Pólipos hiperplásicos da junção gastro-esofágica em idade pediátrica

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Cancer of the colon and rectum.

Shipping list no.: 92-195-P.

Selections from embryological monographs.

I. Crustacea, by Walter Faxon.--II. Echinodermata, by Alexander Agassiz.--III. Acalephs, by J.W. Fewkes; and Polyps, by E.L. Mark.

The Role of IL-25 in Colitis-Associated Colon Cancer and Pulmonary Inflammation

Thesis (Ph.D.)--University of Washington, 2016-06

GFP-tagged CFTR transgene is functional in the G551D cystic fibrosis mouse colon

Trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) is central to its function, with the most common mutation, DeltaF508, resulting in abnormal processing and trafficking. Therefore, there is a significant need to develop tools, which enable the trafficking of CFTR to be studied in vitro and in vivo. In previous studies it has been demonstrated that fusion of the green fluorescent protein (GFP) to the N-terminus of CFTR does lead to functional expression of CFTR chloride channels in epithelial cell lines. The aim of the present study was to examine whether it is possible to express GFP-tagged CFTR as a transgene in colonic and airway epithelial cells of cystic fibrosis (CF) mice and to correct the CF defect. Using the epithelial-specific human cytokeratin promoter K18, we generated bitransgenic mice cftr(G551D/G551D) K18-GFP-CFTR+/-, designated GFP mice. Transcripts for GFP-CFTR could be detected in bitransgenic mice by use of RT-PCR techniques. Expression of GFP-CFTR protein was detected specifically in the colonic epithelium by both direct GFP fluorescence and the use of an anti-GFP antibody. Ussing chamber studies showed that the ion transport defect in colon and airways observed in cftr(G551D/G551D) mice was partially corrected in the bitransgenic animals. Thus, K18-GFP-CFTR is functionally expressed in transgenic mice, which will be a valuable tool in studies on CFTR synthesis, processing and ion transport in native epithelial tissues.

Laparoscopic Swenson procedure - An optimal approach for both primary and secondary pull-through for Hirschsprung's disease

Background/Purpose: Several pull-through procedures are available for the surgical management of Hirschsprung's disease (HD) in children. The authors have adopted a laparoscopic approach since 1995, including laparoscopic Swenson procedure (LSw), both for one-stage primary and 2-stage secondary procedures. The aim of this study was to examine the role of LSw in children with HD in both primary and secondary procedures. Methods: From January 1995 to December 2001, 42 children with biopsy-proven HD underwent laparoscopic pull-through procedure for HD. This group included 29 children who underwent LSw, a detailed analysis of which forms the basis of this report. Results: Sixteen children underwent a single-stage neonatal LSw; the median weight of this group at the time of surgery was 3.2 kg and the median age was 5 days. Secondary LSw was performed in the remaining 13 children, which included 3 children with total colonic HD who underwent laparoscopic total colectomy and LSw. The median operating time was 105 minutes (range, 66 to 175 minutes). The median time to commence full diet was 48 hours (range, 24 to 86 hours), and median time to return to normal play and activity was 72 hours (range, 48 hours to 5 days). There was no difference in operating time between primary and secondary pull-through procedures. There were no intraoperative complications, and no patient required open conversion. Postoperative ileus was noted in 3 children and enterocolitis in 2. The median hospital stay was 4 days (range, 2 to 6 days). Follow-up was between 6 months to 7 years with a median follow-up of 2.2 years. At follow-up, 2 children required laparoscopic antegrade continence enema procedure. A satisfactory continence was noted in 15 of the 19 children who were older than 3 years at the time of last follow-up. Conclusions: LSw seems to be a suitable procedure for laparoscopic management of HD in children. LSw is safe and effective, both for primary and secondary type of pull-through procedures, with good short-term results.

Expression of the cell surface mucin gene family in adenocarcinomas

Cell surface mucins are complex glycoproteins expressed on the apical membrane surface of mucosal epithelial cells. In malignant epithelial cells they are thought to influence cell adhesion, and are clinical targets for tumor immunotherapy and serum tumor marker assays. We have compared expression of MUC1, MUC3, MUC4, MUC11, MUC12 and MUC13 mRNA in epithelial cancers and/or cell lines with non-malignant tissues. In non-malignant tissues, MUC3, 4, 11, 12 and 13 were expressed at highest levels in gastrointestinal tissues, whereas MUC1 was more widely distributed. Significant down-regulation of the MUC4, MUC12 and MUC13 genes was observed in colonic cancers compared with normal tissue, whereas MUC1 was upregulated. In rectal cancers, levels of all six mucin genes were not significantly different to those in normal rectal tissues. Both MUC1 and MUC4 were down-regulated in gastric cancers, whereas cancer and normal tissue levels were similar for MUC3, 11, 12 and 13. In esophageal cancers there was a general trend toward higher levels than in normal tissue for MUC1, 3, 12 and 13. In ovarian cancers MUC1 levels were very high, whereas only low levels of all other mucins were observed. We also report expression in renal cell carcinomas, bladder carcinomas and breast cancer cell lines. The reported expression profiles of the cell surface mucin gene family will help direct biological and clinical studies of these molecules in mucosal biology, and in malignant and inflammatory diseases of epithelial tissues.

Gastrointestinal transit in the common brushtail possum measured by gamma scintigraphy

This paper reports an example of the application of pharmaceutical technology to wildlife management, specifically the design of an oral delivery system for the common brushtail possum in New Zealand. Designing an oral delivery system requires a knowledge of the time taken for particulates to reach target sites within the gastrointestinal tract (GIT). The transit time for fluid and indigestible particles of two different size ranges was determined in the common brushtail possum (Trichosurus vulpecula). Technetium-labelled (Tc-99m) anion exchange resin particles (75-125 or 500-700 mu m diameter) or solution (Tc-99m-labelled diethylenetriamine pentaacetic acid, Tc-99m-DTPA) was administered orally. At predetermined times after dosing (3, 6, 12, 24 or 32 h), the distribution of radioactivity throughout excised gastrointestinal tracts was determined by gamma scintigraphy. The transit profile was similar for the three formulations investigated. Unlike other closely related hindgut fermenting marsupials, there was no evidence to support the presence of a colonic separating mechanism in the common brushtail possum. Gastrointestinal transit was independent of body mass, gender and time of day that the dose is given. To target the hindgut for oral delivery of protein and peptide biocontrol agents, the formulation Would need to protect the bioactive for approximately 12 h prior to release. (c) 2005 Elsevier B.V. All rights reserved.

Effects of the herbicide diuron on the early life history stages of coral

The effects of the herbicide diuron on the early life history stages of broadcast spawning and brooding corals were examined in laboratory experiments. Fertilisation of Acropora millepora and Montipora aequituberculata oocytes were not inhibited at diuron concentrations of up to 1000 mu gl(-1). Metamorphosis of symbiont-free A. millepora larvae was only significantly inhibited at 300 mu gl(-1) diuron. Pocillopora damicornis larvae, which contain symbiotic dinoflagellates, were able to undergo metamorphosis after 24h exposure to diuron at 1000 mu gl(-1). Two-week old P. damicornis recruits on the other hand were as susceptible to diuron as adult colonies, with expulsion of symbiotic dinoflagellates (bleaching) evident at 10 mu gl(-1) diuron after 96 h exposure. Reversible metamorphosis was observed at high diuron concentrations, with fully bleached polyps escaping from their skeletons. Pulse amplitude modulation (PAM) chlorophyll fluorescence techniques demonstrated a reduction in photosynthetic efficiency (Delta F/F'(m)) in illuminated P. dami- cornis recruits after a 2h exposure to 1 mu gl(-1) diuron. The dark-adapted quantum yields (F-v/F-m also declined, indicating chronic photoinhibition and damage to photosystem H. Crown Copyright (c) 2004 Published by Elsevier Ltd. All rights reserved.

Clinically active Crohn's disease in the presence of a low C-reactive protein

Objective. Clinical interest in C-reactive protein (CRP) - a component of the innate immune system - has focused mainly on its worth as an indicator of disease activity. There has been a resurgence of interest in CRP in the Crohn's disease ( CD) literature because several trials of new treatments for active CD have been characterized by both a large proportion of patients with low CRP ( < 10 mg/l) at entry to the trials and by a negative therapeutic outcome. It is therefore of interest to study the clinical characteristics of patients who are thought to have at the same time both active CD and a low CRP. Material and methods. Patients were prospectively recruited as part of the Brisbane IBD clinical and research programme. Subjects were included in the low CRP group only if there were complete datasets for CRP on all occasions of active CD, and CRP was < 10 mg/l. Active disease was defined as CD activity index (CDAI) > 200. The low CRP group was compared with patients in the raised CRP group for a range of clinical variables as well as the major NOD2 variants. Results. There were data sets for 223 CD patients, with a mean disease duration of 12 years. Of these, 22 patients fulfilled the criteria for low CRP. The low CRP group ( group 1) showed significant differences for disease site (p < 0.01) and for BMI (p = 0.006) compared to the raised CRP group ( group 2). Specifically, group 1 had a predominance of pure ileal disease (95% versus 53%) and lack of pure colonic disease (0% versus 24%) compared to group 2, and their BMI was significantly lower (20.3 kg/m(2) versus 25.0 kg/m(2)). Groups 1 and 2 did not differ with respect to Vienna behaviour at diagnosis, smoking, appendicectomy, extra-intestinal manifestations of CD, or NOD2 SNP variants. There was a trend for low CRP patients with previous ileal resection to evolve to a stricturing phenotype. Fat wrapping was noted in 11/13 (85%) of low CRP patients undergoing ileal resections. Conclusions. Patients with CD and a persistently low CRP in the face of active disease were characterized by an almost exclusive ileal disease distribution and a low BMI, compared to those with a raised CRP. These patients had a similar frequency and distribution of NOD2/CARD15 variants. Stricturing ( v inflammatory or penetrating) behaviour may explain some low CRP. Despite the abnormally low BMI, fat wrapping was noted in the majority of low CRP patients undergoing ileal resection.

Diurnal polyp expansion behavior in stony corals may enhance carbon availability for symbionts photosynthesis

Photosynthesis of zooxanthellate stony corals may be limited by inorganic carbon at high irradiances. We demonstrated that oxygen consumption of expanded corals is higher than that of contracted corals in both night-expanding and day-expanding corals. It is assumed that at the single-polyp level, the expansion of tentacles increases the surface area for solute exchange with the surrounding water, which may alleviate potential carbon limitation and excess oxygen levels in the tissue under high irradiance. We investigated this hypothesis using stable carbon isotope (613 C) analysis of coral species from the Red Sea exhibiting different morphologies. delta C-13 ratios in zooxanthellae of branched coral colonies with small polyp size that extend their tentacles during daytime (diurnal morphs) showed lower delta C-13 values in their zooxanthellae - 13.83 +/- 1.45 parts per thousand, compared to corals from the same depth with large polyps, which are usually massive and expand their tentacles only at night (nocturnal morphs). Their algae delta C-13 was significantly higher, averaging - 11.33 +/- 0.59 parts per thousand. Carbon isotope budget of the coral tissue suggests that branched corals are more autotrophic, i.e., that they depend on their symbionts for nutrition compared to massive species, which are more heterotrophic and depend on plankton predation. (c) 2005 Elsevier B.V. All rights reserved.

A study of large-bowel volvulus in urban Australia

Background: Large-bowel volvulus is a rare cause of bowel obstruction in the industrialized world. We analyzed the presentation and outcome of 49 patients at the Princess Alexandra Hospital, Brisbane, Australia, who received a diagnosis of colonic volvulus from 1991 to 2001. Methods: A retrospective chart study was carried out. Results: Twenty-nine patients had sigmoid volvulus (59%), 19 patients had cecal volvulus (39%) and 1 patient had a transverse colon volvulus (2%). The diagnosis of sigmoid volvulus was made accurately on plain abdominal radiography or contrast enema in 90% of cases (n = 26), compared with only 42% of cases (n = 8) of cecal volvulus. Twenty-two patients with sigmoid volvulus were treated initially with endoscopic decompression. The success rate was 64% (n = 14). There was a high early recurrence rate of sigmoid volvulus for those treated by endoscopic decompression alone (43%) during a mean period of 32 days. Of the 14 patients with cecal volvulus who were treated with right hemicolectomy, 12 had primary anastomosis and 2 had end ileostomy with mucous fistula formation. There was no anastomotic leak following right hemicolectomy with primary anastomosis, even though 6 of these patients had an ischemic cecum. Conclusions: Endoscopic decompression of the sigmoid volvulus was safe and effective as an initial treatment but has a high early recurrence rate. Any patient who is fit enough to undergo operation should have a definitive procedure during the same admission to avoid recurrence. Cecal volvulus is associated with a higher incidence of gangrene and is treated effectively by right hemicolectomy with or without anastomosis. The need for swift operative intervention is emphasized.

Neoplastic progression occurs through mutator pathways in hyperplastic polyposis of the colorectum

Aim-Colorectal cancer has been described in association with hyperplastic polyposis but the mechanism underlying this observation is unknown. The aim of this study was to characterise foci of dysplasia developing in the polyps of subjects with hyperplastic polyposis on the basis of DNA microsatellite status and expression of the DNA mismatch repair proteins hMLH1, hMSH2, and hMSH6. Materials and methods-The material was derived from four patients with hyperplastic polyposis and between one and six synchronous colorectal cancers. Normal (four), hyperplastic (13), dysplastic (13), and malignant (11) samples were microdissected and a PCR based approach was used to identify mutations at 10 microsatellite loci, TGF beta IIR, IGF2R, BAX, MSH3, and MSH6. Microsatellite instability-high (MSI-H) was diagnosed when 40% or more of the microsatellite loci showed mutational bandshifts. Serial sections were stained for hMLH1, hMSH2, and hMSH6. Result-DNA microsatellite instability was found in 1/13 (8%) hyperplastic samples, in 7/13 (54%) dysplastic foci, and in 8/11 (73%) cancers. None of the MSI-low (MSI-L) samples (one hyperplastic, three dysplastic, two cancers) showed loss of hMLH1 expression. All four MSI-H dysplastic foci and six MSI-H cancers showed loss of hMLH1 expression. Loss of hMLH1 in MSI-H but not in MSI-L lesions showing dysplasia or cancer was significant (p< 0.001, Fisher's exact test). Loss of hMSH6 occurred in one MSI-H cancer and one MSS focus of dysplasia which also showed loss of hMLH1 staining. Conclusion-Neoplastic changes in hyperplastic polyposis may occur within a hyperplastic polyp. Neoplasia may be driven by DNA instability that is present to a low (MSI-L) or high (MSI-H) degree. MSI-H but not MSI-L dysplastic foci are associated with loss of hMLH1 expression. At least two mutator pathways drive neoplasia in hyperplastic polyposis. The role of the hyperplastic polyp in the histogenesis of sporadic DNA microsatellite unstable colorectal cancer should be examined.

Electrolyte transport in the mammalian colon: mechanisms and implications for disease Kunzelmann and Marcus Mall

Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease. Physiol. Rev. 82: 245-289, 2002.The colonic epithelium has both absorptive and secretory functions. The transport is characterized by a net absorption of NaCl, short-chain fatty acids (SCFA), and water, allowing extrusion of a feces with very little water and salt content. In addition, the epithelium does secret mucus, bicarbonate, and KCl. Polarized distribution of transport proteins in both luminal and basolateral membranes enables efficient salt transport in both directions, probably even within an individual cell. Meanwhile, most of the participating transport proteins have been identified, and their function has been studied in detail. Absorption of NaCl is a rather steady process that is controlled by steroid hormones regulating the expression of epithelial Na+ channels (ENaC), the Na+-K+-ATPase, and additional modulating factors such as the serum- and glucocorticoid-regulated kinase SGK. Acute regulation of absorption may occur by a Na+ feedback mechanism and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl- secretion in the adult colon relies on luminal CFTR, which is a cAMP-regulated Cl- channel and a regulator of other transport proteins. As a consequence, mutations in CFTR result in both impaired Cl- secretion and enhanced Na+ absorption in the colon of cystic fibrosis (CF) patients. Ca2+- and cAMP-activated basolateral K+ channels support both secretion and absorption of electrolytes and work in concert with additional regulatory proteins, which determine their functional and pharmacological profile. Knowledge of the mechanisms of electrolyte transport in the colon enables the development of new strategies for the treatment of CF and secretory diarrhea. It will also lead to a better understanding of the pathophysiological events during inflammatory bowel disease and development of colonic carcinoma.