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[Current management of toxic megacolon].  


Toxic megacolon is a rare and life-threatening complication of severe colitis, defined as a dilatation of the colon > 6 cm in the absence of distal obstruction in combination with signs of systemic toxicity (major criteria: fever, tachycardia, leukocytosis, anaemia). Various triggers are known and the most common causes are underlying ulcerative colitis and Clostridium difficile. Diagnosis can easily be made by clinical examination, routine laboratory parameters and a plain X-ray of the abdomen. Much more difficult is to decide between non-surgical treatment including intensive care treatment or surgery (mostly subtotal colectomy with terminal ileostomy). Non-surgical therapy includes balancing of electrolytes and fluid volumes, broad-spectrum antibiotics including metronidazole, positioning of patients and probably careful intermittent decompression. In case of ulcerative colitis immunosuppression should be started with corticosteroids and potentially with calcineurin inhibitors. In pseudomembranous colitis vancomycin should be given orally and metronidazole should be given intravenously. As far as possible the patient should be treated in a centre with experience in the field. PMID:22383287

Leifeld, L; Kruis, W



Ultrastructural and Histochemical Studies of Murine Megacolon  

PubMed Central

The myenteric plexus of the colon was studied ultrastructurally in a colony of an Ls Ls strain of mice manifesting a piebald coat color mutation associated with a high incidence of genetically determined aganglionic megacolon. Ultrastructural studies were histochemically supplemented by the Maillet technic and stains for acetylcholinesterase and catecholamines. The development of megacolon did not appear to require total aganglionosis, since ostensibly aganglionic areas contained rare ganglion cells. In the distal narrowed segment, both cholinergic and adrenergic fibers in the muscularis, submucosa and mucosa were somewhat reduced. In the mouse, the dilated portion showed an abrupt increase in adrenergic fibers. These findings are related to the pathophysiology of the disorder. The increasing degenerative changes seen in myenteric plexus structures from the fetus to adult suggest that aganglionic megacolon may be an abiotrophy, wherein the congenitally deficient myenteric plexus may be unusually predisposed to postnatal injury and degeneration. ImagesFig 7Fig 8Fig 9Fig 10Fig 11Fig 12Fig 13Fig 14Fig 15Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:5080702

Bolande, Robert P.; Towler, William F.



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


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



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. PMID:23277646

Barnes, Darren C.



Morphometric study of the fibrosis and mast cell count in the circular colon musculature of chronic Chagas patients with and without megacolon.  


A morphometric study of the circular colon musculature was performed, in which the mast cell count was determined and the connective fibrous tissue in this layer was measured. The objective was to gain better understanding of Chagas megacolon morphology and contribute towards the knowledge of fibrosis pathogenesis in Chagas megas. An evaluation was made of 15 distal sigmoid rings from Chagas patients with megacolon (MCC), 15 without megacolon (CSMC) and 15 non-Chagas patients (NC). The rings were fixed in formol, embedded in paraffin, and 7mm thick sections were cut and stained using Azan-Heidenhain and Giemsa. The mast cell count and fibrosis were greater in the MCC group than in the CSMC and NC groups (p< 0,05; Kruskal-Wallis test) and there was no significant difference between the latter two. The fibrosis and increased mast cell count in the colon musculature of the MCC group possibly indicates that there is a relationship between mastocytosis and fibrosis, as has already been demonstrated in other pathologies. PMID:12937722

Pinheiro, Simone Wanderley; Rua, Adilha Misson de Oliveira; Etchebehere, Renata Margarida; Cançado, Cristiane Gobbo; Chica, Javier Em lio Lazo; Lopes, Edison Reis; Adad, Sheila Jorge




PubMed Central

This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon. PMID:25351549

Adad, Sheila Jorge; Etchebehere, Renata Margarida; Jammal, Alessandro Adad



A case report of a giant presacral cystic schwannoma with sigmoid megacolon.  


Schwannomas are peripheral nerve sheath tumours with a slow growth rate. Giant sacral schwannoma with anterior cortex erosion and associated intrapelvic extension are uncommon. Though they tend to be large when initially found, most Giant schwannomas are clinically asymptomatic. The tumour appears heterogenous due to long standing degeneration. Herein, we present a case of a large purely cystic presacral schwannoma in a patient with poliomyelitis, which has displaced adjacent organs including urinary bladder and sigmoid colon, with an initial presentation of constipation. The tumour was partially excised and diagnosis was confirmed by histo-pathology and immunohistochemistry. PMID:22470633

Nyapathy, Vinay; Murthy, Umesh Krishna; Chintamani, Jaiger; Sridhar, Deepak Yedagudde




E-print Network

plexus myentériques ; sur le plan fonctionnel, la motricité caeco-colique est régulière même dans le cas- tine in both normal pigs fed ad libitum on a standard diet and in subjects having rec- tal stricture ani- mals when receiving a daily meal of the same standard diet. Material and methods Four Large White

Paris-Sud XI, Université de


Bloody Stools in Children (Beyond the Basics)  


... Certain antibiotics* Beets Flavored gelatin (red colored) Kool-Aid Red licorice These foods and medicines can make stools look black, like ... children and adolescents Congenital aganglionic megacolon (Hirschsprung ... of necrotizing enterocolitis in newborns Patient information: Angiodysplasia ...


Laparoscopic approach for rectosigmoidian resection in children.  


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



Total Laparoscopic Modified Duhamel Operation in Combination With Transanal Endoscopic Microsurgery  

PubMed Central

Introduction: Laparoscopic-assisted colonic resection has been well described for multiple surgical indications and typically requires an abdominal incision for specimen removal that is associated with most of the postoperative pain. We report the total laparoscopic modified Duhamel operation for megacolon in combination with transanal endoscopic microsurgery for transanal specimen retrieval and anastomosis to avoid the additional abdominal extraction incision. Case Description: Two cases are presented: case 1 was a 15-year-old boy who presented with intermittent abdominal distention, pain, and constipation for 3 years' duration and was diagnosed with Hirschsprung disease, and case 2 was a 60-year-old man who presented with repeated attacks of incomplete intestinal obstruction for 2 years' duration and was diagnosed with adult megacolon. They were treated by the total laparoscopic modified Duhamel operation without an abdominal extraction incision in combination with transanal endoscopic microsurgery. The operations were successfully accomplished without conversion to open surgery. The patients tolerated the procedure well, complained of minimal postoperative pain, and did not require narcotics beyond the day of the operation. No surgical complications occurred. Discharge from the hospital occurred on the ninth postoperative day in case 1 and the 13th postoperative day in case 2. Discussion: The total laparoscopic modified Duhamel operation in combination with transanal endoscopic microsurgery is a feasible and minimally invasive technique for idiopathic megacolon and adult megacolon. This advanced surgical technique was developed by combining laparoscopy with the concept of natural orifice transluminal endoscopic surgery. PMID:24680156

Han, Yi; Lin, Mou-Bin; Zhang, Ya-Jie



Hirschsprung disease, associated syndromes, and genetics: a review  

Microsoft Academic Search

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

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



Lineage Analysis of Circulating Trypanosoma cruzi Parasites and Their Association with Clinical Forms of Chagas Disease in Bolivia  

PubMed Central

Background The causative agent of Chagas disease, Trypanosoma cruzi, is divided into 6 Discrete Typing Units (DTU): Tc I, IIa, IIb, IIc, IId and IIe. In order to assess the relative pathogenicities of different DTUs, blood samples from three different clinical groups of chronic Chagas disease patients (indeterminate, cardiac, megacolon) from Bolivia were analyzed for their circulating parasites lineages using minicircle kinetoplast DNA polymorphism. Methods and Findings Between 2000 and 2007, patients sent to the Centro Nacional de Enfermedades Tropicales for diagnosis of Chagas from clinics and hospitals in Santa Cruz, Bolivia, were assessed by serology, cardiology and gastro-intestinal examinations. Additionally, patients who underwent colonectomies due to Chagasic magacolon at the Hospital Universitario Japonés were also included. A total of 306 chronic Chagas patients were defined by their clinical types (81 with cardiopathy, 150 without cardiopathy, 100 with megacolon, 144 without megacolon, 164 with cardiopathy or megacolon, 73 indeterminate and 17 cases with both cardiopathy and megacolon). DNA was extracted from 10 ml of peripheral venous blood for PCR analysis. The kinetoplast minicircle DNA (kDNA) was amplified from 196 out of 306 samples (64.1%), of which 104 (53.3%) were Tc IId, 4 (2.0%) Tc I, 7 (3.6%) Tc IIb, 1 (0.5%) Tc IIe, 26 (13.3%) Tc I/IId, 1 (0.5%) Tc I/IIb/IId, 2 (1.0%) Tc IIb/d and 51 (25.9%) were unidentified. Of the 133 Tc IId samples, three different kDNA hypervariable region patterns were detected; Mn (49.6%), TPK like (48.9%) and Bug-like (1.5%). There was no significant association between Tc types and clinical manifestations of disease. Conclusions None of the identified lineages or sublineages was significantly associated with any particular clinical manifestations in the chronic Chagas patients in Bolivia. PMID:20502516

del Puerto, Ramona; Nishizawa, Juan Eiki; Kikuchi, Mihoko; Iihoshi, Naomi; Roca, Yelin; Avilas, Cinthia; Gianella, Alberto; Lora, Javier; Gutierrez Velarde, Freddy Udalrico; Renjel, Luis Alberto; Miura, Sachio; Higo, Hiroo; Komiya, Norihiro; Maemura, Koji; Hirayama, Kenji



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 PMID:11694544

Amiel, J.; Lyonnet, S.



Strategies for the Care of Adults Hospitalized for Active Ulcerative Colitis  

PubMed Central

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

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



Gastrointestinal motility disorders and gastrointestinal prokinetic therapy.  


Gastrointestinal motility disorders represent a diagnostic and therapeutic challenge. Disorders of gastrointestinal motility may result in accelerated transit, delayed transit, impaired relaxation, or inappropriate relaxation. The delayed transit disorders are the most important motility disorders of companion animals and may involve the esophagus (hypomotility and megaesophagus), stomach (delayed gastric emptying), small intestine (postoperative ileus and intestinal pseudo-obstruction), or colon (constipation and megacolon). PMID:14552159

Washabau, Robert J



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

Microsoft Academic Search

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

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



Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease  

Microsoft Academic Search

Hirschsprung disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Two susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene and the endothelin B receptor (EDNRB) gene. Hitherto however, homozygosity for EDNRB mutations accounted for the HSCR-Waarden- burg syndrome (WS) association. Here, we report het- erozygous EDNRB missense mutations (G57S, R319W and

Jeanne Amiel; Tania Attié; Dominique Jan; Anna Pelet; Patrick Edery; Christelle Bidaud; Didier Lacombe; Paul Tam; Juliette Simeoni; Elisabeth Flori; Claire Nihoul-Fékété; Arnold Munnich; Stanislas Lyonnet



[Complications in treatment of a patient with total aganglionosis of the large intestine].  


The author presents a patient with an congenital malformation, megacolon congenitum, with total agangliosis of the large bowel. Total colectomy was performed preserving part of the rectum with subsequent Duhamel's operation. After four years, at the age of 5.5 years the postoperative course was complicated by an inflammation of the rectum with the subsequent development of multiple fistulae in the perianal, perineal, gluteal and labial area. The condition had a rapid septic course. The patient was subjected to repeated ileostomy. Under general antibiotic treatment and Sulfasalazine the patient's condition improved. PMID:11787205

Kálavský, M



A young leukemic patient with unusual catastrophic intestinal complication.  


A 14-year-old child with acute lymphoblastic leukemia who had completed induction chemotherapy presented with fever and diffuse musculoskeletal pains which was thought to be a constellation of myositis, arthralgias and arthritis. Investigations revealed initially showed normal peripheral blood counts but had pancytopenia and pre-terminally blasts were seen in the peripheral blood smear. He had bone marrow necrosis. Disseminated intravascular coagulation was suspected with a positive fungal serology. At autopsy, he had evidence of disease relapsed in lymph nodes, liver, spleen, testes and kidneys. There was extensive pseudomembranous colitis and appendicitis with changes of toxic megacolon. PMID:25673592

Vaiphei, Kim; Trehan, Amita; Singh Sachdeva, Man Updesh; Malhotra, Pankaj



Technical Aspects of Ileoanal Pouch Surgery in Patients with Ulcerative Colitis  

PubMed Central

Restorative proctocolectomy with ileal pouch-anal anastomosis is the procedure of choice for patients with ulcerative colitis requiring surgery. A J-pouch with a stapled anastomosis has been the preferred technique because it is quicker, safer, and associated with good functional outcomes. A diverting loop ileostomy is usually created at the time of ileal pouch-anal anastomosis. In patients with severe fulminant colitis or toxic megacolon, restorative proctocolectomy with ileal pouch-anal anastomosis is performed in multistages. The technical aspects of ileal pouch-anal anastomosis in patients with ulcerative colitis are reviewed in this article. PMID:22131894

Kirat, Hasan T.; Remzi, Feza H.



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.


Neurocristopathies presenting with neurologic abnormalities associated with Hirschsprung's disease.  


Neurocristopathies are a group of diverse disorders resulting from defective growth, differentiation, and migration of the neural crest cells. Hirschsprung's disease, namely aganglionic megacolon, is the consequence of defective migration of neural crest cells on to the colonic submucosa and is therefore considered a neurocristopathy. We report on four children in whom was diagnosed a neurocristopathy, associating Hirschsprung's disease with a wide spectrum of neurologic abnormalities. The patients included two children presenting the phenotypic features of the Goldberg-Shprintzen syndrome: distinct dysmorphic facial features, microcephaly, and mental retardation, along with agenesis of the corpus callosum and cortical malformations associated with intractable seizures in one child. The third newborn presented with the Haddad syndrome: short-segment Hirschsprung's disease associated with the congenital central hypoventilation syndrome requiring permanent artificial ventilation. In the fourth child, absence of the corpus callosum was associated with mild dysmorphic features, borderline cognitive abilities, and attention-deficit disorder. Therefore, awareness of a possible neurocristopathy associated with neurologic abnormalities should be taken into account in any patient newly diagnosed with Hirschsprung's disease to detect the abnormalities early and promptly manage them. A thorough neurologic examination and a developmental assessment, including magnetic resonance imaging of the brain and electroencephalography, should be performed for any child presenting with an aganglionic megacolon, especially those presenting with seizures, developmental delay, or even congenital hypoventilation. PMID:12878302

Shahar, Eli; Shinawi, Maruan



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. PMID:24764689

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



Gastrointestinal disorders of the cat.  


Several areas of feline gastroenterology deserve critical attention in the near future. For example, as compared with the dog, little is known about the various causes of malabsorptive disease in the cat. So frequently, intestinal biopsy samples reveal nothing more than intestinal thickening with fibrosis and nonspecific mild cellular infiltration, and the inciting cause is never determined. It is, perhaps, wrong to be critical about the use of the bark of Berberis vulgaris and the root of Rheum in modern feline gastroenterology, since most of us occasionally use unconventional therapies. It has been rumored that I have been known to advocate the daily addition of a tablespoon of pumpkin-pie filling to the food of cats suffering from recurrent constipation and acquired megacolon. The rumors are true, and colonic evacuation is sometimes promoted with the use of this unusual bulking agent after traditional drug therapy has failed. We all have our weaknesses! PMID:6359656

August, J R



Sigmoid volvulus treated by mini-incision.  


Definitive surgical management of sigmoid volvulus is usually via a midline laparotomy or laparoscopy. We report our experience with a series of five consecutive cases over a 10-year period. All patients had definitive surgery via a left iliac fossa mini-incision after prior decompression. For four patients, it was the first episode of sigmoid volvulus and one patient had a recurrent sigmoid volvulus after previous sigmoid colectomy. The latter patient had pan colonic megacolon diagnosed at initial surgery. All five cases were surgically treated successfully via a mini-incision on the left iliac fossa. There were no instances of recurrence at a median follow-up duration of 95 months (range 7-132 months). A left iliac fossa mini-incision is sufficient for the definitive management of non-perforated sigmoid volvulus. Larger studies are warranted to draw definitive conclusions. PMID:25367827

Seow-En, I; Seow-Choen, F



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

PubMed Central

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

Goldstein, AM; Hofstra, RMW; Burns, AJ



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

SciTech Connect

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

Teichgraeber, Ulf Karl-Martin, E-mail:; Streitparth, Florian, E-mail: florian.streitparth@charite.d [Charite Universitaetsmedizin Berlin, Institut fuer Diagnostische und Interventionelle Radiologie (Germany); Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.d [Charite Universitaetsmedizin Berlin, Klinik fuer Strahlenheilkunde (Germany); Benter, Thomas, E-mail: Thomas.Benter@klinikum-rg.d [Elblandkliniken Riesa-Grossenhain gGmbH, Klinik fuer Innere Medizin II Haematologie/Onkologie und Gastroenterologie (Germany)



Plain Abdominal Radiograph as an Evaluation Method of Bowel Dysfunction in Patients With Spinal Cord Injury  

PubMed Central

Objective To evaluate the usefulness of plain abdominal radiography as an evaluation method for bowel dysfunction in patients with spinal cord injury (SCI). Methods Forty-four patients with SCI were recruited. Patients were interviewed about their clinical symptoms, and the constipation score and Bristol stool form scale were assessed. The colon transit time (CTT) was measured by using radio-opaque markers (Kolomark). The degree of stool retention and the presence of megacolon or megarectum were evaluated using plain abdominal radiographs. We examined the relationship between clinical aspects and CTT and plain abdominal radiography. Results The constipation scores ranged from 1 to 13, and the average was 4.19±3.11, and the Bristol stool form scale ranged from 1 to 6, with an average of 4.13±1.45. CTTs were 19.3±16.17, 19.3±13.45, 15.32±13.15, and 52.42±19.14 in the right, left, rectosigmoid, and total colon. Starreveld scores were 3.4±0.7, 1.8±0.86, 2.83±0.82, 2.14±1, and 10.19±2.45 in the ascending, transverse, descending, rectosigmoid, and total colon. Leech scores were 3.28±0.7, 2.8±0.8, 2.35±0.85, and 8.45±1.83 in the right, left, rectosigmoid, and total colon. The number of patients with megacolon and megarectum was 14 (31.8%) and 11 (25%). There were statistically significant correlations between the total CTT and constipation score (p<0.05), and Starreveld and Leech scores (p<0.05). Significant correlations were observed between each segmental CTT and the segmental stool retention score (p<0.05). Conclusion Plain abdominal radiography is useful as a convenient and simple method of evaluation of bowel dysfunction in patients with SCI. PMID:24020036

Park, Hyun Joon; Noh, Se Eung; Kim, Gang Deuk



Characterization of Digestive Involvement in Patients with Chronic T. cruzi Infection in Barcelona, Spain  

PubMed Central

Background Digestive damage due to Chagas disease (CD) occurs in 15–20% of patients diagnosed as a result of peristaltic dysfunction in some endemic areas. The symptoms of chronic digestive CD are non-specific, and there are numerous confounders. Diagnosis of CD may easily be missed if symptoms are not evaluated by a well trained physician. Regular tests, as barium contrast examinations, probably lack the necessary sensitivity to detect early digestive damage. Methods 71 individuals with T. cruzi infection (G1) and 18 without (G2) coming from Latin American countries were analyzed. They were asked for clinical and epidemiological data, changes in dietary habits, and history targeting digestive and cardiac CD symptoms. Serological tests for T. cruzi, barium swallow, barium enema, an urea breath test, and esophageal manometry were requested for all patients. Principal findings G1 and G2 patients did not show differences in lifestyle and past history. Fifteen (21.1%) of G1 had digestive involvement. Following Rezende criteria, esophagopathy was observed in 8 patients in G1 (11.3%) and in none of those in G2. Manometry disorders were recorded in 34 G1 patients and in six in G2. Isolated hypotensive lower esophageal sphincter (LES) was found in sixteen G1 patients (23.9%) and four G2 patients (28.8%). Achalasia was observed in two G1 patients. Among G1 patients, ineffective esophageal motility was seen in six (five with symptoms), diffuse esophageal spasm in two (one with dysphagia and regurgitation), and nutcracker esophagus in three (all with symptoms). There were six patients with hypertonic upper esophageal sphincter (UES) among G1. Following Ximenes criteria, megacolon was found in ten G1 patients (13.9%), and in none of the G2 patients. Conclusions The prevalence of digestive chronic CD in our series was 21.1%. Dysphagia is a non-pathognomonic symptom of CD, but a good marker of early esophageal involvement. Manometry could be a useful diagnostic test in selected cases, mainly in patients with T. cruzi infection and dysphagia in whose situation barium swallow does not evidence alterations. Constipation is a common but non-specific symptom that can be easily managed. Testing for CD is mandatory in a patient from Latin America with constipation or dysphagia, and if diagnosis is confirmed, megacolon and esophageal involvement should be investigated. PMID:25144648

Pinazo, María-Jesús; Lacima, Gloria; Elizalde, José-Ignacio; Posada, Elizabeth-Jesús; Gimeno, Fausto; Aldasoro, Edelweiss; Valls, María-Eugenia; Gascon, Joaquim



Current treatment of ulcerative colitis  

PubMed Central

Ulcerative colitis (UC) is a chronic disease featuring recurrent inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complications of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-? antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice-orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis. PMID:21912469

Meier, Johannes; Sturm, Andreas



Acute abdominal complications following hip surgery.  


Hip surgeries are some of the most common and successful orthopedic procedures. Although rarely, abdominal complications do occur and are associated with unfavorable outcomes.We aimed to identify and describe the severe abdominal complications that appear in patients under-going elective or traumatic hip surgery. A four year retrospective electronic database research identified 408 elective primary hip replacements,51 hip revisions and 1040 intra and extracapsular proximal femur fractures. Out of these, three males and 4 females between 64 - 84 years old were identified to have developed acute abdominal complications: perforated acute ulcer (3),acute cholecystitis (2), volvulus (1), toxic megacolon with peritonitis (1) and acute colonic pseudo-obstruction (1).Complications debuted 3 - 10 days after index orthopedic surgery. Acute perioperative abdominal complications are rarely encountered during orthopedic surgery. When these do occur, they do so almost exclusively in patients with hippathology, comorbidities and most often lead to life threatening situations. We thus emphasize the need for early identification and appropriate management by both orthopedic and general surgery doctors in order to improve patient safety. PMID:24742414

Deleanu, B; Prejbeanu, R; Vermesan, D; Haragus, H; Icma, I; Predescu, V



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. PMID:23824374

Carroll, Karen C.



The history of pediatric surgery in France.  


In 1741, Nicolas Andry, counsellor of King Louis XV, published a book about "orthopedics," inventing this word. The book is interesting as the author refers to beliefs and habits of the time. In 1864, Guersant published Notes About Pediatric Surgery, a real textbook which was translated into English and German and dealt with the importance of children's psychological training, anesthesia, and water or mother's milk after the operation, and also described tracheotomy, draining of cervical adenitis, and lithotrity. The classification of bone affections was still very confused. Tuberculosis and syphilis have an important place; hypospadias is not treated by surgery. In 1905, Froehlich published Pediatric Surgery Studies dealing exclusively with visceral surgery and demonstrating progress compared to Guersant's study. In 1906, Kirmisson published Pediatric Surgical Textbook, containing the first discussion of radiology and the description of the pathology of the omphalomesenteric duct and of other congenital malformations. Osteomyelitis was given its proper name, and cervical fistulas were explained. In 1914, A. Broca achieved further progress describing treatments of megacolon, intussusception, and the operation of Fredet Ramstedt. The book by Ombredanne, already out of date at the time of its publication, showed that he was not aware of the wartime, progress achieved by Ladd and Gross in the USA. French publications have diminished since then, and French pediatric surgery is still trying to find a precise identity. PMID:3095887

Prévot, J



Mapping of panda plumage color locus on the microsatellite linkage map of the Japanese quail  

PubMed Central

Background Panda (s) is an autosomal recessive mutation, which displays overall white plumage color with spots of wild-type plumage in the Japanese quail (Coturnix japonica). In a previous study, the s locus was included in the same linkage group as serum albumin (Alb) and vitamin-D binding protein (GC) which are mapped on chicken (Gallus gallus) chromosome 4 (GGA4). In this study, we mapped the s locus on the microsatellite linkage map of the Japanese quail by linkage analysis. Results Segregation data on the s locus were obtained from three-generation families (n = 106). Two microsatellite markers derived from the Japanese quail chromosome 4 (CJA04) and three microsatellite markers derived from GGA4 were genotyped in the three-generation families. We mapped the s locus between GUJ0026 and ABR0544 on CJA04. By comparative mapping with chicken, this locus was mapped between 10.0 Mb and 14.5 Mb region on GGA4. In this region, the endothelin receptor B subtype 2 gene (EDNRB2), an avian-specific paralog of the mammalian endothelin receptor B gene (EDNRB), is located. Because EDNRB is responsible for aganglionic megacolon and spot coat color in mouse, rat and equine, EDNRB2 is suggested to be a candidate gene for the s locus. Conclusion The s locus and the five microsatellite markers were mapped on CJA04 of the Japanese quail. EDNRB2 was suggested to be a candidate gene for the s locus. PMID:16405738

Miwa, Mitsuru; Inoue-Murayama, Miho; Kobayashi, Naoki; Kayang, Boniface Baboreka; Mizutani, Makoto; Takahashi, Hideaki; Ito, Shin'ichi



Fine Structure Mapping and Deletion Analysis of the Murine Piebald Locus  

PubMed Central

piebald (s) is a recessive mutation that affects the development of two cell types of neural crest origin: the 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. PMID:8138159

Metallinos, D. L.; Oppenheimer, A. J.; Rinchik, E. M.; Russell, L. B.; Dietrich, W.; Tilghman, S. M.



Fine structure mapping and deletion analysis of the murine piebald locus.  


piebald (s) is a recessive mutation that affects the development of two cell types of neural crest origin: the 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. PMID:8138159

Metallinos, D L; Oppenheimer, A J; Rinchik, E M; Russell, L B; Dietrich, W; Tilghman, S M



Molecular characterization of four induced alleles at the Ednrb?locus  

PubMed Central

The piebald locus on mouse chromosome 14 encodes the endothelin-B receptor (EDNRB), a G protein-coupled, seven-transmembrane domain protein, which is required for neural crest-derived melanocyte and enteric neuron development. A spontaneous null allele of Ednrb results in homozygous mice that are predominantly white and die as juveniles from megacolon. To identify the important domains for EDNRB function, four recessive juvenile lethal alleles created by either radiation or chemical mutagens (Ednrb27Pub, Ednrb17FrS, Ednrb1Chlc, and Ednrb3Chlo) were examined at the molecular level. Ednrb27Pub mice harbor a mutation at a critical proline residue in the fifth transmembrane domain of the EDNRB protein. A gross genomic alteration within the Ednrb gene in Ednrb3Chlo results in the production of aberrantly sized transcripts and no authentic Ednrb mRNA. Ednrb17FrS mice exhibited a decreased level of Ednrb mRNA, supporting previous observations that the degree of spotting in piebald mice is dependent on the amount of EDNRB expressed. Finally, no molecular defect was detected in Ednrb1Chlc mice, which produce normal levels of Ednrb mRNA in adult brain, suggesting that the mutation affects important regulatory elements that mediate the expression of the gene during development. PMID:9371807

Shin, Myung K.; Russell, Liane B.; Tilghman, Shirley M.



Biologics in the management of ulcerative colitis – comparative safety and efficacy of TNF-? antagonists  

PubMed Central

Ulcerative colitis can cause debilitating symptoms and complications such as colonic strictures, colonic dysplasia, colorectal cancer, and toxic megacolon or perforation. Goals of treatment in ulcerative colitis include resolution of gastrointestinal symptoms, healing of colonic mucosa, and prevention of disease complications. Our treatment armamentarium has expanded dramatically over the past 10 years, and we now have multiple biologic agents approved for the treatment of moderate-severe disease, in addition to conventional therapies such as 5-aminosalicylates, thiopurines, and corticosteroids. In this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-?) inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab. All three agents are effective for inducing and maintaining clinical response and remission in patients with ulcerative colitis, and they have comparable safety profiles. There are no head-to-head trials comparing their efficacy, and the choice of agent is most often based on insurance coverage, route of administration, and patient preference. Combination therapy with an immunomodulator is proven to be more effective than anti-TNF monotherapy, and patients who lose response to an anti-TNF agent should undergo dose intensification in order to regain clinical response. Despite therapeutic optimization, a significant percentage of patients will not achieve clinical remission with anti-TNF agents, and so newer therapies are on the horizon. PMID:25609972

Fausel, Rebecca; Afzali, Anita



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


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

Reissmann, Monika; Ludwig, Arne



The thyroid and the gut.  


Thyroid disease is common, and its effects on the gastrointestinal system are protean, affecting most hollow organs. Hashimoto disease, the most common cause of hypothyroidism, may be associated with an esophageal motility disorder presenting as dysphagia or heartburn. Dyspepsia, nausea, or vomiting may be due to delayed gastric emptying. Abdominal discomfort, flatulence, and bloating occur in those with bacterial overgrowth and improve with antibiotics. Reduced acid production may be due to autoimmune gastritis or low gastrin levels. Constipation may result from diminished motility, leading to an ileus, megacolon, or rarely pseudoobstruction. Ascites in myxedema is characterized by a high protein concentration. Graves' disease accounts for 60% to 80% of thyrotoxicosis. Hyperthyroidism is accompanied by normal gastric emptying with low acid production, partly due to an autoimmune gastritis with hypergastrinemia. Transit time from mouth to cecum is accelerated, resulting in diarrhea. Steatorrhea is due to hyperphagia and stimulation of the adrenergic system. Diarrhea in medullary carcinoma of the thyroid (MCT) may be due to elevated calcitonin, prostaglandins, or 5-hydroxyindoleacetic acid. Ileal or colonic function may be abnormal. The esophagus may be compressed by benign processes, but more often by malignancies. MRI and CT scans are the best diagnostic modalities. The gastrointestinal manifestations of thyroid disease are generally due to reduced motility in hypothyroidism, increased motility in hyperthyroidism, autoimmune gastritis, or esophageal compression by a thyroid process. Symptoms usually resolve with treatment of the thyroid disease. PMID:20351569

Ebert, Ellen C



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. PMID:25075296

Mijatovic, Dino; Blagaic, Ana; Zupan, Zeljko



Transgenic mice overexpressing the mouse homoeobox-containing gene Hox-1.4 exhibit abnormal gut development.  


The mouse homoeobox-containing genes exhibit temporally and spatially specific patterns of expression in embryonic and adult tissues and are thought to be important in regulation of development and cellular differentiation, perhaps by mechanisms analogous to homoeotic genes in Drosophila melanogaster. There has been no direct demonstration that expression of these mammalian genes can affect developmental processes, however. Hox-1.4, like other mouse homoeobox-containing genes, has been shown to be expressed in specific regions of the mid-gestation embryo, but is unique in that its highest level of expression in the adult animal is restricted to developing male germ cells. We have introduced a construct carrying the mouse Hox-1.4 gene into the germ line of mice to begin to identify the cis-acting elements required for proper expression and to assess the consequences of increasing Hox-1.4 gene expression. The construct was designed to produce normal Hox-1.4 protein from transcripts that are distinguishable from the products of the endogenous gene. The integrated transgene seemed to exhibit the appropriate tissue specificity of expression, but transcript levels were elevated in certain tissues, particularly the embryonic gut. This overexpression correlated with changes in the normal developmental program of the gut, resulting in an inherited abnormal phenotype known as megacolon. PMID:2563568

Wolgemuth, D J; Behringer, R R; Mostoller, M P; Brinster, R L; Palmiter, R D



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. PMID:24676665

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



Surveillance snapshot of Clostridium difficile infection in hospitals across Queensland detects binary toxin producing ribotype UK 244.  


In North America and Europe, the binary toxin positive Clostridium difficile strains of the ribotypes 027 and 078 have been associated with death, toxic megacolon and other adverse outcomes. Following an increase in C. difficile infections (CDIs) in Queensland, a prevalence study involving 175 hospitals was undertaken in early 2012, identifying 168 cases of CDI over a 2 month period. Patient demographics and clinical characteristics were recorded, and C. difficile isolates were ribotyped and tested for the presence of binary toxin genes. Most patients (106/168, 63.1%) were aged over 60 years. Overall, 98 (58.3%) developed symptoms after hospitalisation; 89 cases (53.0%) developed symptoms more than 48 hours after admission. Furthermore, 27 of the 62 (67.7%) patients who developed symptoms in the community ad been hospitalised within the last 3 months. Thirteen of the 168 (7.7%) cases identified had severe disease, resulting in admission to the Intensive Care Unit or death within 30 days of the onset of symptoms. The 3 most common ribotypes isolated were UK 002 (22.9%), UK 014 (13.3%) and the binary toxin-positive ribotype UK 244 (8.4%). The only other binary toxin positive ribotype isolated was UK 078 (n = 1). Of concern was the detection of the binary toxin positive ribotype UK 244, which has recently been described in other parts of Australia and New Zealand. No isolates were of the international epidemic clone of ribotype UK 027, although ribotype UK 244 is genetically related to this clone. Further studies are required to track the epidemiology of ribotype UK 244 in Australia and New Zealand. Commun Dis Intell 2014;38(4):E279-E284. PMID:25631588

Huber, Charlotte A; Hall, Lisa; Foster, Nikki F; Gray, Mareeka; Allen, Michelle; Richardson, Leisha J; Robson, Jennifer; Vohra, Renu; Schlebusch, Sanmarie; George, Narelle; Nimmo, Graeme R; Riley, Thomas V; Paterson, David L



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


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; Antiñolo, Guillermo



Analysis of human chromosome 21 for a locus conferring susceptibility to Hirschsprung Disease  

SciTech Connect

It has been estimated that approximately 5% of patients diagnosed with Hirschsprung disease (HSCR), or aganglionic megacolon, have trisomy 21. Since the incidence of Hirschsprung disease is 1/5000 live births and the incidence of trisomy 21 is approximately 1/1000 live births, the observed occurrence of HSCR in trisomy 21 is fifty times higher than expected. We propose that at least one locus on chromosome 21 predisposes to HSCR. Although at fifty times elevated risk, only 1% of Down Syndrome cases have HSCR. Thus additional genes or genetic events are necessary for HSCR to manifest in patients with trisomy 21. Based on segregation analysis, Badner et al. postulated that recessive genes may be responsible for up to 80% of HSCR. We postulate that at least one such gene is on chromosome 21 and increased homozygosity for common recessive HSCR mutations may be one cause for the elevated risk of HSCR in cases of trisomy 21. To map such a chromosome 21 locus, we are searching for segments of human chromosome 21 which are identical by descent from the parent in whom non-disjunction occurred. These segments will arise either from meiosis I (followed by a crossover between the centromere and the locus) or from meiosis II (followed by no crossovers). Nine nuclear families with a proband diagnosed with HSCR and Down Syndrome have been genotyped for 18 microsatellite markers spanning human chromosome 21q. In all nine cases analyzed thus far, trisomy 21 resulted from maternal non-disjunction at meiosis I. At this point no single IBD region is apparent. Therefore, additional families are being ascertained and additional markers at high density are being genotyped to map the HSCR locus.

Bolk, S.; Duggan, D.J.; Chakravarti, A. [Case Western Reserve Univ., Cleveland, OH (United States)



A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection.  


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 in the background of immunodeficiency. This includes patients with human immunodeficiency virus infection as well as patients receiving immunosuppressive therapy for organ transplant. Currently, only two drugs are approved for the treatment of Chagas' disease, nifurtimox and benznidazole. Both have significant limitations due to common and serious side effects as well as limited availability. A promising group of new drug leads for Chagas' disease is cysteine protease inhibitors targeting cruzain, the major protease of T. cruzi. The inhibitor N-methyl-Pip-F-homoF-vinyl sulfonyl phenyl (N-methyl-Pip-F-hF-VS phi) is in late-stage preclinical development. Therefore, the question arose as to whether protease inhibitors targeting cruzain would have efficacy in Chagas' disease occurring in the background of immunodeficiency. To address this question, we studied the course of infection in recombinase-deficient (Rag1(-/-)) and normal mice infected with T. cruzi. Infections localized to heart and skeletal muscle in untreated normal animals, while untreated Rag1(-/-) mice showed severe infection in all organs and predominantly in liver and spleen. Treatment with the dipeptide N-methyl-Pip-F-hF-VS phi rescued immunodeficient animals from lethal Chagas' infection. The majority (60 to 100%) of inhibitor-treated Rag1(-/-) mice had increased survival, negative PCR, and normal tissues by histopathological examination. PMID:17698625

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



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. PMID:19412548

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



Disrupted SOX10 function causes spongiform neurodegeneration in gray tremor mice.  


Mice homozygous for the gray tremor (gt) mutation have a pleiotropic phenotype that includes pigmentation defects, megacolon, whole body tremors, sporadic seizures, hypo- and dys-myelination of the central nervous system (CNS) and peripheral nervous system, vacuolation of the CNS, and early death. Vacuolation similar to that caused by prions was originally reported to be transmissible, but subsequent studies showed the inherited disease was not infectious. The gt mutation mapped to distal mouse chromosome 15, to the same region as Sox10, which encodes a transcription factor with essential roles in neural crest survival and differentiation. As dominant mutations in mouse or human SOX10 cause white spotting and intestinal aganglionosis, we screened the Sox10 coding region for mutations in gt/gt DNA. An adenosine to guanine transversion was identified in exon 2 that changes a highly conserved glutamic acid residue in the SOX10 DNA binding domain to glycine. This mutant allele was not seen in wildtype mice, including the related GT/Le strain, and failed to complement a Sox10 null allele. Gene expression analysis revealed significant down-regulation of genes involved in myelin lipid biosynthesis pathways in gt/gt brains. Knockout mice for some of these genes develop CNS vacuolation and/or myelination defects, suggesting that their down-regulation may contribute to these phenotypes in gt mutants and could underlie the neurological phenotypes associated with peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease, caused by mutations in human SOX10. PMID:25399070

Anderson, Sarah R; Lee, Inyoul; Ebeling, Christine; Stephenson, Dennis A; Schweitzer, Kelsey M; Baxter, David; Moon, Tara M; LaPierre, Sarah; Jaques, Benjamin; Silvius, Derek; Wegner, Michael; Hood, Leroy E; Carlson, George; Gunn, Teresa M



Well-adjusted children: an alternate view of children with inflammatory bowel disease and functional gastrointestinal complaints.  


Previous studies have suggested impaired psychosocial adjustment in children and adolescents with inflammatory bowel disease (IBD). We examined 62 subjects referred to a regional Pediatric Gastroenterology Clinic with IBD or functional gastrointestinal (FGI) complaints. Characteristics of the clinic include a unified team approach, regularly scheduled appointments at 3-month intervals, proactive medical care emphasizing maintenance of full functioning, and close medical-surgical interaction (joint clinics). A research assistant administered a questionnaire regarding children's perceptions of their illness, as well as the Child Depression Inventory (CDI), the Piers-Harris (PH) test of self-concept, and the Child Behaviour Checklist (CBCL). The 36 children with IBD (25 Crohn's disease, 11 ulcerative colitis, mean age 13.3 +/- 3.0 years) were compared with 26 patients with FGI complaints (16 recurrent abdominal pain, 10 functional megacolon, mean age 11.4 +/- 2.8 years). The scores on the standardized tests were not clinically significant for either group. In comparison, however, children with IBD were less depressed and had fewer behaviour problems than the FGI group. Surprisingly, only 19% (7 of 36) of children with IBD described their illness as a problem to them, compared with 65% (17 of 26) of children with FGI symptoms. The latter children also considered themselves significantly sicker than did those with IBD. We conclude that normal psychosocial adjustment is possible in pediatric patients with IBD. We speculate that this group benefitted from the professional supports that our clinic specifically provides to patients with IBD. The FGI group may have suffered from a lack of such professional supports, as well as from the absence of a specific diagnosis. PMID:10701143

Gold, N; Issenman, R; Roberts, J; Watt, S



Gastrointestinal problems at high altitude.  


Gastrointestinal (GI) problems at high altitude are commonplace. The manifestations differ considerably in short-term visitors, long-term residents and native highlanders. Ethnic food habits and social norms also play a role in causing GI dysfuntion. Symptoms like nausea and vomiting are common manifestations of acute mountain sickness and are seen in 81.4% short-term visitors like mountaineers. Anorexia is almost universal and has a mutifactorial causation including effect of hormones like leptin and cholecystokinin and also due to hypoxia itself. Dyspepsia and flatulence are other common symptoms. Diarrhoea, often related to poor hygiene and sanitation is also frequently seen especially among the short-term visitors. Peptic ulceration and upper gastro-intestinal haemorrhage are reported to be common in native highlanders in the' Peruvian Andes (9.6/10000 population per year) and also from Ladakh in India. A hig h incidence o f gastriccarcinoma is also reported, especially from Bolivia (138.2 cases per 10000 population per year). Megacolon and sigmoid volvulus are common lower GI disorders at high altitude. The latter accounted for 79% of all intestinal obstructions at a Bolivian hospital. Thrombosis of the portosystemic vascultature and splenic hematomas has been reported from India. Malnutrition is multifactorial and mainly due to hypoxia. Fat malabsorption is probably significant only at altitudes > 5000m. Neonatal hyperbilirubinemia was found to be four times more common in babies born at high altitude in Colorado than at sea level. Gall stones disease is common in Peruvian highlands. A high seroprevalence of antibodies to H pylori (95%) has been found in Ladakh but its correlation to the prevalence of upper gastro-intestinal disease has not been proven. PMID:17542291

Anand, A C; Sashindran, V K; Mohan, Latika



[Ejaculatory system cysts: a case report.  


Introduction: Male pelvic floor cysts are a rare clinical entity that include: Wolffian duct remnants, Müllerian duct remnants, cysts of the seminal vesicles, prostate and ejaculatory duct/vas deferens cysts.?Case report: We report the clinical case of a 21-year-old male patient with a history of previous surgery in childhood and more precisely: partial colectomy for congenital megacolon, removal of dysplastic right kidney and subsequent surgical adhesiolysis for bowel obstruction.?At 17, the patient was submitted to MRI for groin pain with an incidental finding of a cystic mass at the level of the right seminal vesicle. Consequently, a TUR-ED was performed at another urology unit, for a suspected seminal vesicle ectasia, without resolution of pain symptoms. The patient was referred to us for persistent genitourinary infections, ejaculation disorder and episodes of gross hematuria. An additional MRI confirmed the presence of a cystic mass of 5,5 cm with a suspected opening into prostatic urethra. Urethrocystoscopy and urethrocystography retrograde confirmed this anatomical communication. For the persistence of the symptoms we performed retropubic surgical exeresis of the mass, with a histopathological finding of benign cyst of the vas deferens.?Two major postoperative complications were reported: a pelvic hematoma that required surgical exploration and a urinary extravasation at the level of prostatic urethra, which resolved with prolonged urethral catheterization.?Conclusions: Male pelvic floor cysts are a rare disease with a complex clinical and therapeutic management. A correct diagnosis is based on clinical signs and symptoms together with imaging studies of the pelvic region. The high risk of erectile dysfunction and ejaculatory disorders correlated to a surgical approach, recommend a treatment of these lesions only for symptomatic cases. PMID:24665031

Moretti, Matteo; Facchini, Francesco; Grande, Marco; Larosa, Michelangelo; Leone, Marco; Ziglioli, Francesco; Carlinfante, Gabriele; Pozzoli, Gian Luigi; Frattini, Antonio



Internal obturator muscle transposition for treatment of perineal hernia in dogs: 34 cases (1998-2012).  


Objective-To evaluate the outcome of dogs with perineal hernia treated with transposition of the internal obturator muscle. Design-Retrospective case series. Animals-34 dogs. Procedures-Medical records of dogs with perineal hernia surgically treated from 1998 to 2012 were reviewed. Diagnostic methods and surgical techniques were recorded. Dogs were assigned preoperative and postoperative clinical sign scores. Complication and recurrence rates were evaluated over time. Risk factors were determined. Results-Median follow-up time was 345 days (range, 22 to 1,423 days). Complications were observed in 10 dogs. Tenesmus (n = 9), dyschezia (7), fecal impaction (3), stranguria (4), hematochezia (2), urinary incontinence (2), diarrhea (1), urinary tract infection (1), and megacolon (1) occurred following surgery. Bladder retroflexion at the time of initial evaluation or surgery was not a risk factor for complication (hazard ratio, 1.72). One year after surgery, 51.2% dogs were free of complications. Three dogs developed a perineal hernia on the contralateral side between 35 and 95 days after surgery. The 1-year recurrence rate was 27.4%. Median time for recurrence was 28 days after surgery (range, 2 to 364 days). Postoperative tenesmus was a risk factor for the development of recurrence (hazard ratio, 2.29). Conclusions and Clinical Relevance-Internal obturator muscle transposition was used for primary repair of perineal hernia in dogs. Recurrence was recorded as long as 1 year after surgery. Tenesmus was a risk factor for the development of recurrence after treatment of perineal hernia with internal obturator muscle transposition. PMID:25587732

Shaughnessy, Magen; Monnet, Eric



Clostridium difficile associated infection, diarrhea and colitis  

PubMed Central

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



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. PMID:23933118

Thakker, Rajesh V.



Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis).  


Chagas' disease (American trypanosomiasis) is an endemic parasitic disease in some areas of Latin America. About 16-18 million persons are infected with the aetiological agent of the disease, Trypanosoma cruzi, and more than 100 million are living at risk of infection. There are different modes of infection: (1) via blood sucking vector insects infected with T. cruzi, accounting for 80-90% of transmission of the disease; (2) via blood transfusion or congenital transmission, accounting for 0.5-8% of transmission; (3) other less common forms of infection, eg, from infected food or drinks or via infected organs used in transplants. The acute phase of the disease can last from weeks to months and typically is asymptomatic or associated with fever and other mild nonspecific manifestations. However, life-threatening myocarditis or meningoencephalitis can occur during the acute phase. The death rate for persons in this phase is about 10%. Approximately 10-50% of the survivors develop chronic Chagas' disease, which is characterized by potentially lethal cardiopathy and megacolon or megaoesophagus. There are two drugs available for the aetiological treatment of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Nfx is a nitrofurane and Bz is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is widely accepted. However, their use in the treatment of the chronic phase is controversial. The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The most frequent adverse effects observed in the use of Nfx are: anorexia, loss of weight, psychic alterations, excitability, sleepiness, digestive manifestations such as nausea or vomiting, and occasionally intestinal colic and diarrhoea. In the case of Bz, skin manifestations are the most notorious (e.g., hypersensitivity, dermatitis with cutaneous eruptions, generalized oedema, fever, lymphoadenopathy, articular and muscular pain), with depression of bone marrow, thrombocytopenic purpura and agranulocytosis being the more severe manifestations. Experimental toxicity studies with Nfx evidenced neurotoxicity, testicular damage, ovarian toxicity, and deleterious effects in adrenal, colon, oesophageal and mammary tissue. In the case of Bz, deleterious effects were observed in adrenals, colon and oesophagus. Bz also inhibits the metabolism of several xenobiotics biotransformed by the cytochrome P450 system and its reactive metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and were shown to be tumorigenic or carcinogenic in some studies. The toxic side effects of both nitroheterocyclic derivatives require enzymatic reduction of their nitro group. Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved. PMID:16937919

Castro, José A; de Mecca, Maria Montalto; Bartel, Laura C