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Toxic megacolon  


... of bowel sounds . Tests: Abdominal x-ray Blood electrolytes Complete blood count ... You will get fluids and electrolytes to help prevent dehydration and shock. The process that leads to megacolon can be treated. However, this is usually not enough ...


Acute and chronic megacolon.  


Megacolon, defined as dilation of the abdominal colon, may occur acutely or in a chronic form. Acute megacolon that occurs in association with severe inflammation of the colon is known as toxic megacolon, whereas acute megacolon without obvious colonic disease is known as Ogilvie's syndrome. The pathophysiology and management of toxic megacolon, Ogilvie's syndrome, and chronic megacolon in adults differ significantly, and it is critically important to distinguish among these entities. Toxic megacolon is a medical emergency that requires coordinated intensive medical and surgical management. In addition to vigorous resuscitation with fluids, electrolytes, and blood products, medical treatment consists of parenteral corticosteroids, broad-spectrum antibiotics, and close monitoring of the patient. Surgical intervention is required if there is no improvement, or deterioration after 12 to 24 hours of intensive medical management, or if there is evidence of colon perforation. Ogilvie's syndrome usually occurs in hospitalized patients with serious underlying medical or surgical illnesses. Management is directed at preventing ischemia and perforation of the distended colon. Supportive therapy includes nasogastric suction, correction of fluid and electrolyte imbalances, stopping potentially aggravating medications, and decompressing the colon with a rectal tube and positional changes. Intravenous neostigmine is the only pharmacologic agent of proven efficacy; colonoscopic decompression is an alternative in patients who do not respond to neostigmine or who have conditions that contraindicate its use. Daily oral administration of polyethylene glycol electrolyte solutions appears to decrease the relapse rate after initial decompression is achieved. Chronic megacolon in adults represents advanced colon failure that does not respond to pharmacologic stimulation. Goals of therapy are to cleanse the colon, prevent impaction, and minimize stool volume and gas buildup. For patients with disabling symptoms, surgical exclusion of the colon, decompression and antegrade enemas via cecostomy, or subtotal or segmental resection may be palliative. PMID:17547862

Hanauer, Stephen B; Wald, Arnold



Megacolon in Rats  

Microsoft Academic Search

Four months of sigmoid colon intrinsic denervation of young male Wistar rats resulted in typical megacolon. Average 46.0% denervation of the Auerbach plexus was obtained by serosal application of benzalkonium chloride (0.2% v\\/v). Denervation was assessed by ganglion cell counts in a 480-nm extension of the treated segment. Increased thickness of the megacolon wall was due to muscle hypertrophy (+117.4%)

Samuel M. Oliveira; M. A. S. Llorach-Velludo; V. N. Sales-Neto



Vincristine-induced megacolon  

Microsoft Academic Search

Three cases of vincristine-induced megacolon are described with radiographic correlation. Vincristine is a widely used chemotherapeutic agent with neuropathic side effects causing colonic dilatation and constipation. The radiologist should be aware of this entity to prevent unnecessary procedures and, possibly, surgery.

Richard F. Rosenberg; James G. Caridi



Surgery of chagasic megacolon  

Microsoft Academic Search

Chagas' disease is an endemic clinical entity caused byTrypanosoma cruzi,a parasite that is transmitted to humans by the hematophagic Triatominae insects. It affects several million persons in Latin America, mostly in Brazil, Argentina, Chile, Paraguay, and Bolivia. Megacolon, the most common complication of intestinal trypanosomiasis, results in severe constipation, for which surgery is indicated. A variety of procedures have been

Daher E. Cutait; Raul Cutait



Megacolon in adults  

Microsoft Academic Search

\\u000a Summary  In a series of 17 adult patients with megacolon, six seemed to have Hirschsprung’s disease. All were said to have had the\\u000a disease in childhood and all had normal rectums, but biopsies were done in only two cases. One of the patients was treated\\u000a conservatively, but he died of pneumonia two years later, and collapse of the lungs secondary to

E. S. R. Hughes; K. J. Hardy; A. M. Cuthbertson



Toxic megacolon complicating pseudomembranous enterocolitis  

Microsoft Academic Search

PURPOSE: Toxic megacolon is a rare complication of pseudomembranous enterocolitis. We reviewed our recent experience with this complication. METHODS: The first five patients of the series were studied retrospectively, and six others were followed prospectively. RESULTS: Between June 1992 and May 1994, 11 patients (8 male, 3 female) developed toxic megacolon secondary to pseudomembranous enterocolitis. Mean age was 60.7 ±11.8

Judith L. Trudel; Marc DeschÊnes; Serge Mayrand; Alan N. Barkun



[Surgical treatment of idiopathic megacolon].  


The authors discuss own experience in diagnosis and surgical treatment of 32 patients with idiopathic megacolon. Three surgical techniques were compared: 1) partial excision of the colon, 2) nearly complete excision of the colon with cecum-rectal anastomosis, and 3) total colectomy with ileorectal anastomosis. Basing on the authors' own experience and available literature the third approach is recommended as the most appropriate in the treatment of the persistent, chronic constipation accompanying idiopathic megacolon. PMID:1669459

Tuszewski, M; Kiersz, A; Góral, R; Szmeja, A



Microsoft Academic Search

The incidence of megacolon has been studied in an inbred strain of mice (NZY) and in the descendants of NZY mice outcrossed to two other inbred strains (NZC, NZB) and to a fertile pituitary dwarf.The results of this study indicate that megacolon is an inheritable disease associated with \\

Marianne Bielschowsky; GC Schofield



Toxic megacolon associated Clostridium difficile colitis  

PubMed Central

Toxic megacolon is a severe complication of Clostridium difficile (C. difficile) colitis. As the prevalence of C. difficile colitis increases and treatments become more refractory, clinicians will encounter more patients with C. difficile associated toxic megacolon in the future. Here, we review a case of toxic megacolon secondary to C. difficile colitis and review the current literature on diagnosis and management. We identify both clinical and radiologic criteria for diagnosis and discuss both medical and surgical options for management. Ultimately, we recommend using the Jalen criteria in conjunction with daily abdominal radiographs to help establish the diagnosis of toxic megacolon and to make appropriate treatment recommendations. Aggressive medical management using supportive measures and antibiotics should remain the mainstay of treatment. Surgical intervention should be considered if the patient does not clinically improve within 2-3 d of initial treatment.

Sayedy, Leena; Kothari, Darshan; Richards, Robert J



Sigmoid volvulus with and without megacolon  

Microsoft Academic Search

Sixty-six consecutive patients, admitted to St. Vincent’s Hospital, Melbourne, with sigmoid volvulus, fell into two groups,\\u000a 60 with-out and six with acquired megacolon. In the former groups, flatus tube decompression was usually successful, and sigmoid\\u000a resection provided a cure. In the group with megacolon, the history was longer; patients more often had bowel symptoms before\\u000a or between acute episodes of

Peter Ryan



Megacolon in teen-aged and adult patients  

Microsoft Academic Search

Summary  Megacolon may be classified as primary or aganglionic, secondary or acquired, and functional or psychogenic. In addition,\\u000a there are other mechanisms, currently poorly understood, that cause megacolon.\\u000a \\u000a Diagnostic studies of the patient with megacolon should include a detailed history, physical examination, rectal and sigmoidoscopic\\u000a examinations, a rectal biopsy, and (for functional megacolon) psychiatric evaluation. Age of onset, encopresis, and dilatation

Joseph L. Ponka; Carlos Grodsinsky; Brock E. Brush



Pseudomembranous colitis leading to toxic megacolon associated with antineoplastic chemotherapy  

Microsoft Academic Search

Pseudomembranous colitis and toxic megacolon are rare complications of antineoplastic chemotherapy. Twelve cases of pseudomembranous colitis and four cases of toxic megacolon, both occurring as complications of chemotherapy, have been reported in the medical literature. These diseases occurred as separate and distinct entities. Fulminating pseudomembranous colitis leading to toxic megacolon in the setting of chemotherapy has not been previously reported.

Vic Velanovich; Anthony J. LaPorta; Wayne L. Garrett; Timothy B. Richards; Patricia A. Cornett



[Toxic megacolon: physiopathologic mechanism and surgical choices].  


Toxic megacolon is the most dreadful complication arising in patients affected with inflammatory bowel diseases. Its incidence is rather rare, bur mortality rate is significantly high (about 40% of cases). Pathological modifications occurring in toxic megacolon deeply influence evolution and prognosis of this complication and, consequently, surgical choices. Starting from the pathophysiology of toxic megacolon, the Authors review their experience with acute colitis, emphasizing the need for a radical treatment, as only total colectomy can assure, versus Turnbull's operation or more decompression of the bowel. To save the colon means, in fact, to leave the source of sepsis "in situ". The authors experienced Turnbull's procedure only in one of the patients observed with "quoad vitam" poor results. PMID:2518307

Bucci, L; Gentile, M; Mazzeo, F


Colectomy for idiopathic megarectum and megacolon  

Microsoft Academic Search

The outcome in 40 patients who underwent colectomy for idiopathic megacolon and megarectum over an 18 year period was evaluated. All patients had a radiologically dilated bowel and a bowel frequency of less than two per week. Twenty two patients had a caecorectal anastomosis, 11 had an ileorectal anastomosis (including one with a previous caecorectal anastomosis and four with a

G Stabile; M A Kamm; P R Hawley; J E Lennard-Jones



Toxic megacolon secondary to pseudomembranous colitis  

Microsoft Academic Search

Toxic megacolon has rarely been reported in the course of antibiotic-induced pseudomembranous colitis. We have been able to\\u000a collect 20 cases from the literature and add one new case. The mortality in the collected series was 33 per cent. The critical\\u000a factor in improving survival is early recognition of the pseudomembranous colitis. Most patients can be managed medically\\u000a by removal

John B. Cone; William Wetzel



Enteric innervation in idiopathic megarectum and megacolon  

Microsoft Academic Search

.   We have studied the resection specimens from 5 patients with idiopathic megarectum and megacolon and 10 control subjects\\u000a with non-obstructing colonic cancer. Histological staining with haematoxylin and eosin, and immunocytochemical staining for\\u000a protein gene product 9.5 (PGP 9.5), S100 protein, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide\\u000a (CGRP), and histochemical localization of NADPH diaphorase was performed. The amount

J. M. Gattuso; C. H. V. Hoyle; P. Milner; M. A. Kamm; G. Burnstock



A life-threatening complication of undiagnosed congenital idiopathic megacolon  

PubMed Central

A case of undiagnosed congenital idiopathic megacolon in a 16-year-old boy who presented with toxic megacolon and cardiovascular instability with a background of longstanding constipation is presented. He underwent life-saving subtotal colectomy from which he made a full recovery.

Kabeer, Syed; Dvorkin, Lee; Carrannante, James; Linehan, Ian



Hirschsprung's disease and idiopathic megacolon in adults and adolescents  

Microsoft Academic Search

The distinction between Hirschsprung's disease and idiopathic megacolon in childhood dates from the classic clinical, radiological, and histological studies of Bodian, Stephens, and Ward. This article describes clinical experience over 15 years of 94 patients in whom megacolon of these two types was recognised for the first time after the age of 10, to illustrate the problems of diagnosis and

P R Barnes; J E Lennard-Jones; P R Hawley; I P Todd



Toxic megacolon: the knee-elbow position relieves bowel distension  

Microsoft Academic Search

Toxic megacolon complicating inflammatory or infective colitis carries a high morbidity and mortality and surgical intervention is necessary in up to 80% of cases. Perforation complicates toxic megacolon in about 35% of cases. After perforation, the death rate nears 50%. Gaseous distension of the bowel causes considerable discomfort to the patient and increases transmural pressure. The latter is thought to

M Z Panos; M J Wood; P Asquith



Enterochromaffin cell hyperplasia and megacolon: report of a case.  

PubMed Central

A case of megacolon is described in which there was an unusual and focal hyperplasia of enterochromaffin cells in the mucosa. These formed discrete spherical acini in the lamina propria. These acini were not neoplastic and their significance is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5

Lindop, G B



Clinical features of idiopathic megarectum and idiopathic megacolon  

Microsoft Academic Search

BACKGROUND: Dilatation of the rectum and\\/or colon, in the absence of demonstrable organic disease, is an uncommon and poorly characterised condition. AIMS: To characterise the clinical and diagnostic features, and response to treatment, of patients with idiopathic megarectum (IMR) and idiopathic megacolon (IMC). METHODS: A retrospective review was undertaken of all patients operated on for these conditions over a 23

J M Gattuso; M A Kamm



Partial colectomy and coloanal anastomosis for idiopathic megarectum and megacolon  

Microsoft Academic Search

Adult patients with an idiopathic megarectum or megacolon can experience severe constipation requiring surgical treatment. Some of these patients have a proximal colon of normal diameter, with dilatation involving only the left or distal colon and rectum. The results of partial colonic and rectal resection with coloanal anastomosis in such patients have been reviewed. Seven patients (two female and five

Giorgio Stabile; Michael A. Kamm; Robin K. S. Phillips; Peter R. Hawley; John E. Lennard-Jones



A deficiency of interstitial cells of Cajal in Chagasic megacolon  

Microsoft Academic Search

Disordered gut motor activity is a feature of patients with Chagas’ disease: colonic involvement leads to the development of megacolon and symptoms of constipation. Interstitial cells of Cajal are thought to modulate gut motility. The aim of this study was to test the hypothesis that there is an abnormality of the density of distribution of interstitial cells of Cajal in

Robert Hagger; Caroline Finlayson; Fiona Kahn; R De Oliveira; L Chimelli; Devinder Kumar



Results of stoma formation for idiopathic megarectum and megacolon  

Microsoft Academic Search

Bowel resection for idiopathic megarectum and megacolon does not always predictably relieve symptoms and has a significant morbidity. We have therefore evaluated the results of stoma formation in this condition. All patients had a bowel frequency of less than one per week, and all had a dilated rectum or colon. Eight patients, six of whom had had a previous unsuccessful

G. Stabile; M. A. Kamm; P. R. Hawley; J. E. Lennard-Jones



Megacolon in patients with chronic spinal cord injury  

Microsoft Academic Search

Purpose: To investigate the clinical and functional correlates of megacolon in individuals with chronic spinal cord injury (SCI).Patients and methods: This is a cross-sectional study of 128 patients consecutively admitted to a SCI in-patient service in a US Veterans Administration Medical Centre (mean age 57±15 years, mean years since injury 20±13, 97% male) who underwent plain abdominal radiography for study

D Harari; K L Minaker



Electrical activity of the intestine of mice with hereditary megacolon and absence of enteric ganglion cells  

Microsoft Academic Search

Mice with a recessive gene which reduces the number of ganglion cells of the large intestine and produces megacolon similar to Hirschsprung's disease were studied. Electrical activity of the small bowel consisted of electrical slow waves and action potentials and showed no difference between the mice with megacolon and their normal siblings. Electrical slow waves and action potentials occurred in

J. D. Wood



Toxic megacolon: Role of CT in evaluation and detection of complications  

Microsoft Academic Search

The purpose of this study is to determine the role of CT in the evaluation and in detecting complications in patients with toxic megacolon. A retrospective analysis of CT findings of 18 consecutive patients with toxic megacolon was performed. Underlying etiology included 12 patients with pseudomembranous colitis (PC), four patients with ulcerative colitis and two patients with cytomegalovirus colitis. Eleven

Massimo Imbriaco; Emil J. Balthazar



Toxic megacolon due to Salmonella : a case report and review of the literature  

Microsoft Academic Search

Background and aims: Salmonella colitis is an unusual cause of toxic megacolon. We provide an overview of this condition and report a single case. Patients and methods: A 62-year-old man underwent subtotal colectomy with ileostomy formation for toxic megacolon due to Salmonella enteritidis phage type 4 colitis, followed by reversal with an ileorectal anastomosis. Results: Twenty-seven cases have been described

A. Chaudhuri; B. A. Bekdash



A case of toxic megacolon in ulcerative colitis associated with cytomegalovirus infection  

Microsoft Academic Search

Cytomegalovirus (CMV) infection, which has been shown to complicate the course of ulcerative colitis (UC), has been implicated\\u000a as a possible etiologic factor in the exacerbation of UC, especially in toxic megacolon. However, CMV infection in patients\\u000a with UC accompanied by toxic megacolon has rarely been reported. Here we report a case of CMV infection of the colon accompanied\\u000a by

Hitoshi Kotanagi; Takemi Fukuoka; Yutaka Shibata; Toshiaki Yoshioka; Osamu Aizawa; Yuri Saito; Kenji Koyama; Michiro Otaka; Mitsuro Chiba; Masahiro Saito



Mutation of the Sry-Related Sox10 Gene in Dominant megacolon, a Mouse Model for Human Hirschsprung Disease  

Microsoft Academic Search

The spontaneous mouse mutant Dominant megacolon (Dom) is a valuable model for the study of human congenital megacolon (Hirschsprung disease). Here we report that the defect in the Dom mouse is caused by mutation of the gene encoding the Sry-related transcription factor Sox10. This assignment is based on (i) colocalization of the Sox10 gene with the Dom mutation on chromosome

Beate Herbarth; Veronique Pingault; Nadege Bondurand; Kirsten Kuhlbrodt; Irm Hermans-Borgmeyer; Aldamaria Puliti; Nicole Lemort; Michel Goossens; Michael Wegner



[A case of pseudomembranous colitis concomitant with toxic megacolon and paralytic ileus].  


A 60-year-old man was diagnosed as pseudomembranous colitis with chief complaint of fever and abdominal distension after a cerebral operation. It was ineffective although vancomycin hydrochloride (VCM) was given orally. Complications occurred. The patient had toxic megacolon and paralytic ileus. VCM was administrated via an ileus tube. In addition, the bowel was lavaged and VCM was sprayed by colonoscopy. This therapy was very effective. Generally, a patient with pseudomembranous colitis concomitant with toxic megacolon or/and paralytic ileus is considered to have a poor prognosis, however, he completely recovered by a combination of medical treatment. PMID:22863963

Aoki, Takaya; Kataoka, Mikinori; Sou, Yoshiya; Naitou, Sakiko; Takeuchi, Mami; Tsuji, Yuichirou; Harada, Asuka; Sugimoto, Hiroko; Hayama, Yasutaka; Yamamoto, Kei; Nonaka, Masaya; Yagi, Kenji; Fujiwara, Mari; Fukuzawa, Masakatsu; Kawakami, Kouhei; Kawai, Takashi; Moriyasu, Fuminori



A New Look at Toxic Megacolon: An Update and Review of Incidence, Etiology, Pathogenesis, and  

Microsoft Academic Search

Toxic megacolon (TM) is an infrequent but devastating complication of colitis. Numerous forms of colonic inflam- mation can give rise to TM but the majority occur in individuals with inflammatory bowel disease (IBD). Re- cently there has been a marked increase in the number of reports of TM associated with pseudomembranous colitis. Because of the associated high morbidity and mortality,

P. L. Beck


Subtotal colectomy by rectal pull-through for treatment of idiopathic megacolon in 2 cats  

PubMed Central

Surgical management of idiopathic megacolon is described in 2 cats by a rectal pull-through with subtotal colectomy performed outside of the abdomen. This newly described technique facilitates access to the rectum for suturing an anastamosis without the need for pubic osteotomy and with minimal risk of abdominal contamination.

Barnes, Darren C.



Neuron count reevaluation in the myenteric plexus of chagasic megacolon after morphometric neuron analysis  

Microsoft Academic Search

This study was made with the objective of reevaluating the colon denervation in chronic Chagas' disease. The diameters of neuron perikaryons of the myenteric plexus were measured on paraffin sections in a ring from the sigmoid in Chagas' disease patients, 17 with and 10 without megacolon and in 10 non-chagasic controls. All neurons were counted in ten en-echelon sections. Neuron

Sheila J. Adad; Cristiane G. Cançado; Renata M. Etchebehere; Vicente P. A. Teixeira; Uilho A. Gomes; Edmundo Chapadeiro; Edison R. Lopes



A new look at toxic megacolon: an update and review of incidence, etiology, pathogenesis, and management  

Microsoft Academic Search

Toxic megacolon (TM) is an infrequent but devastating complication of colitis. Numerous forms of colonic inflammation can give rise to TM but the majority occur in individuals with inflammatory bowel disease (IBD). Recently there has been a marked increase in the number of reports of TM associated with pseudomembranous colitis. Because of the associated high morbidity and mortality, early recognition

S. Ian Gan; P. L Beck



AIDS related Kaposi's sarcoma presenting as ulcerative colitis and complicated by toxic megacolon  

Microsoft Academic Search

Gastrointestinal Kaposi's sarcoma is a well described and usually asymptomatic manifestation of the acquired immune deficiency syndrome. We report a patient who had extensive colonic Kaposi's sarcoma and presented with an ulcerative colitis like illness. Total colectomy was subsequently required as an emergency procedure for toxic megacolon. The patient remains well on maintenance interferon therapy 21 months after surgery.

B A Biggs; S M Crowe; C R Lucas; M Ralston; I L Thompson; K J Hardy



Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon  

Microsoft Academic Search

Background & Aims Colonic inflammation may lead to motility disturbances, including severe atony. Nitric oxide is released by inflamed tissue and induces smooth muscle relaxation. The aim of this study was to analyze NO generation pathways in colonic tissue from patients who had ulcerative colitis with or without toxic megacolon and in tumor-free samples from patients with colonic neoplasm. Methods

Marisabel Mourelle; Francesc Casellas; Francisco Guarner; Antonio Salas; Valentina Riveros-Moreno; Salvador Moncada; Juan-R. Malagelada



Cell-mediated immune response in megacolon from patients with chronic chagas' disease  

Microsoft Academic Search

PURPOSE: The mechanisms that control chronic infectionin vivo and the immunologic mechanisms involved in the pathogenesis of chagasic megacolon are not completely characterized. Although autoimmunity may play a role in the pathogenesis of Chagas' disease, recent studies, both in mice and in humans, suggest a positive association of tissue parasitism, inflammation, and severity of lesions. The aim of this study

Carlos E. P. Corbett; Ulysses Ribeiro; Maria das Graças Prianti; Angelita Habr-Gama; Masayuki Okumura; Joaquim Gama-Rodrigues



A high-resolution genetic map of mouse Chromosome 15 encompassing the Dominant megacolon ( Dom ) locus  

Microsoft Academic Search

Dominant megacolon (Dom) is one of four mutations in the mouse that can produce a phenotype similar to Hirschsprung disease in human. The Dom gene product is not known, and no candidate region has been defined for a possible human homolog. In this publication we report mapping the Dom locus with high definition, using several intra- and interspecific crosses and

A. Puliti; M. O. Prehu; D. Simon-Chazottes; L. Ferkdadji; M. Peuchmaur; M. Goossens; J. L. Guénet



Clinical features of idiopathic megarectum and idiopathic megacolon.  

PubMed Central

BACKGROUND: Dilatation of the rectum and/or colon, in the absence of demonstrable organic disease, is an uncommon and poorly characterised condition. AIMS: To characterise the clinical and diagnostic features, and response to treatment, of patients with idiopathic megarectum (IMR) and idiopathic megacolon (IMC). METHODS: A retrospective review was undertaken of all patients operated on for these conditions over a 23 year period. In addition all patients treated over a three year period were prospectively studied by means of a questionnaire, contrast studies of the upper and lower intestine, spine x rays to exclude spinal dysraphism, anorectal physiological studies, and assessment of clinical outcome. Patients with Hirschsprung's disease and other known causes of gut dilatation were excluded. RESULTS: (i) Retrospective study: Of 63 operated patients, 22 had IMR, 23 had IMR and IMC, and 18 had IMC only. Five patients with IMC had previous sigmoid volvulus, and three had associated non-gastrointestinal congenital abnormalities. Faecal incontinence was always associated with rectal impaction and 14 patients (82%) with IMR alone had had manual disimpaction. (ii) Prospective study: Twenty two patients had IMR, with a median rectal diameter of 10 cm (normal < 6.5 cm). Six patients had IMC and one patient had IMR and IMC. Patients with IMR were significantly (p = 0.0007) younger than patients with IMC. All patients with IMR became symptomatic in childhood, compared with half the patients with IMC who developed symptoms as adults. Patients with IMR all presented with soiling and impaction, compared with patients with IMC whose symptoms were variable and included constipation or increased bowel frequency, pain, and variable need for laxatives. No upper gut dilatation was seen in either group of patients. Spinal dysraphism was seen in two of 18 patients with IMR and two of four with IMC, suggesting extrinsic denervation as a possible cause in a minority. Twelve of 22 patients with IMR had a maximum anal resting pressure below normal, indicating sphincter damage or inhibition. Both IMR and IMC patients had altered rectal sensitivity to distension, suggesting that despite lack of dilatation the rectum in IMC has altered viscoelasticity, tone, or sensory function. Fifteen of 22 patients with IMR were successfully managed with laxatives or enemas, but seven required surgery. Two of seven patients with IMC required surgery, including one for sigmoid volvulus. CONCLUSIONS: Patients with IMR differ clinically, diagnostically, and in their outcome from patients with IMC. These conditions demand specific investigation, and intensive treatment, to achieve optimum care.

Gattuso, J M; Kamm, M A



A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.  

PubMed Central

The Ncx/Hox11L.1 gene, a member of the Hox11 homeobox gene family, is mainly expressed in neural crest-derived tissues. To elucidate the role of Ncx/Hox11L.1, the gene has been inactivated in embryonic stem cells by homologous recombination. The homozygous mutant mice were viable. These mice developed megacolon with enteric ganglia by age 3-5 wk. Histochemical analysis of the ganglia revealed that the enteric neurons hyperinnervated in the narrow segment of megacolon. Some of these neuronal cells degenerated and neuronal cell death occurred in later stages. We propose that Ncx/Hox11L.1 is required for maintenance of proper functions of the enteric nervous system. These mutant mice can be used to elucidate a novel pathogenesis for human neuronal intestinal dysplasia.

Hatano, M; Aoki, T; Dezawa, M; Yusa, S; Iitsuka, Y; Koseki, H; Taniguchi, M; Tokuhisa, T



Total colectomy with ileorectal anastomosis in surgical management of toxic megacolon.  


Twenty-five patients with toxic megacolon are reported. The most frequent etiology of this syndrome was ulcerative colitis and the main complication colonic perforation. Toxic dilatation generally involved the transverse colon. Twenty patients were treated by a surgical procedure, namely two enterostomies and eighteen colectomies. A total colectomy with ileorectal anastomosis was performed in ten patients. Mortality for the whole series was 32%, but was reduced to 14% in the last 4 years. There were no deaths and no complications needing surgical management in the group of patients treated by total colectomy with ileorectal anastomosis. However, the method resulted in one failure. The satisfactory results obtained with this procedure must be emphasized. Despite the small number of so-treated patients reported in world literature, it is suggested that total colectomy with ileorectal anastomosis must be regarded as the procedure of choice for toxic megacolon without peritonitis. PMID:6645727

Jamart, J; Boissel, P; Debs, A; Grosdidier, J



A newborn with ring chromosome 10, aganglionic megacolon, and renal hypoplasia  

Microsoft Academic Search

A newborn infant is reported who had aganglionic megacolon, renal hypoplasia, severe growth retardation, generalised hypotonia, and various dysmorphic features. Chromosome analysis of lymphocytes and fibroblasts showed a ring chromosome 10 with breakpoints at p13-15 and q26. AluI digestion showed that the ring chromosome was monocentric. FISH with an alpha satellite probe specific for chromosome 10 showed one signal only

G Calabrese; P G Franchi; L Stuppia; R Mingarelli; C Rossi; L Ramenghi; M Marino; E Morizio; R Peila; A Antonucci



Toxic Megacolon and Acute Ischemia of the Colon due to Sigmoid Stenosis Related to Diverticulitis  

PubMed Central

We present a rare case of toxic megacolon accompanied by necrosis of the colon due to chronic dilation caused by stenosis of the sigmoid colon as a complication of diverticulitis. The patient presented at the emergency department with diffuse abdominal pain, fever (38.8°C) and tachycardia (120 beats/min). Physical examination revealed distension and tenderness on deep palpation on the left lower quadrant without peritoneal signs. Abdominal computed tomography showed located stenosis in the sigmoid colon and marked dilation of the descending (12 cm diameter) and transverse (7.5 cm diameter) colon. A few hours later, the patient developed severe septic shock with electrolyte abnormalities. He had a history of two prior admissions to our hospital due to crises of acute diverticulitis. Based on Jalan's criteria the diagnosis was compatible with toxic megacolon. The patient's condition deteriorated suddenly and an emergency colectomy was performed. The operative findings revealed a necrotic colon. Histology examination confirmed the diagnosis of ischemia of the colon. To our knowledge this is the first published report in the literature which refers to a rare complication of diverticulitis, namely chronic stenosis which complicated to colonic ischemia and toxic megacolon.

Antonopoulos, P.; Almyroudi, M.; Kolonia, V.; Kouris, S.; Troumpoukis, N.; Economou, N.



[Plication of diaphragm for eventration of diaphragm caused by megacolon; report of a case].  


A 70-year-old woman with severe respiratory distress was admitted to our hospital by ambulance. Chest X-ray revealed marked elevation of left diaphragm and invagination of megacolon. Colectomy was performed to improve the respiratory distress, but continuous mechanical ventilation was necessary after operation due to hypoxia and hypercapnea. Therefore, plication of diaphragm was additionally performed. With 10 rows of nonabsorbable sutures, 6 to 8 pleats were formed. The following day of operation, she was successfully relieved from the ventilator. PMID:23445657

Nakano, Jun; Okamura, Norihito; Irie, Masahiro; Noguchi, Misa; Fujiwara, Atsushi; Yamashina, Akihiko; Matsuoka, Tomoaki; Kameyama, Kotaro



Toxic megacolon associated with cytomegalovirus infection in a patient with steroid-naïve ulcerative colitis.  


Most cases of cytomegalovirus (CMV) colitis in patients with inflammatory bowel disease (IBD) occur in those treated with immunosuppressants and/or corticosteroids. We herein present the case of a 57-year-old man with toxic megacolon associated with CMV colitis in corticosteroid-naïve ulcerative colitis (UC). To date, there have been only eight previous case reports of CMV colitis in steroid-naïve UC. We discuss the need to consider CMV colitis when making a differential diagnosis of patients with refractory UC who are not receiving corticosteroid treatment. PMID:23037465

Inoue, Ken; Wakabayashi, Naoki; Fukumoto, Kohei; Yamada, Shinya; Bito, Nobukatsu; Yoshida, Naohisa; Katada, Kazuhiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Handa, Osamu; Takagi, Tomohisa; Konishi, Hideyuki; Yagi, Nobuaki; Kokura, Satoshi; Kishimoto, Mitsuo; Yanagisawa, Akio; Naito, Yuji




PubMed Central

Of 20 patients under 15 years of age with proven diagnoses of megacolon, ten were treated surgically with either partial colectomy or resection of the entire colon down to the rectosigmoid junction after thorough trial of medical management. Follow-up shows five of these patients as 100 per cent relieved, one as 75 per cent relieved. Three were entirely well a few months after operation but have not been heard from since. One died of peritonitis on the 16th postoperative day. In four cases in which lumbar sympathectomy was done, the result was partial, temporary or no improvement. Of the patients not operated upon, several have been lost to follow-up, some are doing well on medical treatment, one died in early infancy, and resection is being considered for two. For children with congenital megacolon the authors recommend first a thorough trial of medical treatment consisting of diet, vitamins, drugs and enemas. This should be started as soon as possible after the diagnosis is made, in an attempt to prevent the distention and hypertrophy of the bowel from progressing. If distention remains after a reasonable trial period and the child is not gaining weight adequately, requires repeated hospitalization, and is three years of age or more, then resection of the affected portion of the colon is indicated. The risk of operation has been somewhat reduced with better supportive measures and chemotherapy now available. Since infants and extremely young children do not stand operation on the colon as well as older children, decision to operate should take into consideration the age of the patient. In the reported series, the patient who died following operation was the youngest—2½ years of age.

Yeazell, Louise A.; Bell, H. Glenn



Conservative surgical treatment for toxic megacolon due to Clostridium difficile infection in a transplanted pediatric patient.  


Severe disease caused by Clostridium difficile is frequently encountered in transplant recipients and carries a high mortality. Numerous studies have been published on this subject in the adult population, but few in the pediatric setting. A 4-year-old boy who had undergone heart transplant 20 months earlier was admitted to the pediatric intensive care unit after humoral rejection. Seven days after admission, he developed septic shock, abdominal distension, and paralytic ileus without diarrhea. Pseudomembranous colitis due to C. difficile was confirmed by microbiological and radiological studies. Despite treatment with rectal vancomycin and intravenous metronidazole, the patient did not improve and required decompressive laparotomy; because of the poor subsequent clinical course, terminal ileostomy and cecostomy were performed in a second operation. Recovery was satisfactory, and surgical reconstruction of intestinal tract was performed 3 months later without complications. Although early surgery with total colectomy is indicated, when there is a poor response to medical treatment in cases of C. difficile toxic megacolon, the case we present responded favorably to a conservative surgical approach that enabled intestinal integrity to be restored 3 months later. In the pediatric population, less aggressive therapeutic options should be considered, as they have benefits on the subsequent quality of life of the patient. PMID:22726419

Castillo, A; López, J; Panadero, E; Cerdá, J; Padilla, B; Bustinza, A



Function of the striated anal sphincter during straining in control subjects and constipated patients with a radiologically normal rectum or idiopathic megacolon  

Microsoft Academic Search

The function of the striated anal sphincter during defaecation straining was recorded by manometry and electromyography (E.M.G.) in 31 constipated patients who were unable to expel a water-filled rectal balloon with effort. This group was divided on the basis of measurement of colonic diameter into those with megacolon and those with a normal sized colon. The latter group was further

P. R. H. Barnes; J. E. Lennard-Jones



Idiopathic acquired megacolon  

Microsoft Academic Search

Forty-eight patients treated for chronic incapacitating constipation by surgical resection were reviewed. Thirty-seven had\\u000a subtotal colectomy, eight had left colectomy, two had right hemicolectomy, and one had ileostomy, colectomy, and a Hartmann\\u000a pouch. There were significant complications (21 per cent) and one mortality (2 per cent). A long-term successful outcome was\\u000a found in 81 per cent of the patients on

Paul Belliveau; Stanley M. Goldberg; David A. Rothenberger; Santhat Nivatvongs



Toxic megacolon due to Campylobacter colitis  

Microsoft Academic Search

Campylobacter jejuni is a common cause of acute infectious diarrhoea. Most patients recover in less than a week, but 20 per cent may have a prolonged or severe illness [1]. We describe a patient who developed a fulminant toxic dilatation of the colon necessitating a subtotal colectomy.

J. B. Anderson; A. H. Tanner; A. J. M. Brodribb



Towards a radiologic definition of idiopathic megacolon  

Microsoft Academic Search

Measurements of bowel width and rectal area were used to define normal limits of size in 50 double-contrast barium enema films. Two types of patient with constipation were defined by comparison with these results. In 18 women with prolonged whole-gut transit time, the measurements were within the normal range. Of 11 men and 9 women with a previous radiologic diagnosis

David M. Preston; John E. Lennard-Jones; Brian M. Thomas



The Surgical Treatment of Megaesophagus and Megacolon  

Microsoft Academic Search

The effect of Chagas’ disease on the digestive tract is evaluated based on the experience acquired in the surgical management of 929 cases of megaesophagus: 807 in the nonadvanced state of the disease and 122 with dolichomegaesophagus. The 807 subjects with nonadvanced megaesophagus were submitted to wide esophagocardiomyectomy on the anterior esophagogastric junction combined with an antirefl·ux valvuloplasty procedure. There

H. W. Pinotti; A. Habr-Gama; I. Cecconello; V. N. Felix; B. Zilberstein



Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon  

Microsoft Academic Search

Background & Aims: A variety of gastrointestinal motility disorders have been attributed to alterations of interstitial cells of Cajal and malformations of the enteric nervous system. This study evaluates both the distribution of interstitial cells of Cajal and the pathohistology of the enteric nervous system in 2 severe human colorectal motility disorders. Methods: Colonic specimens obtained from patients with slow-transit

Thilo Wedel; Juliane Spiegler; Stefan Soellner; Uwe J. Roblick; Thomas H. K. Schiedeck; Hans-Peter Bruch; Heinz-Juergen Krammer



Loss of interstitial cells and a fibromuscular layer on the luminal side of the colonic circular muscle presenting as megacolon in an adult patient  

Microsoft Academic Search

BACKGROUNDAnimal studies have shown that the neuromuscular structures on the luminal side of the colonic circular muscle coordinate circular muscle activity. These structures have been identified by electron microscopy in the normal human colon, but have never been thoroughly studied in patients with acquired intestinal hypoganglionosis.AIMSTo perform histological, immunocytochemical, and electron microscopic examinations of the colon of a patient with

M S Faussone-Pellegrini; P Fociani; R Buffa; G Basilisco



Gastric emptying and small intestinal transit in the piebald mouse model for Hirschsprung's disease  

SciTech Connect

Gastric emptying and small intestinal transit were investigated in the piebald mouse model for Hirschsprung's disease. These mice exhibited aganglionosis of the terminal segment of the large intestine. This condition was accompanied by fecal stasis and megacolon. Gastric emptying of saline or milk meals was slower in the mice with aganglionic or induced megacolon than in the normal mice, but the rate of emptying was faster than after administration of morphine (10 mg/kg). In the small intestine, the distribution of the radiolabeled marker and the advancing edge of the marker profile were abnormal in the mice with megacolon. There were small differences between the megacolonic and normal mice in the distance traversed by the advancing edge of the intraluminal profile of the marker. These results are evidence for disturbances of gastric and small intestinal motor function that occur in mice secondary to development of megacolon.

Cooke, H.J.; Pitman, K.; Starr, G.; Wood, J.D.



Pseudomembranous colitis  


... disorder, but other medicines may also be used. Electrolyte solutions or fluids given through a vein may ... Dehydration with electrolyte imbalance Perforation of (hole through) the colon Toxic megacolon


Infant botulism mimicking Hirschprung's disease.  


We report a case of infant botulism presenting as primary colonic ileus--mimicking Hirschprung's megacolon. Infant botulism should be considered in any infant with constipation and neurologic abnormalities. PMID:19853738

O'Reilly, Eamon B; Montenegro, Brian; Arnold, John; Tomita, Sandra



Infant botulism mimicking Hirschprung's disease  

Microsoft Academic Search

We report a case of infant botulism presenting as primary colonic ileus—mimicking Hirschprung's megacolon. Infant botulism should be considered in any infant with constipation and neurologic abnormalities.

Eamon B. O'Reilly; Brian Montenegro; John Arnold; Sandra Tomita



Timing and Indications for Colectomy in Chronic Ulcerative Colitis: Surgical Consideration  

Microsoft Academic Search

Total proctocolectomy (TPC) cures a patient of the intestinal manifestation of chronic ulcerative colitis. The timing of surgery during the illness will influence the choice of operation, the frequency of post-operative complications, and the long-term functional outcomes. Surgery is divided into emergency, urgent, and elective procedures. Emergency cases are performed for complications of fulminant colitis: hemorrhage, perforation, toxic megacolon or

Robert R. Cima



Comparison of the Premier Toxin A and B Assay and the TOX A\\/B II Assay for Diagnosis of Clostridium difficile Infection  

Microsoft Academic Search

Clostridium difficile causes nosocomial diarrhea and is responsible for complications such as pseudomem- branous colitis, megacolon, and perforation. Using 442 stool specimens, we compared the sensitivities and specificities of the Premier toxin A and B (Meridian Bioscience, Inc.) and C. difficile TOX A\\/B II (TechLab, Inc., Blacksburg, VA) immunoassays in the Virology Department of the Kaiser Permanente Regional Reference Laboratories.

Susan M. Novak-Weekley; Michele H. Hollingsworth



Hirschsprung disease, associated syndromes, and genetics: a review  

Microsoft Academic Search

Hirschsprung disease (HSCR, aganglionic megacolon) is the main genetic cause of functional intestinal obstruction with an incidence of 1\\/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has dramatically decreased mortality and morbidity, which

Jeanne Amiel; Stanislas Lyonnet; M Garcia-Barcelo; F Lantieri; G Burzynski; S Borrego; A Pelet; S Arnold; X Miao; P Griseri; A S Brooks; G Antinolo; L de Pontual; M Clement-Ziza; A Munnich; C Kashuk; K K-Y Wong; A Chakravarti; P K-H Tam; I Ceccherini; R M W Hofstra; R Fernandez



Strategies for the care of adults hospitalized for active ulcerative colitis.  


Ulcerative colitis is a chronic inflammatory disease of the colon; as many as 25% of patients with this disease require hospitalization. The goals of hospitalization are to assess disease severity, exclude infection, administer rapidly acting and highly effective medication regimens, and determine response. During hospitalization, patients should be given venous thromboembolism prophylaxis and monitored for the development of toxic megacolon. Patients who do not respond to intravenous corticosteroids should be considered for rescue therapy with infliximab or cyclosporine. Patients who are refractory to medical therapies or who develop toxic megacolon should be evaluated promptly for colectomy. Patients who do respond to medical therapies should be discharged on an appropriate maintenance regimen when they meet discharge criteria. We review practical evidence-based management principles and propose a day-by-day algorithm for managing patients hospitalized for ulcerative colitis. PMID:22835577

Pola, Suresh; Patel, Derek; Ramamoorthy, Sonia; McLemore, Elisabeth; Fahmy, Marianne; Rivera-Nieves, Jesus; Chang, John T; Evans, Elisabeth; Docherty, Michael; Talamini, Mark; Sandborn, William J



Ichthyosis, deafness, and Hirschsprung's disease.  


An infant with congenital ichthyosis and deafness developed Hirschsprung's disease. No evidence of keratitis was present. No previous cases of ichthyosis have been associated with aganglionic megacolon. Although no corneal changes were observed, we believe that the clinical features of ichthyosis and deafness suggest the diagnosis of KID (keratitis, ichthyosis, deafness) syndrome. Whether corneal changes would have occurred is unknown, since the infant died of malnutrition and infectious complications. PMID:2704659

Mallory, S B; Haynie, L S; Williams, M L; Hall, W



Placement of a Port Catheter Through Collateral Veins in a Patient with Central Venous Occlusion  

Microsoft Academic Search

Long-term utilization of central venous catheters (CVCs) for parenteral nutrition has a high incidence of central venous complications including infections, occlusions, and stenosis. We report the case of a 31-year-old woman presenting with a malabsorption caused by short gut syndrome due to congenital aganglionic megacolon. The patient developed a chronic occlusion of all central neck and femoral veins due to

Ulf Karl-Martin Teichgraeber; Florian Streitparth; Bernhard Gebauer; Thomas Benter



Placement of a Port Catheter Through Collateral Veins in a Patient with Central Venous Occlusion  

Microsoft Academic Search

Long-term utilization of central venous catheters (CVCs) for parenteral nutrition has a high incidence of central venous complications\\u000a including infections, occlusions, and stenosis. We report the case of a 31-year-old woman presenting with a malabsorption\\u000a caused by short gut syndrome due to congenital aganglionic megacolon. The patient developed a chronic occlusion of all central\\u000a neck and femoral veins due to

Ulf Karl-Martin Teichgräber; Florian Streitparth; Bernhard Gebauer; Thomas Benter



Mutations of the RET proto-oncogene in Hirschsprung's disease  

Microsoft Academic Search

HIRSCHSPRUNG'S disease (HSCR)1 is a common condition (1 in 5,000 live births) resulting in intestinal obstruction in neonates2 and megacolon in infants and adults3. This disease has been ascribed to the absence of autonomic ganglion cells, which are derived from the neural crest, in the terminal hindgut4. Segregation analyses have suggested incompletely penetrant dominant inheritance in familial HSCR5. Recently, a

Patrick Edery; Stanislas Lyonnet; Lois M. Mulligan; Anna Pelet; Eleanore Dow; Laurent Abel; Susan Holder; Claire Nihoul-Fékété; Bruce A. J. Ponder; Arnold Munnich



Volvulus of the sigmoid colon in Brazil: A report of 230 cases  

Microsoft Academic Search

Summary  Etiologic and physiopathologic aspects of volvulus of the sigmoid colon in Brazil are presented. It is believed that sigmoidal\\u000a volvulus in Brazil is a frequent complication of megacolon caused by Chagas' disease, differing in some characteristics from\\u000a volvulus found in other countries.\\u000a \\u000a A review of 230 cases treated between 1938 and 1974 in the Surgical Department of Hospital das Clínicas,

Angelita Habr Gama; Jorge Haddad; Oscar Simonsen; Paulo Warde; Angelino Manzione; José Hyppölito da Silva; Massahiro Ioshimoto; Daher Cutait; Arrigo Raia



Review of medical and surgical management of Clostridium difficile infection  

Microsoft Academic Search

Clostridium difficile infection (CDI) has become an important area in our daily clinical practice. C. difficile is known to cause a broad spectrum of conditions ranging from asymptomatic carriage, through mild or moderately severe disease\\u000a with watery diarrhoea, to the life-threatening pseudomembranous colitis (PMC), with toxic megacolon and ileus. Peoples who\\u000a have been treated with broad-spectrum antibiotics, patients with serious

B. FarisA; A. Blackmore; N. Haboubi



Human GFRA1: Cloning, Mapping, Genomic Structure, and Evaluation as a Candidate Gene for Hirschsprung Disease Susceptibility  

Microsoft Academic Search

Congenital aganglionic megacolon, commonly known as Hirschsprung disease (HSCR), is the most frequent cause of congenital bowel obstruction. Germline mutations in theRETreceptor tyrosine kinase have been shown to cause HSCR. Knockout mice forRETand for its ligand, glial cell line-derived neurotrophic factor (GDNF), exhibit both complete intestinal aganglionosis and renal defects. Recently, GDNF and GFRA1 (GDNF family receptor, also known as

Misha Angrist; Shuqian Jing; Stacey Bolk; Kimberly Bentley; Sudha Nallasamy; Marc Halushka; Gary M. Fox; Aravinda Chakravarti



Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection  

NASA Astrophysics Data System (ADS)

Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.

Surawicz, Christina M.


Technical Aspects of Ileoanal Pouch Surgery in Patients with Ulcerative Colitis  

PubMed Central

Restorative proctocolectomy with ileal pouch-anal anastomosis is the procedure of choice for patients with ulcerative colitis requiring surgery. A J-pouch with a stapled anastomosis has been the preferred technique because it is quicker, safer, and associated with good functional outcomes. A diverting loop ileostomy is usually created at the time of ileal pouch-anal anastomosis. In patients with severe fulminant colitis or toxic megacolon, restorative proctocolectomy with ileal pouch-anal anastomosis is performed in multistages. The technical aspects of ileal pouch-anal anastomosis in patients with ulcerative colitis are reviewed in this article.

Kirat, Hasan T.; Remzi, Feza H.



Positive correlation between symptoms and circulating motilin, pancreatic polypeptide and gastrin concentrations in functional bowel disorders.  

PubMed Central

Motilin, pancreatic polypeptide and gastrin blood concentrations in response to drinking water have been studied in 40 patients with functional bowel disease and compared with results in two groups of healthy control subjects. Patients with slow transit constipation and idiopathic megacolon showed impaired motilin release. Pancreatic polypeptide release was reduced in patients with slow transit constipation, but increased in those with functional diarrhoea. Gastrin release was impaired in all groups complaining of chronic constipation. Circulating motilin, pancreatic polypeptide and gastrin concentrations appear to bear some relationship to intestinal transit time in patients with functional bowel disorders.

Preston, D M; Adrian, T E; Christofides, N D; Lennard-Jones, J E; Bloom, S R



[Morbus Crohn (enteritis regionalis)].  


Crohn's disease (regional enteritis) is a chronic non-specific inflammatory intestinal disorder of unknown etiology. Most commonly the terminal ileum in involved, a segmentary involvement of the bowel wall is rather characteristic. Main symptoms are recurrent abdominal pain, fever, diarrhea and weight loss. Radiological and endoscopic examination confirms the diagnosis, granulomas in the biopsy specimen are pathognomonic. In differential diagnosis ulcerative and ischaemic colitis have to be ruled out. Conservative therapy with prednisolone and salazopyrin is the method of choice, however, complications like small bowel obstruction, toxic megacolon and fistulae ask for surgical intervention. PMID:5346

Phillip, J



Multiple endocrine neoplasia 2B presenting with pseudo-Hirschsprung's disease.  

PubMed Central

Multiple endocrine neoplasia type 2B (MEN 2B) is a rare syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and typical phenotypic features, such as marfanoid habitus, multiple mucosal ganglioneuromas and thickened corneal nerves. Individuals with MEN 2B may develop megacolon and pseudo-obstruction due to intestinal ganglioneuromatosis simulating Hirschsprung's (HSCR) disease. We hereby describe the clinical and genetic features of a 21-year-old male patient with MEN 2B associated with pseudo-HSCR disease. The patient had MTC, pheochromocytoma, marfanoid habitus, multiple mucosal ganglioneuromas, thickened corneal nerves and severe gastrointestinal involvement. Emergent laparotomy was performed when he was presented with acute bowel obstruction. The myenteric and submucosal nerve plexuses in the small and large intestines were composed of diffusely hyperplasic, disorganized, mature ganglion cells. Genetic testing revealed a de novo ret proto-oncogene germline mutation in codon 918 in exon 16. Megacolon and pseudo-obstruction similar to the HSCR disease may develop in patients with MEN 2B. However, the observed dysmotility is the result of an abnormal proliferation of intramural ganglion cells in contrast to the absence of enteric ganglia which were present in the HSCR disease. Attentiveness about the phenotypic characteristics and unusual findings might lead to early and correct diagnosis of the MEN 2B syndrome. This approach improves the survival rate and quality of life considerably. Images Figure 1

Erdogan, Murat Faik; Gulec, Bulent; Gursoy, Alptekin; Pekcan, Mesut; Azal, Omer; Gunhan, Omer; Bayer, Atilla



Placement of a port catheter through collateral veins in a patient with central venous occlusion.  


Long-term utilization of central venous catheters (CVCs) for parenteral nutrition has a high incidence of central venous complications including infections, occlusions, and stenosis. We report the case of a 31-year-old woman presenting with a malabsorption caused by short gut syndrome due to congenital aganglionic megacolon. The patient developed a chronic occlusion of all central neck and femoral veins due to long-term use of multiple CVCs over more than 20 years. In patients with central venous occlusion and venous transformation, the implantation of a totally implanted port system by accessing collateral veins is an option to continue long-term parenteral nutrition when required. A 0.014-in. Whisper guidewire (Terumo, Tokyo) with high flexibility and steerability was chosen to maneuver and pass through the collateral veins. We suggest this approach to avoid unfavorable translumbar or transhepatic central venous access and to conserve the anatomically limited number of percutaneous access sites. PMID:19504152

Teichgräber, Ulf Karl-Martin; Streitparth, Florian; Gebauer, Bernhard; Benter, Thomas



Unsuspected invasive neonatal gastrointestinal mucormycosis: A clinicopathological study of six cases from a tertiary care hospital  

PubMed Central

Aim: To analyse the clinicopathological features of neonatal mucormycosis Materials and Methods: Retrospective analysis of cases of neonatal gastrointestinal mucormycosis. Results: There were six neonates with male: female ratio of 1:1. Except one all were preterm babies. The clinical presentation was abdominal distension in the majority. All were clinically diagnosed as either NEC or toxic megacolon with perforation. Neonatal gastrointestinal mucormycosis was not suspected clinically in any. All the children were explored immediately. Biopsy revealed transmural hemorrhagic necrosis/infarction of the intestinal wall with fungal hyphae. Conclusions: The physicians should have a high index of suspicion for gastrointestinal tract mucormycosis in neonates with metabolic disturbances who present with abdominal distension and pneumoperitoneum. Early diagnosis and aggressive medical and surgical treatment may improve the outcome of neonates with this potentially lethal invasive disease.

Patra, Sushma; Vij, Mukul; Chirla, Dinesh K.; Kumar, Narendar; Samal, Subash C.



Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome).  


We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome). Mutation analysis of the zinc finger homeo box 1 B (ZFHX1 B) gene revealed a de novo 7 bp deletion (TGGCCCC) at nucleotide 1773 (1773 delTGGCCCC) resulting in a frameshift and leading to a termination codon at amino acid residue 604 (604 X) in exon 8 C. The zinc finger homeo box 1 B (Smad interacting protein-1) is a transcription corepressor of Smad target genes with functions in the patterning of neural crest derived cells, CNS, and midline structures. Mutations in ZFHX1 B can lead to neurological disorders in addition to dysmorphic features, megacolon, and other malformations. PMID:14681759

Sztriha, L; Espinosa-Parrilla, Y; Gururaj, A; Amiel, J; Lyonnet, S; Gerami, S; Johansen, J G



Stapled anastomosis in colorectal surgery.  


The authors review their experience with stapled anastomosis in colorectal and ileorectal resections for malignant and benign lesions of the large bowel. They describe the technique and results in a series of 49 patients (24 with cancer of the rectum and rectosigmoid junction; six with familial polyposis, associated with cancer in four; 12 with chagastic megacolon; three, Crohn's disease; two, ulcerative colitis; and one each, diverticular sigmoiditis and ischemic sigmoiditis). Anterior resection was performed in 38 patients and total colectomy with ileorectal anastomosis in 11. Main complications and mortality are presented. They conclude that stapled anastomosis is an efficient method for intestinal reconstruction after resection for malignant and benign lesions of the large bowel. PMID:7227128

Cutait, D E; Cutait, R; da Silva, J H; Manzione, A; Kiss, D R; Lourenção, J L; Calache, J E



Liquorrhoea associated with intrapelvic meningocele resection successfully treated by conservative therapy: a case report.  


Asymptomatic intrapelvic meningocele is rare. Here, we report the case of a 30-year-old Chinese man who underwent sigmoidectomy due to megacolon. During the operation, an intrapelvic cyst was found and resected. Meningocele was confirmed by histological examination. The patient recovered well postoperatively with the exception of liquorrhoea. Conservative therapy was initiated, including draining, anti-infection and specific posture maintenance. During the following week, liquorrhoea was generally relieved and the patient was discharged. This is the first known report of liquorrhoea associated with intrapelvic meningocele resection successfully treated by conservative therapy. Our case indicates that conservative treatment may be considered for similar cases so that a second surgery is avoided. PMID:23720680

Xie, Xiju; Yang, Xiaodong; Xu, Hao; Wang, Feng; Hu, Youfang



Building a brain in the gut: development of the enteric nervous system.  


The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, is an essential component of the gut neuromusculature and controls many aspects of gut function, including coordinated muscular peristalsis. The ENS is entirely derived from neural crest cells (NCC) which undergo a number of key processes, including extensive migration into and along the gut, proliferation, and differentiation into enteric neurons and glia, during embryogenesis and fetal life. These mechanisms are under the molecular control of numerous signaling pathways, transcription factors, neurotrophic factors and extracellular matrix components. Failure in these processes and consequent abnormal ENS development can result in so-called enteric neuropathies, arguably the best characterized of which is the congenital disorder Hirschsprung disease (HSCR), or aganglionic megacolon. This review focuses on the molecular and genetic factors regulating ENS development from NCC, the clinical genetics of HSCR and its associated syndromes, and recent advances aimed at improving our understanding and treatment of enteric neuropathies. PMID:23167617

Goldstein, A M; Hofstra, R M W; Burns, A J



Umbilical incision laparoscopic surgery with one assist port for an elderly patient with recurrent sigmoid volvulus.  


Single-port access laparoscopic surgery has recently emerged as a method to improve morbidity and cosmetic benefit of conventional laparoscopic surgery. Herein, we report the experience of transumbilical incision laparoscopic sigmoidectomy with one assist port in a 71-year-old man who had developed recurrent sigmoid volvulus in these several years since his first visit to the hospital. The patient presented abdominal distension and severe constipation. A plain x-ray film and CT of the abdomen showed grossly distended sigmoid colon loops and stenosis of recto-sigmoid colon. Sigmoid volvulus associated with megacolon was diagnosed and emergence endoscopic decompression was performed. After his condition improved, transumbilical incision laparoscopic sigmoidectomy was carried out as the minimally invasive approach, due to the several risk of patient such as aging and pulmonary disorder. Postoperative course was uneventful and on postoperative visit to the hospital he reported resolution of abdominal distension. PMID:23235104

Matsuoka, Tasuku; Osawa, Naoshi; Yoh, Taiho; Hirakawa, Kosei



An unusual case of an ulcerative colitis flare resulting in disseminated intravascular coagulopathy and a bladder hematoma: a case report  

PubMed Central

Background Disorders of coagulation have long been associated with inflammatory bowel disease. Children, as well as adults, with both active and inactive ulcerative colitis have been found to have abnormal coagulation and fibrinolysis. Disseminated intravascular coagulation arises from an overwhelming of the haemostatic regulatory mechanisms leading to an excessive generation of thrombin and a failure of the normal inhibitory pathways to prevent systemic effects of this enzyme. Ulcerative colitis has been associated with disseminated intravascular coagulation in conjunction with septicemia, toxic megacolon and surgery. Case presentation A fourteen-year-old boy with a history of poorly controlled ulcerative colitis presented with nonbilious emesis, hematochezia, and hematuria. Laboratory workup revealed disseminated intravascular coagulation. He was placed on triple antibiotics therapy. An infectious workup came back negative. A computerized tomography (CT) scan of the abdomen revealed a marked thickening and irregularity of the bladder wall as well as wall thickening of the rectosigmoid, ascending, transverse, and descending colon. Patient's clinical status remained stable despite a worsening of laboratory values associated with disseminated intravascular coagulation. Patient was begun on high dose intravenous steroids with improvement of the disseminated intravascular coagulation laboratory values within 12 hours and resolution of disseminated intravascular coagulopathy within 4 days. A thorough infectious workup revealed no other causes to his disseminated intravascular coagulation. Conclusions The spectrum of hypercoagulable states associated with ulcerative colitis varies from mild to severe. Although disseminated intravascular coagulation associated with ulcerative colitis is usually related to septicemia, toxic megacolon or surgery, we present a case of an ulcerative colitis flare resulting in disseminated intravascular coagulation and a bladder hematoma.

Suskind, David L; Murray, Karen; Christie, Dennis



Pleiotropic effects of coat colour-associated mutations in humans, mice and other mammals.  


The characterisation of the pleiotropic effects of coat colour-associated mutations in mammals illustrates that sensory organs and nerves are particularly affected by disorders because of the shared origin of melanocytes and neurocytes in the neural crest; e.g. the eye-colour is a valuable indicator of disorders in pigment production and eye dysfunctions. Disorders related to coat colour-associated alleles also occur in the skin (melanoma), reproductive tract and immune system. Additionally, the coat colour phenotype of an individual influences its general behaviour and fitness. Mutations in the same genes often produce similar coat colours and pleiotropic effects in different species (e.g., KIT [reproductive disorders, lethality], EDNRB [megacolon] and LYST [CHS]). Whereas similar disorders and similar-looking coat colour phenotypes sometimes have a different genetic background (e.g., deafness [EDN3/EDNRB, MITF, PAX and SNAI2] and visual diseases [OCA2, RAB38, SLC24A5, SLC45A2, TRPM1 and TYR]). The human predilection for fancy phenotypes that ignore disorders and genetic defects is a major driving force for the increase of pleiotropic effects in domestic species and laboratory subjects since domestication has commenced approximately 18,000 years ago. PMID:23583561

Reissmann, Monika; Ludwig, Arne



The transcription factor Sox10 is a key regulator of peripheral glial development  

PubMed Central

The molecular mechanisms that determine glial cell fate in the vertebrate nervous system have not been elucidated. Peripheral glial cells differentiate from pluripotent neural crest cells. We show here that the transcription factor Sox10 is a key regulator in differentiation of peripheral glial cells. In mice that carry a spontaneous or a targeted mutation of Sox10, neuronal cells form in dorsal root ganglia, but Schwann cells or satellite cells are not generated. At later developmental stages, this lack of peripheral glial cells results in a severe degeneration of sensory and motor neurons. Moreover, we show that Sox10 controls expression of ErbB3 in neural crest cells. ErbB3 encodes a Neuregulin receptor, and down-regulation of ErbB3 accounts for many changes in development of neural crest cells observed in Sox10 mutant mice. Sox10 also has functions not mediated by ErbB3, for instance in the melanocyte lineage. Phenotypes observed in heterozygous mice that carry a targeted Sox10 null allele reproduce those observed in heterozygous Sox10Dom mice. Haploinsufficiency of Sox10 can thus cause pigmentation and megacolon defects, which are also observed in Sox10Dom/+ mice and in patients with Waardenburg-Hirschsprung disease caused by heterozygous SOX10 mutations.

Britsch, Stefan; Goerich, Derk E.; Riethmacher, Dieter; Peirano, Reto I.; Rossner, Moritz; Nave, Klaus-Armin; Birchmeier, Carmen; Wegner, Michael



Male and female differential reproductive rate could explain parental transmission asymmetry of mutation origin in Hirschsprung disease  

PubMed Central

Hirschsprung disease (HSCR, aganglionic megacolon) is a complex and heterogeneous disease with an incidence of 1 in 5000 live births. Despite the multifactorial determination of HSCR in the vast majority of cases, there is a monogenic subgroup for which private rare RET coding sequence mutations with high penetrance are found (45% of HSCR familial cases). An asymmetrical parental origin is observed for RET coding sequence mutations with a higher maternal inheritance. A parent-of-origin effect is usually assumed. Here we show that a differential reproductive rate for males and females also leads to an asymmetrical parental origin, which was never considered as a possible explanation till now. In the case of HSCR, we show a positive association between penetrance of the mutation and parental transmission asymmetry: no parental transmission asymmetry is observed in sporadic RET CDS mutation carrier cases for which penetrance of the mutation is low, whereas a parental transmission asymmetry is observed in affected sib-pairs for which penetrance of the mutation is higher. This allows us to conclude that the explanation for this parental asymmetry is that more severe mutations have resulted in a differential reproductive rate between male and female carriers.

Jannot, Anne-Sophie; Amiel, Jeanne; Pelet, Anna; Lantieri, Francesca; Fernandez, Raquel M; Verheij, Joke B G M; Garcia-Barcelo, Merce; Arnold, Stacey; Ceccherini, Isabella; Borrego, Salud; Hofstra, Robert M W; Tam, Paul K H; Munnich, Arnold; Chakravarti, Aravinda; Clerget-Darpoux, Francoise; Lyonnet, Stanislas



Involvement of SOX10 in the pathogenesis of Hirschsprung disease: report of a truncating mutation in an isolated patient  

PubMed Central

SOX10 protein is a key transcription factor during neural-crest development. Mutations in SOX10 are associated with several neurocristopathies such as Waardenburg syndrome type IV (WS4), a congenital disorder characterized by the association of hearing loss, pigmentary abnormalities and absence of ganglion cells in the myenteric and submucosal plexus of the gastrointestinal tract, also known as aganglionic megacolon or Hirschsprung disease (HSCR). Several mutations at this locus are known to cause a high percentage of WS4 cases, but no SOX10 mutations had been ever reported associated to isolated HSCR patient. Therefore, non-syndromic HSCR disease was initially thought not to be associated to mutations at this particular locus. In the present study, we describe the evaluation of the SOX10 gene in a series of 196 isolated HSCR cases, the largest patient series evaluated so far, and report a truncating c.153-155del mutation. This is the first time that a SOX10 mutation is detected in an isolated HSCR patient, which completely changes the scenario for the implications of SOX10 mutations in human disease, giving us a new tool for genetic counselling.

Sanchez-Mejias, Avencia; Watanabe, Yuli; Fernandez, Raquel M.; Lopez-Alonso, Manuel; Antinolo, Guillermo; Bondurand, Nadege; Borrego, Salud



Long-term natural history and complications of collagenous colitis  

PubMed Central

Microscopic forms of colitis have been described, including collagenous colitis, a possibly heterogeneous disorder. Collagenous colitis most often appears to have an entirely benign clinical course that usually responds to limited treatment. Sometimes significant extracolonic disorders, especially arthritis, spondylitis, thyroiditis and skin disorders, such as pyoderma gangrenosum, dominate the clinical course and influence the treatment strategy. However, rare fatalities have been reported and several complications, some severe, have been attributed directly to the colitis. Toxic colitis and toxic megacolon may develop. Concomitant gastric and small intestinal inflammatory disorders have been described including celiac disease and more extensive collagenous inflammatory disease. Colonic ulceration has been associated with the use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn disease, may evolve directly from collagenous colitis. Submucosal ‘dissection’, colonic fractures, or mucosal tears and perforation, possibly from air insufflation during colonoscopy, have been reported. Similar changes may result from increased intraluminal pressures that may occur during radiological imaging of the colon. Neoplastic disorders of the colon may also occur during the course of collagenous colitis, including colon carcinoma and neuroendocrine tumours (ie, carcinoids). Finally, lymphoproliferative disease has been reported.

Freeman, Hugh J



Diagnosis of Clostridium difficile infection: an ongoing conundrum for clinicians and for clinical laboratories.  


Clostridium difficile is a formidable nosocomial and community-acquired pathogen, causing clinical presentations ranging from asymptomatic colonization to self-limiting diarrhea to toxic megacolon and fulminant colitis. Since the early 2000s, the incidence of C. difficile disease has increased dramatically, and this is thought to be due to the emergence of new strain types. For many years, the mainstay of C. difficile disease diagnosis was enzyme immunoassays for detection of the C. difficile toxin(s), although it is now generally accepted that these assays lack sensitivity. A number of molecular assays are commercially available for the detection of C. difficile. This review covers the history and biology of C. difficile and provides an in-depth discussion of the laboratory methods used for the diagnosis of C. difficile infection (CDI). In addition, strain typing methods for C. difficile and the evolving epidemiology of colonization and infection with this organism are discussed. Finally, considerations for diagnosing C. difficile disease in special patient populations, such as children, oncology patients, transplant patients, and patients with inflammatory bowel disease, are described. As detection of C. difficile in clinical specimens does not always equate with disease, the diagnosis of C. difficile infection continues to be a challenge for both laboratories and clinicians. PMID:23824374

Burnham, Carey-Ann D; Carroll, Karen C



Hirschsprung disease, associated syndromes and genetics: a review.  


Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development. PMID:17965226

Amiel, J; Sproat-Emison, E; Garcia-Barcelo, M; Lantieri, F; Burzynski, G; Borrego, S; Pelet, A; Arnold, S; Miao, X; Griseri, P; Brooks, A S; Antinolo, G; de Pontual, L; Clement-Ziza, M; Munnich, A; Kashuk, C; West, K; Wong, K K-Y; Lyonnet, S; Chakravarti, A; Tam, P K-H; Ceccherini, I; Hofstra, R M W; Fernandez, R



Use of Propolis Hydroalcoholic Extract to Treat Colitis Experimentally Induced in Rats by 2,4,6-Trinitrobenzenesulfonic Acid  

PubMed Central

This study focused on the therapeutic effect of a propolis SLNC 106PI extract on experimental colitis. Wistar adult rats received 0.8?mL rectal dose of one of the following solutions: saline (group S), 20?mg TNBS in 50% ethanol (group TNBS), 20?mg TNBS in 50% ethanol and propolis extract in saline (group TNBS-P), propolis extract in saline (group SP), and 20?mg TNBS in 50% ethanol and 50?mg/kg mesalazine (group TNBS-M). The animals were euthanized 7 or 14 days after the colitis induction. Samples of the distal colon were harvested for the analysis of myeloperoxidase (MPO) enzyme activity and for morphometric analysis in paraffin-embedded histological sections with hematoxylin-eosin or histochemical staining. The animals treated with TNBS exhibited the typical clinical signs of colitis. Increased MPO activity confirmed the presence of inflammation. TNBS induced the development of megacolon, ulceration, transmural inflammatory infiltrate, and thickened bowel walls. Treatment with propolis moderately reduced the inflammatory response, decreased the number of cysts and abscesses, inhibited epithelial proliferation, and increased the number of goblet cells. The anti-inflammatory activity of the propolis SLNC 106 extract was confirmed by the reductions in both the inflammatory infiltrate and the number of cysts and abscesses in the colon mucosa.

Goncalves, Cely Cristina Martins; Hernandes, Luzmarina; Bersani-Amado, Ciomar Aparecida; Franco, Selma Lucy; Silva, Joaquim Felipe de Souza



Acquired immune deficiency syndrome (AIDS). Indications for abdominal surgery, pathology, and outcome.  

PubMed Central

Thirty-six major abdominal operations were performed on 35 Acquired Immune Deficiency Syndrome (AIDS) patients (33 men, two women). Twenty-two elective operations were indicated for diagnosis of abdominal or retroperitoneal mass (6), incomplete bowel obstruction (5), intra-abdominal infection (4), biliary symptoms (3), thrombocytopenia (3), and toxic megacolon (1). Fourteen emergency operations were for perforated viscus or peritonitis (11), massive gastrointestinal bleeding (2), and cecal volvulus (1). In 5 of 22 (23%) elective operations AIDS was unknown to the treating physicians until diagnosed by the surgical pathology; in contrast, all 14 emergency operations were in patients who had a known diagnosis of AIDS. The operative findings were related to AIDS in 34 of 36 (94%) operations. Cytomegalovirus was the most common pathogen, isolated or identified microscopically in 11 patients (eight emergency and three elective operations). Mycobacterial infections presented as retroperitoneal adenopathy or splenic abscess in six patients. Non-Hodgkins lymphoma was the most common malignancy found, presenting as an abdominal mass (4), bowel obstruction (3), or with gastrointestinal bleeding (2). Kaposi's sarcoma was diagnosed at laparotomy in four patients. The 1-month operative mortality rate for elective operation was 9% (2 of 22) and 46% (6 of 13) in emergencies. Postoperative complications included 1 reoperation for sepsis caused by inadequately resected CMV colitis; 1 pancreatic fistula; 1 wound dehiscence, and 2 minor wound infections.

Wilson, S E; Robinson, G; Williams, R A; Stabile, B E; Cone, L; Sarfeh, I J; Miller, D R; Passaro, E



Acquired immune deficiency syndrome (AIDS). Indications for abdominal surgery, pathology, and outcome.  


Thirty-six major abdominal operations were performed on 35 Acquired Immune Deficiency Syndrome (AIDS) patients (33 men, two women). Twenty-two elective operations were indicated for diagnosis of abdominal or retroperitoneal mass (6), incomplete bowel obstruction (5), intra-abdominal infection (4), biliary symptoms (3), thrombocytopenia (3), and toxic megacolon (1). Fourteen emergency operations were for perforated viscus or peritonitis (11), massive gastrointestinal bleeding (2), and cecal volvulus (1). In 5 of 22 (23%) elective operations AIDS was unknown to the treating physicians until diagnosed by the surgical pathology; in contrast, all 14 emergency operations were in patients who had a known diagnosis of AIDS. The operative findings were related to AIDS in 34 of 36 (94%) operations. Cytomegalovirus was the most common pathogen, isolated or identified microscopically in 11 patients (eight emergency and three elective operations). Mycobacterial infections presented as retroperitoneal adenopathy or splenic abscess in six patients. Non-Hodgkins lymphoma was the most common malignancy found, presenting as an abdominal mass (4), bowel obstruction (3), or with gastrointestinal bleeding (2). Kaposi's sarcoma was diagnosed at laparotomy in four patients. The 1-month operative mortality rate for elective operation was 9% (2 of 22) and 46% (6 of 13) in emergencies. Postoperative complications included 1 reoperation for sepsis caused by inadequately resected CMV colitis; 1 pancreatic fistula; 1 wound dehiscence, and 2 minor wound infections. PMID:2552944

Wilson, S E; Robinson, G; Williams, R A; Stabile, B E; Cone, L; Sarfeh, I J; Miller, D R; Passaro, E



History of and current issues affecting surgery for pediatric ulcerative colitis.  


Pediatric ulcerative colitis (UC) is reportedly more extensive and progressive in its clinical course than adult UC. Therefore, more aggressive initial therapies and more frequent colectomies are needed. When physicians treat pediatric UC, they must consider the therapeutic outcome as well as the child's physical and psychological development. Mucosal proctocolectomy with ileal J-pouch anal anastomosis is currently recommended as a standard curative surgical procedure for UC in both children and adults worldwide. This procedure was developed 100 years after the first surgical therapy, which treated UC by colon irrigation through a temporary inguinal colostomy. Predecessors in the colorectal and pediatric surgical fields have struggled against several postoperative complications and have long sought a surgical procedure that is optimal for children. We herein describe the history of the development of surgical procedures and the current issues regarding the surgical indications for pediatric UC. These issues differ from those in adults, including the definition of toxic megacolon on plain X-rays, the incidence of colon carcinoma, preoperative and postoperative steroid complications, and future growth. Surgeons treating children with UC should consider the historical experiences of pioneer surgeons to take the most appropriate next step to improve the surgical outcomes and patients' quality of life. PMID:23203770

Uchida, Keiichi; Araki, Toshimitsu; Kusunoki, Masato



Ogilvie's syndrome following posterior spinal arthrodesis for scoliosis  

PubMed Central

We report Ogilvie's syndrome following posterior spinal arthrodesis on a patient with thoracic and lumbar scoliosis associated with intraspinal anomalies. Postoperative paralytic ileus can commonly complicate scoliosis surgery. Ogilvie's syndrome as a cause of abdominal distension and pain has not been reported following spinal deformity correction and can mimic post-surgical ileus. 12 year old female patient with double thoracic and lumbar scoliosis associated with Arnold-Chiari 1 malformation and syringomyelia. The patient underwent posterior spinal fusion from T4 to L3 with segmental pedicle screw instrumentation and autogenous iliac crest grafting. She developed abdominal distension and pain postoperatively and this deteriorated despite conservative management. Repeat ultrasounds and abdominal computer tomography scans ruled out mechanical obstruction. The clinical presentation and blood parameters excluded toxic megacolon and cecal volvulus. As the symptoms persisted, a laparotomy was performed on postoperative day 16, which demonstrated ragged tears of the colon and cecum. A right hemi-colectomy followed by ileocecal anastomosis was required. The pathological examination of surgical specimens excluded inflammatory bowel disease and vascular abnormalities. The patient made a good recovery following bowel surgery and at latest followup 3.2 years later she had no abdominal complaints and an excellent scoliosis correction. Ogilvie's syndrome should be included in the differential diagnosis of postoperative ileus in patients developing prolonged unexplained abdominal distension and pain after scoliosis correction. Early diagnosis and instigation of conservative management can prevent major morbidity and mortality due to bowel ischemia and perforation.

Tsirikos, Athanasios I; Sud, Alok



Total colectomy with ileorectal anastomosis leads to appreciable loss in quality of life irrespective of primary diagnosis.  


Total colectomy with ileorectal anastomosis (TC) is a well-accepted procedure for many colonic pathologies but data on faecal incontinence and related quality of life after TC are lacking. The aims of this study were to assess the long-term bowel frequency, degree of incontinence and quality of life with respect to faecal incontinence and to compare them with the outcome for TC for different diagnostic groups. We identified 54 patients who had undergone TC at Singapore General Hospital and interviewed them using two questionnaires: the faecal incontinence quality of life (FIQL) scale and the Wexner faecal incontinence score (WS). The patients were allocated in 3 groups based on the primary diagnosis leading to operation, i. e. slow-transit constipation or megacolon (STC), colonic neoplasm (CA) and complicated pan-colonic diverticular disease (DD). Median bowel frequencies for STC and DD groups were 2.5/day; for CA, it was 3.5/day (p=0.042). There was no significant difference in the FIQL score and WS between the groups. Eleven patients had some degree of faecal incontinence based on WS. Many patients (20.4%) with perfect continence had fear of faecal leakage affecting their quality of life. In conclusion, patients with frequent stools do not need to have incontinence to suffer from the fear of it. The primary pathology leading to TC made no difference to the faecal incontinence or bowel urgency problems. PMID:11862562

Lim, J F; Ho, Y H



Hirschsprung's disease: diagnosis and management.  


Hirschsprung's disease (congenital megacolon) is caused by the failed migration of colonic ganglion cells during gestation. Varying lengths of the distal colon are unable to relax, causing functional colonic obstruction. Hirschsprung's disease most commonly involves the rectosigmoid region of the colon but can affect the entire colon and, rarely, the small intestine. The disease usually presents in infancy, although some patients present with persistent, severe constipation later in life. Symptoms in infants include difficult bowel movements, poor feeding, poor weight gain, and progressive abdominal distention. Early diagnosis is important to prevent complications (e.g., enterocolitis, colonic rupture). A rectal suction biopsy can detect hypertrophic nerve trunks and the absence of ganglion cells in the colonic submucosa, confirming the diagnosis. Up to one third of patients develop Hirschsprung's-associated enterocolitis, a significant cause of mortality. Patients should be monitored closely for enterocolitis for years after surgical treatment of Hirschsprung's disease. With proper treatment, most patients will not have long-term adverse effects and can live normally. PMID:17087425

Kessmann, Jennifer



Fl-160. A surface antigen of Trypanosoma cruzi that mimics mammalian nervous tissue  

PubMed Central

Chagas' disease, caused by Trypanosoma cruzi, is an excellent model for autoimmune disease induced by an infectious agent. Transfer of T cells, directed against crossreactive antigens of T. cruzi and nervous tissue, have been shown to reproduce pathology found in chronic Chagas' disease. We used recombinant DNA technology to characterize one of these crossreactive antigens (Fl-160). We have cloned DNA from T. cruzi, which expresses a protein corresponding to a 160-kD protein found on the surface of the trypanosome, overlying the flagellum. This clone hybridizes to a 4.5-kb poly(A)+ RNA that is distributed in a differentiation-specific manner, suggesting expression of this protein is transcriptionally controlled. Antibodies to this protein crossreact with a 48-kD mammalian nervous tissue protein found in sciatic nerve, brain, and myenteric plexi of gut. The myenteric plexi are destroyed by inflammatory infiltrates in Chagas' disease, leading to the characteristic megaesophagus and megacolon Chagas' disease pathology. Thus, this antigen is a candidate antigen for autoimmune mimicry leading to nervous tissue pathology.



Discovery of LFF571: An Investigational Agent for Clostridium difficile Infection  

SciTech Connect

Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection.

LaMarche, Matthew J.; Leeds, Jennifer A.; Amaral, Adam; Brewer, Jason T.; Bushell, Simon M.; Deng, Gejing; Dewhurst, Janetta M.; Ding, Jian; Dzink-Fox, JoAnne; Gamber, Gabriel; Jain, Akash; Lee, Kwangho; Lee, Lac; Lister, Troy; McKenney, David; Mullin, Steve; Osborne, Colin; Palestrant, Deborah; Patane, Michael A.; Rann, Elin M.; Sachdeva, Meena; Shao, Jian; Tiamfook, Stacey; Trzasko, Anna; Whitehead, Lewis; Yifru, Aregahegn; Yu, Donghui; Yan, Wanlin; Zhu, Qingming (Novartis)



Sporadic Hirschsprung`s disease due to a novel nonsense mutation in the RET protooncogene  

SciTech Connect

Hirschsprung`s disease (HSCR, aganglionic megacolon) is characterized by a lack of ganglion cells along variable lengths of the hindgut. This is most likely due to a failure of the progenitor cells (that are destined to become the ganglion cells of the submucosal and myenteric plexuses) to complete their distal migration in the colon. Recently, mutations in the RET protoocogene have been reported in association with HSCR. We report a novel nonsense mutation resulting in a severely truncated protein. Germline DNA from a panel of 6 HSCR patients was analyzed by SSCP for 20 exons of RET. Eight exons were also directly sequenced. We identified a novel mutation within RET exon 2. The mutation (TAC{sub 36}{yields}TAG{sub 36}), which occurs at nucleotide position 108, involves the replacement of tyrosine with a stop codon and results in a truncated 35 amino acid protein. This mutation is the most 5{prime} nonsense mutation reported thus far. Interestingly, the patient has no prior family history of HSCR and was also diagnosed with multiple developmental anomalies including dysplastic kidney. Recent gene targeting studies with mouse models have shown that RET is essential for normal renal development. However, a parallel phenotype has not been seen in other reported HSCR patients with RET mutations. The observations reported here provide evidence that RET plays a role in human renal development. Ongoing studies will determine the extent of RET involvement in sporadic cases of HSCR.

Carlson, K.M.; Donis-Keller, H.; Langer, J.C. [and others



Fine structure mapping and deletion analysis of the murine piebald locus  

SciTech Connect

Piebald (s) is a recessive mutation that affects the development of two cell types of neural crest origin: melanocytes, responsible for pigment synthesis in the skin, and enteric ganglia, which innervate the lower bowel. As a result, mice carrying piebald mutations exhibit white spotting in the coat and aganglionic megacolon. Previously the gene had been localized to the distal half of mouse chromosome 14. To determine its precise location relative to molecular markers, an intersubspecific backcross was generated. Two anchor loci of chromosome 14, slaty and hypogonadal, in addition to simple sequence length repeat markers, were used to localize s to a 2-cM interval defined by the markers D14Mit38 and D14Mit42. The molecular markers were also used to characterize nine induced s alleles. Three of these mutations exhibited no deletions or rearrangements of the flanking markers, whereas the other six had two or more of these markers deleted. The extent of the deletions was found to be consistent with the severity of the homozygous phenotype. The location of deletion breakpoints in the induced alleles, coupled with the recombination breakpoints in the backcross progeny, provide useful molecular landmarks to define the location of the piebald gene.

Metallinos, D.L.; Tilghman, S.M. (Princeton Univ., NJ (United States)); Oppenheimer, A.J. (Harvard Medical School, Boston, MA (United States)); Rinchik, E.M.; Russell, L.B. (Oak Ridge National Laboratory, TN (United States)); Dietrich, W. (Whitehead Institute for Biomedical Research, Cambridge, MA (United States))



Mutation detection in autosomal dominant Hirschsprung disease: SSCP analysis of the RET proto-oncogene  

SciTech Connect

Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most common cause of congenital bowel obstruction, with an incidence of 1 in 5000. Recently, linkage of an incompletely penetrant, dominant form of HSCR to the pericentromeric region of chromosome 10 was reported, followed by identification of mutations in the RET proto-oncogene in HSCR patients. RET mutations have also been reported in both sporadic and familial forms of three neuroendrocrine tumor syndromes. Unlike the clustered RET mutations observed in these syndromes, the 18 reported HSCR mutations are distributed throughout the extracellular and tryosine kinase domains of RET. In an effort to determine the frequency of RET mutations in HSCR and correlate genotype with phenotype, we have begun to screen for mutations among 80 HSCR probands representing a wide range of phenotypes and pedigree structures. Non-isotopic single strand conformation of polymorphism (SSCP) analysis was carried out using the Pharmacia PhastSystem{trademark}. Initial screening of exons 2 through 6 detected variants in 11 patients not seen in 24 controls. One additional band shift in exon 6 has been observed in both patients and controls. Preliminary sequence analysis has revealed two putative familial mutations in exon 2: a single base pair deletion (49Pro del C 296) and a point mutation that leads to a conservative amino acid substitution (93Gly{r_arrow}Ser). These results suggest that HSCR may be associated with a range of alterations in the coding sequence of the RET extracellular domain. Additional mutations will be described.

Angrist, M.; Bolk, S.; Chakravarti, A. [Case Western Reserve Univ., Cleveland, OH (United States)



Use of propolis hydroalcoholic extract to treat colitis experimentally induced in rats by 2,4,6-trinitrobenzenesulfonic Acid.  


This study focused on the therapeutic effect of a propolis SLNC 106 (PI) extract on experimental colitis. Wistar adult rats received 0.8?mL rectal dose of one of the following solutions: saline (group S), 20?mg TNBS in 50% ethanol (group TNBS), 20?mg TNBS in 50% ethanol and propolis extract in saline (group TNBS-P), propolis extract in saline (group SP), and 20?mg TNBS in 50% ethanol and 50?mg/kg mesalazine (group TNBS-M). The animals were euthanized 7 or 14 days after the colitis induction. Samples of the distal colon were harvested for the analysis of myeloperoxidase (MPO) enzyme activity and for morphometric analysis in paraffin-embedded histological sections with hematoxylin-eosin or histochemical staining. The animals treated with TNBS exhibited the typical clinical signs of colitis. Increased MPO activity confirmed the presence of inflammation. TNBS induced the development of megacolon, ulceration, transmural inflammatory infiltrate, and thickened bowel walls. Treatment with propolis moderately reduced the inflammatory response, decreased the number of cysts and abscesses, inhibited epithelial proliferation, and increased the number of goblet cells. The anti-inflammatory activity of the propolis SLNC 106 extract was confirmed by the reductions in both the inflammatory infiltrate and the number of cysts and abscesses in the colon mucosa. PMID:24101941

Gonçalves, Cely Cristina Martins; Hernandes, Luzmarina; Bersani-Amado, Ciomar Aparecida; Franco, Selma Lucy; Silva, Joaquim Felipe de Souza; Natali, Maria Raquel Marçal



Outcomes in patients tested for Clostridium difficile toxins.  


Clostridium difficile testing is shifting from toxin detection to C. difficile detection. Yet, up to 60% of patients with C. difficile by culture test negative for toxins and it is unclear whether they are infected or carriers. We reviewed medical records for 7046 inpatients with a C. difficile toxin test from 2005 to 2009 to determine the duration of diarrhea and rate of complications and mortality among toxin-positive (toxin+) and toxin- patients. Overall, toxin- patients had less severe diarrhea, fewer diarrhea days, and lower mortality (P < 0.001, all comparisons) than toxin+ patients. One toxin- patient (n = 1/6121; 0.02%) was diagnosed with pseudomembranous colitis, but there were no complications such as megacolon or colectomy for fulminant CDI among toxin- patients. These data suggest that C. difficile-attributable complications are rare among patients testing negative for C. difficile toxins. More studies are needed to evaluate the clinical significance of C. difficile detection in toxin- patients. PMID:23009731

Polage, Christopher R; Chin, David L; Leslie, Jhansi L; Tang, Jevon; Cohen, Stuart H; Solnick, Jay V



[Esophageal achalasia: 20 years' experience with non surgical treatment].  


The purpose of this paper is to report the experience acquired in pneumatic dilatation in achalasia of the esophagus up to 1990. Two hundred and six patients were studied in that period (X 50, 7 years, M/F 1:1). According to X Rays the distribution was: grade I 17.4%, grade II 54.8%, grade III 14% and grade IV 13.5%. The associated esophageal pathology was: hiatus hernia 9.7%, esophagitis 5.8%, benign stenosis 2.4%, cancer 1.4%, ulcer and diverticula 0.9% and Schatzki's ring and leiomyoma 0.4% respectively Serology for Chagas disease was positive in 23% Chagasic megacolon was more frequent than chagasic heart disease (4.3% Vs. 1.4%). Out of these, one hundred and twenty patients were treated by pneumatic dilatation. To this group we shall refer in more detail. One hundred ant two patients were dilated once and the remaining 18 twice. Esophageal manometry showed a vigorous pattern in 7.7%. The LES' pressure pre-treatment was 24.5 mm Hg and post-dilatation 13.7 mm Hg in 75.8% of the cases the result was good. The morbidity was 5% and the mortality 0.7%. Relapse was seen in 25.8% of the cases. The follow-up was X 38 months. We conclude that pneumatic dilatation is the election procedure in the treatment of achalasia since it offers good results with low morbimortality. Surgery is indicated after failure of 2 dilatations, in children, and association with esophageal neoplasms, hiatus hernia and esophageal diverticula. PMID:1811399

Salis, G B; Chiocca, J C; Perissé, E; Acosta, E; Mazure, P A



Impaired growth and differentiation of diploid but not immortal melanoblasts from endothelin receptor B mutant (piebald) mice.  


Endothelin 3 (Edn3) and its preferred receptor, endothelin receptor B (Ednrb), are implicated in development, especially that of two neural-crest-derived cell lineages: melanocytes and enteric ganglion cells. Mice and humans with a null mutation at either locus can show major deficiencies in both cell types: congenital white spotting and aganglionic megacolon (Hirschsprung disease in human). Numbers of early (migrating) embryonic melanoblasts are low in Ednrb(ls) mutant mice, while added Edn3 appears to promote the growth of melanocyte precursors in neural crest cultures. However, it is hard to assess cell differentiation in these mixed cultures, and it is not known whether Ednrb has any role in the postnatal melanocytic lineage. We have therefore studied primary cultures of neonatal melanoblasts homozygous for the piebald (Ednrb(s)) mutation. These mutant melanoblasts showed severe impairment of both net cell growth and differentiation compared to wild-type melanoblasts. They were also unresponsive to stimulation of growth by cholera toxin. We have established three immortal lines of melanoblasts and one of melanocytes homozygous for Ednrb(s). These immortal lines, however, had no detectable deficiency of growth or differentiation as judged by cell counts, induced pigmentation and immunocytochemistry for melanocytic markers. Consistent with this, neither Ednrb nor Edn3 mRNA was detected in 3/3 tested immortal lines of mouse melanoblasts and 5/5 lines of melanocytes, of various genotypes. We also report for the first time a method to grow immortal melanoblasts in pure culture, without feeder cells. PMID:9853966

Sviderskaya, E V; Easty, D J; Bennett, D C



C. difficile 630?erm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA  

PubMed Central

Clostridium difficile is a Gram positive, anaerobic bacterium that can form highly resistant endospores. The bacterium is the causative agent of C. difficile infection (CDI), for which the symptoms can range from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon. Endospore formation in Firmicutes, including C. difficile, is governed by the key regulator for sporulation, Spo0A. In Bacillus subtilis, this transcription factor is also directly or indirectly involved in various other cellular processes. Here, we report that C. difficile Spo0A shows a high degree of similarity to the well characterized B. subtilis protein and recognizes a similar binding sequence. We find that the laboratory strain C. difficile 630?erm contains an 18bp-duplication near the DNA-binding domain compared to its ancestral strain 630. In vitro binding assays using purified C-terminal DNA binding domain of the C. difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and sigH, early sporulation genes and several other putative targets. In vitro binding assays suggest that the gene encoding the major clostridial toxin TcdB may be a direct target of Spo0A, but supernatant derived from a spo0A negative strain was no less toxic towards Vero cells than that obtained from a wild type strain, in contrast to previous reports. These results identify for the first time direct (putative) targets of the Spo0A protein in C. difficile and make a positive effect of Spo0A on production of the large clostridial toxins unlikely.

Rosenbusch, Katharina E.; Bakker, Dennis; Kuijper, Ed J.; Smits, Wiep Klaas



Clostridium difficile Spore-Macrophage Interactions: Spore Survival  

PubMed Central

Background Clostridium difficile is the main cause of nosocomial infections including antibiotic associated diarrhea, pseudomembranous colitis and toxic megacolon. During the course of Clostridium difficile infections (CDI), C. difficile undergoes sporulation and releases spores to the colonic environment. The elevated relapse rates of CDI suggest that C. difficile spores has a mechanism(s) to efficiently persist in the host colonic environment. Methodology/Principal Findings In this work, we provide evidence that C. difficile spores are well suited to survive the host’s innate immune system. Electron microscopy results show that C. difficile spores are recognized by discrete patchy regions on the surface of macrophage Raw 264.7 cells, and phagocytosis was actin polymerization dependent. Fluorescence microscopy results show that >80% of Raw 264.7 cells had at least one C. difficile spore adhered, and that ?60% of C. difficile spores were phagocytosed by Raw 264.7 cells. Strikingly, presence of complement decreased Raw 264.7 cells’ ability to phagocytose C. difficile spores. Due to the ability of C. difficile spores to remain dormant inside Raw 264.7 cells, they were able to survive up to 72 h of macrophage infection. Interestingly, transmission electron micrographs showed interactions between the surface proteins of C. difficile spores and the phagosome membrane of Raw 264.7 cells. In addition, infection of Raw 264.7 cells with C. difficile spores for 48 h produced significant Raw 264.7 cell death as demonstrated by trypan blue assay, and nuclei staining by ethidium homodimer-1. Conclusions/Significance These results demonstrate that despite efficient recognition and phagocytosis of C. difficile spores by Raw 264.7 cells, spores remain dormant and are able to survive and produce cytotoxic effects on Raw 264.7 cells.

Paredes-Sabja, Daniel; Cofre-Araneda, Glenda; Brito-Silva, Christian; Pizarro-Guajardo, Marjorie; Sarker, Mahfuzur R.



Hirschsprung disease: a developmental disorder of the enteric nervous system.  


Hirschsprung disease (HSCR), which is also called congenital megacolon or intestinal aganglionosis, is characterized by an absence of enteric (intrinsic) neurons from variable lengths of the most distal bowel. Because enteric neurons are essential for propulsive intestinal motility, infants with HSCR suffer from severe constipation and have a distended abdomen. Currently the only treatment is surgical removal of the affected bowel. HSCR has an incidence of around 1:5,000 live births, with a 4:1 male:female gender bias. Most enteric neurons arise from neural crest cells that emigrate from the caudal hindbrain and then migrate caudally along the entire gut. The absence of enteric neurons from variable lengths of the bowel in HSCR results from a failure of neural crest-derived cells to colonize the affected gut regions. HSCR is therefore regarded as a neurocristopathy. HSCR is a multigenic disorder and has become a paradigm for understanding complex factorial disorders. The major HSCR susceptibility gene is RET. The penetrance of several mutations in HSCR susceptibility genes is sex-dependent. HSCR can occur as an isolated disorder or as part of syndromes; for example, Type IV Waardenburg syndrome is characterized by deafness and pigmentation defects as well as intestinal aganglionosis. Studies using animal models have shown that HSCR genes regulate multiple processes including survival, proliferation, differentiation, and migration. Research into HSCR and the development of enteric neurons is an excellent example of the cross fertilization of ideas that can occur between human molecular geneticists and researchers using animal models. WIREs Dev Biol 2013, 2:113-129. doi: 10.1002/wdev.57 For further resources related to this article, please visit the WIREs website. PMID:23799632

McKeown, Sonja J; Stamp, Lincon; Hao, Marlene M; Young, Heather M



Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease.  


Hirschsprung disease (HSCR, aganglionic megacolon) is a common congenital malformation leading to bowel obstruction, with an incidence of 1/5,000 live births. It is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract. As enteric neurons are derived from the vagal neural crest, HSCR is regarded as a neurocristopathy. On the basis of a skewed sex-ratio (M/F = 4/1) and a risk to relatives much higher than the incidence in the general population, HSCR has long been regarded as a sex-modified multifactorial disorder. Accordingly, segregation analysis suggested an incompletely penetrant dominant inheritance in HSCR families with aganglionosis extending beyond the sigmoid colon. We and others have mapped a dominant gene for HSCR to chromosome 10q11.2 and have ascribed the disease to mutations in the RET proto-oncogene. However, the lack of genotype-phenotype correlation, the low penetrance and the sex-dependent effect of RET mutations supported the existence of one or more modifier gene(s) in familial HSCR. In addition, thus far, RET mutations only accounted for 50% and 15-20% of familial and sporadic HSCR patients, respectively. RET encodes a tyrosine kinase receptor whose ligand was unknown. Recently, the Glial cell line-derived neurotrophic factor (GDNF) has been identified to be a ligand for RET. Moreover, Gdnf-/- knockout mutant mice display congenital intestinal aganglionosis and renal agenesis, a phenotype very similar to the Ret-/- mouse. These data prompted us to hypothesize that mutations of the gene encoding GDNF could either cause or modulate the HSCR phenotype in some cases. PMID:8896569

Salomon, R; Attié, T; Pelet, A; Bidaud, C; Eng, C; Amiel, J; Sarnacki, S; Goulet, O; Ricour, C; Nihoul-Fékété, C; Munnich, A; Lyonnet, S



The influence of diet and dimethylhydrazine on the small and large intestine of vervet monkeys.  

PubMed Central

The morphological features of the intestine in monkeys on various diets with and without carcinogen were studied. Seventy adult female vervet monkeys were divided into seven treatment groups. Four groups received a Western high-fat low fibre diet (WD); two a Prudent low-fat higher fibre diet (PD) and one a control low-fat high fibre diet (CD). Three groups (2 WD, I PD) received dimethylhydrazine 10 mg/kg intramuscularly at 14 days intervals. After 18 months, monkeys of two groups on the WD were transferred to the PD and 30 months later all were terminated. Small and large intestine were examined macroscopically, histologically with morphometry, histochemically for acid and neutral, sialo- and sulphomucins and enzyme-histochemically for mucosal gamma-glutamyltranspeptidase (GGT) activity. Large intestines in all other than CD, particularly in WD-treated animals were dilated, thin walled, less corrugated and contained more residual contents. Diverticulosis was found to be mostly associated with WD. Apparently histologically normal colonic mucosa showed changed mucin secretion, predominantly in WD groups, and also GGT activity in all but CD groups. Changes which could be associated with pre-malignancy occurred predominantly but not exclusively in carcinogen treated animals. Within 4 years of feeding to monkeys, diets used by affluent western man caused distinct changes suggestive of the development of intestinal diseases such as megacolon, diverticulosis and cancer. Feeding a prudent diet resulted in only a mild reduction of these signs, whereas they were absent in a usual monkey diet that was much lower in animal products and refined carbohydrates. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7

Jaskiewicz, K.; Rossouw, J. E.; Kritchevsky, D.; van Rensburg, S. J.; Fincham, J. E.; Woodroof, C. W.



The developmental etiology and pathogenesis of Hirschsprung disease.  


The enteric nervous system is the part of the autonomic nervous system that directly controls the gastrointestinal tract. Derived from a multipotent, migratory cell population called the neural crest, a complete enteric nervous system is necessary for proper gut function. Disorders that arise as a consequence of defective neural crest cell development are termed neurocristopathies. One such disorder is Hirschsprung disease (HSCR), also known as congenital megacolon or intestinal aganglionosis. HSCR occurs in 1/5000 live births and typically presents with the inability to pass meconium, along with abdominal distension and discomfort that usually requires surgical resection of the aganglionic bowel. This disorder is characterized by a congenital absence of neurons in a portion of the intestinal tract, usually the distal colon, because of a disruption of normal neural crest cell migration, proliferation, differentiation, survival, and/or apoptosis. The inheritance of HSCR disease is complex, often non-Mendelian, and characterized by variable penetrance. Extensive research has identified a number of key genes that regulate neural crest cell development in the pathogenesis of HSCR including RET, GDNF, GFR?1, NRTN, EDNRB, ET3, ZFHX1B, PHOX2b, SOX10, and SHH. However, mutations in these genes account for only ?50% of the known cases of HSCR. Thus, other genetic mutations and combinations of genetic mutations and modifiers likely contribute to the etiology and pathogenesis of HSCR. The aims of this review are to summarize the HSCR phenotype, diagnosis, and treatment options; to discuss the major genetic causes and the mechanisms by which they disrupt normal enteric neural crest cell development; and to explore new pathways that may contribute to HSCR pathogenesis. PMID:23528997

Butler Tjaden, Naomi E; Trainor, Paul A



RET and NRG1 interplay in Hirschsprung disease.  


Hirschsprung disease (HSCR, aganglionic megacolon) is a complex genetic disorder of the enteric nervous system (ENS) characterized by the absence of enteric neurons along a variable length of the intestine. While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1. Importantly, RVs in the CDS of these two genes are also associated with the disorder. To assess independent and joint effects between the different types of RET and NRG1 variants identified in HSCR patients, we used 254 Chinese sporadic HSCR patients and 143 ethnically matched controls for whom the RET and/or NRG1 variants genotypes (rare and common) were available. Four genetic risk factors were defined and interaction effects were modeled using conditional logistic regression analyses and pair-wise Kendall correlations. Our analysis revealed a joint effect of RET CVs with RET RVs, NRG1 CVs or NRG1 RVs. To assess whether the genetic interaction translated into functional interaction, mouse neural crest cells (NCCs; enteric neuron precursors) isolated from embryonic guts were treated with NRG1 (ErbB2 ligand) or/and GDNF (Ret ligand) and monitored during the subsequent neural differentiation process. Nrg1 inhibited the Gdnf-induced neuronal differentiation and Gdnf negatively regulated Nrg1-signaling by down-regulating the expression of its receptor, ErbB2. This preliminary data suggest that the balance neurogenesis/gliogenesis is critical for ENS development. PMID:23400839

Gui, Hongsheng; Tang, Wai-Kiu; So, Man-Ting; Proitsi, Petroola; Sham, Pak C; Tam, Paul K; Sau-Wai Ngan, Elly; Cherny, Stacey S; Garcia-Barceló, Maria-Mercè



[Colorectal Crohn's disease: indications to surgical treatment].  


Colorectal Crohns Disease (CRCD) represents the 25% of all cases of Crohns Disease (CD). Between January 1984 and December 2000 we have operated 68 patients with CRCD, that represent 10.3% of the patients operated for CD. Thirtythree patients (48.5%) were men and 35 (51.5%) were women. The median age at diagnosis was 37.3 +/- 13.1 years, with the highest incidence during the fourth decade. In most cases the disease involved the left colon and rectum (65.9%), while in 6.3% and in 3.8% of cases the right and the transverse colon respectively. In the 27.9% of cases the entire colon was involved. At the time of surgery, the disease behaviour was stenosing in 30.9% of patients, inflammatory in 22.1%, and penetrating in 47% of cases with the presence of fistulae (coloenteric in 6 patients, colo-bladder in 2 cases, rectouretral in 1 case, colo-cutaneous in 4 cases and intramesenteric in 2 cases) and abscesses (23.5% of patients). In three patients the CRCD had led to neoplastic transformation. Fourteen patients had undergone an emergency surgical procedure for severe acute colitis, 2 for toxic megacolon, 1 for an intraabdominal abscess and one for intestinal occlusion. In the segmentary forms we have always practiced a resection of the diseased colonic segment without total colectomy. In the cases with diffuse colonic involvement in which the rectum was free from disease a total colectomy with ileorectal anastomosis was performed. In the cases with rectal disease (26 cases) the sphinteric function was preserved with low rectal resection or with colo-anal anastomosis. In 4 patients with rectal disease and in 4 cases with fistulae, we complited the intervention with a permanent stoma. During the median follow-up of 83.7 months (12-207) the surgical relapse was of 27.3%. We suggest to treat CRCD with resections limited to the diseased segment. Moreover, it is possible to preserve the sphinteric function every time the rectum or the anal canal are normal, without postoperative complications or early relapses. PMID:15206808

Tonelli, F; Paroli, G M


[Chagasic myocardiopathy: historical perspective].  


Considerable advances in the clinical pathological and pathogenic aspects of Chagas disease have been made since the Brazilian physician Carlos Chagas described the disease in 1909. The disease caused by the flagellate protozoon parasite Trypanosoma cruzi is transmitted to humans by a blood sucking triatomine and much less frequently by blood transfusion. It is estimated that 18 million are infected and that about 100 million people from Latin America are at risk of contracting T. cruzi infection. One of the most important contributions to the knowledge of Chagas' disease has been the recognition of the natural history of the disease, which can be divided into three well defined periods: 1. The acute stage; 2. An undetermined or undifferentiated stage and 3. The chronic stage. The primary infection (first stage) occurs mostly unrecognized and clinically apparent acute chagasic myocarditis may appear in less than 5% of the infected individuals, usually children living in endemic areas. The majority of the cases of acute myocarditis are mild and reversible. Autopsied cases of acute chagasic myocarditis are uncommon and correspond to exceptionally severe or fulminant forms showing diffuse myocardial damage with myocytolisis, degenerative changes of myocardial fibers and marked intersticial cellular infiltration. The acute clinical manifestations of the infected individuals include fever, muscular pain, sweating, swollen lymph nodes, hepatospienomegaly. Following this initial stage, all patients enter the undifferentiated or undetermined stage of the chronic period (second stage), which lasts between 10 to 20 years. Of these, 20 to 30% (depending on marked geographical differences) develop symptoms or signs of visceral damage conforming the cohort that enter the third stage. Although megaesophagous and megacolon are not uncommon (mainly in Brazil), the most frequent and important clinical manifestation is a dilated cardiomyopathy. Thus, 70% or more of the infected individuals will never show any clinical manifestation of the disease. The ajmaline test and the endomyocardial biopsy are, probably, the most sensitive methods to unmask latent forms of chagasic myocarditis during the undifferentiated stage. In the most advanced stages of chronic chagasic myocarditis, pathological findings are those of a dilated cardiomyopathy. At autopsy, the apical aneurysm with thrombus in it is a frequent and distinctive finding. The histopathological picture is that of an active and chronic microfocal and disseminated myocarditis. In some cases fibrosis may be confluent, which accounts for the electrocardiographic patterns of myocardial necrosis. The widespread distribution of cardiac lesions also constitute the substrate for atrioventricular and intraventricular conduction disturbances and for atrial and ventricular arrhythmias. The clinical diagnosis of Chagas' heart disease is based on a triad of: positive epidemiology, positive serology and a combination of clinical findings (suggestive electrocardiograhic abnormalities, apical aneurysm, cardiac enlargement). The electrocardiogram in the most advanced forms, usually shows sinus bradycardia, right bundle branch block with or without left anterior hemiblock, primary T wave abnormalities, pathological Q waves and multiform ventricular premature beats. The pathogenesis of the myocardial lesions of acute and also chronic chagasic myocarditis appears to be related in large part to autoimmune mechanisms. The lack of correlation between the location and number of parasitized fibers and the severity, type, and extension of degenerative and inflammatory lesions supports this assumption. Experimental and clinical studies have demonstrated the presence of antibodies directed against different components of T. cruzi and crossreacting with human antigens in patients with chronic chagasic myocarditis. Microvascular dysfunction, myocardial ischemia and autonomic nervous system impairment have also been implica PMID:10668240

Elizari, M V