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Sample records for megacolon

  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. Chagasic megacolon: enteric neurons and related structures.

    PubMed

    Jabari, Samir; de Oliveira, Enio C; Brehmer, Axel; da Silveira, Alexandre B M

    2014-09-01

    Megacolon, the irreversible dilation of a colonic segment, is a structural sign associated with various gastrointestinal disorders. In its hereditary, secondary form (e.g. in Hirschsprung's disease), dilation occurs in an originally healthy colonic segment due to an anally located, aganglionic zone. In contrast, in chronic Chagas' disease, the dilated segment itself displays pathohistological changes, and the earliest and most prominent being found was massive loss of myenteric neurons. This neuron loss was partial and selective, i.e. some neurons containing neuronal nitric oxide synthase and/or vasoactive intestinal peptide (VIP) were spared from neuron death. This disproportionate survival of inhibitory neurons, however, did not completely correlate with the calibre change along the surgically removed, megacolonic segments. A better correlation was observed as to potentially contractile muscle tissue elements and the interstitial cells of Cajal. Therefore, the decreased densities of ?-smooth muscle actin- and c-kit-immunoreactive profiles were estimated along resected megacolonic segments. Their lowest values were observed in the megacolonic zones itself, whereas less pronounced decreases were found in the non-dilated, transitional zones (oral and anal to dilation). In contrast to the myenteric plexus, the submucosal plexus displayed only a moderate neuron loss. Neurons co-immunoreactive for VIP and calretinin survived disproportionately. As a consequence, these neurons may have contributed to maintain the epithelial barrier and allowed the chagasic patients to survive for decades, despite their severe disturbance of colonic motility. Due to its neuroprotective and neuroeffectory functions, VIP may play a key role in the development and duration of chagasic megacolon. PMID:25059649

  3. Ultrastructural and Histochemical Studies of Murine Megacolon

    PubMed Central

    Bolande, Robert P.; Towler, William F.

    1972-01-01

    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

  4. Partial, selective survival of nitrergic neurons in chagasic megacolon.

    PubMed

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

    2011-01-01

    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. PMID:21184236

  5. Partial, selective survival of nitrergic neurons in chagasic megacolon

    PubMed Central

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

    2010-01-01

    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. PMID:21184236

  6. Toxic megacolon complicating Escherichia coli O157 infection.

    PubMed

    Nayar, Deepa M; Vetrivel, Shanmu; McElroy, Jack; Pai, Pearl; Koerner, Roland J

    2006-04-01

    Toxic megacolon is a well known complication in inflammatory bowel disease such as ulcerative colitis or Crohn's disease. The development of toxic megacolon as a complication of infectious colitis is rare. However it is recognised as a complication of enteric infections caused by Clostridium difficile, Campylobacter jejuni, Shigella, Salmonella species, Cytomegalovirus and amoebae. We describe a case of necrotising haemorrhagic ileo-colitis in a previously fit and healthy young adult female caused by Escherichia coli O157 where toxic megacolon developed as a complication along with hemolytic uremic syndrome (HUS). PMID:16126276

  7. Myxedema megacolon after external neck irradiation

    SciTech Connect

    Borrie, M.J.; Cape, R.D.; Troster, M.M.; Fung, S.T.

    1983-04-01

    Myxedema megacolon is a rare manifestation of hypothyroidism. It may respond to appropriate treatment but is sometimes irreversible, resulting in fatal complications. Two possible mechanisms to explain the colonic atony include (1) myxomatous infiltration of the submucosa with separation of the muscular fibers from the ganglia of Auerbach's plexus, and (2) severe autonomic neuropathy affecting the extrinsic nerves to the colon and the myenteric plexus. Histology from our case supports the first proposed mechanism. Urecholine challenge and manometric measure response may help predict reversibility of colonic atony. Treatment should be individualized and should include factors such as age, duration of symptoms, and other medical illness. Low-dose oral or intravenous triiodothyronine is effective. Hypothyroidism following external radiation of the neck for lymphoma is not uncommon, and the risk increases following one or more lymphangiograms. Such patients should be followed up with regular TSH estimations for at least three years.

  8. [Megas and cancer. Cancer of the large intestine in chagasic patients with megacolon].

    PubMed

    Meneses, A C; Lopes, M A; Rocha, A; Fatureto, M C; Lopes, G P; Lopes, E R; Chapadeiro, E

    1989-01-01

    This is a review of 4.690 necropsies and 24.209 surgical pathology specimens describing the association between megacolon chagasic and malignant tumors of the large bowel. The prevalence of malignant tumors of the large bowel was not higher in megacolon. PMID:2513795

  9. Toxic megacolon complicating a Clostridium difficile infection in a pregnant woman.

    PubMed

    Candiotto, Alberto; Pascoli, Irene; Gritti, Alessandra; Busato, Enrico; Dal Pozzo, Giuseppe

    2010-01-01

    Clostridium difficile infection (CDI) in non-hospitalized patients has been reported with increased frequency, whereas an association between CDI and pregnancy has not been highlighted. We report a case of toxic megacolon complicating a severe CDI during the second trimester of pregnancy in a patient without traditional risk factors, such as antibiotic use, immunodeficiency, and prolonged and recent hospitalization. PMID:19745034

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

    PubMed Central

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

    2013-01-01

    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. PMID:24163654

  11. Fecal Transplant for Treatment of Toxic Megacolon Associated With Clostridium Difficile Colitis in a Patient With Duchenne Muscular Dystrophy.

    PubMed

    Yu, Shipeng; Abdelkarim, Ahmed; Nawras, Ali; Hinch, Bryan Thomas; Mbaso, Chimaka; Valavoor, Shahul; Safi, Fadi; Hammersley, Jeffrey; Tang, Jianlin; Assaly, Ragheb

    2016-01-01

    Clostridium difficile (C diff) colitis infection is the most common cause of nosocomial infectious diarrhea and the prevalence is increasing worldwide. Toxic megacolon is a severe complication of C diff colitis associated with high mortality. Gastrointestinal (GI) comorbidity and impaired smooth muscle contraction are risk factors for the development of C diff-associated toxic megacolon. We present a case of fulminant C diff colitis with toxic megacolon in a patient with Duchenne muscular dystrophy (DMD) in the intensive care unit. C diff colitis was diagnosed by clinical presentation and positive C diff DNA amplification test (polymerase chain reaction). The impairment of GI tract due to DMD predisposes these patients to severe C diff infection and toxic megacolon, as observed in this case report. For the same reason, the recovery of GI function in these patients can be prolonged. While surgery was conducted for relieving the pressure from toxic megacolon, fecal microbiota transplantation through colonoscopy resulted in successful resolution of the C diff symptoms, although the recovery is prolonged due to DMD. PMID:24858336

  12. Recurrent severe gastrointestinal bleeding and malabsorption due to extensive habitual megacolon

    PubMed Central

    Mecklenburg, Ingo; Leibig, Markus; Weber, Christof; Schmidbauer, Stefan; Folwaczny, Christian

    2005-01-01

    Dilatation of the colon and the rectum, which is not attributable to aganglionosis, is a rare finding and can be the result of intractable chronic constipation. We report a rare case of a 29-year-old male patient with impressive megacolon, in whom Hirschsprung’s or Chagas disease was ruled out. In the present case, dilatation of the colon was most likely due to a behavioral disorder with habitual failure of defecation. Chronic stool retention led to a bizarre bulging of the large bowel with displacement of the other abdominal organs and severe occult blood loss. Because of two episodes of life-threatening gastrointestinal bleeding despite conventional treatment of constipation, a surgical approach for bowel restoration was necessary. Temporary loop ileostomy had to be performed for depressurization of the large bowel and the subsequent possibility for effective antegrade colonic lavage to remove impacted stools. Shortly after the operation, the patient was healthy and could easily manage the handling of the ileostomy. However, the course of the megacolon in this young adult cannot be predicted and the follow-up will have to reveal if regression of this extreme colonic distension with reestablishment of regular rectal perception will occur. PMID:16437700

  13. Treating congenital megacolon by transplanting GDNF and GFRα-1 double genetically modified rat bone marrow mesenchymal stem cells.

    PubMed

    Zhou, C B; Peng, C H; Pang, W B; Zhang, D; Chen, Y J

    2015-01-01

    We studied the survival and gene expression of glial cell line-derived neurotrophic factor (GDNF) and GDNF receptor α-1 (GFRα-1) double-genetically modified rat bone marrow mesenchymal stem cells (BMSCs) transplanted into the intestinal walls of the rat models with congenital megacolon and determine the feasibility of treatment by transplantation of double-genetically modified rat BMSCs. The rat colorectal intestinal wall nerve plexus was treated with the cationic surface active agent benzalkonium chloride to establish an experimental megacolon model. The rat target genes GDNF and GFRα-1 were extracted and ligated into pEGFP-N1. Eukaryotic fluorescent expression vectors carrying the GDNF and GFRα-1 genes were transfected into BMSCs by in vitro culture. We treated congenital megacolon by transplanting double-genetically modified rat bone marrow mesenchymal stem cells. The pEGFP-EGFP-GDNF-GFRα-1 double-gene co-expressing the eukaryotic expression plasmid vector was successfully established. Protein gene protein 9.5 and vasoactive intestinal peptide-positive ganglion cells showed no positive expression in the phosphate-buffered saline transplantation group based on an immunofluorescence test at 1, 2, and 4 weeks after transplantation of BMSCs. Additionally, compared with the phosphate-buffered saline transplantation group, the expression of rearranged during transfection, GDNF, and GFRα-1 mRNA in the stem cell transplantation group increased gradually. The double-genetically modified BMSCs colonized and survived in the intestinal wall of the experimental megacolon rat model and expressed related genes, partially recovering the colonic neuromuscular regulatory functions and thus providing an experimental basis for treating congenital megacolon by cellular transplantation. PMID:26345878

  14. Minimally invasive approach to chagasic megacolon: laparoscopic rectosigmoidectomy with posterior end-to-side low colorectal anastomosis.

    PubMed

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

    2014-06-01

    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

  15. Could the complications of megacolon be avoided by monitoring the risk patients? cases report.

    PubMed

    Toro, A; Cappello, G; Mannino, M; Di Carlo, I

    2014-01-01

    We report 2 cases of megacolon associated with cerebrovascular accident and neuropsychiatric drug consumption. Case report 1: a 75-year-old woman with diabetes mellitus, hypertension, tachycardia with atrial fibrillation, bilateral pleural effusions and previous cerebral hemorrhage was admitted in our hospital. She presented clouded sensorium and abdominal distension, with closed alvus. The CT scan showed a distension of the colon, with severe fecal impaction. A volvulus of the sigma was found at surgical intervention.Case report 2: a 59-year-old man with a medical history of oligophrenia was admitted to our hospital for acute abdomen.He presented stupor and closed alvus with abdominal distension. The abdominal CT scan showed a dolichosigma, with fecal impaction. The patient was submitted to a laparotomy and a two millimetres perforation of the sigma was found.The sigma had a diameter of 28 cm and a length of 75 cm.Even if a clear correlation has not been found yet, anomalies of the regulation of the gastro-intestinal motility can occur at different levels in patients with psychiatric or cerebrovascular diseases and drug consumption with anticholinergic properties,and they should be carefully monitored. The purpose is an early diagnosis of colon function anomalies in order to avoid potentially fatal complications. PMID:25149623

  16. Induction of potentially lethal hypermagnesemia, ischemic colitis, and toxic megacolon by a preoperative mechanical bowel preparation: report of a case.

    PubMed

    Sugiyama, Masahiko; Kusumoto, Eiji; Ota, Mitsuhiko; Kimura, Yasue; Tsutsumi, Norifumi; Oki, Eiji; Sakaguchi, Yoshihisa; Kusumoto, Tetsuya; Ikejiri, Koji; Maehara, Yoshihiko

    2016-12-01

    A 67-year-old man was diagnosed with rectal cancer. The tumor invaded the subserosal layer, but it was not large, and there was no sign of obstruction. Neo-adjuvant chemotherapy reduced the size of the tumor. The patient was admitted to our hospital for surgery. For mechanical bowel preparation, he ingested 34 g of magnesium citrate (Magcorol P®), but then developed severe shock, a disturbance of consciousness, and acidemia, and he required catecholamines and mechanical ventilation. X-ray, CT, and laboratory tests revealed ischemic colitis, toxic megacolon, and hypermagnesemia (16.3 mg/dL). After 2 days of temporary hemodialysis and an enema to reduce his blood magnesium concentration, he recovered and left the intensive care unit. However, the left side of his colon had suffered ischemic damage and become irreversibly atrophied. One month later, he underwent laparoscopic abdominoperineal resection and left-side colectomy for the rectal cancer and severe ischemic colitis of the left side of the colon. Histopathology confirmed the rectal cancer with a grade 2 chemotherapeutic effect and severe ischemic colitis of the left side of the colon. Hence, the present case suggests that severe ischemic colitis, toxic megacolon, and hypermagnesemia can occur after taking a magnesium laxative without obstruction of the intestine. PMID:26943694

  17. BLOOD VESSELS IN GANGLIA IN HUMAN ESOPHAGUS MIGHT EXPLAIN THE HIGHER FREQUENCY OF MEGAESOPHAGUS COMPARED WITH MEGACOLON

    PubMed Central

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

    2014-01-01

    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

  18. Male-Biased Aganglionic Megacolon in the TashT Mouse Line Due to Perturbation of Silencer Elements in a Large Gene Desert of Chromosome 10

    PubMed Central

    Touré, Aboubacrine M.; Béland, Mélanie; Raiwet, Diana L.; Silversides, David W.; Pilon, Nicolas

    2015-01-01

    Neural crest cells (NCC) are a transient migratory cell population that generates diverse cell types such as neurons and glia of the enteric nervous system (ENS). Via an insertional mutation screen for loci affecting NCC development in mice, we identified one line—named TashT—that displays a partially penetrant aganglionic megacolon phenotype in a strong male-biased manner. Interestingly, this phenotype is highly reminiscent of human Hirschsprung’s disease, a neurocristopathy with a still unexplained male sex bias. In contrast to the megacolon phenotype, colonic aganglionosis is almost fully penetrant in homozygous TashT animals. The sex bias in megacolon expressivity can be explained by the fact that the male ENS ends, on average, around a “tipping point” of minimal colonic ganglionosis while the female ENS ends, on average, just beyond it. Detailed analysis of embryonic intestines revealed that aganglionosis in homozygous TashT animals is due to slower migration of enteric NCC. The TashT insertional mutation is localized in a gene desert containing multiple highly conserved elements that exhibit repressive activity in reporter assays. RNAseq analyses and 3C assays revealed that the TashT insertion results, at least in part, in NCC-specific relief of repression of the uncharacterized gene Fam162b; an outcome independently confirmed via transient transgenesis. The transcriptional signature of enteric NCC from homozygous TashT embryos is also characterized by the deregulation of genes encoding members of the most important signaling pathways for ENS formation—Gdnf/Ret and Edn3/Ednrb—and, intriguingly, the downregulation of specific subsets of X-linked genes. In conclusion, this study not only allowed the identification of Fam162b coding and regulatory sequences as novel candidate loci for Hirschsprung’s disease but also provides important new insights into its male sex bias. PMID:25786024

  19. The KIT gene is associated with the english spotting coat color locus and congenital megacolon in Checkered Giant rabbits (Oryctolagus cuniculus).

    PubMed

    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

    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

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

    PubMed Central

    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

    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 (θ = 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

  1. Perianal neuroendocrine tumor with suspected lymph node metastasis causing colonic compression and subsequent megacolon

    PubMed Central

    Joudrey, Scott D.; Robinson, Duane A.; Blair, Robert; McLaughlin, Leslie D.; Gaschen, Lorrie

    2015-01-01

    An 8-year-old spayed female domestic shorthair cat was presented with a 4- to 5-month history of a progressively growing mass above her anus and an inability to defecate for 3 to 4 wk. External perianal and internal regional masses were subsequently identified and diagnosed as tumors of neuroendocrine origin through surgical excision and histopathologic evaluation. The cat was treated with 2 courses of chemotherapy and radiation therapy. PMID:25750442

  2. [Prevalence of visceromegalies in necropsies carried out in Triângulo Mineiro from 1954 to 1988].

    PubMed

    Lopes, E R; Rocha, A; Meneses, A C; Lopes, M A; Fatureto, M C; Lopes, G P; Chapadeiro, E

    1989-01-01

    One thousand seven hundred and eight chronic chagasic post-mortem examinations studied from a total of 4690 autopsies performed at our Institution. Two hundred and seventy-three chagasic had megas. Megacolon was the most frequent, followed by megaesophagus. Megacolon associated with megaesophagus was the third most common finding. Our data are discussed and compared with the literature. Megacolon and megaesophagus were more prevalent in man, as shown by other workers. Higher parasitemia perhaps could explain this finding. PMID:2518668

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

    SciTech Connect

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

    1984-08-01

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

  4. Mucosal layers and related nerve fibres in non-chagasic and chagasic human colon--a quantitative immunohistochemical study.

    PubMed

    Jabari, Samir; da Silveira, Alexandre B M; de Oliveira, Enio C; Quint, Karl; Wirries, André; Neuhuber, Winfried; Brehmer, Axel

    2014-10-01

    Chagasic megacolon is accompanied by extensive myenteric and, simultaneously, moderate submucosal neuron loss. Here, we examined changes of the innervation pattern of the lamina propria (LP) and muscularis mucosae (MM). Two alternating sets of cryosections were taken from seven non-chagasic colonic and seven chagasic megacolonic specimens (the latter included both the dilated megacolonic and the non-dilated transitional oral and anal zones) and were immunohistochemically triple-stained for smooth-muscle actin (SMA), synaptophysin (SYN) and glial acid protein S100 and, alternatively, for SMA, vasoactive intestinal peptide (VIP) and somatostatin (SOM). Subsequent image analysis and statistical evaluation of nervous tissue profile areas revealed that, in LP, the most extreme differences (i.e. increase in thickness or decrease in nerve, glia and muscle tissue profile area, respectively) compared with control values occurred in the dilated megacolonic zone itself. In contrast, the most extreme differences in the MM were in the anal-to-megacolonic zone (except the profile area of muscle tissue, which was lowest in the megacolonic zone). This parallels our previous results in the external muscle coat. A partial and selective survival of VIP-immunoreactive in contrast to SOM-immunoreactive nerve fibres was observed in both mucosal layers investigated. Thus, VIPergic nerve elements might be crucial for the maintenance of the mucosal barrier. The differential changes of neural tissue parameters in LP and MM might reflect a multifactorial rather than a pure neurogenic development of megacolon in chronic Chagas' disease. PMID:24962547

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

    PubMed Central

    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

    2010-01-01

    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

  6. Strategies for the Care of Adults Hospitalized for Active Ulcerative Colitis

    PubMed Central

    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

    2014-01-01

    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

  7. A case of giant fecaloma in a 24-year-old woman.

    PubMed

    Zurabishvili, K; Rekhviashvili, A; Sakhamberidze, M; Tsiklauri, K

    2015-03-01

    Chronic constipation is a very common complaint at outpatient clinics. It can progress to fecal impaction, and rarely to fecalomas if not managed promptly. Fecaloma is characterized by a hardened large mass of feces frequently localized in sigmoid colon and rectum and is difficult to discharge. Fecaliths, stagnating and hardening by time, may cause intestinal obstruction,ulcer development and colonic wall perforation. We present the case of a 24-year-old woman who admitted to our hospital with complaints of severe constipation with 1 bowel movement every third-fifth day with passage of hard stools only with using laxatives and meteorism. This is a rare case of fecalomas and megacolon, when conservative measures were absolutely ineffective and surgical treatment was needed. Therefore, diagnosis of fecaloma must be considered in patients presenting with chronic constipation and abdominal mass.Further investigations are mandatory to delineate guidelines for clinical management of megacolon especially in women of childbearing age. PMID:25879551

  8. [Motility disorders of the colon].

    PubMed

    Müller-Lissner, S

    2015-06-01

    The motility of the colon is modulated by the enteric nervous system. It is very complex, governing backward and forward movements of the feces. Primary megacolon and megarectum are clinically diverse. Megacolon refractory to laxative treatment may be subject to colectomy, while megarectum should be treated by consistent laxation. Acute colonic pseudo-obstruction may occur with severe systemic diseases and electrolyte disturbances or it may be postoperatively and/or medically induced. A small proportion of chronically constipated patients suffer from slow transit constipation, others from disordered defecation. In the remaining patients no objective cause of the complaints may be found. In slow transit constipation, propulsive colonic motility is disturbed, dietary fiber is ineffective, and the response to bisacodyl is blunted. Pelvic floor dyssynergia is characterized by a voluntary (although unconscious) contraction of the anal sphincter simultaneously with the abdominal muscles. It can be treated by avoiding straining and by sphincter training. PMID:25940144

  9. Selective survival of calretinin- and vasoactive-intestinal-peptide-containing nerve elements in human chagasic submucosa and mucosa.

    PubMed

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

    2012-08-01

    Chronic Chagas' disease is frequently characterized by massive myenteric neuron loss resulting in megacolon with severely and irreversibly disturbed motility. Here, we focused on two submucosal neuron populations, immunoreactive for calretinin (CALR) or somatostatin (SOM), and their respective mucosal nerve fibres in chagasic megacolon. Surgically removed megacolonic segments of seven chagasic patients were compared with seven age- and region-matched non-chagasic control segments. Evaluation included immunohistochemical triple-staining of cryosections for CALR, SOM and peripherin or for CALR and vasoactive intestinal peptide (VIP) and of submucosal whole-mounts for CALR, SOM and the pan-neuronal marker anti-HuC/D. Submucosal neuron counts in chagasic tissue revealed neuron numbers reduced to 51.2 % of control values. In cryosections, nerve fibre area measurements revealed 8.6 % nerve fibre per mucosal area in control segments, but this value decreased to 1.5 % in megacolonic segments. In both evaluations, a disproportionate decrease of SOM-reactive nerve elements was observed. The proportions of SOM-positive neurons related to the total neuron number declined to 2 % (control 10 %) and the proportion of SOM-reactive mucosal nerve fibres related to the whole mucosal area to 0.014 % (control 1.8 %)in chagasic tissue. The second set of cryosections revealed extensive colocalization of CALR with VIP in both surviving submucosal perikarya and mucosal nerve fibres. We suggest that VIP, a neuroprotective and neuroeffectory peptide typically contained in submucosal neurons, allows both the VIP-containing neurons to endure and the patients to survive by maintaining their mucosal barrier, despite the almost complete loss of colonic motility for decades. PMID:22555304

  10. Quantitative evaluation of neurons in the mucosal plexus of adult human intestines.

    PubMed

    Kramer, Kerstin; da Silveira, Alexandre B M; Jabari, Samir; Kressel, Michael; Raab, Marion; Brehmer, Axel

    2011-07-01

    The consequence of presence versus absence of mucosal neurons is not consistently assessed. Here, we addressed two questions. First, based on resected gut specimens of 65 patients/body donors suffering from different diseases, counts of mucosal neurons per mm(2) were analysed with respect to age, gender and region. Second, we evaluated resected megacolonic specimens of four patients suffering from chronic Chagas' disease. Mucosal wholemounts were triple-stained for calretinin (CALR), peripherin (PER) and human neuronal protein Hu C/D (HU). Counts revealed no clear correlation between the presence of mucosal neurons and age, gender or region. Mucosal neurons were present in 30 of 36 specimens derived from males (83%) and in 20 of 29 from females (69%). The numbers per mm(2) increased from duodenum to ileum (1.7-10.8) and from ascending to sigmoid colon (3.2-9.9). Out of 149 small intestinal mucosal neurons, 47% were co-reactive for CALR, PER and HU (large intestine: 76% of 300 neurons) and 48% for PER and HU only (large intestine: 23%). In 12 megacolonic specimens (each 3 from 4 patients), all 23 mucosal neurons found (1.9 per mm(2)) displayed co-reactivity for CALR, PER and HU. We suggest that the presence or the absence of mucosal neurons is variable, ongoing studies will address our assumption that they correspond in their morphochemical characteristics to submucosal neurons. Furthermore, both the architecture and neuron number of the megacolonic mucosal plexus displayed no dramatic changes indicating that mucosal nerves might be less involved in chagasic/megacolonic neurodegeneration as known from the myenteric plexus. PMID:21461752

  11. Ichthyosis, deafness, and Hirschsprung's disease.

    PubMed

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

    1989-03-01

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

  12. Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection

    NASA Astrophysics Data System (ADS)

    Surawicz, Christina M.

    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.

  13. Functional Aerophagia in Children: A Frequent, Atypical Disorder

    PubMed Central

    Morabito, Giuliana; Romeo, Claudia; Romano, Claudio

    2014-01-01

    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

  14. Clostridium difficile colitis in solid organ transplantation--a single-center experience.

    TOXLINE Toxicology Bibliographic Information

    Stelzmueller I; Goegele H; Biebl M; Wiesmayr S; Berger N; Tabarelli W; Ruttmann E; Albright J; Margreiter R; Fille M; Bonatti H

    2007-11-01

    Clostridium difficile (CD) is one of the most common causes of diarrhea in solid organ transplantation (SOT). Between 1996 and 2005, a total of 2474 solid organ transplants were performed at our institution, of which 43 patients developed CD-associated diarrhea. There were 3 lung, 3 heart, 20 liver, 8 kidney-pancreas, 6 kidney, 1 composite tissue, and 2 multivisceral recipients. Onset of CD infection ranged from 5 to 2453 days posttransplant. All patients presented with abdominal pain and watery diarrhea. Toxins A and B were detected using rapid immunoassay or enzyme immunoassay. Treatment consisted of reduction of immunosuppression, fluid and electrolyte replacement, metronidazole (n=20), oral vancomycin (n=20), and a combination of metronidazole and vancomycin (n=2). Toxic megacolon was seen in five patients. Two of them had colonoscopic decompression, and the remaining three required colonic resection. One of these patients died due to multiorgan failure after cured CD enteritis. The remaining patients were discharged with well-functioning grafts and all are currently alive. CD colitis was a rare complication prior to 2000; 38 of the 43 cases occurred thereafter. We conclude that CD colitis represents a severe complication following SOT. Recently, a dramatic increase in the incidence of this complication has been observed. The development of life-threatening toxic megacolon must be considered in solid organ recipients.

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

    PubMed Central

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

    2014-01-01

    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

  16. Fulminant ulcerative colitis in a healthy pregnant woman

    PubMed Central

    Orabona, Rossana; Valcamonico, Adriana; Salemme, Marianna; Manenti, Stefania; Tiberio, Guido AM; Frusca, Tiziana

    2015-01-01

    This case report concerns a 25-year-old patient with 6-7 bloody stools/d, abdominal pain, tachycardia, and weight loss occurring during the third trimester of pregnancy. Severe ulcerative colitis complicated by toxic megacolon and gravidic sepsis was diagnosed by clinical evaluation, colonoscopy, and rectal biopsy that were performed safely without risk for the mother or baby. The patient underwent a cesarean section at 28+6 wk gestation. The baby was transferred to the neonatal intensive care unit of our hospital and survived without complications. Fulminant colitis was managed conservatively by combined colonoscopic decompression and medical treatment. Although current European guidelines describe toxic megacolon as an indication for emergency surgery for both pregnant and non-pregnant women, thanks to careful monitoring, endoscopic decompression, and intensive medical therapy with nutritional support, we prevented the woman from having to undergo emergency pancolectomy. Our report seems to suggest that conservative management may be a helpful tool in preventing pancolectomy if the patient’s condition improves quickly. Otherwise, surgery is mandatory. PMID:26019473

  17. A unique strain of community-acquired Clostridium difficile in severe complicated infection and death of a young adult

    PubMed Central

    2013-01-01

    Background Clostridium difficile is the major cause of nosocomial antibiotic-associated diarrhoea with the potential risk of progressing to severe clinical outcomes including death. It is not unusual for Clostridium difficile infection to progress to complications of toxic megacolon, bowel perforation and even Gram-negative sepsis following pathological changes in the intestinal mucosa. These complications are however less commonly seen in community-acquired Clostridium difficile infection than in hospital-acquired Clostridium difficile infection. To the best of our knowledge, this was the first case of community-acquired Clostridium difficile infection of its type seen in Jamaica. Case presentation We report a case of a 22-year-old female university student who was admitted to the University Hospital of the West Indies, Jamaica with a presumptive diagnosis of pseudomembranous colitis PMC. She presented with a 5-day history of diarrhoea following clindamycin treatment for coverage of a tooth extraction due to a dental abscess. Her clinical condition deteriorated and progressed from diarrhoea to toxic megacolon, bowel perforation and Gram-negative sepsis. Clostridium difficile NAP12/ribotype 087 was isolated from her stool while blood cultures grew Klebsiella pneumoniae. Despite initial treatment intervention with empiric therapy of metronidazole and antibiotic clearance of Klebsiella pneumoniae from the blood, the patient died within 10 days of hospital admission. Conclusions We believe that clindamycin used for coverage of a dental abscess was an independent risk factor that initiated the disruption of the bowel micro-flora, resulting in overgrowth of Clostridium difficile NAP12/ribotype 087. This uncommon strain, which is the same ribotype (087) as ATCC 43255, was apparently responsible for the increased severity of the infection and death following toxic megacolon, bowel perforation and pseudomembranous colitis involving the entire large bowel. K. pneumoniae sepsis, resolved by antibiotic therapy was secondary to Clostridium difficile infection. The case registers community-acquired Clostridium difficile infection as producing serious complications similar to hospital-acquired Clostridium difficile infection and should be treated with the requisite importance. PMID:23815405

  18. [Total colonic form of Hirschsprung disease. Treatment and long-term follow-up in 16 cases].

    PubMed

    Azzis, O; Fremond, B; Dabadie, A; Jouan, J; Bracq, H; Babut, J M

    1996-01-01

    From 1971 to 1994, 16 cases of total colon Hirschsprung's disease were treated at the University Hospital in Rennes. Diagnosis have been at 2 days to 3 months. Two children had a family history of Hirschsprung disease among which one associated megacolon and multiple endocrine neoplasia. This family had a mutation of the RET proto oncogene. Six children died before complete surgical cure, among whom 4 before total parenteral nutrition. Six were treated according to Lester Martin, 3 according to Duhamel, and 1 to Swenson. Diarrhea and occlusions happened during the first postoperative years. None had any enterocolitis. Eight of 9 followed children are continent. Technique had no influence on long term outcome. Early neonatal occlusion management seems to decrease enterocolitis's incidence. We abandoned Lester's technique and kept Duhamel's technique. The problems encountered during ileostomy period do not encourage us to forward the age of definitive surgery procedure. PMID:8945832

  19. [Surgical treatment of ulcerous colitis].

    PubMed

    Labas, P; Jablonický, S; Michalko, L; Svec, R; Huorka, M

    1995-03-01

    Ulcerative colitis, being a typical medical disease, is encountered by the surgeon only in the stage of toxic megacolon or in case of sever complications during conservative treatment such as perforation, haemorrhage or obstruction. The authors operated six young women where they performed as the only choice total proctocolectomy with formation of an ileal reservoir which was sutured to the rectum stripped of the mucosa. Despite the serious condition at the time of operation, the patients survive the operation, although the percentage of postoperative complications is high, with the exception of one patient who died on the 126th day after operation. The remainder survive in a fair condition with complete and continence. PMID:7761948

  20. Fulminant primary manifestation of Crohn's colitis "Hot Crohn's disease".

    PubMed

    Heise, W; Kersten, O; Kassner, K M; Birkenmeyer, G; Grosse, G; Niedobitek, F

    1997-06-01

    Following the very short course of a disease with watery diarrhea, fever, nausea, meteorism and a severe feeling of general illness, a 22-year-old patient was diagnosed as having a toxic megacolon, and a subtotal colectomy was carried out. The postoperative progression was uncomplicated and the patient recovered quickly. The examination of the operation specimen revealed a serious ulcerous colitis with relative omission of the rectum and the distal sigmoid colon. After critical evaluation of the histological findings, it was judged to be a fulminant Crohn's colitis and, for the purposes of differential diagnosis, differentiated from ulcerative colitis and colitis indeterminate. The formal pathogenesis of the inflammatory-ulcerous processes is discussed, in particular with regard to the activation of the macrophages and the very short anamnesis in a clinically established primary manifestation of the disease. PMID:9231992

  1. Slow-transit Constipation.

    PubMed

    Bharucha, Adil E.; Philips, Sidney F.

    2001-08-01

    Idiopathic slow-transit constipation is a clinical syndrome predominantly affecting women, characterized by intractable constipation and delayed colonic transit. This syndrome is attributed to disordered colonic motor function. The disorder spans a spectrum of variable severity, ranging from patients who have relatively mild delays in transit but are otherwise indistinguishable from irritable bowel syndrome to patients with colonic inertia or chronic megacolon. The diagnosis is made after excluding colonic obstruction, metabolic disorders (hypothyroidism, hypercalcemia), drug-induced constipation, and pelvic floor dysfunction (as discussed by Wald ). Most patients are treated with one or more pharmacologic agents, including dietary fiber supplementation, saline laxatives (milk of magnesia), osmotic agents (lactulose, sorbitol, and polyethylene glycol 3350), and stimulant laxatives (bisacodyl and glycerol). A subtotal colectomy is effective and occasionally is indicated for patients with medically refractory, severe slow-transit constipation, provided pelvic floor dysfunction has been excluded or treated. PMID:11469989

  2. Antioxidant therapy for treatment of inflammatory bowel disease: Does it work?

    PubMed Central

    Moura, Fabiana Andréa; de Andrade, Kívia Queiroz; dos Santos, Juliana Célia Farias; Araújo, Orlando Roberto Pimentel; Goulart, Marília Oliveira Fonseca

    2015-01-01

    Oxidative stress (OS) is considered as one of the etiologic factors involved in several signals and symptoms of inflammatory bowel diseases (IBD) that include diarrhea, toxic megacolon and abdominal pain. This systematic review discusses approaches, challenges and perspectives into the use of nontraditional antioxidant therapy on IBD, including natural and synthetic compounds in both human and animal models. One hundred and thirty four papers were identified, of which only four were evaluated in humans. Some of the challenges identified in this review can shed light on this fact: lack of standardization of OS biomarkers, absence of safety data and clinical trials for the chemicals and biological molecules, as well as the fact that most of the compounds were not repeatedly tested in several situations, including acute and chronic colitis. This review hopes to stimulate researchers to become more involved in this fruitful area, to warrant investigation of novel, alternative and efficacious antioxidant-based therapies. PMID:26520808

  3. Paralytic ileus following "subcutaneous bortezomib" therapy: focus on the clinical emergency-report of two cases.

    PubMed

    Mele, Giuseppe; Coppi, Maria Rosaria; Melpignano, Angela; Quarta, Giovanni

    2016-02-01

    We retrospectively analyzed the medical history of 19 elderly myeloma patients treated with the "novel subcutaneous formulation of bortezomib." In our experience, two patients (10 %) discontinued treatment for paralytic ileus. The exact pathogenetic mechanisms of toxic megacolon and paralytic ileus due to "novel subcutaneous formulation of bortezomib" are unclear. Probably, it may be related to possible damage of the autonomic nerve fibers that control organ functions. Adequate prevention and management of the gastrointestinal (GI) toxicities with the use of fluid intake and prokinetic and laxative drugs (at least two types of agents in a suboptimal dose) especially in patients with risk factors for GI side effects (anti-myeloma novel agents, opioids or antiemetics, iron supplements, spinal and cord compression, immobility, history of constipation) can decrease the possibility of interruption of administration of drug and increase adherence to treatment. Clearly this complication must be borne in mind whenever a patient develops acute abdominal pain and distension. PMID:25600700

  4. Antioxidant therapy for treatment of inflammatory bowel disease: Does it work?

    PubMed

    Moura, Fabiana Andréa; de Andrade, Kívia Queiroz; dos Santos, Juliana Célia Farias; Araújo, Orlando Roberto Pimentel; Goulart, Marília Oliveira Fonseca

    2015-12-01

    Oxidative stress (OS) is considered as one of the etiologic factors involved in several signals and symptoms of inflammatory bowel diseases (IBD) that include diarrhea, toxic megacolon and abdominal pain. This systematic review discusses approaches, challenges and perspectives into the use of nontraditional antioxidant therapy on IBD, including natural and synthetic compounds in both human and animal models. One hundred and thirty four papers were identified, of which only four were evaluated in humans. Some of the challenges identified in this review can shed light on this fact: lack of standardization of OS biomarkers, absence of safety data and clinical trials for the chemicals and biological molecules, as well as the fact that most of the compounds were not repeatedly tested in several situations, including acute and chronic colitis. This review hopes to stimulate researchers to become more involved in this fruitful area, to warrant investigation of novel, alternative and efficacious antioxidant-based therapies. PMID:26520808

  5. LUMBAR SYMPATHECTOMY BY ELECTROCOAGULATION—Its Use in the Management of Certain Vascular and Visceral Disorders

    PubMed Central

    Raney, R. B.; Raney, Aidan A.; Silver, Harrison E.

    1954-01-01

    Although normally the sympathetic nerves aid vascular dilatation during effort, in certain diseases of the vascular system they have a reverse effect. Abolition of sympathetic vasoconstrictive impulses by sympathectomy is the most effective treatment in some chronic peripheral vascular conditions. The authors have used electrocoagulation for a number of years and found it quick, effective and more likely to prevent regeneration of the affected nerves. Improvement was obtained by sympathectomy in arteriosclerotic vascular insufficiency, thromboangiitis obliterans, Raynaud's disease, reflex sympathetic dystrophy following thrombophlebitis or trauma, scleroderma, spinal sympathetic dystrophy and acquired megacolon. A case of causalgia was aggravated by the operation. Abstention from the use of tobacco appears to be sufficient for control of symptoms in many cases. Since vasospasm is manifested in many conditions long before a thrombotic catastrophe occurs, not only relief of symptoms but prevention of irreversible changes may be achieved by early operation. ImagesFigure 1.Figure 2. PMID:13116029

  6. Chagas disease

    PubMed Central

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

    2006-01-01

    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. PMID:17148699

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

    SciTech Connect

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

    2010-04-15

    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.

  8. Neuroendocrine disorders of the gut.

    PubMed Central

    Yee, L F; Mulvihill, S J

    1995-01-01

    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. PMID:8533409

  9. [Consensus document for the detection and management of Chagas disease in primary health care in a non-endemic areas].

    PubMed

    Roca Saumell, Carme; Soriano-Arandes, Antoni; Solsona Díaz, Lluís; Gascón Brustenga, Joaquim

    2015-05-01

    Chagas disease is caused by the protozoan Trypanosoma cruzi. Although it is commonly transmitted by an insect vector in continental Latin-America, in recent decades, due migration, has been diagnosed in other countries such Spain, the European country with a largest immigrant population of Latin American. For a long time, the patient remains asymptomatic, but some years after this stage, the symptoms can be serious (dilated cardiomyopathy, megacolon, megaesophagus). In addition, detection in pregnant women has a high priority because of the route of vertical transmission. Several specific guidelines about Chagas disease has been developed on the Banks of blood, maternal hospitals, HIV co-infection, organ transplant. But due to the detection of lack of information to primary care professionals, we consider to will be useful this document written and agreed to by family phisicians, pediatricians and specialists in International Health. PMID:25704793

  10. Nutrition in inflammatory bowel diseases.

    PubMed

    Mihai, C?t?lina; Prelipcean, Cristina Cijevschi; Pintilie, Iulia; Nedelciuc, Otilia; Jigaranu, Anca-Olivia; Dranga, Mihaela; Mihai, B

    2013-01-01

    The relationship between nutrition and inflammatory bowel disease (IBD) is a complex one, the evaluation and correction of nutritional deficits being integral part of therapy in these patients. The diet that consists in excessive consumption of meat, sugar, fats (with a higher 0 6 /o) 3 polyunsaturated fatty acids ratio) are factors involved in the epidemiology and pathogenesis of IBD. Malnutrition is present among most IBD patients, being the result of multiple mechanisms from digestive symptoms to inflammatory process, intestinal resection and administration of medications. Oral diet is high-calorie, high protein at correcting the vitamin and mineral deficiencies. Enteral diet has both an adjuvant role and that of inducing and maintaining remission as single treatment, particularly in children. Parenteral nutrition is reserved for patients with obstruction, fistula, toxic megacolon, short bowel syndrome, severe malabsorption, and other conditions that make enteral nutrition impossible or inefficient. PMID:24502032

  11. Adult Hirschsprung's disease diagnosed during forensic autopsy.

    PubMed

    Chatelain, Denis; Manaouil, Cécile; Marc, Bernard; Ricard, Jannick; Brevet, Marie; Montpellier, Dominique; Defouilloy, Christian; Jardé, Olivier

    2006-09-01

    We report a case of fatal Hirschsprung's disease (HD) discovered at autopsy. A 20-year-old man collapsed at home. Emergency medical personnel found him in cardiac arrest and all resuscitative efforts failed. He had a past history of chronic constipation since infancy. Forensic autopsy revealed a megacolon full of gas and stools. Microscopic examination showed absence of ganglion cells in a short segment of the rectum and enterocolitis in the left and transverse colon. HD is rarely described in adults. In many cases, patients complained of constipation since infancy but the affection remained misdiagnosed. The relative good tolerance of the disease is usually due to a short aganglionic bowel segment. Enterocolitis is a frequent and severe complication of HD in children but is rarely described in adults. This case suggests the importance of HD diagnosis in childhood in order to avoid fatal complications with forensic consequences. PMID:17018101

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

    PubMed Central

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

    2014-01-01

    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

  13. A Novel Mutation in the Endothelin B Receptor Gene in a Moroccan Family with Shah-Waardenburg Syndrome

    PubMed Central

    Doubaj, Yassamine; Pingault, Véronique; Elalaoui, Siham C.; Ratbi, Ilham; Azouz, Mohamed; Zerhouni, Hicham; Ettayebi, Fouad; Sefiani, Abdelaziz

    2015-01-01

    Waardenburg syndrome (WS) is a neurocristopathy disorder combining sensorineural deafness and pigmentary abnormalities. The presence of additional signs defines the 4 subtypes. WS type IV, also called Shah-Waardenburg syndrome (SWS), is characterized by the association with congenital aganglionic megacolon (Hirschsprung disease). To date, 3 causative genes have been related to this congenital disorder. Mutations in the EDNRB and EDN3 genes are responsible for the autosomal recessive form of SWS, whereas SOX10 mutations are inherited in an autosomal dominant manner. We report here the case of a 3-month-old Morrocan girl with WS type IV, born to consanguineous parents. The patient had 3 cousins who died in infancy with the same symptoms. Molecular analysis by Sanger sequencing revealed the presence of a novel homozygous missense mutation c.1133A>G (p.Asn378Ser) in the EDNRB gene. The proband's parents as well as the parents of the deceased cousins are heterozygous carriers of this likely pathogenic mutation. This molecular diagnosis allows us to provide genetic counseling to the family and eventually propose prenatal diagnosis to prevent recurrence of the disease in subsequent pregnancies. PMID:25852447

  14. Hirschsprung’s disease: Historical notes and pathological diagnosis on the occasion of the 100th anniversary of Dr. Harald Hirschsprung’s death

    PubMed Central

    Sergi, Consolato

    2015-01-01

    Hirschsprung’s disease (HSCR) or congenital megacolon is one of the differential diagnoses of chronic constipation mostly in infancy and may indeed represent a challenge for pediatricians, pediatric surgeons, and pediatric pathologists. The diagnosis relies clearly on the identification of the absence of ganglion cells at the plexuses (submucosus and myentericus) of the bowel wall. HSCR is usually located at the terminal (distal) rectum with potential pre-terminal or proximal extension to the less distal large bowel (sigmoid colon). Astonishingly, there is some evidence that Hindu surgeons of prehistoric India may have been exposed and had considerable knowledge about HSCR, but this disease is notoriously and eponymously named to Dr. Harald Hirschsprung (1830-1916), who brilliantly presented two infants with fatal constipation at the Berlin conference of the German Society of Pediatrics more than one century ago. Historical milestones and diagnosis of HSCR (originally called “Die Hirschsprungsche Krankheit”) are reviewed. More than 100 years following his meticulous and broad description, HSCR is still a puzzling disease for both diagnosis and treatment. HSCR remains a critical area of clinical pediatrics and pediatric surgery and an intense area of investigation for both molecular and developmental biologists. PMID:26566484

  15. [Incidence of severe local complications in ulcerative colitis and Crohn disease].

    PubMed

    Schneider, W; Rosahl, W

    1986-10-01

    At the example of the severe and foudroyant courses of the ulcerous colitis in patients who died or underwent a resection (n = 93) the severe local complications are demonstrated. 70 patients with resection of the intestine, 21 patients with diagnostic laparotomy as well as 32 deceased patients with Crohn's disease were compared with them. Transmigration peritonitides (3.3% of 458 patients with ulcerous colitis except haemorrhagic proctitis), perforation peritonitides (2.0%) as well as the toxic megacolon (3.3%) alone or in combination are the most frequent severe complications. Therapy-resistant intestinal haemorrhages (1.1%) are infrequent. In 0.9% of the cases colorectal carcinomata appear. The acute or chronic mechanical ileus is the most frequent complication in Crohn's disease (21.1% of 171 patients altogether). Intraabdominal abscesses are found in 11.7%. In participation of the colon fistulae are nearly twice as frequent as in localisation of the small intestine. Free perforations of the small intestine (3.8%) are more frequently observed than perforations of the colon (2.2%). PMID:3492827

  16. Evaluation and treatment of constipation in infants and children.

    PubMed

    Biggs, Wendy S; Dery, William H

    2006-02-01

    Constipation in children usually is functional and the result of stool retention. However, family physicians must be alert for red flags that may indicate the presence of an uncommon but serious organic cause of constipation, such as Hirschsprung's disease (congenital aganglionic megacolon), pseudo-obstruction, spinal cord abnormality, hypothyroidism, diabetes insipidus, cystic fibrosis, gluten enteropathy, or congenital anorectal malformation. Treatment of functional constipation involves disimpaction using oral or rectal medication. Polyethylene glycol is effective and well tolerated, but a number of alternatives are available. After disimpaction, a maintenance program may be required for months to years because relapse of functional constipation is common. Maintenance medications include mineral oil, lactulose, milk of magnesia, polyethylene glycol powder, and sorbitol. Education of the family and, when possible, the child is instrumental in improving functional constipation. Behavioral education improves response to treatment; biofeedback training does not. Because cow's milk may promote constipation in some children, a trial of withholding milk may be considered. Adding fiber to the diet may improve constipation. Despite treatment, only 50 to 70 percent of children with functional constipation demonstrate long-term improvement. PMID:16477894

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

    PubMed Central

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

    2013-01-01

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

  18. The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

    PubMed Central

    Sun, Xingmin; Hirota, Simon A.

    2014-01-01

    Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

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

    PubMed Central

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

    2012-01-01

    Hirschsprung disease (HSCR, aganglionic megacolon) is a complex and heterogeneous disease with an incidence of 1 in 5000 live births. Despite the multifactorial determination of HSCR in the vast majority of cases, there is a monogenic subgroup for which private rare RET coding sequence mutations with high penetrance are found (45% of HSCR familial cases). An asymmetrical parental origin is observed for RET coding sequence mutations with a higher maternal inheritance. A parent-of-origin effect is usually assumed. Here we show that a differential reproductive rate for males and females also leads to an asymmetrical parental origin, which was never considered as a possible explanation till now. In the case of HSCR, we show a positive association between penetrance of the mutation and parental transmission asymmetry: no parental transmission asymmetry is observed in sporadic RET CDS mutation carrier cases for which penetrance of the mutation is low, whereas a parental transmission asymmetry is observed in affected sib-pairs for which penetrance of the mutation is higher. This allows us to conclude that the explanation for this parental asymmetry is that more severe mutations have resulted in a differential reproductive rate between male and female carriers. PMID:22395866

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

    PubMed

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

    2012-09-01

    Hirschsprung disease (HSCR, aganglionic megacolon) is a complex and heterogeneous disease with an incidence of 1 in 5000 live births. Despite the multifactorial determination of HSCR in the vast majority of cases, there is a monogenic subgroup for which private rare RET coding sequence mutations with high penetrance are found (45% of HSCR familial cases). An asymmetrical parental origin is observed for RET coding sequence mutations with a higher maternal inheritance. A parent-of-origin effect is usually assumed. Here we show that a differential reproductive rate for males and females also leads to an asymmetrical parental origin, which was never considered as a possible explanation till now. In the case of HSCR, we show a positive association between penetrance of the mutation and parental transmission asymmetry: no parental transmission asymmetry is observed in sporadic RET CDS mutation carrier cases for which penetrance of the mutation is low, whereas a parental transmission asymmetry is observed in affected sib-pairs for which penetrance of the mutation is higher. This allows us to conclude that the explanation for this parental asymmetry is that more severe mutations have resulted in a differential reproductive rate between male and female carriers. PMID:22395866

  1. Hirschsprung disease, associated syndromes and genetics: a review.

    PubMed

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

    2008-01-01

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

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

    SciTech Connect

    Angrist, M.; Bolk, S.; Chakravarti, A.

    1994-09-01

    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.

  3. Discovery of LFF571: An Investigational Agent for Clostridium difficile Infection

    SciTech Connect

    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

    2012-11-09

    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.

  4. A novel mutation in the endothelin B receptor gene in a moroccan family with shah-waardenburg syndrome.

    PubMed

    Doubaj, Yassamine; Pingault, Véronique; Elalaoui, Siham C; Ratbi, Ilham; Azouz, Mohamed; Zerhouni, Hicham; Ettayebi, Fouad; Sefiani, Abdelaziz

    2015-02-01

    Waardenburg syndrome (WS) is a neurocristopathy disorder combining sensorineural deafness and pigmentary abnormalities. The presence of additional signs defines the 4 subtypes. WS type IV, also called Shah-Waardenburg syndrome (SWS), is characterized by the association with congenital aganglionic megacolon (Hirschsprung disease). To date, 3 causative genes have been related to this congenital disorder. Mutations in the EDNRB and EDN3 genes are responsible for the autosomal recessive form of SWS, whereas SOX10 mutations are inherited in an autosomal dominant manner. We report here the case of a 3-month-old Morrocan girl with WS type IV, born to consanguineous parents. The patient had 3 cousins who died in infancy with the same symptoms. Molecular analysis by Sanger sequencing revealed the presence of a novel homozygous missense mutation c.1133A>G (p.Asn378Ser) in the EDNRB gene. The proband's parents as well as the parents of the deceased cousins are heterozygous carriers of this likely pathogenic mutation. This molecular diagnosis allows us to provide genetic counseling to the family and eventually propose prenatal diagnosis to prevent recurrence of the disease in subsequent pregnancies. PMID:25852447

  5. Hypoganglionosis in pregnancy: a case report

    PubMed Central

    2012-01-01

    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. PMID:22974065

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

    PubMed Central

    Mijatovic, Dino; Blagaic, Ana; Zupan, Zeljko

    2014-01-01

    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

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

    PubMed Central

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

    2013-01-01

    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

  8. RET promoter variations in familial African degenerative leiomyopathy (ADL): first report of a possible genetic-environmental interaction.

    PubMed

    Van Rensburg, C; Moore, S W; Zaahl, M

    2012-12-01

    African degenerative leiomyopathy (ADL, DL, Bantu pseudo-Hirschsprung's disease) is a distinctive visceral myopathy, of unknown etiology, occurring in Africa. It has a classical clinical and histologic picture in young indigenous African children. It presents as intestinal pseudo-obstruction with a massive megacolon due to degeneration of smooth muscle without aganglionosis. Because of its late presentation and geographical and ethnic distribution, it is thought to be an acquired degenerative hollow visceral myopathy. Only one previous report of familial recurrence exists. The main Hirschsprung susceptibility gene RET is a potential candidate gene in this condition, because of its role in the development of the intrinsic innervation and ganglia of the smooth muscle layers of the gastro-intestinal tract. We report a second case of familial ADL recurrence and explore possible etiologic causes including variations of the RET gene. Multiple variations in the RET promoter were identified in this case which leads to the possibility of a genetic-environmental predisposition for this condition. We therefore hypothesize that RET may play a modulating role in ADL susceptibility (and possibly other visceral myopathies). It is possible that subtle malformations in the ENS may result from RET dysfunction which then predisposes the individual to environmental influences which initiate the later onset of muscle degeneration. PMID:23053599

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

    SciTech Connect

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

    1994-01-01

    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.

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

    PubMed

    Reissmann, Monika; Ludwig, Arne

    2013-01-01

    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

  11. Hirschsprung's disease: Historical notes and pathological diagnosis on the occasion of the 100(th) anniversary of Dr. Harald Hirschsprung's death.

    PubMed

    Sergi, Consolato

    2015-11-01

    Hirschsprung's disease (HSCR) or congenital megacolon is one of the differential diagnoses of chronic constipation mostly in infancy and may indeed represent a challenge for pediatricians, pediatric surgeons, and pediatric pathologists. The diagnosis relies clearly on the identification of the absence of ganglion cells at the plexuses (submucosus and myentericus) of the bowel wall. HSCR is usually located at the terminal (distal) rectum with potential pre-terminal or proximal extension to the less distal large bowel (sigmoid colon). Astonishingly, there is some evidence that Hindu surgeons of prehistoric India may have been exposed and had considerable knowledge about HSCR, but this disease is notoriously and eponymously named to Dr. Harald Hirschsprung (1830-1916), who brilliantly presented two infants with fatal constipation at the Berlin conference of the German Society of Pediatrics more than one century ago. Historical milestones and diagnosis of HSCR (originally called "Die Hirschsprungsche Krankheit") are reviewed. More than 100 years following his meticulous and broad description, HSCR is still a puzzling disease for both diagnosis and treatment. HSCR remains a critical area of clinical pediatrics and pediatric surgery and an intense area of investigation for both molecular and developmental biologists. PMID:26566484

  12. A chicken model of pharmacologically-induced Hirschsprung disease reveals an unexpected role of glucocorticoids in enteric aganglionosis

    PubMed Central

    Gasc, Jean-Marie; Clemessy, Maud; Corvol, Pierre; Kempf, Hervé

    2015-01-01

    The enteric nervous system originates from neural crest cells that migrate in chains as they colonize the embryonic gut, eventually forming the myenteric and submucosal plexus. Failure of the neural crest cells to colonize the gut leads to aganglionosis in the terminal gut, a pathological condition called Hirschsprung disease (HSCR) in humans, also known as congenital megacolon or intestinal aganglionosis. One of the characteristics of the human HSCR is its variable penetrance, which may be attributable to the interaction between genetic factors, such as the endothelin-3/endothelin receptor B pathway, and non-genetic modulators, although the role of the latter has not well been established. We have created a novel HSCR model in the chick embryo allowing to test the ability of non-genetic modifiers to alter the HSCR phenotype. Chick embryos treated by phosphoramidon, which blocks the generation of endothelin-3, failed to develop enteric ganglia in the very distal bowel, characteristic of an HSCR-like phenotype. Administration of dexamethasone influenced the phenotype, suggesting that glucocorticoids may be environmental modulators of the penetrance of the aganglionosis in HSCR disease. PMID:25836673

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

    PubMed Central

    Carroll, Karen C.

    2013-01-01

    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

  14. Deletions at the SOX10 Gene Locus Cause Waardenburg Syndrome Types 2 and 4

    PubMed Central

    Bondurand, Nadege ; Dastot-Le Moal, Florence ; Stanchina, Laure ; Collot, Nathalie ; Baral, Viviane ; Marlin, Sandrine ; Attie-Bitach, Tania ; Giurgea, Irina ; Skopinski, Laurent ; Reardon, William ; Toutain, Annick ; Sarda, Pierre ; Echaieb, Anis ; Lackmy-Port-Lis, Marilyn ; Touraine, Renaud ; Amiel, Jeanne ; Goossens, Michel ; Pingault, Veronique 

    2007-01-01

    Waardenburg syndrome (WS) is an auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. Depending on additional symptoms, WS is classified into four subtypes, WS1–WS4. Absence of additional features characterizes WS2. The association of facial dysmorphic features defines WS1 and WS3, whereas the association with Hirschsprung disease (aganglionic megacolon) characterizes WS4, also called “Waardenburg-Hirschsprung disease.” Mutations within the genes MITF and SNAI2 have been identified in WS2, whereas mutations of EDN3, EDNRB, and SOX10 have been observed in patients with WS4. However, not all cases are explained at the molecular level, which raises the possibility that other genes are involved or that some mutations within the known genes are not detected by commonly used genotyping methods. We used a combination of semiquantitative fluorescent multiplex polymerase chain reaction and fluorescent in situ hybridization to search for SOX10 heterozygous deletions. We describe the first characterization of SOX10 deletions in patients presenting with WS4. We also found SOX10 deletions in WS2 cases, making SOX10 a new gene of WS2. Interestingly, neurological phenotypes reminiscent of that observed in WS4 (PCWH syndrome [peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, WS, and Hirschsprung disease]) were observed in some WS2-affected patients with SOX10 deletions. This study further characterizes the molecular complexity and the close relationship that links the different subtypes of WS. PMID:17999358

  15. Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4.

    PubMed

    Bondurand, Nadege; Dastot-Le Moal, Florence; Stanchina, Laure; Collot, Nathalie; Baral, Viviane; Marlin, Sandrine; Attie-Bitach, Tania; Giurgea, Irina; Skopinski, Laurent; Reardon, William; Toutain, Annick; Sarda, Pierre; Echaieb, Anis; Lackmy-Port-Lis, Marilyn; Touraine, Renaud; Amiel, Jeanne; Goossens, Michel; Pingault, Veronique

    2007-12-01

    Waardenburg syndrome (WS) is an auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. Depending on additional symptoms, WS is classified into four subtypes, WS1-WS4. Absence of additional features characterizes WS2. The association of facial dysmorphic features defines WS1 and WS3, whereas the association with Hirschsprung disease (aganglionic megacolon) characterizes WS4, also called "Waardenburg-Hirschsprung disease." Mutations within the genes MITF and SNAI2 have been identified in WS2, whereas mutations of EDN3, EDNRB, and SOX10 have been observed in patients with WS4. However, not all cases are explained at the molecular level, which raises the possibility that other genes are involved or that some mutations within the known genes are not detected by commonly used genotyping methods. We used a combination of semiquantitative fluorescent multiplex polymerase chain reaction and fluorescent in situ hybridization to search for SOX10 heterozygous deletions. We describe the first characterization of SOX10 deletions in patients presenting with WS4. We also found SOX10 deletions in WS2 cases, making SOX10 a new gene of WS2. Interestingly, neurological phenotypes reminiscent of that observed in WS4 (PCWH syndrome [peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, WS, and Hirschsprung disease]) were observed in some WS2-affected patients with SOX10 deletions. This study further characterizes the molecular complexity and the close relationship that links the different subtypes of WS. PMID:17999358

  16. C620R mutation of the murine ret proto-oncogene: loss of function effect in homozygotes and possible gain of function effect in heterozygotes.

    PubMed

    Yin, Luo; Puliti, Aldamaria; Bonora, Elena; Evangelisti, Cecilia; Conti, Valerio; Tong, Wei-Min; Medard, Jean-Jacques; Lavoué, Marie-France; Forey, Nathalie; Wang, Lily C; Manié, Serge; Morel, Gérard; Raccurt, Mireille; Wang, Zhao-Qi; Romeo, Giovanni

    2007-07-15

    Germline RET mutations are responsible for different inherited disorders: Hirschsprung disease (congenital aganglionic megacolon), caused by loss of function mutations, familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2, caused by gain of function mutations. Intriguingly, some RET mutations, including C620R, are associated with both types of diseases. To investigate the dual role of such RET mutations, a mouse model with a targeted mutation ret(C620R) was generated. ret(C620R/C620R) offspring die during the first postnatal day, and show kidney agenesis and intestinal aganglionosis. Decreased outgrowth of the Ret-positive cells was observed in ret(C620R/C620R) neuronal cell cultures, which is suggestive of an impaired migration, proliferation or survival of the Ret-expressing cells. Electronmicroscopy revealed the absence of membrane-bound Ret in ret(C620R/C620R) cells as compared to ret(+/+) and ret(+/C620R) cells. On the other hand, aged ret(+/C620R) mice develop precancerous lesions in the adrenal gland or in the thyroid. Our results suggest that the ret(C620R) mutation has a loss of function effect in homozygotes and exhibits a dominant gain of function effect with low penetrance causing hyperplasia in heterozygotes. PMID:17372903

  17. Disrupted SOX10 function causes spongiform neurodegeneration in gray tremor mice

    PubMed Central

    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.

    2014-01-01

    Mice homozygous for the gray tremor (gt) mutation have a pleiotropic phenotype that includes pigmentation defects, megacolon, whole body tremors, sporadic seizures, hypo- and dysmyelination of the CNS and PNS, 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 (PCWH) disease, caused by mutations in human SOX10. PMID:25399070

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

    SciTech Connect

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

    1994-09-01

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

  19. Clostridium difficile infection: epidemiology, diagnosis and understanding transmission.

    PubMed

    Martin, Jessica S H; Monaghan, Tanya M; Wilcox, Mark H

    2016-04-01

    Clostridium difficile infection (CDI) continues to affect patients in hospitals and communities worldwide. The spectrum of clinical disease ranges from mild diarrhoea to toxic megacolon, colonic perforation and death. However, this bacterium might also be carried asymptomatically in the gut, potentially leading to 'silent' onward transmission. Modern technologies, such as whole-genome sequencing and multi-locus variable-number tandem-repeat analysis, are helping to track C. difficile transmission across health-care facilities, countries and continents, offering the potential to illuminate previously under-recognized sources of infection. These typing strategies have also demonstrated heterogeneity in terms of CDI incidence and strain types reflecting different stages of epidemic spread. However, comparison of CDI epidemiology, particularly between countries, is challenging due to wide-ranging approaches to sampling and testing. Diagnostic strategies for C. difficile are complicated both by the wide range of bacterial targets and tests available and the need to differentiate between toxin-producing and non-toxigenic strains. Multistep diagnostic algorithms have been recommended to improve sensitivity and specificity. In this Review, we describe the latest advances in the understanding of C. difficile epidemiology, transmission and diagnosis, and discuss the effect of these developments on the clinical management of CDI. PMID:26956066

  20. Clostridium difficile infection among kidney transplant recipients: frequency, clinical presentation, and outcome.

    PubMed

    Lionaki, Sophia; Panagiotellis, Konstantinos; Moris, Demetrios; Daikos, George; Psyhogiou, Mina; Vernadakis, Spiridon; Zavos, Georgios; Boletis, John N

    2015-03-01

    The objective of this study was to evaluate the frequency of Clostridium Difficile Infection (CDI) among kidney transplant recipients and describe the clinical picture in correlation with the presence of certain risk factors. We included kidney transplant recipients with a functioning graft, who were admitted during the period 1/2012-12/2013, and patients with ESRD who were admitted to undergo Kidney Transplantation (KTx) from a deceased or a living donor in the same period. Patients were screened following clinical indication of gastrointestinal infection. CDI diagnosis was based on a positive stool sample for CD toxins and stool culture. Within the period 2012-2013, we recorded 24 cases of CDI in 19 patients, accounting for a frequency of 5.4% of CDI in our population. In addition to diarrhea, 63.15% of the patients presented with fever, 31.25% with anorexia, while abdominal pain was a rare symptom (0.53%). None of the patients had ileus, bowel obstruction or megacolon. Fourteen patients (73.7%) had a history of recent exposure (15 days) to antimicrobial agents prior to the evolution of CDI symptoms. A relapse of the CDI infection was identified in five cases. CDI infection is a significant factor of morbidity in patients with KTx and should be considered in the clinical setting of diarrhea, even in cases with no exposure to antibiotic agents. PMID:25556694

  1. In the Endemic Setting, Clostridium difficile Ribotype 027 Is Virulent But Not Hypervirulent

    PubMed Central

    Aitken, Samuel L.; Alam, M. Jahangir; Khaleduzzaman, Mohammed; Walk, Seth T.; Musick, William L.; Pham, Vy P.; Christensen, Jennifer L.; Atmar, Robert L.; Xie, Yang; Garey, Kevin W.

    2016-01-01

    BACKGROUND Conflicting reports have been published on the association between Clostridium difficile ribotypes and severe disease outcomes in patients with C. difficile infection (CDI); several so-called hypervirulent ribotypes have been described. We performed a multicenter study to assess severe disease presentation and severe outcomes among CDI patients infected with different ribotypes. METHODS Stool samples that tested positive for C. difficile toxin were collected and cultured from patients who presented to any of 7 different hospitals in Houston, Texas (2011–2013). C. difficile was characterized using a fluorescent PCR ribotyping method. Medical records were reviewed to determine clinical characteristics and ribotype association with severe CDI presentation (ie, leukocytosis and/or hypoalbuminemia) and severe CDI outcomes (ie, ICU admission, ileus, toxic megacolon, colectomy, and/or in-hospital death). RESULTS Our study included 715 patients aged 61 ± 18 years (female: 63%; median Charlson comorbidity index: 2.5 ± 2.4; hospital-onset CDI: 45%; severe CDI: 36.7%; severe CDI outcomes: 12.3%). The most common ribotypes were 027, 014-020, FP311, 002, 078-126, and 001. Ribotype 027 was a significant independent predictor of severe disease (adjusted odds ratio [aOR], 2.24; 95% confidence interval [CI], 1.53–3.29; P < .001) and severe CDI outcomes (aOR, 1.71; 95% CI, 1.02–2.85; P = .041) compared with all other ribotypes in aggregate. However, in an analysis using all common ribotypes as individual variables, ribotype 027 was not associated with severe CDI outcomes more often than other ribotypes. CONCLUSION Ribotype 027 showed virulence equal to that of other ribotypes identified in this endemic setting. Clinical severity markers of CDI may be more predictive of severe CDI outcomes than a particular ribotype. PMID:26288985

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

    PubMed

    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

    2014-12-01

    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. PMID:25631588

  3. Long segment and short segment familial Hirschsprung's disease: variable clinical expression at the RET locus.

    PubMed Central

    Edery, P; Pelet, A; Mulligan, L M; Abel, L; Attié, T; Dow, E; Bonneau, D; David, A; Flintoff, W; Jan, D

    1994-01-01

    Hirschsprung's disease (aganglionic megacolon, HSCR) is a frequent condition of unknown origin (1/5000 live births) resulting in intestinal obstruction in neonates and severe constipation in infants and adults. In the majority of cases (80%), the aganglionic tract involves the rectum and the sigmoid colon only (short segment HSCR), while in 20% of cases it extends toward the proximal end of the colon (long segment HSCR). In a previous study, we mapped a gene for long segment familial HSCR to the proximal long arm of chromosome 10 (10q11.2). Further linkage analyses in familial HSCR have suggested tight linkage of the disease gene to the RET protoncogene mapped to chromosome 10q11.2. Recently, nonsense and missense mutations of RET have been identified in HSCR patients. However, the question of whether mutations of the RET gene account for both long segment and short segment familial HSCR remained unanswered. We have performed genetic linkage analyses in 11 long segment HSCR families and eight short segment HSCR families using microsatellite DNA markers of chromosome 10q. In both anatomical forms, tight pairwise linkage with no recombinant events was observed between the RET proto-oncogene locus and the disease locus (Zmax = 2.16 and Zmax = 5.38 for short segment and long segment HSCR respectively at 0 = 0%) Multipoint linkage analyses performed in the two groups showed that the maximum likelihood estimate was at the RET locus. Moreover, we show that point mutations of the RET proto-oncogene occur either in long segment or in short segment HSCR families and we provide evidence for incomplete penetrance of the disease causing mutation. These data suggest that the two anatomical forms of familial HSCR, which have been separated on the basis of clinical and genetic criteria, may be regarded as the variable clinical expression of mutations at the RET locus. PMID:7815416

  4. NAP1 Strain Type Predicts Outcomes from Clostridium difficile Infection

    PubMed Central

    See, Isaac; Mu, Yi; Cohen, Jessica; Beldavs, Zintars G.; Winston, Lisa G.; Dumyati, Ghinwa; Holzbauer, Stacy; Dunn, John; Farley, Monica M.; Lyons, Carol; Johnston, Helen; Phipps, Erin; Perlmutter, Rebecca; Anderson, Lydia; Gerding, Dale N.; Lessa, Fernanda C.

    2015-01-01

    Background Studies conflict regarding the importance of the fluoroquinolone-resistant North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) outcome. We describe strain types causing CDI and evaluate their association with patient outcomes. Methods CDI cases were identified from population-based surveillance. Multivariate regression models were used to evaluate the associations of strain type with severe disease (ileus, toxic megacolon, or pseudomembranous colitis within 5 days; or white blood cell count ?15,000/mm3 within one day of positive test), severe outcome (intensive care unit admission after positive test, colectomy for C. difficile infection, or death within 30 days of positive test), and death within 14 days of positive test. Results Strain typing results were available for 2,057 cases. Severe disease occurred in 363 (17.7%) cases, severe outcome in 100 (4.9%), and death within 14 days in 56 (2.7%). The most common strain types were NAP1 (28.4%), NAP4 (10.2%) and NAP11 (9.1%). In unadjusted analysis, NAP1 was associated with greater odds of severe disease than other strains. After controlling for patient risk factors, healthcare exposure, and antibiotic use, NAP1 was associated with severe disease (adjusted odds ratio [aOR] 1.74, 95% confidence interval [CI], 1.36–2.22), severe outcome (aOR 1.66, 95% CI, 1.09–2.54), and death within 14 days (aOR 2.12, 95% CI, 1.22–3.68). Conclusion NAP1 was the most prevalent strain and a predictor of severe disease, severe outcome, and death. Strategies to reduce NAP1 prevalence, such as antibiotic stewardship to reduce fluoroquinolone use, might reduce CDI morbidity. PMID:24604900

  5. Clinical Factors Associated with Development of Severe-Complicated Clostridium difficile Infection

    PubMed Central

    Shivashankar, Raina; Khanna, Sahil; Kammer, Patricia P.; Harmsen, W. Scott; Zinsmeister, Alan R.; Baddour, Larry M.; Pardi, Darrell S.

    2013-01-01

    Background & Aims Clostridium difficile infection (CDI) can cause life-threatening complications. Severe complicated CDI is characterized by hypotension, shock, sepsis, ileus, megacolon, and colon perforation. We created a model to identify clinical factors associated with severe complicated CDI. Methods We analyzed data from 1446 inpatient cases of CDI (48.6% female, median age 62.5 y, range 0.1–103.7 y) at the Mayo Clinic from June 28, 2007 through June 25, 2010. Patients with severe complicated CDI (n=487) were identified as those who required admission to the intensive-care unit (ICU) or colectomy, or died, within 30 days of CDI diagnosis. Logistic regression models were used to identify variables that were independently associated with the occurrence of severe complicated CDI in 2 cohorts. One cohort comprised all hospitalized patients; the other comprised a subset of these inpatients who were residents of Olmsted County, MN, to assess the association of comorbid conditions with the development of severe complicated infection in a population-based cohort. The linear combinations of variables identified using logistic regression models provided scores to predict the risk of developing severe-complicated CDI. Results In a multivariable model that included all inpatients, increasing age, leukocyte count >15×109/L, increase in serum level of creatinine >1.5-fold from baseline, and use of proton pump inhibitors or narcotic medications were independently associated with severe complicated CDI. In the secondary analysis, which included only patients from Olmsted County, comorbid conditions were not significantly associated with severe complicated CDI. Conclusion Older age, high numbers of leukocytes in blood samples, an increased serum level of creatinine, gastric acid suppression, and use of narcotic medications were independently associated with development of severe complicated CDI in hospitalized patients. Early aggressive monitoring and intervention could improve outcomes. PMID:23702192

  6. Disrupted SOX10 function causes spongiform neurodegeneration in gray tremor mice.

    PubMed

    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

    2015-02-01

    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

  7. Is Clostridium difficile associated with the ‘4C’ antibiotics? A retrospective observational study in diabetic foot ulcer patients

    PubMed Central

    Collier, A; McLaren, J; Godwin, J; Bal, A

    2014-01-01

    Aims Clostridium difficile is an anaerobic cytotoxin-producing bacterium that can cause infectious diarrhoea, pseudomembranous colitis and toxic megacolon. The major risk factors for developing C. difficile infection include recent or current antimicrobial use, diabetes, age over 65, proton pump inhibitor use, immunosuppression and previous infection with C. difficile. Most diabetic foot ulcers are polymicrobial. Methods As a result guidelines advise treatment with broad spectrum antibiotics which include the ‘4C's’ (clindamycin, cephalosporins, co-amoxiclav and ciprofloxacin) which are associated with a higher risk of C. difficile infection. Retrospective observational data (June 2008 to January 2012) for the diabetes foot ulcers were gathered from the Diabetes/Podiatry Clinic database in NHS Ayrshire and Arran and cross-matched with the NHS Ayrshire and Arran Microbiology database. There were 111 patients with mean age 59 years (range 24–94 years), 33 type 1 patients, 78 type 2 patients, mean duration of diabetes 16 years (6 months–37 years) and mean HbA1c 67 mmol/mol (54–108 mmol/mol) [8.3% (7.1–12%)]. Results The total number of days antimicrobials prescribed for all patients was 7938 (mean number of antimicrobial days per patient = 71.5 days). There was one case of C. difficile infection of 111 patients giving an incidence of 1.25 cases per 10,000 patient-days of antibiotics/1 case per 209 foot ulcers. Conclusions Large doses, numbers and greater duration of antibiotic therapy all result in a greater degree of normal gut flora depletion. It is possible that the alterations in gut flora in diabetic foot ulcer patients protect them from antibiotic-induced C. difficile overgrowth. PMID:24499256

  8. Clinical Severity of Clostridium difficile PCR Ribotype 027: A Case-Case Study

    PubMed Central

    Morgan, Oliver W.; Rodrigues, Boaventura; Elston, Tony; Verlander, Neville Q.; Brown, Derek F. J.; Brazier, Jonathan; Reacher, Mark

    2008-01-01

    Background Clostridium difficile is a leading infectious cause of health care associated diarrhoea. Several industrialised countries have reported increased C. difficile infections and outbreaks, which have been attributed to the emergent PCR ribotype 027 strain. Methods and Findings We conducted a case-case study to compare severity of C. difficile disease for patients with 027 versus non-027 ribotypes. We retrospectively collected clinical information about 123/136 patients with C. difficile infections admitted to hospitals in the East of England region in 2006 and from whom stool isolates were cultured and ribotyped as part of an earlier national survey. We defined severe C. difficile disease as having one or more of shock, paralytic ileus, pseudo membranous colitis or toxic megacolon. Patient median age was 83 years old (range 3 to 98, interquartile range 75 to 89), 86% were prescribed antibiotics in the eight weeks before illness onset, 41% had ribotype 027 and 30-day all cause mortality during hospital admission was 21%. Severe disease occurred in 24% (95%CI 13% to 37%) and 17% (95%CI 9% to 27%) of patients with PCR ribotype 027 and non-027 ribotypes respectively. In a multivariable model, ribotype 027 was not associated with severe disease after adjusting for sex, discharge from hospital prior to 60 days of current admission, gastroenteritis on admission, number of initiator antibiotics for C. difficile disease, and hospital where the patient was admitted. Conclusions Our study found no evidence to support previous assertions that ribotype 027 is more virulent than other PCR ribotypes. This finding raises questions about the contribution of this strain to the recent increase in C. difficile disease throughout North America and Europe. PMID:18350149

  9. [Acute colonic pseudo-obstruction: Ogilvie syndrome].

    PubMed

    Keller, J; Layer, P

    2015-10-01

    Acute colonic pseudo-obstruction (ACPO) is characterized by marked colonic dilatation which develops over several days. ACPO is due to a motility disorder and is not caused by colonic obstruction and occurs in patients with severe, often acute underlying diseases or postoperatively. It is associated with a 25-30% mortality overall that increases to up to 50% in patients who develop complications (e.g. colonic ischemia and perforation). The pathogenesis of the disorder has not yet been clarified and clinical symptoms and signs are relatively unspecific. In particular, ACPO has to be differentiated from colonic obstruction and toxic megacolon. For this blood tests and radiological tests are required, e.g. plain abdominal radiograph, abdominal computed tomography (CT) and water soluble contrast enema, which are also required for detection of complications. Patients with ACPO should generally receive supportive therapy for decompression of the gastrointestinal tract (e.g. gastric and rectal tubes) and to minimize predisposing factors. In most uncomplicated cases this leads to resolution of colonic dilatation. Clinical and radiological controls at close intervals are required until the condition is resolved. If patients do not respond within 1-2 days or if ACPO has already reached a critical duration (>3-4 days) or extent (i.e. cecal diameter ≥12 cm), neostigmine should be administered and leads to durable success in approximately 3 out of 4 patients. Patients who are still refractory to treatment should receive endoscopic decompression. More invasive therapeutic options, such as cecostomy or (segmental) colonic resection should only be considered for patients who still do not respond to treatment or present with the abovementioned complications. PMID:26400054

  10. Current approaches to the management of new-onset ulcerative colitis

    PubMed Central

    Marchioni Beery, Renée; Kane, Sunanda

    2014-01-01

    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. PMID:24872716

  11. [The Latin-American Consensus on Chronic Constipation].

    PubMed

    Schmulson Wasserman, Max; Francisconi, Carlos; Olden, Kevin; Aguilar Paíz, Luis; Bustos-Fernández, Luis; Cohen, Henry; Passos, Maria Carmo; González-Martínez, Marina Alejandra; Iade, Beatriz; Iantorno, Guido; Ledesma Ginatta, Carlos; López-Colombo, Aurelio; Pérez, Cesar Louis; Madrid-Silva, Ana María; Quilici, Flavio; Quintero Samudio, Isaac; Rodríguez Varón, Alberto; Suazo, Jorge; Valenzuela, Jorge; Zolezzi, Alberto

    2008-02-01

    The Latin-American Consensus on Chronic Constipation aimed to establish guidelines to improve the identification, diagnosis and treatment of this disorder in the region. Two coordinators and an honorary coordinator established the process and the topics to be discussed, based on a systematic review of the literature published in the previous 10 years, since 1995. Seventeen members participated with the support of their local gastroenterology societies. The members reviewed the different subjects based on the levels of evidence and grades of recommendation; the topics were then discussed in a plenary session. A written report was drafted and the coordinators prepared the final declarations to be submitted to a vote by all the members in October 2006. The consensus concluded that chronic constipation has an estimated prevalence of 5-21% in the region, with a female-to-male ratio of 3:1. Among individuals with constipation, 75% use some type of medication, with more than 50% using home remedies. A diagnosis based on Rome Criteria was recommended and diagnostic testing only in persons older than 50 years or with alarm symptoms. The use of barium enema as an initial investigation was recommended only in countries with a high prevalence of idiopathic megacolon or Chagas' disease. Recommendations on treatment included an increase in dietary fiber of up to 25-30 g/day (grade C). No evidence was found to recommend measures such as exercise, increased water intake, or frequent visits to the toilet. Fiber supplements such as Psyllium received a grade B and pharmacological treatments such as tegaserod and polyethylene glycol, both grade A. There was insufficient evidence to recommend lactulose, but the consensus did not disadvise its use when necessary. Complementary investigations such as colonic transit followed by anorectal manometry and defecography were only recommended to rule out colonic inertia and/or obstructive defecation in patients not responding to treatment. Biofeedback was recommended (grade B) for those with pelvic dyssynergia. PMID:18279643

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

    PubMed Central

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

    2012-01-01

    Clostridium difficile is a Gram positive, anaerobic bacterium that can form highly resistant endospores. The bacterium is the causative agent of C. difficile infection (CDI), for which the symptoms can range from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon. Endospore formation in Firmicutes, including C. difficile, is governed by the key regulator for sporulation, Spo0A. In Bacillus subtilis, this transcription factor is also directly or indirectly involved in various other cellular processes. Here, we report that C. difficile Spo0A shows a high degree of similarity to the well characterized B. subtilis protein and recognizes a similar binding sequence. We find that the laboratory strain C. difficile 630?erm contains an 18bp-duplication near the DNA-binding domain compared to its ancestral strain 630. In vitro binding assays using purified C-terminal DNA binding domain of the C. difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and sigH, early sporulation genes and several other putative targets. In vitro binding assays suggest that the gene encoding the major clostridial toxin TcdB may be a direct target of Spo0A, but supernatant derived from a spo0A negative strain was no less toxic towards Vero cells than that obtained from a wild type strain, in contrast to previous reports. These results identify for the first time direct (putative) targets of the Spo0A protein in C. difficile and make a positive effect of Spo0A on production of the large clostridial toxins unlikely. PMID:23119071

  13. Pathophysiology of motility dysfunction in bowel obstruction: role of stretch-induced COX-2

    PubMed Central

    Lin, You-Min; Powell, Don W.; Sarna, Sushil K.

    2011-01-01

    In gastrointestinal conditions such as bowel obstruction, pseudo-obstruction, and idiopathic megacolon, the lumen of affected bowel segments is distended and its motility function impaired. Our hypothesis is that mechanical stretch of the distended segments alters gene expression of cyclooxygenase-2 (COX-2), which impairs motility function. Partial obstruction was induced with a silicon band in the distal colon of rats for up to 7 days, and wild-type and COX-2 gene-deficient mice for 4 days. Mechanical stretch was mimicked in vitro in colonic circular muscle strips and in primary culture of colonic circular smooth muscle cells (SMC) with a Flexercell system. The rat colonic circular muscle contractility was significantly decreased in the distended segment oral to obstruction, but not in the aboral segment. This change started as early as day 1 and persisted for at least 7 days after obstruction. The expression of COX-2 mRNA and protein increased dramatically also in the oral, but not aboral, segment. The upregulation of COX-2 expression started at 12 h and the effect persisted for 7 days. At 24 h after obstruction, the COX-2 mRNA level in the oral segment increased 26-fold compared with controls. This was not accompanied by any significant increase of myeloperoxidase or inflammatory cytokines. Immunohistochemical studies showed that COX-2 was selectively induced in the colonic SMC. In vitro stretch of colonic muscle strips or cultured SMC drastically induced COX-2 expression. Incubation of circular muscle strips from obstructed segment with COX-2 inhibitor NS-398 restored the contractility. The impairment of muscle contractility in obstructed colon was attenuated in the COX-2 gene-deficient mice. In conclusion, mechanical stretch in obstruction induces marked expression of COX-2 in the colonic SMC, and stretch-induced COX-2 plays a critical role in the suppression of smooth muscle contractility in bowel obstruction. PMID:21051526

  14. The developmental etiology and pathogenesis of Hirschsprung disease.

    PubMed

    Butler Tjaden, Naomi E; Trainor, Paul A

    2013-07-01

    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

  15. Contemporary outcomes for ulcerative colitis inpatients admitted to pediatric hospitals in the United Kingdom.

    TOXLINE Toxicology Bibliographic Information

    Russell RK; Protheroe A; Roughton M; Croft NM; Murphy MS; Spray C; Rodrigues AF; Wilson DC; Puntis J; Cosgrove M; Tamok A; Rao P; Down C; Arnott ID; Mitton SG

    2013-06-01

    BACKGROUND: Pediatric ulcerative colitis (UC) care is variable with a lack of appropriate guidelines to guide practice until recently.METHODS: UC inpatients <17 years old admitted to 23 U.K. pediatric hospitals had clinical details collected between September 2010 and 2011. Comparative data for 248 patients were available from a previous audit in 2008.RESULTS: One hundred and seventy-six patients (98 males) of median age 13 years (interquartile range, 10-13) were analyzed; 23 were elective surgical admissions, 47 new diagnoses, and 106 needed acute medical care for established UC. Median length of stay was 6 days (interquartile range, 3-10) with no deaths. Eighty-eight of 126 patients (70%) with active disease had standard stool cultures performed (3 [2%] were positive), and 57 (45%) had Clostridium difficile toxin tested (none positive). Twenty-five of 66 (38%) emergency admissions had an abdominal x-ray on admission, and 13 of 66 patients (20%) had a Pediatric Ulcerative Colitis Activity Index score. There were 3 cases of toxic megacolon and 2 thromboses. Eighty-one of 116 patients (71%) responded to steroids. Nineteen patients who did not respond adequately to steroids received rescue therapy (7 infliximab, 11 ciclosporin, and 1 both) with overall response rate of 90%; 7 patients needed surgery acutely, 5 without previous rescue therapy. Compared with the 2008 data, stool culture rates improved significantly (86 of 121 [71%] versus 76 of 147 [52%], P = 0.001) as did heparinization rates (15 of 150 [10%] versus 5 of 215 [2%], P = 0.002) and rescue therapy usage (17 of 33 [52%] versus 10 of 38 [26%], P = 0.03).CONCLUSIONS: There were signs of improving UC care with significantly increased rates of stool culture and rescue therapy. The majority of sites, however, did not use Pediatric Ulcerative Colitis Activity Index scores.

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

    SciTech Connect

    Bolk, S.; Duggan, D.J.; Chakravarti, A.

    1994-09-01

    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.

  17. A Retrospective Analysis of 7 Human Immunodeficiency Virus-Negative Infants Infected by Penicillium marneffei

    PubMed Central

    Zeng, Wen; Qiu, Ye; Lu, DeCheng; Zhang, Jianquan; Zhong, Xiaoning; Liu, Guangnan

    2015-01-01

    Abstract Infection with Penicillium marneffei has rarely been reported in human immunodeficiency virus (HIV)-negative infants. We aimed to determine the epidemiological, clinical, pathological, and immunological characteristics of 7 HIV-negative infants infected by P. marneffei, and to provide insights into its diagnosis and treatment. We retrospectively reviewed the cases of 7 HIV-negative infants infected by P. marneffei who presented to the First Affiliated Hospital of Guangxi Medical University between January 1, 2003 and December 1, 2014. The infants’ median age was 23.43 months (SD?=?8.34), and all lived in Guangxi Province in China, where P. marneffei is endemic. The median time from disease onset to diagnosis was 2.29 months (SD?=?2.12). Of the cases studied, 5 (71.43%) had medical histories that included frequent pneumonia or bronchopneumonia, thrush, congenital megacolon, glucose-6-phosphate dehydrogenase deficiency, and hemophagocytic syndrome. The most common symptoms were fever, cough, and anemia, followed by lymphadenopathy, hepatosplenomegaly, and being underweight. Four patients had slightly elevated white blood cell counts. The lymphocyte and CD4+ T-cell counts were normal. The CD8+ T-cell counts, serum immunoglobulin (Ig) G titer, and serum IgA titer were low in 5 patients, and the serum IgM titers were high in 3 infants. Caseous necrosis was observed in 3 patients whose lymph nodes were affected. One case who received intravenous amphotericin B and 3 cases who received intravenous voriconazole improved, and these patients were cured after continual treatment with oral voriconazole for 6 or 12 months. The remaining patients died before they received antifungal treatment. P. marneffei causes severe disease and disseminated infections, and it has high mortality rates in HIV-negative infants in endemic areas. P. marneffei susceptibility may be associated with immunodeficiencies or immune disorders. In endemic areas, clinicians should aware of disseminated P. marneffei infections when infants present with serious or recurrent infections, even if they are HIV negative. P. marneffei is highly susceptible to amphotericin B and voriconazole. Timely diagnosis and treatment can improve patients’ prognoses. Intravenous voriconazole could be recommended as the initial antifungal agent for HIV-negative infants infected by P. marneffei, because of its low nephrotoxicity, high sensitivity, and high efficacy levels. PMID:26313802

  18. Clostridium difficile associated infection, diarrhea and colitis

    PubMed Central

    Hookman, Perry; Barkin, Jamie S

    2009-01-01

    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

  19. Comparative genetics of albinism.

    PubMed

    Searle, A G

    1990-09-01

    Albinism in laboratory mammals is equivalent to human tyrosinase-negative oculocutaneous albinism, and thus the result of recessive mutation in the structural locus for tyrosinase (TYR), which prevents melanin biosynthesis. In the mouse, eight mutant alleles are now known at this locus, with differing effects on eye colour and on the degree of reduction in eumelanin and phaeomelanin pigmentation. Three of these alleles, namely chinchilla, himalayan (acromelanistic) and albino (c) itself, have also been recognized in a number of other species but only albino has been identified in man so far. The himalayan allele (equivalent to Siamese in the cat) is of particular interest because it converts tyrosinase into a thermolabile form, with greater production of melanin in colder areas of the body. The optic track misrouting found in human albinos also occurs in albino alleles in other mammals, which may also show reduced activity and stress responses. The TYR locus is on human chromosome 11, which now has at least 11 loci with homologues on mouse 7. However, their order is markedly different in the two species. For instance, c and Hbb (beta-globin), which are closely linked in mouse, rabbit, cat etc., are far apart on human 11q and 11p respectively. Moreover, some loci (e.g., Fes and Mod-2) which are close to c in the mouse appear to be on human chromosomes other than 11. This extensive chromosomal restructuring in mammalian evolution means that the effects of human albino deletions may differ greatly from those studied in the mouse, which are associated with defects of kidney, liver and thymus. Tyrosinase-positive albinos or near-albinos are known at a number of loci in mice and other mammals. They are the result of the absence or inhibition of melanocytes in the affected areas, so that no melanin is produced. In general they are associated with pathological pleiotropisms which may lead to anaemia, inner ear defects, megacolon, neurological effects, skeletal defects, microphthalmia, osteopetrosis, spina bifida, sterility and so on. Homologies between these and human loci affecting pigmentation are now being discovered. PMID:2126367