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1

Toxic megacolon  

MedlinePLUS

... 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 ...

2

Acute and chronic megacolon.  

PubMed

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

2007-06-01

3

Risk factors in toxic megacolon  

Microsoft Academic Search

A retrospective analysis of data from a series of 22 patients with toxic megacolon complicating ulcerative colitis was performed in an attempt to detect factors associated with the fatal outcome of the attack. Of the 25 clinical findings studied, significant differences between survivors (17) and nonsurvivors (5) were observed in only seven. In nonsurvivors, duration of the disease was longer

R. Caprilli; P. Vernia; O. Colaneri; G. Frieri

1980-01-01

4

Water intoxication in congenital megacolon  

Microsoft Academic Search

Summary  The literature on water intoxication following water enemas is reviewed, and a typical case is reported. Blood chemistries\\u000a and therapy are reported in detail.\\u000a \\u000a It is seen that the simple tap water or soapsud enema may be a not infrequent cause of serious water intoxication in congenital\\u000a megacolon. The best therapy consists of the prevention of this complication by adherence

Melvin E. Levinson

1954-01-01

5

[Toxic megacolon: surgical timing important!].  

PubMed

Toxic megacolon is defined as a fulminant attack of colitis with total or segmental dilatation of the colon. Toxic megacolon is mostly a complication of nonspecific ulcerative colitis or Crohn's colitis but it may also occur in pseudomembranous colitis and other forms of infectious colitis. Toxic dilatation of the colon is a sign of transmural acute inflammation in which perforation of the colon is impending or may already have occurred. Free perforation means a fourfold increase in the mortality of a fulminant attack of colitis. Dilatation of the colon is not by itself an indication for immediate operation. The dilatation may increase, fluctuate or even disappear, leaving the patient still severely ill with toxic colitis requiring immediate surgery. The indication and optimal timing of surgical intervention require optimal interdisciplinary collaboration between surgeons and gastroenterologists. The procedure of choice for surgical treatment of toxic megacolon is colectomy and ileostomy. The mortality and morbidity of urgent surgery have been decreased by avoiding rectal excision. The rectal stump is either closed as a pelvic Hartmann's pouch or the sigmoid remnant is exteriorized as a mucous fistula or closed subcutaneously. Progress in intensive therapy and perioperative patient management has relegated simple decompression by diverting loop ileostomy and skin-level colostomy as advocated by Turnbull et al nearly 30 years ago to the role of an obsolete procedure which seems hardly ever preferable to resection of the diseased bowel. PMID:10063546

Aeberhard, P

1998-01-01

6

Toxic megacolon after abdominoplasty: a case report.  

PubMed

After an accepted technique of abdominoplasty, a 66-year-old woman developed Clostridium difficile-associated diarrhea, leading to toxic megacolon and subsequent subtotal colectomy. The presumed etiology is chronic use of a proton pump inhibitor. This was addressed in a 2012 "white paper" warning issued by the Food and Drug Administration. This article presents the course of this case as well as a review of the pertinent literature. PMID:24667886

Wade, James W

2014-06-01

7

Partial, selective survival of nitrergic neurons in chagasic megacolon  

PubMed Central

One frequent chronic syndrome of Chagas’ disease is megacolon, an irreversible dilation of a colonic segment. Extensive enteric neuron loss in the affected segment is regarded as key factor for deficient motility. Here, we assessed the quantitative balance between cholinergic and nitrergic neurons representing the main limbs of excitatory and inhibitory colonic motor innervation, respectively. From surgically removed megacolonic segments of four patients, each three myenteric wholemounts (from non-dilated oral, megacolonic and non-dilated anal parts) was immunohistochemically triple-stained for choline acetyltransferase, neuronal nitric oxide synthase (NOS) and the panneuronal human neuronal protein Hu C/D. Degenerative changes were most pronounced in the megacolonic and anal regions, e.g. bulked, honeycomb-like ganglia with few neurons which were partly enlarged or atrophic or vacuolated. Neuron counts from each 15 ganglia of 12 megacolonic wholemounts were compared with those of 12 age- and region-matched controls. Extensive neuron loss, mainly in megacolonic and anal wholemounts, was obvious. In all three regions derived from megacolonic samples, the proportion of NOS-positive neurons (control: 55%) was significantly increased: in non-dilated oral parts to 61% (p = 0.003), in megacolonic regions to 72% (p < 0.001) and in non-dilated anal regions to 78% (p < 0.001). We suggest the chronic dilation of megacolonic specimens to be due to the preponderance of the nitrergic, inhibitory input to the intestinal muscle. However, the observed neuronal imbalance was not restricted to the dilated regions: the non-dilated anal parts may be innervated by ascending, cholinergic axons emerging from less affected, more anally located regions.

Jabari, Samir; da Silveira, Alexandre B. M.; de Oliveira, Enio C.; Neto, Salustiano G.; Quint, Karl; Neuhuber, Winfried

2010-01-01

8

Is really megacolon a contraindication to infliximab in Crohn's disease?  

PubMed

Toxic megacolon (TM) is a rare complication of severe ulcerative colitis (UC) and colonic Crohn's disease (CD), defined as a clinical syndrome accompanied by radiographic evidence of colonic dilatation that in many cases must be treated aggressively with surgical intervention (1). We report two cases of steroid and antibiotic-refractory fulminant Crohn's colitis, complicated by toxic megacolon, who were successfully treated with infliximab (IFX), thus avoiding surgical intervention. Although there are no well defined recommendation about the correct timing of colectomy in CD-associated TM, and despite the fact that it may be imprudent to advocate delaying surgery in favour of anti-tumor necrosis (anti-TNF) factor therapy in these cases, we think that a medical "rescue therapy" can be considered in a subset of patients with stable clinical condition during corticosteroid treatment. PMID:24592552

Sinagra, Emanuele; Orlando, Ambrogio; Renna, Sara; Criscuoli, Valeria; La Seta, Francesco; Olivo, Mirko; Ciofalo, Marco; Cottone, Mario

2013-12-01

9

[The differential diagnosis of megacolon in childhood (author's transl)].  

PubMed

The diagnosis of Hirschsprung's disease can be established praeoperatively by the histochemical demonstration of an increased acethylcholinesterase activity in rectal mucosal biopsies. Furthermore the intraoperative diagnosis of the extension of the aganglionary or hypoganglionary segment can be improved by histochemical demonstration of dehydrogenases in the intramural parasympathetic plexus. By these means it becomes easy to localize the correct position of the enterostoma as well as to determine the length of the segment, which should be resected. The results of our histochemical investigation on 92 cases of megacolon, especially on 12 cases of Hirschsprung's disease were reported. The histochemical diagnosis was confirmed finally by an extensive examination of the resected bowel segment. PMID:934675

Kreiner, I

1976-01-01

10

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

PubMed Central

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 in about 20% of interphase nuclei. It is suggested that aganglionic megacolon could result from dynamic somatic mosaicism owing to loss of the ring chromosome. Images

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

1994-01-01

11

Silver sulfadiazine induced Clostridium difficile toxic megacolon in a burn patient: a case report  

Microsoft Academic Search

A 53 yr old diabetic male presented with a 34% total body surface area (TBSA) deep partial- and full-thickness burns. On post burn days 4 and 9, all of his burns were excised and grafted. Although he had only been treated with topical antibiotics, he developed Clostridium difficile colitis after his second surgery that progressed to Toxic Megacolon and perforation.

Lawrence J Jennings; Marella Hanumadass

1998-01-01

12

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.

2012-01-01

13

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

1997-01-01

14

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.

2013-01-01

15

Constipation and megacolon in rats related to treatment with oxodipine, a calcium antagonist.  

PubMed

The constipatory effects of oxodipine, a dihyrdopyridine-type calcium antagonist, have been described in a 3-mo, 12-mo, and 30-mo feeding toxicity study in rats. This paper reports the occurrence of megacolon in rats as a result of the constipatory effects of chronic administration of oxodipine. The first mortality due to oxodipine was seen after about 1 yr of treatment at a dose of 225 mg/kg/day. The toxic effects noted were dose-, time-, and sex-related. Female rats appeared more sensitive to the constipatory effects of the drug. The dose at which the effect occurred in both male and female rats was from about 75 to 675 times the recommended therapeutic dose for humans. To the best knowledge of the authors, this is the first report of a calcium channel blocker causing constipation in rats. PMID:7732276

Nyska, A; Waner, T; Galiano, A; Fich, A

1994-01-01

16

Minimally Invasive Approach to Chagasic Megacolon: Laparoscopic Rectosigmoidectomy With Posterior End-to-Side Low Colorectal Anastomosis.  

PubMed

The effectiveness of anterior resection for the surgical treatment of Chagasic megacolon and the advantages of laparoscopy for performing colorectal surgery are well known. However, current experience with laparoscopic surgery for Chagasic megacolon is restricted. Moreover, associated long-term results remain poorly analyzed. The aims of the present study were to ascertain the immediate results of laparoscopic anterior resection for the surgical treatment of Chagasic megacolon, to identify risk factors associated with adverse outcomes, and to settle late results. A retrospective review of a prospective database was conducted. Between November 2000 and September 2012, 44 patients with Chagasic megacolon underwent laparoscopic anterior resection with posterior end-to-side low colorectal anastomosis. Fifteen (34.1%) patients were male. Mean age was 51.6 years (31 to 77 y). The mean body mass index (BMI) was 22.9 kg/m (16.9 to 36.7 kg/m). Thirty-four previous abdominal operations had been performed. Mean operative time was 265 minutes (105 to 500 min). Four surgeons operated on all cases. Surgeon's experience with the operation was not associated with surgical time (P=0.36: linear regression). Mean operative time between patients with and without previous abdominal surgery was similar (237.7 vs. 247.5 min: P=0.78). There was no association between BMI and the duration of the operation (P=0.22). Intraoperative complications occurred in 2 (4.5%) cases. Conversion was necessary in 3 (6.8%) cases. There was no association between conversion and previous abdominal surgery (P=0.56) or between conversion and surgeon's experience (P=0.43). However, a significant association (P=0.01) between BMI and conversion was observed. Postoperative complications occurred in 10 (22.7%) cases. Anastomotic-related complications occurred in 4 cases. Two of them required diversion ileostomy. Restoration of transanal evacuation was achieved in all cases. Mean duration of postoperative hospital stay was 9.8 days (4 to 45 d). Of 19 patients with known clinical late follow-up, only 1 (5.3%) reported use of enemas and 5 (26.3%) reported use of laxatives. Thirteen (68.4%) patients reported daily bowel movements. There was no association between postoperative complications and use of laxatives (P=0.57). It was concluded that laparoscopic anterior resection for Chagasic megacolon is safe. Obesity was a risk factor for conversion. Restoration of transanal evacuation after surgical treatment of infectious complications was achieved. Minimally invasive surgery for Chagasic megacolon is associated with satisfactory late intestinal function with no significant constipation relapse. PMID:24710265

Araujo, Sergio E A; Bertoncini, Alexandre B; Nahas, Sergio C; Cecconello, Ivan

2014-06-01

17

[Early infantile autism and excessive aerophagy with symptomatic megacolon and ileus in a case of Ehlers-Danlos syndrome].  

PubMed

A case of Ehlers-Danlos syndrome is reported, which was associated with mental retardation and early infantile autism. The patient died at the age of 19 by ectasy of the stomach as the result of extreme aerophagy causing a megacolon and by compression so finally resulting in a mechanical ileus. Investigation of the cerebellum revealed a significant rarefication and diminuation of the Purkinjč cells as well as the cells of the stratum granulare in the lobuli VI and VII, obviously due to a genetically determined malformation. PMID:8259320

Fehlow, P; Bernstein, K; Tennstedt, A; Walther, F

1993-01-01

18

The KIT Gene Is Associated with the English Spotting Coat Color Locus and Congenital Megacolon in Checkered Giant Rabbits (Oryctolagus cuniculus).  

PubMed

The English spotting coat color locus in rabbits, also known as Dominant white spotting locus, is determined by an incompletely dominant allele (En). Rabbits homozygous for the recessive wild-type allele (en/en) are self-colored, heterozygous En/en rabbits are normally spotted, and homozygous En/En animals are almost completely white. Compared to vital en/en and En/en rabbits, En/En animals are subvital because of a dilated ("mega") cecum and ascending colon. In this study, we investigated the role of the KIT gene as a candidate for the English spotting locus in Checkered Giant rabbits and characterized the abnormalities affecting enteric neurons and c-kit positive interstitial cells of Cajal (ICC) in the megacolon of En/En rabbits. Twenty-one litters were obtained by crossing three Checkered Giant bucks (En/en) with nine Checkered Giant (En/en) and two en/en does, producing a total of 138 F1 and backcrossed rabbits. Resequencing all coding exons and portions of non-coding regions of the KIT gene in 28 rabbits of different breeds identified 98 polymorphisms. A single nucleotide polymorphism genotyped in all F1 families showed complete cosegregation with the English spotting coat color phenotype (??=?0.00 LOD ?=?75.56). KIT gene expression in cecum and colon specimens of En/En (pathological) rabbits was 5-10% of that of en/en (control) rabbits. En/En rabbits showed reduced and altered c-kit immunolabelled ICC compared to en/en controls. Morphometric data on whole mounts of the ascending colon showed a significant decrease of HuC/D (P<0.05) and substance P (P<0.01) immunoreactive neurons in En/En vs. en/en. Electron microscopy analysis showed neuronal and ICC abnormalities in En/En tissues. The En/En rabbit model shows neuro-ICC changes reminiscent of the human non-aganglionic megacolon. This rabbit model may provide a better understanding of the molecular abnormalities underlying conditions associated with non-aganglionic megacolon. PMID:24736498

Fontanesi, Luca; Vargiolu, Manuela; Scotti, Emilio; Latorre, Rocco; Faussone Pellegrini, Maria Simonetta; Mazzoni, Maurizio; Asti, Martina; Chiocchetti, Roberto; Romeo, Giovanni; Clavenzani, Paolo; De Giorgio, Roberto

2014-01-01

19

The KIT Gene Is Associated with the English Spotting Coat Color Locus and Congenital Megacolon in Checkered Giant Rabbits (Oryctolagus cuniculus)  

PubMed Central

The English spotting coat color locus in rabbits, also known as Dominant white spotting locus, is determined by an incompletely dominant allele (En). Rabbits homozygous for the recessive wild-type allele (en/en) are self-colored, heterozygous En/en rabbits are normally spotted, and homozygous En/En animals are almost completely white. Compared to vital en/en and En/en rabbits, En/En animals are subvital because of a dilated (“mega”) cecum and ascending colon. In this study, we investigated the role of the KIT gene as a candidate for the English spotting locus in Checkered Giant rabbits and characterized the abnormalities affecting enteric neurons and c-kit positive interstitial cells of Cajal (ICC) in the megacolon of En/En rabbits. Twenty-one litters were obtained by crossing three Checkered Giant bucks (En/en) with nine Checkered Giant (En/en) and two en/en does, producing a total of 138 F1 and backcrossed rabbits. Resequencing all coding exons and portions of non-coding regions of the KIT gene in 28 rabbits of different breeds identified 98 polymorphisms. A single nucleotide polymorphism genotyped in all F1 families showed complete cosegregation with the English spotting coat color phenotype (??=?0.00 LOD ?=?75.56). KIT gene expression in cecum and colon specimens of En/En (pathological) rabbits was 5–10% of that of en/en (control) rabbits. En/En rabbits showed reduced and altered c-kit immunolabelled ICC compared to en/en controls. Morphometric data on whole mounts of the ascending colon showed a significant decrease of HuC/D (P<0.05) and substance P (P<0.01) immunoreactive neurons in En/En vs. en/en. Electron microscopy analysis showed neuronal and ICC abnormalities in En/En tissues. The En/En rabbit model shows neuro-ICC changes reminiscent of the human non-aganglionic megacolon. This rabbit model may provide a better understanding of the molecular abnormalities underlying conditions associated with non-aganglionic megacolon.

Fontanesi, Luca; Vargiolu, Manuela; Scotti, Emilio; Latorre, Rocco; Faussone Pellegrini, Maria Simonetta; Mazzoni, Maurizio; Asti, Martina; Chiocchetti, Roberto; Romeo, Giovanni; Clavenzani, Paolo; De Giorgio, Roberto

2014-01-01

20

Electrical and contractile behavior of large intestinal musculature of piebald mouse model for Hirschsprung's disease  

Microsoft Academic Search

These studies were directed toward better characterization of the abnormalities of motor function in the large intestine of mutant mice with congenital aganglionosis and megacolon. Analysis of pressure-volume relations in the megacolon and aganglionic terminal segment showed increased intestinal wall compliance in the dilated colon and reduced wall compliance in the aganglionic region as compared to normal littermates. Migrating contractile

J. D. Wood; L. R. Brann; D. L. Vermillion

1986-01-01

21

Pseudomembranous colitis  

MedlinePLUS

... 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

22

Hirschsprung Disease  

MedlinePLUS

... appear months or years later. Hirschsprung disease can cause constipation, diarrhea, and vomiting and sometimes lead to serious colon complications, like enterocolitis and toxic megacolon, which can be life threatening. So it's ... The large intestine moves digested material through the ...

23

Laparoscopic approach for rectosigmoidian resection in children.  

PubMed

Abdominoperineal approach for rectosigmoidian resection,first imagined and performed in 1948 by Orwar Swenson,was the surgical technique that opened the pathway in the treatment of congenital megacolon (1). B. Duhamel (1956) and F. Soave (1964) intended to correct the postoperative complications appeared after the Duhamel technique and proposed surgical procedures that keep the aganglionic rectum in transit (2,3). In 1994 K. Bax reproduces the Duhamel procedure using laparoscopic approach (4). K.Georgeson, in 1995, reproduced the Swenson technique for rectosigmoidian resection using minimal invasive surgery (5).Today, this approach represents the most frequently used procedure for the radical treatment of congenital megacolon. PMID:24524481

Oancea, M; Vatra, L; Kadar, A; Cop?escu, C

2014-01-01

24

A Cysteine Protease Inhibitor Cures Chagas' Disease in an Immunodeficient-Mouse Model of Infection  

Microsoft Academic Search

Chagas' disease, caused by the parasite Trypanosoma cruzi, remains the leading cause of cardiopathy in Latin America with about 12 million people infected. Classic clinical manifestations derive from infection of muscle cells leading to progressive cardiomyopathy, while some patients develop megacolon or megaesophagus. A very aggressive clinical course including fulminant meningoencephalitis has been reported in patients who contract Chagas' disease

Patricia S. Doyle; Yuan M. Zhou; Juan C. Engel; James H. McKerrow

2007-01-01

25

Surgical diseases of the colon and rectum in small animals  

Microsoft Academic Search

COLORECTAL disease is a common problem in dogs and cats. As an umbrella term, it covers a wide range of conditions from congenital abnormalities, such as rectovaginal fistula, through acquired disease, such as megacolon, to neoplastic disease. This article reviews the relevant surgical anatomy and general principles of colorectal surgery before focusing on the clinical features and surgical approach to

Kathryn Pratschke

2005-01-01

26

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

2010-01-01

27

Hirschsprung disease, postaxial polydactyly, and atrial septal defect.  

PubMed

We report on an infant girl with Hirschsprung disease, postaxial polydactyly, and atrial septal defect who was born to a consanguineous Iraqi couple. A similar condition of aganglionic megacolon, postaxial polydactyly, and ventricular septal defect with a presumed autosomal recessive (AR) inheritance was reported by Laurence in two sibs [Laurence et al.; J Med Genet 12: 334-338, 1975]. PMID:8986280

Nowaczyk, M J; James, A G; Superina, R; Siegel-Bartelt, J

1997-01-10

28

Hirschsprung disease, associated syndromes, and genetics: a review  

PubMed Central

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 has allowed the emergence of familial cases. HSCR appeared to be a multifactorial malformation with low, sex dependent penetrance and variable expression according to the length of the aganglionic segment, suggesting the involvement of one or more gene(s) with low penetrance. So far, eight genes have been found to be involved in HSCR. This frequent congenital malformation now stands as a model for genetic disorders with complex patterns of inheritance.???Keywords: Hirschsprung disease; aganglionic megacolon; genetics

Amiel, J.; Lyonnet, S.

2001-01-01

29

Expression of the SOX10 gene during human development  

Microsoft Academic Search

SOX10, a new member of the SOX gene family, is a transcription factor defective in the Dom (Dominant megacolon) mouse and in the human Shah-Waardenburg syndrome. To help unravel its physiological role during human development, we studied SOX10 gene expression in embryonic, fetal, and adult human tissues by Northern blot and in situ hybridization. As in mice, the human SOX10

Nadege Bondurand; Alexandra Kobetz; Veronique Pingault; Nicole Lemort; Ferechte Encha-Razavi; Gerard Couly; Derk E Goerich; Michael Wegner; Marc Abitbol; Michel Goossens

1998-01-01

30

Protective Human Leucocyte Antigen Haplotype, HLA-DRB1*01-B*14, against Chronic Chagas Disease in Bolivia  

PubMed Central

Background Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. Methodology Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. Principal Findings The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011haplotype was associated with resistance against chronic Chagas disease. Conclusions This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

del Puerto, Florencia; Nishizawa, Juan Eiki; Kikuchi, Mihoko; Roca, Yelin; Avilas, Cinthia; Gianella, Alberto; Lora, Javier; Velarde, Freddy Udalrico Gutierrez; Miura, Sachio; Komiya, Norihiro; Maemura, Koji; Hirayama, Kenji

2012-01-01

31

Degenerative leiomyopathy in children. A clinico-pathological study  

Microsoft Academic Search

The syndrome of degenerative leiomyopathy (DL) causing intestinal obstruction clinically manifests in young indigenous African children as massive megacolon without aganglionosis. We report on a clinico-pathologic study of 18 children seen over a 15-year period. All patients came from the same geographic area. Mean age at presentation was 9.5 years with mean duration of symptoms 4.3 years. The youngest infant

H. Rode; S. W. Moore; R. O. C. Kaschula; R. A. Brown; S. Cywes

1992-01-01

32

Slow transit constipation  

Microsoft Academic Search

Opinion statement  The diagnosis of slow transit functional constipation is based upon diagnostic testing of patients with idiopathic constipation\\u000a who responded poorly to conservative measures such as fiber supplements, fluids, and stimulant laxatives [1••]. These tests\\u000a include barium enema or colonoscopy, colonic transit of radio-opaque markers, anorectal manometry, and expulsion of a water-filled\\u000a balloon [2•]. Plain abdominal films can identify megacolon,

Arnold Wald

2002-01-01

33

Does whipworm increase the pathogenicity of Campylobacter jejuni? A clinical correlate of an experimental observation.  

PubMed

Campylobacter jejuni is a leading cause of acute diarrhea worldwide, usually mild and self-limiting. No adequate hypothesis has yet been formulated to explain why in an otherwise healthy host this infection is occasionally severe. In a pig model, C jejuni has been shown to be pathogenic only in the presence of swine whipworm. A human case of life-threatening C jejuni colitis leading to toxic megacolon and acute renal failure, associated with concomitant whipworm (Trichuris suis) ova in the feces, is reported. The potential of T suis to potentiate C jejuni in humans deserves further study. PMID:15054492

Shin, Jennifer L; Gardiner, Geoffrey W; Deitel, Wayne; Kandel, Gabor

2004-03-01

34

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.

35

Imaging findings in 11 cats with feline dysautonomia.  

PubMed

Dysautonomia is caused by degeneration of the autonomic ganglia. Failure of the autonomic system affecting the gastrointestinal and urinary tracts can cause oesophageal distension and/or dysfunction, gastric and bowel distension and hypomotility, and urinary bladder distension. The aim of this retrospective study was to describe diagnostic imaging findings in cats with dysautonomia. Common findings were megaoesophagus and/or oesophageal dysfunction, gastric distension and signs of intestinal ileus. Associated aspiration pneumonia and megacolon appeared less commonly. Although diagnostic imaging findings are not specific for this disease, if findings in multiple systems are detected, along with consistent clinical signs and neurological deficits, dysautonomia should be considered among the differential diagnosis. PMID:20452794

Novellas, Rosa; Simpson, Kerry E; Gunn-Moore, Daničlle A; Hammond, Gawain J C

2010-08-01

36

Functional Aerophagia in Children: A Frequent, Atypical Disorder  

PubMed Central

Aerophagia is a functional gastrointestinal disorder characterized by repetitive air swallowing, abdominal distension, belching and flatulence. Pathologic aerophagia is a condition caused by the swallowing of excessive volumes of air with associated various gastrointestinal symptoms, such as burping, abdominal cramps, flatulence and a reduced appetite. It is a clinical entity that can simulate pediatric gastrointestinal motility disorders, such as gastroparesis, megacolon and intestinal pseudo-obstruction, and presents more frequently in children with mental retardation. Early recognition and diagnosis of functional aerophagia or pathologic aerophagia is required to avoid unnecessary, expensive diagnostic investigations or serious clinical complications. Functional aerophagia is frequent in the adult population, but rarely discussed in the pediatric literature. We present two pediatric clinical cases with a history of functional constipation in whom gaseous abdominal distension was the most important symptom. Mechanical intestinal obstruction, chronic intestinal pseudo-obstruction, malabsorption and congenital aganglionic megacolon were ruled out. Extensive gaseous abdominal distension was due to aerophagia, and treatment consisted of parents’ reassurance and psychological counseling.

Morabito, Giuliana; Romeo, Claudia; Romano, Claudio

2014-01-01

37

Failed stapled rectal resection in a constipated patient with rectal aganglionosis  

PubMed Central

A rare case of a severely constipated patient with rectal aganglionosis is herein reported. The patient, who had no megacolon/megarectum, underwent a STARR, i.e., stapled transanal rectal resection, for obstructed defecation, but her symptoms were not relieved. She started suffering from severe chronic proctalgia possibly due to peri-retained staples fibrosis. Intestinal transit times were normal and no megarectum/megacolon was found at barium enema. A diverting sigmoidostomy was then carried out, which was complicated by an early parastomal hernia, which affected stoma emptying. She also had a severe diverting proctitis, causing rectal bleeding, and still complained of both proctalgia and tenesmus. A deep rectal biopsy under anesthesia showed no ganglia in the rectum, whereas ganglia were present and normal in the sigmoid at the stoma site. As she refused a Duhamel procedure, an intersphincteric rectal resection and a refashioning of the stoma was scheduled. This case report shows that a complete assessment of the potential causes of constipation should be carried out prior to any surgical procedure.

Pescatori, Lorenzo C; Villanacci, Vincenzo; Pescatori, Mario

2014-01-01

38

Partial Requirement of Endothelin Receptor B in Spiral Ganglion Neurons for Postnatal Development of Hearing*  

PubMed Central

Impairments of endothelin receptor B (Ednrb/EDNRB) cause the development of Waardenburg-Shah syndrome with congenital hearing loss, hypopigmentation, and megacolon disease in mice and humans. Hearing loss in Waardenburg-Shah syndrome has been thought to be caused by an Ednrb-mediated congenital defect of melanocytes in the stria vascularis (SV) of inner ears. Here we show that Ednrb expressed in spiral ganglion neurons (SGNs) in inner ears is required for postnatal development of hearing in mice. Ednrb protein was expressed in SGNs from WT mice on postnatal day 19 (P19), whereas it was undetectable in SGNs from WT mice on P3. Correspondingly, Ednrb homozygously deleted mice (Ednrb?/? mice) with congenital hearing loss showed degeneration of SGNs on P19 but not on P3. The congenital hearing loss involving neurodegeneration of SGNs as well as megacolon disease in Ednrb?/? mice were markedly improved by introducing an Ednrb transgene under control of the dopamine ?-hydroxylase promoter (Ednrb?/?;DBH-Ednrb mice) on P19. Neither defects of melanocytes nor hypopigmentation in the SV and skin in Ednrb?/? mice was rescued in the Ednrb?/?;DBH-Ednrb mice. Thus, the results of this study indicate a novel role of Ednrb expressed in SGNs distinct from that in melanocytes in the SV contributing partially to postnatal hearing development.

Ida-Eto, Michiru; Ohgami, Nobutaka; Iida, Machiko; Yajima, Ichiro; Kumasaka, Mayuko Y.; Takaiwa, Kazutaka; Kimitsuki, Takashi; Sone, Michihiko; Nakashima, Tsutomu; Tsuzuki, Toyonori; Komune, Shizuo; Yanagisawa, Masashi; Kato, Masashi

2011-01-01

39

Failed stapled rectal resection in a constipated patient with rectal aganglionosis.  

PubMed

A rare case of a severely constipated patient with rectal aganglionosis is herein reported. The patient, who had no megacolon/megarectum, underwent a STARR, i.e., stapled transanal rectal resection, for obstructed defecation, but her symptoms were not relieved. She started suffering from severe chronic proctalgia possibly due to peri-retained staples fibrosis. Intestinal transit times were normal and no megarectum/megacolon was found at barium enema. A diverting sigmoidostomy was then carried out, which was complicated by an early parastomal hernia, which affected stoma emptying. She also had a severe diverting proctitis, causing rectal bleeding, and still complained of both proctalgia and tenesmus. A deep rectal biopsy under anesthesia showed no ganglia in the rectum, whereas ganglia were present and normal in the sigmoid at the stoma site. As she refused a Duhamel procedure, an intersphincteric rectal resection and a refashioning of the stoma was scheduled. This case report shows that a complete assessment of the potential causes of constipation should be carried out prior to any surgical procedure. PMID:24764689

Pescatori, Lorenzo C; Villanacci, Vincenzo; Pescatori, Mario

2014-04-21

40

Outcomes of patients who develop symptomatic Clostridium difficile infection after solid organ transplantation.  

PubMed

Clostridium difficile-associated diarrhea is the most common cause of hospital-associated diarrhea in the UK. Infection can produce a spectrum of manifestations from mild diarrhea to toxic megacolon, colonic perforation, and death. The aim of this study was to evaluate the outcomes of patients who developed symptomatic Clostridium difficile infection (CDI) within the first year after solid organ transplantation. Between 2004 and 2007, we performed 682 transplantation: 433 from deceased-donor kidney, 143 live-donor kidney, 18 pancreas-only, and 88 simultaneous kidney and pancreas transplants. Within the first year of transplantation, 24 patients developed symptomatic CDI. No single risk factor or antimicrobial agent was associated with acquiring infection. Among this group, 2 patients developed toxic megacolon requiring subtotal colectomy and recovered. Although 5 patients who developed CDI died within the first year, CDI was not the primary cause of death. The overall mortality of patients who developed CDI within the first year of transplantation accounted for 0.7% of all transplanted patients. Increased awareness of CDI and barrier nursing can minimize the impact of CDI on the morbidity and mortality associated with transplantation. Patients should be informed of the risk of CDI during consenting for transplantation, because the 3.5% incidence is more common than that of graft loss due to thrombosis. PMID:20832558

Mitu-Pretorian, O M; Forgacs, B; Qumruddin, A; Tavakoli, A; Augustine, T; Pararajasingam, R

2010-09-01

41

Functional aerophagia in children: a frequent, atypical disorder.  

PubMed

Aerophagia is a functional gastrointestinal disorder characterized by repetitive air swallowing, abdominal distension, belching and flatulence. Pathologic aerophagia is a condition caused by the swallowing of excessive volumes of air with associated various gastrointestinal symptoms, such as burping, abdominal cramps, flatulence and a reduced appetite. It is a clinical entity that can simulate pediatric gastrointestinal motility disorders, such as gastroparesis, megacolon and intestinal pseudo-obstruction, and presents more frequently in children with mental retardation. Early recognition and diagnosis of functional aerophagia or pathologic aerophagia is required to avoid unnecessary, expensive diagnostic investigations or serious clinical complications. Functional aerophagia is frequent in the adult population, but rarely discussed in the pediatric literature. We present two pediatric clinical cases with a history of functional constipation in whom gaseous abdominal distension was the most important symptom. Mechanical intestinal obstruction, chronic intestinal pseudo-obstruction, malabsorption and congenital aganglionic megacolon were ruled out. Extensive gaseous abdominal distension was due to aerophagia, and treatment consisted of parents' reassurance and psychological counseling. PMID:24847194

Morabito, Giuliana; Romeo, Claudia; Romano, Claudio

2014-01-01

42

[Diagnosis and therapy of severe acute colitis, still an open issue. Our experience].  

PubMed

From a review of a series of 12 cases of whom 52 operated and of the literature, the Authors discuss about aetiology, pathogenesis and diagnosis of severe colitis. Clinical and laboratory findings, CT and plain films of the abdomen and at last colonoscopy should be evaluated very carefully for certainty diagnosis of a severe acute colitis or toxic megacolon. They suggest a multidisciplinary approach as fundamental for medical management, for indications and correct timing of surgical procedures and to decrease postoperative morbility and mortality. Total colectomy with ileostomy is recommended in emergency surgical treatment of this colonic acute diseases, whereas for urgency operation, performed not later than 48-72 hour of adequate medical treatment, colectomy is suggested with ileorectal or ileoanal anastomosis and ileostomy. PMID:14569926

Bruzzese, A; Campisi, C; D'Aulerio, A; Mercuri, D; Stella, S

2003-01-01

43

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.

2012-01-01

44

Distant Ureteral Metastasis from Colon Adenocarcinoma: Report of a Case and Review of the Literature  

PubMed Central

Carcinomas arising from organs neighbouring the ureter can directly infiltrate the ureter. Distant ureteral metastasis from colon adenocarcinoma is extremely rare and usually an incidental finding in performed autopsies. We report a case of a right ureteral metastasis in a 65-year-old Caucasian male with a history of rectal cancer for which he had been treated 4 years before. He presented with asymptomatic moderate right hydronephrosis. The patient underwent a right nephroureterectomy. Histology of the ureter revealed transmural adenocarcinoma with infiltration of the mucosa. Infiltration of the muscular coat of the bladder was found 2 years later. Thus, cystectomy and left ureterocutaneostomy were performed. The patient died 6 months later due to toxic megacolon during chemotherapy. The differential diagnosis of ureteral adenocarcinoma, especially in patients with previous history of colon adenocarcinoma, should include the possibility of distant metastasis from the primary colonic tumor.

Nikolaos, Ferakis; Panagiotis, Anastasopoulos; Konstantinos, Bouropoulos; Vassilios, Samaras; Iraklis, Poulias

2014-01-01

45

Acute colonic pseudo-obstruction.  

PubMed

Acute colonic pseudo-obstruction (ACPO) is a syndrome of massive dilation of the colon without mechanical obstruction that develops in hospitalised patients with serious underlying medical and surgical conditions. ACPO is associated with significant morbidity and mortality, and, therefore, requires urgent gastroenterologic evaluation. Appropriate evaluation of the markedly distended colon involves excluding mechanical obstruction and other causes of toxic megacolon such as Clostridium difficile infection, and assessing for signs of ischemia and perforation. Increasing age, cecal diameter, delay in decompression, and status of the bowel significantly influence mortality, which is approximately 40% when ischemia or perforation is present. The risk of colonic perforation in ACPO increases when cecal diameter exceeds 12cm and when the distention has been present for greater than 6days. Appropriate management includes supportive therapy and selective use of neostigmine and colonoscopy for decompression. Early recognition and management are critical in minimising complications. PMID:17643908

Saunders, Michael D

2007-01-01

46

Acute colonic pseudo-obstruction.  

PubMed

Acute colonic pseudo-obstruction (ACPO) is a syndrome of massive dilation of the colon without mechanical obstruction that develops in hospitalized patients with serious underlying medical and surgical conditions. Increasing age, cecal diameter, delay in decompression, and status of the bowel significantly influence mortality, which is approximately 40% when ischemia or perforation is present. Evaluation of the markedly distended colon involves excluding mechanical obstruction and other causes of toxic megacolon such as Clostridium difficile infection and assessing for signs of ischemia and perforation. The risk of colonic perforation in ACPO increases when cecal diameter exceeds 12 cm and when the distention has been present for greater than 6 days. Appropriate management includes supportive therapy and selective use of neostigmine and colonoscopy for decompression. Early recognition and management are critical in minimizing complications. PMID:17556152

Saunders, Michael D

2007-04-01

47

Colonic pseudo-obstruction: the dilated colon in the ICU.  

PubMed

Acute colonic pseudo-obstruction is a syndrome of massive dilation of the colon without mechanical obstruction that develops in hospitalized patients with serious underlying medical and surgical conditions. Increasing age, cecal diameter, delay in decompression, and status of the bowel significantly influence mortality, which is approximately 40% when ischemia or perforation is present. Evaluation of the markedly distended colon in the intensive care unit setting involves excluding mechanical obstruction and other causes of toxic megacolon such as Clostridium difficile infection, and assessing for signs of ischemia and perforation. The risk of colonic perforation in acute colonic pseudo-obstruction increases when cecal diameter exceeds 12 cm and when the distention has been present for greater than 6 days. Appropriate management includes supportive therapy and selective use of neostigmine and colonoscopy for decompression. Early recognition and management are critical in minimizing complications. PMID:12610851

Saunders, Michael D; Kimmey, Michael B

2003-01-01

48

MELAS syndrome presenting as an acute surgical abdomen.  

PubMed

MELAS (mitochondrial cytopathy, encephalomyopathy, lactic acidosis and stroke-like episodes) is a syndrome in which signs and symptoms of gastrointestinal disease are uncommon if not rare. We describe the case of a young woman who presented as an acute surgical emergency, diagnosed as toxic megacolon necessitating an emergency total colectomy. MELAS syndrome was suspected postoperatively owing to persistent lactic acidosis and neurological symptoms. The diagnosis was later confirmed with histological and genetic studies. This case highlights the difficulties in diagnosing MELAS because of its unpredictable presentation and clinical course. We therefore recommend a high index of suspicion in cases of an acute surgical abdomen with additional neurological features or raised lactate. PMID:24417855

Dindyal, S; Mistry, K; Angamuthu, N; Smith, G; Hilton, D; Arumugam, P; Mathew, J

2014-01-01

49

Neuroendocrine disorders of the gut.  

PubMed Central

The regulation of gastrointestinal function is known to involve elements of the enteric nervous system. Processes such as secretion, motility, blood flow, and immune function are all influenced by a complex network of neurons whose cell bodies lie in the gut. These neurons use a wide spectrum of substances as neurotransmitters, although the majority use peptides once thought to function only as gut hormones. It has been increasingly recognized that abnormalities of this neuroendocrine regulatory system underlie many gastrointestinal disorders. The most obvious are states of peptide excess found in patients with gut endocrine tumors such as carcinoid, gastrinoma, and somatostatinoma. Conversely, other disorders appear to be related to deficiency states. Examples include both achalasia and Hirschsprung's disease (congenital megacolon), where the loss of inhibitory neural action leads to abnormalities of peristalsis and sphincter function. Evidence for abnormal neuroendocrine regulation leading to disease states is increasing for many other gastrointestinal disorders.

Yee, L F; Mulvihill, S J

1995-01-01

50

Slow Transit Constipation.  

PubMed

The diagnosis of slow transit functional constipation is based upon diagnostic testing of patients with idiopathic constipation who responded poorly to conservative measures such as fiber supplements, fluids, and stimulant laxatives. These tests include barium enema or colonoscopy, colonic transit of radio-opaque markers, anorectal manometry, and expulsion of a water-filled balloon. Plain abdominal films can identify megacolon, which can be further characterized by barium or gastrografin studies. Colonic transit of radio-opaque markers identifies patients with slow transit with stasis of markers in the proximal colon. However, anorectal function should be characterized to exclude outlet dysfunction, which may coexist with colonic inertia. Because slow colonic transit is defined by studies during which patients consume a high-fiber diet, fiber supplements are generally not effective, nor are osmotic laxatives that consist of unabsorbed sugars. Stimulant laxatives are considered first-line therapy, although studies often show a diminished colonic motor response to such agents. There is no evidence to suggest that chronic use of such laxatives is harmful if they are used two to three times per week. Polyethylene glycol with or without electrolytes may be useful in a minority of patients, often combined with misoprostol. I prefer to start with misoprostol 200 mg every other morning and increase to tolerance or efficacy. I see no advantage in prescribing misoprostol on a TID or QID basis or even daily because it increases cramping unnecessarily. This drug is not acceptable in young women who wish to become pregnant. An alternative may be colchicine, which is reported to be effective when given as 0.6 mg TID. Long-term efficacy has not been studied. Finally, biofeedback is a risk-free approach that has been reported as effective in approximately 60% of patients with slow transit constipation in the absence of outlet dysfunction. Although difficult to understand conceptually, it is worth attempting and certainly so in patients with associated pelvic floor dyssynergia. Subtotal colectomy with ileorectal anastomosis is often effective in those patients with colonic inertia, normal anorectal function, and lack of evidence of generalized intestinal dysmotility. However, morbidity is significant both early and late in the disease process and must be balanced against current disability. Ileostomy is preferred in the presence of anorectal dysfunction or with associated impairment of continence mechanisms. Similar considerations apply to the patient with disabling functional megacolon. An alternative approach is ileostomy with disconnection of the colon, which is more acceptable to some patients who may hope for future reconnection if recovery occurs. An additional alternative approach for patients with colonic inertia or megacolon who are not good surgical risks is tube cecostomy (or in children, use of the appendix as a conduit to the cecum). This permits either decompression (in megacolon) or antegrade enemas (in colonic inertia). Our surgeons are not enthusiastic about this approach, and I have little experience with it. In general, the use of partial resections of the colon should be discouraged, because marker studies do not define pathophysiology in patients with slow transit constipation. PMID:12095475

Wald, Arnold

2002-08-01

51

Chagas disease  

PubMed Central

Chagas disease is the clinical condition triggered by infection with the protozoan Trypanosoma cruzi. The infection is transmitted by triatomine insects while blood feeding on a human host. Field studies predict that one third of an estimated 18 million T cruzi?infected humans in Latin America will die of Chagas disease. Acute infections are usually asymptomatic, but the ensuing chronic T cruzi infections have been associated with high ratios of morbidity and mortality: Chagas heart disease leads to unexpected death in 37.5% of patients, 58% develop heart failure and die and megacolon or megaoesophagus has been associated with death in 4.5%. The pathogenesis of Chagas disease appears to be related to a parasite?induced mutation of the vertebrate genome. Currently, treatment is unsatisfactory.

Teixeira, A R L; Nitz, N; Guimaro, M C; Gomes, C

2006-01-01

52

[Dolichomegacolon of the Andes and intestinal volvulus due to altitude].  

PubMed

Sigmoid volvulus is a frequent cause of emergencies in hospitals in the Andean area, representing more than 50% of all intestinal obstructions. Andean dolichomegacolon (DCMA) and retractile mesocolonitis are the main contributing factors for volvulus. The mesocolonitis nears the proximal and distal segment of the sigmoid handle, favoring its torsion. Copious intake of fermentable food is the precipitating factor for volvulus. The majority of patients are seen during sowing and harvest periods, in which the consumption of this type of food increases. Andean people who live at an altitude of 3,000 m have a larger and thicker colon than coastal residents. We call this acquired characteristic the Andean dolichomegacolon (DCMA). A fiber-rich diet may inhibit the histological phenomenon known as elastogenesis, developing--over the years--the megacolon. Another important factor may be the lower atmospheric pressure in the altitude, and according to Boyle and Mariotte's physical law, the expansion of intraluminal gas may have an influence on intestinal enlargement. DCMA has many special anatomic, clinical, radiological, histological and serological features which make it different from the . chagasic megacolon. Mild emergency procedures may be performed to treat the sigmoid volvulus, such as endoscopic disvolvulation. Changing the colon rotation is helpful in diminishing abdominal pressure and restore complete blood circulation. An emergency surgery treatment must take the patient's general condition and the colon handle condition during surgery as a guiding point. High rates of mortality are found in relation to elderly patients, disease evolution time and stage of intestinal ischemia. Other new therapeutic procedures such as percutaneous sigmoidpexy, laparoscopic sigmoidectomy and mesosigmoplasty are under review, and have precise indications. Wider series are needed to evaluate them better. PMID:18958141

Frisancho, Oscar

2008-01-01

53

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))

1994-01-01

54

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease  

PubMed Central

Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels.

Gonzalez-Mejia, Martha Elba; Torres-Rasgado, Enrique; Porchia, Leonardo M; Salgado, Hilda Rosas; Totolhua, Jose-Luis; Ortega, Arturo; Hernandez-Kelly, Luisa Clara Regina; Ruiz-Vivanco, Guadalupe; Baez-Duarte, Blanca G; Perez-Fuentes, Ricardo

2014-01-01

55

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

2013-01-01

56

Clostridium difficile 027-associated pseudomembranous colitis after short-term treatment with cefuroxime and cephalexin in an elderly orthopedic patient: a case report  

PubMed Central

Background Clostridium difficile ribotype 027 has become increasingly prevalent in European countries. The clinical picture varies from self-limiting diarrhea to pseudomembranous colitis with toxic megacolon and ultimately death. Use of antibiotics is the principal risk factor; others include comorbidity, advanced age and hospitalization. However even with extensive knowledge of risk factors, it remains difficult to define “minimum risk,” as illustrated by the following case. Case presentation An 80-year-old Danish man in good health was hospitalized for a penetrating knee injury. He received 5 days of intravenous cefuroxime after surgical revision and was discharged with oral cephalexin. Post-discharge he suffered from abdominal discomfort and was readmitted with ileus 4 days after discharge, i.e. 10 days after initiation of antibiotic treatment. His condition deteriorated, and pseudomembranous colitis was diagnosed. Due to lack of response to vancomycin and metronidazole, a total colectomy was performed. Stool cultures were positive for CD 027. Conclusion Short-term use of cephalosporins may have induced CD 027 infection, and the patient’s age was the only identifiable risk factor for the fulminant course. Thus, even short-term prophylactic treatment with cephalosporins cannot be considered entirely safe.

2012-01-01

57

Piebaldism-Waardenburg syndrome: histopathologic evidence for a neural crest syndrome.  

PubMed

Piebaldism, an autosomal dominant trait, is characterized by patchy hypopigmentation of the face, anterior chest, abdomen, and limbs, heterochromia/bicolored irises, congenital megacolon, and deafness. A 4-month-old Inuit (Eskimo) boy with these manifestations also had left pulmonic artery stenosis, ocular ptosis, and unilateral duplication of the renal collecting system. Evidence is presented for both qualitative and quantitative derangement of neural crest derivatives in this syndrome. Histologically, hypoganglionosis, hyperganglionosis, and ectopic ganglia in lamina propria (neuronal colonic dysplasia [NCD]) were documented in the rectum. The appendix, proximal to the clinical transition zone, showed similar dysplasia. In the hypopigmented skin, multiple microscopic sections were devoid of melanocytes, with no melanin in adjacent basal cells. The hyperpigmented skin contained melanin throughout the basal layer, but the melanocytes were unevenly distributed. Most tissues affected in this boy are of neural crest origin; pathogenesis could be due to faulty migration along the established pathways involving either the borders (basal laminae) or the components of the extracellular matrix (fibronectin, cytotactin, laminin, glycosaminoglycans, and collagen). The similarities between piebaldism and the Waardenburg syndromes are discussed. PMID:3228147

Kaplan, P; de Chaderévian, J P

1988-11-01

58

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs  

PubMed Central

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

Nogueira-Paiva, Nivia Carolina; Fonseca, Katia da Silva; Vieira, Paula Melo de Abreu; Diniz, Livia Figueiredo; Caldas, Ivo Santana; de Moura, Sandra Aparecida Lima; Veloso, Vanja Maria; Guedes, Paulo Marcos da Matta; Tafuri, Washington Luiz; Bahia, Maria Terezinha; Carneiro, Claudia Martins

2013-01-01

59

E. coli Meningitis Presenting in a Patient with Disseminated Strongyloides stercoralis.  

PubMed

Introduction. Spontaneous Escherichia coli meningitis is an infrequent condition in adults and is associated with some predisposing factors, including severe Strongyloides stercoralis (SS) infections. Case Presentation. A 43-year-old Hispanic man, with history of travelling to the jungle regions of Peru and Brazil two decades ago, and who received prednisone due to Bell's palsy for three weeks before admission, presented to the Emergency Department with diarrhea, fever, and hematochezia. A week after admission he developed drowsiness, meningeal signs, abdominal distension, and constipation. A cerebrospinal fluid culture showed extended spectrum ? -lactamase producing E. coli. A colonoscopy was performed and showed pancolitis. Three days after the procedure the patient became unstable and developed peritoneal signs. He underwent a laparotomy, which ended up in a total colectomy and partial proctectomy due to toxic megacolon. Three days later the patient died in the intensive care unit due to septic shock. Autopsy was performed and microscopic examination revealed the presence of multiple Strongyloides larvae throughout the body. Conclusion. Strongyloides stercoralis infection should be excluded in adults with spontaneous E. coli meningitis, especially, if gastrointestinal symptoms and history of travelling to an endemic area are present. Even with a proper diagnosis and management, disseminated strongyloidiasis has a poor prognosis. PMID:24324900

Gomez, Juliana B; Maque, Yvan; Moquillaza, Manuel A; Anicama, William E

2013-01-01

60

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)

1994-09-01

61

Hypoganglionosis in pregnancy: a case report  

PubMed Central

Introduction We report a very rare case of isolated hypoganglionosis first diagnosed during early pregnancy, which should be discussed from an obstetric and a gastroenterological point of view. Case presentation A pregnant 18-year-old Caucasian woman presented at twelve weeks of gestation with lower abdominal pain, mild constipation and a large abdominal mass. Abdominal and pelvic magnetic resonance imaging demonstrated a megarectum and megasigmoid, and our patient was managed with medical therapy during her pregnancy, which occurred without major incidents. At the onset of labor, a fecaloma obstructing the pelvic outlet was detected, which required manual disimpaction. However, during the procedure a sudden continuous fetal bradycardia was detected. An emergency Cesarean section was performed but the fetus suffered hypoxic ischemic encephalopathy. One year after the delivery, our patient underwent a sigmoid resection. A histopathological analysis revealed a reduction of nerve cells in the myenteric and submucous plexus, suggesting hypoganglionosis. Conclusion Although there are some reports of pregnancies complicated by megacolon, they are too few and too old to delineate guidelines for clinical orientation. In our article, we discuss several issues regarding the management of these rare intestinal innervation disorders during pregnancy that we believe will enhance their obstetric and gastroenterological management during pregnancy.

2012-01-01

62

Small bowel obstruction caused by inflammatory cytomegalovirus tumor in a renal transplant recipient: report of a rare case and review of the literature.  

PubMed

Cytomegalovirus (CMV) infection in renal transplant recipients can present as asymptomatic viremia or CMV syndrome or, in more severe cases, as tissue-invasive disease. CMV enteritis, a common manifestation of CMV invasive disease, usually presents with fever, abdominal pain, anorexia, nausea, and diarrhea, and can be rarely complicated by colon perforation, hemorrhage, or megacolon. CMV infection occurs primarily in the first 6 months post transplantation, when immunosuppression is more intense. We describe the case of a female renal transplant recipient with small bowel obstruction caused by CMV disease 7 years post renal transplantation. The patient presented with diarrhea and abdominal pain. Because of elevated CMV viral load, she was initially treated with antiviral therapy with transient response. Endoscopy and imaging tests showed obstruction of the terminal ileum and, subsequently, the patient underwent exploratory laparotomy when a right hemicolectomy was performed. Biopsy results confirmed the diagnosis of CMV enteritis. Epidemiologic characteristics, clinical presentation, diagnostic workup, therapeutic options, and morbidity-mortality rates of CMV infection/disease, in renal transplant recipients, are reviewed. PMID:22931132

Papadimitriou, G; Koukoulaki, M; Vardas, K; Florou, E; Argyrakos, T; Lakiotis, G; Apostolou, T; Drakopoulos, S

2012-10-01

63

[Personal experience in colonoscopy and polypectomy].  

PubMed

The purpose of this presentation is to point out the importance of this new diagnosis and treatment method, recently incorporated. The studies were done with the Fibroscope F9-A with doble channel, equipped with an desection smear for polipectomies and an extracting forceps. The patients arrive with their intestine perfectly cleaned with classical methods. This detail is most important for the polipectomies. If the local conditions aren't the desired, presence of bowels or barium of an previous enema, we postpone both, examination and polipectomy, because those are causes of false diagnosis in the first case or eventual accidents in the second condition. Regarding this, we had an performing doing a biopsy in an stenosing neoplasm of the sigmoid colon. We believe it convenient to prevent this complication, to reduce the air pressure before performing the biopsy. Of the 160 patients examinated, 54 had no patology, 32 had polips and of this group 4 had multiple poliposis, 4 had association with diverticulosis and 3 associated with neoplasm. (4 were neoplasm, 10 stenosis without mucous lesions, 1 villous adenoma, 1 megacolon and 1 rectitis). We made 12 polipectomies, 10 with the conventional technique and 2 associated with surgery. We had no accidents and one of them was an early stage of colon cancer. PMID:742324

Baccaro, J C; González, B

1978-05-01

64

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)

2012-11-09

65

E. coli Meningitis Presenting in a Patient with Disseminated Strongyloides stercoralis  

PubMed Central

Introduction. Spontaneous Escherichia coli meningitis is an infrequent condition in adults and is associated with some predisposing factors, including severe Strongyloides stercoralis (SS) infections. Case Presentation. A 43-year-old Hispanic man, with history of travelling to the jungle regions of Peru and Brazil two decades ago, and who received prednisone due to Bell's palsy for three weeks before admission, presented to the Emergency Department with diarrhea, fever, and hematochezia. A week after admission he developed drowsiness, meningeal signs, abdominal distension, and constipation. A cerebrospinal fluid culture showed extended spectrum ?-lactamase producing E. coli. A colonoscopy was performed and showed pancolitis. Three days after the procedure the patient became unstable and developed peritoneal signs. He underwent a laparotomy, which ended up in a total colectomy and partial proctectomy due to toxic megacolon. Three days later the patient died in the intensive care unit due to septic shock. Autopsy was performed and microscopic examination revealed the presence of multiple Strongyloides larvae throughout the body. Conclusion. Strongyloides stercoralis infection should be excluded in adults with spontaneous E. coli meningitis, especially, if gastrointestinal symptoms and history of travelling to an endemic area are present. Even with a proper diagnosis and management, disseminated strongyloidiasis has a poor prognosis.

Gomez, Juliana B.; Maque, Yvan; Moquillaza, Manuel A.; Anicama, William E.

2013-01-01

66

Rectal suction biopsy for the diagnosis of Hirschsprung's disease.  

PubMed Central

The diagnosis of Hirschsprung's disease is at times difficult, particularly in the young patient. Since 1972 we have used rectal suction biopsy as a screening technique in neonates and infants with failure to pass meconium or evidence of obstruction. In addition, it is used to confirm the diagnosis of Hirschsprung's disease when suspected by barium enema study. This technique has been used in 444 patients, 302 of whom were less than one year of age. No anesthesia is necessary, and there have been no associated complications. Only one patient early in the study had an initial misdiagnosis. There have been no false-positive or false-negative specimens since this initial problem, and no patients have undergone inappropriate pull-through procedures for suspected Hirschsprung's disease. It is recommended that all neonates who do not pass meconium in the first 48 hours of life undergo rectal suction biopsy to establish the diagnosis of congenital megacolon. Images Fig. 1a. Fig. 1b. Fig. 2. Fig. 3.

Andrassy, R J; Isaacs, H; Weitzman, J J

1981-01-01

67

Ogilvie's syndrome following posterior spinal arthrodesis for scoliosis.  

PubMed

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. PMID:23960287

Tsirikos, Athanasios I; Sud, Alok

2013-07-01

68

Chronic phase of Chagas disease: why should it be treated? A comprehensive review.  

PubMed

The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i) eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii) promote tissue regeneration to prevent fibrosis, (iii) reverse existing fibrosis, (iv) prevent cardiomyopathy, megaoesophagus and megacolon and (v) reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i) repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii) combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis. PMID:22012216

Coura, José Rodrigues; Borges-Pereira, José

2011-09-01

69

[The beginning of the disease].  

PubMed

Originating from the ancient enzootic cycle of Trypanosoma cruzi, human Chagas disease (HCD) emerged focally in different points of America, in the Pre Christian period. Being slowly expanded as a consequence of internal migrations, HCD was settled in those locals where some vector species reached domiciliation and where different kinds of reservoirs entered in domestic environment , with major expression in the post Columbus era, particularly between the final of XIX Century and the middle of XX Century, when the maximum prevalence rates were attained. Originally, scarce evidences of acute cases, chronic cardiopathy and megacolon could be detected in different points of the Region, but the diagnosis of such clinical pictures was not easily ascertained. Nevertheless, the megaoesophagus picture proved to be the more specific marker of ancient HCD, with several descriptions of its occurrence in different Brazilian regions, mainly since the XVIII Century. The social burden of HCD depends basically of the presence of chronic cardiopathy, and only after its recognition, control actions of the disease were definitely lounged in endemic countries. PMID:21584351

Prata, Aluízio; Dias, Joăo Carlos Pinto; Coura, José Rodrigues

2011-01-01

70

Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories  

PubMed Central

SUMMARY 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.

Carroll, Karen C.

2013-01-01

71

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs.  

PubMed

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model. PMID:24271001

Nogueira-Paiva, Nívia Carolina; Fonseca, Kátia da Silva; Vieira, Paula Melo de Abreu; Diniz, Lívia Figueiredo; Caldas, Ivo Santana; Moura, Sandra Aparecida Lima de; Veloso, Vanja Maria; Guedes, Paulo Marcos da Matta; Tafuri, Washington Luiz; Bahia, Maria Terezinha; Carneiro, Cláudia Martins

2014-02-01

72

Case Report: Severe form of hemolytic-uremic syndrome with multiple organ failure in a child: a case report  

PubMed Central

Introduction: Hemolytic-uremic syndrome (HUS) is a leading cause of acute renal failure in infants and young children. It is traditionally defined as a triad of acute renal failure, hemolytic anemia and thrombocytopenia that occur within a week after prodromal hemorrhagic enterocolitis. Severe cases can also be presented by acute respiratory distress syndrome (ARDS), toxic megacolon with ileus, pancreatitis, central nervous system (CNS) disorders and multiple organ failure (MOF). Case presentation: A previously healthy 4-year old Caucasian girl developed acute renal failure, thrombocytopenia and hemolytic anemia following a short episode of abdominal pain and bloody diarrhea. By the end of the first week the diagnosis of the typical HUS was established. During the second week the disease progressed into MOF that included ileus, pancreatitis, hepatitis, coma and ARDS, accompanied by hemodynamic instability and extreme leukocytosis. Nonetheless, the girl made a complete recovery after one month of the disease. She was successfully treated in the intensive care unit and significant improvement was noticed after plasmapheresis and continuous veno-venous hemodialysis. Conclusions: Early start of plasmapheresis and meticulous supportive treatment in the intensive care unit, including renal placement therapy, may be the therapy of choice in severe cases of HUS presented by MOF. Monitoring of prognostic factors is important for early performance of appropriate diagnostic and therapeutical interventions.

Mijatovic, Dino; Blagaic, Ana; Zupan, Zeljko

2014-01-01

73

RET and NRG1 interplay in Hirschsprung disease.  

PubMed

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; Ngan, Elly Sau-Wai; Sau-Wai Ngan, Elly; Cherny, Stacey S; Garcia-Barceló, Maria-Mercč

2013-05-01

74

Hirschsprung's disease as a model of complex genetic etiology.  

PubMed

Hirschsprung disease (HSCR), or aganglionic megacolon, is a developmental disorder characterised by the absence of ganglion cells along variable length of the distal gastrointestinal tract, leading to the most common form of functional intestinal obstruction in neonates and children. Aganglionosis is attributed to a failure of neural crest cells to migrate, proliferate, differentiate or survive during enteric nervous system (ENS) development in the embryonic stage. The incidence of HSCR is estimated at 1/5000 live births and most commonly presents sporadically with reduced penetrance and male predominance, although it can be familial and may be inherited as autosomal dominant or autosomal recessive. In 70% of cases, HSCR occurs as an isolated trait and in the other 30% HSCR is associated with other congenital malformation syndromes. HSCR has a complex genetic etiology with several genes and loci being described as associated with either isolated or syndromic forms. These genes encode for receptors, ligands (especially those participating in the RET and EDNRB signaling transduction pathways), transcriptional factors or other cell elements that are usually involved in the neural crest cell development and migration that give rise to ENS. Nevertheless, the RET proto-oncogene is considered the major disease causing gene in HSCR. A common RET variant within the conserved transcriptional enhancer sequence in intron 1 has been shown to be associated with a great proportion of sporadic cases and could act as a modifier by modulating the penetrance of mutations in other genes and possibly of those mutations in the RET proto-oncogene itself. PMID:23605783

Borrego, Salud; Ruiz-Ferrer, Macarena; Fernández, Raquel M; Antińolo, Guillermo

2013-09-01

75

In vitro and in vivo effects on neural crest stem cell differentiation by conditional activation of Runx1 short isoform and its effect on neuropathic pain behavior  

PubMed Central

Introduction Runx1, a Runt domain transcription factor, controls the differentiation of nociceptors that express the neurotrophin receptor Ret, regulates the expression of many ion channels and receptors, and controls the lamina-specific innervation pattern of nociceptive afferents in the spinal cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. We investigated whether conditional activation of Runx1 short isoform (Runx1a), which lacks a transcription activation domain, influences differentiation of neural crest stem cells (NCSCs) in vitro and in vivo during development and whether postnatal Runx1a activation affects the sensitivity to neuropathic pain. Methods We activated ectopic expression of Runx1a in cultured NCSCs using the Tet-ON gene regulatory system during the formation of neurospheres and analyzed the proportion of neurons and glial cells originating from NCSCs. In in vivo experiments we applied doxycycline (DOX) to pregnant mice (days 8–11), i.e. when NCSCs actively migrate, and examined the phenotype of offsprings. We also examined whether DOX-induced activation of Runx1a in adult mice affects their sensitivity to mechanical stimulation following a constriction injury of the sciatic nerve. Results Ectopic Runx1a expression in cultured NCSCs resulted in predominantly glial differentiation. Offsprings in which Runx1a had been activated showed retarded growth and displayed megacolon, pigment defects, and dystrophic dorsal root ganglia. In the neuropathic pain model, the threshold for mechanical sensitivity was markedly increased following activation of Runx1a. Conclusion These data suggest that Runx1a has a specific role in NCSC development and that modulation of Runx1a activity may reduce mechanical hypersensitivity associated with neuropathic pain.

Kanaykina, Nadezda; Abelson, Klas; King, Dale; Liakhovitskaia, Anna; Schreiner, Silke; Wegner, Michael

2010-01-01

76

Dosage Effects of Cohesin Regulatory Factor PDS5 on Mammalian Development: Implications for Cohesinopathies  

PubMed Central

Cornelia de Lange syndrome (CdLS), a disorder caused by mutations in cohesion proteins, is characterized by multisystem developmental abnormalities. PDS5, a cohesion protein, is important for proper chromosome segregation in lower organisms and has two homologues in vertebrates (PDS5A and PDS5B). Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown. To delineate genetic interactions between Pds5A and Pds5B and explore mechanisms underlying phenotypic variability, we generated Pds5A-deficient mice. Curiously, these mice exhibit multiple abnormalities that were previously observed in Pds5B-deficient mice, including cleft palate, skeletal patterning defects, growth retardation, congenital heart defects and delayed migration of enteric neuron precursors. They also frequently display renal agenesis, an abnormality not observed in Pds5B?/? mice. While Pds5A?/? and Pds5B?/? mice die at birth, embryos harboring 3 mutant Pds5 alleles die between E11.5 and E12.5 most likely of heart failure, indicating that total Pds5 gene dosage is critical for normal development. In addition, characterization of these compound homozygous-heterozygous mice revealed a severe abnormality in lens formation that does not occur in either Pds5A?/? or Pds5B?/? mice. We further identified a functional missense mutation (R1292Q) in the PDS5B DNA-binding domain in a familial case of CdLS, in which affected individuals also develop megacolon. This study shows that PDS5A and PDS5B functions other than those involving chromosomal dynamics are important for normal development, highlights the sensitivity of key developmental processes on PDS5 signaling, and provides mechanistic insights into how PDS5 mutations may lead to CdLS.

Zhang, Bin; Chang, Jufang; Fu, Ming; Huang, Jie; Kashyap, Rakesh; Salavaggione, Ezequiel; Jain, Sanjay; Shashikant, Kulkarni; Deardorff, Matthew A.; Uzielli, Maria L. Giovannucci; Dorsett, Dale; Beebe, David C.; Jay, Patrick Y.; Heuckeroth, Robert O.; Krantz, Ian; Milbrandt, Jeffrey

2009-01-01

77

Dosage effects of cohesin regulatory factor PDS5 on mammalian development: implications for cohesinopathies.  

PubMed

Cornelia de Lange syndrome (CdLS), a disorder caused by mutations in cohesion proteins, is characterized by multisystem developmental abnormalities. PDS5, a cohesion protein, is important for proper chromosome segregation in lower organisms and has two homologues in vertebrates (PDS5A and PDS5B). Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown. To delineate genetic interactions between Pds5A and Pds5B and explore mechanisms underlying phenotypic variability, we generated Pds5A-deficient mice. Curiously, these mice exhibit multiple abnormalities that were previously observed in Pds5B-deficient mice, including cleft palate, skeletal patterning defects, growth retardation, congenital heart defects and delayed migration of enteric neuron precursors. They also frequently display renal agenesis, an abnormality not observed in Pds5B(-/-) mice. While Pds5A(-/-) and Pds5B(-/-) mice die at birth, embryos harboring 3 mutant Pds5 alleles die between E11.5 and E12.5 most likely of heart failure, indicating that total Pds5 gene dosage is critical for normal development. In addition, characterization of these compound homozygous-heterozygous mice revealed a severe abnormality in lens formation that does not occur in either Pds5A(-/-) or Pds5B(-/-) mice. We further identified a functional missense mutation (R1292Q) in the PDS5B DNA-binding domain in a familial case of CdLS, in which affected individuals also develop megacolon. This study shows that PDS5A and PDS5B functions other than those involving chromosomal dynamics are important for normal development, highlights the sensitivity of key developmental processes on PDS5 signaling, and provides mechanistic insights into how PDS5 mutations may lead to CdLS. PMID:19412548

Zhang, Bin; Chang, Jufang; Fu, Ming; Huang, Jie; Kashyap, Rakesh; Salavaggione, Ezequiel; Jain, Sanjay; Kulkarni, Shashikant; Shashikant, Kulkarni; Deardorff, Matthew A; Uzielli, Maria L Giovannucci; Dorsett, Dale; Beebe, David C; Jay, Patrick Y; Heuckeroth, Robert O; Krantz, Ian; Milbrandt, Jeffrey

2009-01-01

78

The developmental etiology and pathogenesis of Hirschsprung disease.  

PubMed

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

2013-07-01

79

Current approaches to the management of new-onset ulcerative colitis  

PubMed Central

Ulcerative colitis (UC) is an idiopathic, inflammatory gastrointestinal disease of the colon. As a chronic condition, UC follows a relapsing and remitting course with medical maintenance during periods of quiescent disease and appropriate escalation of therapy during times of flare. Initial treatment strategies must not only take into account current clinical presentation (with specific regard for extent and severity of disease activity) but must also take into consideration treatment options for the long-term. The following review offers an approach to new-onset UC with a focus on early treatment strategies. An introduction to the disease entity is provided along with an approach to initial diagnosis. Stratification of patients based on clinical parameters, disease extent, and severity of illness is paramount to determining course of therapy. Frequent assessments are required to determine clinical response, and treatment intensification may be warranted if expected improvement goals are not appropriately reached. Mild-to- moderate UC can be managed with aminosalicylates, mesalamine, and topical corticosteroids with oral corticosteroids reserved for unresponsive cases. Moderate-to-severe UC generally requires oral or intravenous corticosteroids in the short-term with consideration of long-term management options such as biologic agents (as initial therapy or in transition from steroids) or thiopurines (as bridging therapy). Patients with severe or fulminant UC who are recalcitrant to medical therapy or who develop disease complications (such as toxic megacolon) should be considered for colectomy. Early surgical referral in severe or refractory UC is crucial, and colectomy may be a life-saving procedure. The authors provide a comprehensive evidence-based approach to current treatment options for new-onset UC with discussion of long-term therapeutic efficacy and safety, patient-centered perspectives including quality of life and medication compliance, and future directions in related inflammatory bowel disease care.

Marchioni Beery, Renee; Kane, Sunanda

2014-01-01

80

Gastrointestinal Manifestations of Multiple Endocrine Neoplasia Type 2  

PubMed Central

Objective To determine the clinical features, natural history, and role of surgery for gastrointestinal manifestations of the multiple endocrine neoplasia type 2 (MEN 2) syndromes. Summary Background Data The MEN 2 syndromes are characterized by medullary thyroid carcinoma and other endocrinopathies. In addition, some patients with MEN 2A develop Hirschsprung’s disease (HD), and all patients with MEN 2B have intestinal neuromas and megacolon that can cause significant gastrointestinal problems. Methods From 83 families with MEN 2A, eight patients with HD were identified (MEN 2A-HD). These and all patients with MEN 2B followed at the authors’ institution (n = 53) were sent questionnaires to describe the onset and type of gastrointestinal symptoms and treatment they had before the diagnosis of MEN 2. Records of all patients responding were reviewed, including radiographic imaging, histology, surgical records, and genetic testing. Results Thirty-six of the 61 patients (59%) responded (MEN 2A = 8, MEN 2B = 28) to the questionnaires. All patients with MEN 2A-HD were operated on for HD 2 to 63 years before being diagnosed with MEN 2. All patients responding were underweight as infants and had symptoms of abdominal pain, distention, and constipation. Eighty-eight percent had hematochezia, 63% had emesis, and 33% had intermittent diarrhea before surgery. All patients with MEN 2A-HD had rectal biopsies with a diverting colostomy as the initial surgical procedure. This was followed by a colostomy takedown and pull-through procedure at a later interval. Ninety-three percent of patients with MEN 2B had gastrointestinal symptoms 1 to 24 years before the diagnosis of MEN 2. Symptoms included flatulence (86%), abdominal distention or being underweight as a child (64%), abdominal pain (54%), constipation or diarrhea (43%), difficulty swallowing (39%), and vomiting (14%). Seventy-one percent of patients with MEN-2B with gastrointestinal symptoms had radiographic imaging, 32% were admitted to the hospital, and 29% underwent surgery. Conclusions Patients with MEN 2A-HD had a typical HD presentation and always required surgery. Patients with MEN 2B have significant gastrointestinal symptoms, but less than a third had surgical intervention. Understanding the clinical course and differences in these patients will improve clinical management.

Cohen, Mark S.; Phay, John E.; Albinson, Charlotte; DeBenedetti, Mary K.; Skinner, Michael A.; Lairmore, Terry C.; Doherty, Gerard M.; Balfe, Dennis M.; Wells, Samuel A.; Moley, Jeffrey F.

2002-01-01

81

Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4)  

PubMed Central

Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors involving two or more endocrine glands within a single patient. Four major forms of MEN, which are autosomal dominant disorders, are recognized and referred to as: MEN type 1 (MEN1), due to menin mutations; MEN2 (previously MEN2A) due to mutations of a tyrosine kinase receptor encoded by the rearranged during transfection (RET) protoncogene; MEN3 (previously MEN2B) due to RET mutations; and MEN4 due to cyclin-dependent kinase inhibitor (CDNK1B) mutations. Each MEN type is associated with the occurrence of specific tumors. Thus, MEN1 is characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumors; MEN2 is characterized by the occurrence of medullary thyroid carcinoma (MTC) in association with phaeochromocytoma and parathyroid tumors; MEN3 is characterized by the occurrence of MTC and phaeochromocytoma in association with a marfanoid habitus, mucosal neuromas, medullated corneal fibers and intestinal autonomic ganglion dysfunction, leading to megacolon; and MEN4, which is also referred to as MENX, is characterized by the occurrence of parathyroid and anterior pituitary tumors in possible association with tumors of the adrenals, kidneys, and reproductive organs. This review will focus on the clinical and molecular details of the MEN1 and MEN4 syndromes. The gene causing MEN1 is located on chromosome 11q13, and encodes a 610 amino-acid protein, menin, which has functions in cell division, genome stability, and transcription regulation. Menin, which acts as scaffold protein, may increase or decrease gene expression by epigenetic regulation of gene expression via histone methylation. Thus, menin by forming a subunit of the mixed lineage leukemia (MLL) complexes that trimethylate histone H3 at lysine 4 (H3K4), facilitates activation of transcriptional activity in target genes such as cyclin-dependent kinase (CDK) inhibitors; and by interacting with the suppressor of variegation 3–9 homolog family protein (SUV39H1) to mediate H3K methylation, thereby silencing transcriptional activity of target genes. MEN1-associated tumors harbor germline and somatic mutations, consistent with Knudson’s two-hit hypothesis. Genetic diagnosis to identify individuals with germline MEN1 mutations has facilitated appropriate targeting of clinical, biochemical and radiological screening for this high risk group of patients for whom earlier implementation of treatments can then be considered. MEN4 is caused by heterozygous mutations of CDNK1B which encodes the 196 amino-acid CDK1 p27Kip1, which is activated by H3K4 methylation.

Thakker, Rajesh V.

2014-01-01

82

Clostridium difficile associated infection, diarrhea and colitis.  

PubMed

A new, hypervirulent strain of Clostridium difficile, called NAP1/BI/027, has been implicated in C. difficile outbreaks associated with increased morbidity and mortality since the early 2000s. The epidemic strain is resistant to fluoroquinolones in vitro, which was infrequent prior to 2001. The name of this strain reflects its characteristics, demonstrated by different typing methods: pulsed-field gel electrophoresis (NAP1), restriction endonuclease analysis (BI) and polymerase chain reaction (027). In 2004 and 2005, the US Centers for Disease Control and Prevention (CDC) emphasized that the risk of C. difficile-associated diarrhea (CDAD) is increased, not only by the usual factors, including antibiotic exposure, but also gastrointestinal surgery/manipulation, prolonged length of stay in a healthcare setting, serious underlying illness, immune-compromising conditions, and aging. Patients on proton pump inhibitors (PPIs) have an elevated risk, as do peripartum women and heart transplant recipients. Before 2002, toxic megacolon in C. difficile-associated colitis (CDAC), was rare, but its incidence has increased dramatically. Up to two-thirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors. Fulminant colitis is reported more frequently during outbreaks of C. difficile infection in patients with inflammatory bowel disease (IBD). C. difficile infection with IBD carries a higher mortality than without underlying IBD. This article reviews the latest information on C. difficile infection, including presentation, vulnerable hosts and choice of antibiotics, alternative therapies, and probiotics and immunotherapy. We review contact precautions for patients with known or suspected C. difficile-associated disease. Healthcare institutions require accurate and rapid diagnosis for early detection of possible outbreaks, to initiate specific therapy and implement effective control measures. A comprehensive C. difficile infection control management rapid response team (RRT) is recommended for each health care facility. A communication network between RRTs is recommended, in coordination with each country's department of health. Our aim is to convey a comprehensive source of information and to guide healthcare professionals in the difficult decisions that they face when caring for these oftentimes very ill patients. PMID:19340897

Hookman, Perry; Barkin, Jamie S

2009-04-01

83

Outbreak of Clostridium difficile 027 infection in Vienna, Austria 2008-2009.  

PubMed

From November 2008 to 15 April 2009, 36 isolates of CD027 identified in Austria, all originating from four hospitals in Vienna. All isolates were positive for toxin A, toxin B and the binary toxin, and showed a characteristic 18 bp deletion in the tcdC gene. Clostridium difficile is an anaerobic spore-forming bacterium. Some strains may cause diarrhoea due to formation of toxins. Symptomatic C. difficile infection (CDI) is primarily linked with hospital admission and antibiotic treatment, although antibiotic exposure is neither necessary nor sufficient for CDI [1,2]. In Belgium, for instance, one third of CDI cases reported in the hospital surveillance system are not hospital-associated [3]. Symptoms range from mild diarrhoea to serious manifestations such as pseudomembranous colitis, toxic megacolon or perforation of the colon. C. difficile challenges hygiene standards as it is forms spores. The risk of infection rises with increasing age, underlying disease and immunodeficiency [4]. In recent years, a particularly virulent strain, ribotype 027 (CD027), has emerged in a number of countries, particularly in connection with hospital outbreaks, but also in community-acquired diarrhoea cases [5]. The risk of serious disease and death associated with CD027 exceeds that of other C. difficile strains. The classical CD027 is characterised - among other things - by an increased production of toxins A and B, production of a binary toxin and resistance to newer fluoroquinolones such as moxifloxacin. The first three Austrian cases of CD027 occurred in 2006 and in March 2008 [6,7]. Since August 2006, the Austrian National Reference Centre for C. difficile has ribotyped approximately 2,700 human C. difficile isolates received from all nine Austrian provinces. In recent months, a drastic increase in CD027 cases has been noted, all originating from four hospitals in Vienna. From November 2008 to 15 April 2009, 36 isolates of CD027 were received at the National Reference Centre. The Figure summarises these C. difficile 027 cases by month of reception of the sample at the reference centre. PMID:19422768

Indra, A; Huhulescu, S; Fiedler, A; Kernbichler, S; Blaschitz, M; Allerberger, F

2009-04-30

84

The economic burden of treatment failure amongst patients with irritable bowel syndrome with constipation or chronic constipation: a retrospective analysis of a Medicaid population.  

PubMed

Abstract Objective: To compare healthcare resource utilization (HRU) and costs between patients with irritable bowel syndrome with constipation (IBS-C) or chronic constipation (CC) with and without evidence of treatment failure. Methods: Claims data from the Missouri Medicaid program were used to identify adults with IBS-C or CC treated for constipation. IBS-C patients were required to have ?2 constipation therapy claims, and the index date was defined as the date of the first constipation therapy claim within 12 months after an IBS diagnosis. For CC, the index date was defined as the date of the first constipation treatment claim followed by a second claim for constipation treatment or diagnosis between 60 days and 12 months later. Indicators of treatment failure were: switch/addition of constipation therapy, IBS- or constipation-related inpatient/emergency admission, megacolon/fecal impaction, constipation-related surgery/procedure, or aggressive prescription treatments. Annual incremental HRU and costs (public payer perspective) were compared between patients with and without treatment failure. Incidence rate ratios (IRRs) and cost differences are reported. Results: In total, 2830 patients with IBS-C and 8745 with CC were selected. Approximately 50% of patients had ?1 indicator of treatment failure. After adjusting for confounding factors, patients with treatment failure experienced higher HRU, particularly in inpatient days (IRR?=?1.75 for IBS-C; IRR?=?1.54 for CC) and higher total healthcare costs of $4353 in IBS-C patients and $2978 in CC patients. Medical service costs were the primary driver of the incremental costs associated with treatment failure, making up 71.3% and 67.0% of the total incremental healthcare costs of the IBS-C and CC samples, respectively. Limitations: Sample was limited to Medicaid patients in Missouri. Claims data were used to infer treatment failure. Conclusion: Treatment failure is frequent among IBS-C and CC patients, and sub-optimal treatment response with available IBS-C and CC therapies may lead to substantial HRU and healthcare costs. PMID:24811855

Guerin, Annie; Carson, Robyn T; Lewis, Barbara; Yin, Donald; Kaminsky, Michael; Wu, Eric

2014-08-01