigger retrograde contractions in its proximal portion. These contractions slow transit through the limb and result in Roux stasis. Current nonsurgical treatment of the syndrome includes the use of prokinetic agents and intestinal pacing, neither of which has demonstrated long-term benefits. A near-total gastrectomy may speed upper gastrointestinal transit somewhat, but stasis in the Roux limb often persists. Our current approach aims at preventing the syndrome by the use of an ‘uncut’ Roux limb, an operation which preserves myoneural continuity between the duodenal pacemaker and the Roux limb and so prevents the appearance of ectopic pacemakers and stasis in the limb.     

Intramesenteric fetal rat small-bowel transplantation

Previous studies have shown that transplantation of fetal rat small bowel into the greater omentum of adult recipient animals can be successfully carried out. However, the surface area of the omentum limits the length of implantable fetal small bowel. Furthermore, clinical experience has shown that due to adhesions, the greater omentum is no longer suitable as an implantation site after multiple laparotomies, which often precede a short-bowel syndrome. We wanted to examine whether recipient mesentery is a further possible site of fetal gut implantation. Four weeks after transplantation of the fetal graft into the mesentery of adult rats, mature intestine was found in 80% of the animals. Macroscopically, the developed transplants looked like bowel duplications"; light-microscopic examinations documented their morphologic integrity.     

Pediatric intestinal transplantation

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960’s, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.     

The effect of polycythemic hyperviscosity on ischemic bowel necrosis

It is known that polycythemia decreases the fluidity of the blood and impairs tissue perfusion due to red-cell sludging in the microcirculation. In this study, the effect of polycythemic hyperviscosity (PH) on bowel necrosis was evaluated in an experimental model of intestinal ischemia. Twenty-eight Wistar albino rats (90–170 g) were divided into two groups: group 1 was transfused to create hyperviscosity and then intestinal ischemia was produced (n = 16); in group 2 ischemia was produced without transfusion (n = 12). Intestinal ischemia was produced by clamping the superior mesenteric artery and the collateral arcades of the right colic artery for 30 min. Gross and histopathologic evaluations were performed by either immediate necropsy or relaparotomy 24 h later. Microscopic findings were graded from 0 to 3 according to the degree of ischemic changes. In group 1, 2 animals (12.5%) died before 24 h postoperatively; coagulation necrosis with grade 2 or 3 ischemic changes was observed in 10 animals (62.5%). In group 2 only a few hypertrophied Peyer's patches and capillary dilation were found, and all histopathologic changes were between grades 0 and 1. The difference between the histopathologic gradings of the two groups was significant (P < 0.001). It appears that in addition to reduced splanchnic blood flow, a secondary effect of PH is needed to induce ischemic coagulation necrosis. PH of the newborn must be considered a risk factor for necrotizing enterocolitis, so-called spontaneous intestinal perforations, and even intestinal atresia.Presented at the 1st European Congress of Pediatric Surgery, Graz/Austria, May 4–6, 1995     

Interactions of Phosphodiester and Phosphorothioate Oligonucleotides with Intestinal Epithelial Caco-2 Cells

Purpose. Oral bioavailability for antisense oligonucleotides has recently been reported but the mechanistic details are not known. The proposed oral delivery of nucleic acids will, therefore, require an understanding of the membrane binding interactions, cell uptake and transport of oligonucleotides across the human gastro-intestinal epithelium. In this initial study, we report on the cell-surface interactions of oligonucleotides with human intestinal cells. Methods. We have used the Caco-2 cell line as an in vitro model of the human intestinal epithelium to investigate the membrane binding interactions of 20-mer phosphodiester (PO) and phosphorothioate (PS) oligonucleotides. Results. The cellular association of both an internally [³H]-labelled and a 5end [³²P]-labelled PS oligonucleotide (3.0% at 0.4 µM extracellular concentration) was similar and was an order of magnitude greater than that of the 5end [³²P]-labelled PO oligonucleotide (0.2%) after 15 minutes incubation in these intestinal cells. The cellular association of PS was highly saturable with association being reduced to 0.9% at 5 µM whereas that of PO was less susceptible to competition (0.2% at 5 µM, 0.1% at 200 µM). Differential temperature-dependence was demonstrated; PS interactions were temperature-independent whereas the cellular association of PO decreased by 75% from 37°C to 17°C. Cell association of oligonucleotides was length and pH-dependent. A decrease in pH from 7.2 to 5.0 resulted in a 2- to 3-fold increase in cell-association for both backbone types. This enhanced association was not due to changes in lipophilicity as the octanol:aqueous buffer distribution coefficients remained constant over this pH range. The ability of NaCl washes to remove surface-bound PS oligonucleotides in a concentration-dependent manner suggests their binding may involve ionic interactions at the cell surface. Cell-surface washing with the proteolytic enzyme, Pronase^®, removed approximately 50% of the cell-associated oligonucleotide for both backbone types. Conclusions. Binding to surface proteins seems a major pathway for binding and internalization for both oligonucleotide chemistries and appear consistent with receptor (binding protein)-mediated endocytosis. Whether this binding protein-mediated entry of oligonucleotides can result in efficient transepithelial transport, however, requires further study.     

The Use of the Biliopancreatic Diversion as a Treatment for Failed Gastric Partitioning in the Morbidly Obese

The dilemma with which every bariatric surgeon is confronted is: What to do with the inevitable failures? In vertical gastric partitioning, revising the gastroplasty results in a high second failure rate. In an effort to improve the Success rate in failed gastroplasty patients who request revisionary surgery, the biliopancreatic bypass (classic Scopinaro procedure) was carried out on 57 patients. They have been followed for up to 10 years. The long-term weight loss has averaged 69.4 lb, which is 87% of the pregastroplasty excess weight. The price paid by these patients, in terms of complications, has been significant. Twenty-two Percent have developed hypoalbuminemia with its accompanying peripheral edema; 24% have required i.v. hyperalimintation because Of malnutrition. Sixteen percent of the patients developed a late post-op bowel obstruction, one resulting in death. Osteomalacia, spontaneous fractures have occurred. The biliopancreatic diversion procedure (BPD) is an effective weight-loss operation in the failed gastroplasty patients, but a significant price must be paid in terms of careful follow-up, nutritional deficiencies, and rehospitalizations.     

ALTERATIONS OF THE ENTERIC NERVOUS SYSTEM IN NEONATAL NECROTIZING ENTEROCOLITIS REVEALED BY WHOLE-MOUNT IMMUNOHISTOCHEMISTRY

Pathology reports on neonatal necrotizing enterocolitis (NNEC) rarely consider its effects on the enteric nervous system (ENS). Thus, the aim of this study has been to perform a two-dimensional assessment of neuropathologic lesions within the three ganglionated plexuses of the intestinal wall by means of whole-mount immunohistochemistry. Resected segments of ileum and colon affected by acute NNEC were submitted to immunohistochemical procedures using antibodies against neuronal (protein gene product 9.5) and glial (protein S-100, glial fibrillary acidic protein) proteins. Examination of the myenteric plexus and external submucosal plexus revealed a noticeable reduction in glial cells concomitant with the gradual deterioration of nerve cells, both findings predominating in the antimesenteric intestinal circumference, where ischemic lesions tend to appear first. The most severe damage of nervous tissue was observed in the plexus submucosus internus dependent on the depth of mucosal injury. The destroyed ganglia appeared like "empty baskets" (residual tangles) and housed deteriorated nerve and glial cells. Taking the anatomy of the intestinal vascular blood supply into consideration, the characteristic topography of neuropathologic lesions gives further support to an ischemic event within the cascade of different pathogenetic factors culminating in NNEC. Moreover, the demonstrated alterations of the ENS and their potential adverse effects on intestinal motility and neuroimmunologic interactions may contribute to the complex pathogenesis of NNEC, which remains a field of further investigation.