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Sample records for megacolon

  1. Toxic megacolon

    MedlinePlus

    ... disease - toxic megacolon; Crohn disease - toxic megacolon; Ulcerative colitis - toxic megacolon ... people with an inflamed colon due to: Ulcerative colitis , or Crohn disease that is not well controlled ...

  2. [Current management of toxic megacolon].

    PubMed

    Leifeld, L; Kruis, W

    2012-03-01

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

  3. Toxic megacolon after abdominoplasty: a case report.

    PubMed

    Wade, James W

    2014-01-01

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

  4. [Megacolon and sigmoid volvulus: incidence and physiopathology].

    PubMed

    Saravia Burgos, Jaime; Acosta Canedo, Abel

    2015-01-01

    The etiology of Megacolon is multiple. One of these causes and the most frequent is Chagas disease. Its complication: sigmoid volvulus was de main diagnosis in the admitted patients at the Bolivian and Japanese Gastroenterological Institute of Cochabamba Bolivia. It usually affects people of a low economic income. In this Gastroenterological Hospital a transversal and prospective study has been done, in order to know the real incidence and the physiopathology of this disease. In a six year period, from 2000 to 2006, 8.954 patients were admitted to the Hospital: of these, 814 (9.09%), where diagnosticated as lower intestinal obstruction. In 608 (74.7%) the final diagnosis was sigmoid torsion. Radiological diagnosis was made in 84% of the patients and endoscopic decompression was successful in 88.7%. As reported in the medical literature, the main cause of megacolon in this part of the world is Chagas disease. In our investigation 22% (98 patients), were serology positive to Chagas disease, and another 21.44% (95 patients) were serology negative. They were coca leaf chewers. One of coca leaf compounds is cocaine which blocks the adrenaline and noradrenaline degradation by mean of monoamine oxidase inactivation. These two hormones stay a long term of time in the target organ: the large bowel. By this mean chronic and persistent vessel constriction develops intestinal wall atrophy and lower resistance to the intraintestinal pressure.

  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. 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.

  7. Toxic megacolon in ulcerative rectocolitis. Current trends in clinical evaluation, diagnosis and treatment.

    PubMed

    Miniello, Stefano; Marzaioli, Rinaldo; Balzanelli, Mario Giosué; Dantona, Caterina; Lippolis, Anna Stella; Barnabà, Diana; Nacchiero, Michele

    2014-01-01

    Toxic megacolon is a clinical condition associated to high risk of colonic perforation, that significantly increases--even triplicates--the megacolon-related mortality when causing diffuse peritonitis. Abdominal and pelvic helical CT scan proved to be a fundamental diagnostic tool, in defining the colic dilatation and perforation. Conservative treatment is initially indicated in the event of toxic megacolon arising at the onset of a severe or toxic colitis. However it should be avoided when the toxic megacolon appears on corticosteroid therapy. Non operative management must not exceed 48 hours. The rationale of this strategy lies on the fact that early surgery is burdened by a mortality rate that, although moderate, is still higher than medical treatment. Nevertheless, successful conservative management does not exempt from surgery, which must be performed as soon as possible, in an elective setting, to prevent the recurrence of toxic megacolon. In emergency total colectomy and end ileostomy is the gold standard procedure. Bowel continuity will be restored, evaluating case by case, by performing an ileorectal anastomosis or proctectomy and ileoanal pouch anastomosis. Primary ileorectal anastomosis should be reserved to selected cases. In the elective setting, after proper therapy and regression of toxic megacolon, proctocolectomy and ileoanal pouch anastomosis is indicated.

  8. Clinical features of idiopathic megarectum and idiopathic megacolon.

    PubMed Central

    Gattuso, J M; Kamm, M A

    1997-01-01

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

  9. [Frequency, clinical evolution and prognosis of toxic megacolon].

    PubMed

    Magallón-Tapia, Marcos; Ceniceros, Rodrigo Alberto; Arenas-Osuna, Jesús; Juarez-Leal, Cinthia Lizeth; Peralta-Amaro, Ana Lilia

    2015-01-01

    Introducción: el megacolon tóxico (MT) es una complicación potencialmente mortal de la colitis infl amatoria, isquémica e infecciosa. Usualmente se relaciona con la colitis ulcerosa inespecífica y la colitis de Crohn. Recientemente, se ha observado un repunte de la colitis pseudomembranosa como causa del MT. El objetivo fue describir la frecuencia, evolución clínica y pronóstico de los pacientes con MT.Métodos: estudio retrospectivo de enero de 2009 a enero de 2014 se hospitalizaron 1500 pacientes en el departamento de Coloproctología. De estos pacientes, se incluyeron a 13 de ellos con diagnóstico de MT de acuerdo a los criterios de Jalan y corroborados por cirugía. Se utilizó estadística descriptiva.Resultados: se estudiaron 13 pacientes con MT. Las enfermedades más frecuentemente asociadas al MT fueron: colitis ulcerosa inespecífica, colitis pseudomembranosa y colitis neutropénica, enfermedad de Crohn y colitis isquémica. En el 84.6 % se realizó colectomía subtotal más ileostomía terminal; hemicolectomía derecha extendida con ileostomía más fístula mucosa en el 7.7 %, y hemicolectomía derecha extendida con ileostomía más bolsa de Hartmann en el 7.7 %. La mortalidad fue del 61.5 %. La prevalencia en los 5 años fue de 13/1500 pacientes (0.86 %).Conclusiones: la prevalencia del MT es baja, con alta mortalidad. El diagnóstico y tratamiento oportunos puede mejorar el mal pronóstico de estos pacientes.

  10. Lower oesophageal sphincter response to pentagastrin in chagasic patients with megaoesophagus and megacolon.

    PubMed Central

    Padovan, W; Godoy, R A; Dantas, R O; Meneghelli, U G; Oliveira, R B; Troncon, L E

    1980-01-01

    Intraluminal manometric studies were performed in 14 chagasic patients with megaoesophagus, 10 chagasic patients with megacolon, and 15 control subjects. Basal lower oesophageal sphincter pressure was 20.27+/-1.16 mmHg (mean+/-SEM) in controls as compared wtih 15.16+/-1.53 mmHg in chagasics with megaoesophagus and 14.38+/-1.50 mmHg in chagasics with megacolon. Dose-response studies to intravenous pentagastrin showed that the chagasic patients exhibited a lower sensitivity to the stimulant than did the controls, as demonstrated by shifting of the dose-response curve to the right and higher individual values of the dose for half maximal contraction (D50). No difference was noted between the calculated maximal contraction (Vmax) of oesophageal sphincter of controls and chagasics. These data are compatible with the hypothesis of an interaction between pentagastrin and cholinergic nervous excitation on oesophageal sphincteric smooth muscle. PMID:6769753

  11. 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

  12. 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.

  13. Overo lethal white foal syndrome: equine model of aganglionic megacolon (Hirschsprung disease).

    PubMed

    McCabe, L; Griffin, L D; Kinzer, A; Chandler, M; Beckwith, J B; McCabe, E R

    1990-07-01

    The lethal white foal syndrome (LWFS) is a congenital abnormality of overo spotted horses which is a model for human aganglionic megacolon or Hirschsprung disease. Foals with LWFS have an all white, or nearly all white, coat. They also present clinically with an intestinal obstruction that proves fatal within the first few days of life. The LWFS involves both melanocytes and intestinal ganglion cells, and appears to result from a genetic defect involving neural crest cells. This report describes pathologic studies of two recent cases of LWFS. Two different hypothetical models of inheritance of LWFS are presented and discussed.

  14. 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

  15. Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color.

    PubMed Central

    Gariepy, C E; Cass, D T; Yanagisawa, M

    1996-01-01

    Mutations in the gene encoding the endothelin receptor type B (EDNRB) produce congenital aganglionic megacolon and pigment abnormalities in mice and humans. Here we report a naturally occurring null mutation of the EDNRB gene in spotting lethal (sl) rats, which exhibit aganglionic megacolon associated with white coat color. We found a 301-bp deletion spanning the exon 1-intron 1 junction of the EDNRB gene in sl rats. A restriction fragment length polymorphism caused by this deletion perfectly cosegregates with the sl phenotype. The deletion leads to production of an aberrantly spliced EDNRB mRNA that lacks the coding sequence for the first and second putative transmembrane domains of the G-protein-coupled receptor. Radioligand binding assays revealed undetectable levels of functional EDNRB in tissues from homozygous sl/sl rats. We conclude that EDNRB plays an essential role in the normal development of two neural crest-derived cell lineages, epidermal melanocytes and enteric neurons, in three mammalian species--humans, mice, and rats. The EDNRB-deficient rat may also prove valuable in defining the postnatal physiologic role of this receptor. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8570650

  16. Blood vessels in ganglia in human esophagus might explain the higher frequency of megaesophagus compared with megacolon.

    PubMed

    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.

  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. Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term Murine Model of Tripanosoma cruzi Infection.

    PubMed

    Campos, Camila França; Cangussú, Silvia Dantas; Duz, Ana Luiza Cassin; Cartelle, Christiane Teixeira; Noviello, Maria de Lourdes; Veloso, Vanja Maria; Bahia, Maria Terezinha; Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2016-01-01

    We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized (acute-phase group) and another sub-group was treated with benznidazole and euthanized 15 months after infection (chronic-phase group). Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatory-induced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, the architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months) pathogenesis of Chagasic megacolon in mice that mimics the human disease, which persists for several years and has not been fully elucidated. We hypothesize that the long

  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. Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term Murine Model of Tripanosoma cruzi Infection

    PubMed Central

    Duz, Ana Luiza Cassin; Cartelle, Christiane Teixeira; Noviello, Maria de Lourdes; Veloso, Vanja Maria; Bahia, Maria Terezinha; Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2016-01-01

    We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized (acute-phase group) and another sub-group was treated with benznidazole and euthanized 15 months after infection (chronic-phase group). Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatory-induced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, the architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months) pathogenesis of Chagasic megacolon in mice that mimics the human disease, which persists for several years and has not been fully elucidated. We hypothesize that the long

  2. Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term Murine Model of Tripanosoma cruzi Infection.

    PubMed

    Campos, Camila França; Cangussú, Silvia Dantas; Duz, Ana Luiza Cassin; Cartelle, Christiane Teixeira; Noviello, Maria de Lourdes; Veloso, Vanja Maria; Bahia, Maria Terezinha; Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2016-01-01

    We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized (acute-phase group) and another sub-group was treated with benznidazole and euthanized 15 months after infection (chronic-phase group). Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatory-induced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, the architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months) pathogenesis of Chagasic megacolon in mice that mimics the human disease, which persists for several years and has not been fully elucidated. We hypothesize that the long

  3. 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 (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

  4. 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

  5. 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.

  6. Total Laparoscopic Modified Duhamel Operation in Combination With Transanal Endoscopic Microsurgery

    PubMed Central

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

    2014-01-01

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

  7. Congenital aganglionosis in a 3-day-old Holstein calf

    PubMed Central

    2005-01-01

    Abstract Necropsy of a 3-day-old Holstein heifer revealed proximal megacolon and distal colorectal hypoplasia. Histologically, the hypoplastic distal colon and rectum lacked submucosal and myenteric ganglia. Clinical history, physical examination, and pathologic findings were consistent with intestinal aganglionosis, a congenital anomaly well documented in humans and foals but not previously reported in cattle. PMID:15943121

  8. 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

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

    PubMed Central

    Amiel, J.; Lyonnet, S.

    2001-01-01

    Hirschsprung disease (HSCR, aganglionic megacolon) is the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has dramatically decreased mortality and morbidity, which has allowed the emergence of familial cases. HSCR appeared to be a multifactorial malformation with low, sex dependent penetrance and variable expression according to the length of the aganglionic segment, suggesting the involvement of one or more gene(s) with low penetrance. So far, eight genes have been found to be involved in HSCR. This frequent congenital malformation now stands as a model for genetic disorders with complex patterns of inheritance.


Keywords: Hirschsprung disease; aganglionic megacolon; genetics PMID:11694544

  10. Internal hemipelvectomy for treatment of obstipation secondary to pelvic malunion in 3 cats.

    PubMed

    DeGroot, Whitney; Gibson, Thomas W G; Reynolds, Debbie; Murphy, Kim A

    2016-09-01

    Pelvic fractures are a common injury in cats, and both surgical and conservative management approaches have been described. One of the major complications of pelvic fractures managed conservatively is narrowing of the pelvic canal. Severe pelvic canal narrowing can result in constipation and subsequent megacolon. The purpose of this case series is to describe the long-term outcome for 3 cats with obstipation treated with internal hemipelvectomy because of megacolon secondary to pelvic canal narrowing after conservative management. All cats had a good functional outcome of the affected limb. Two cats required ongoing medical management for recurrent constipation. Overall, internal hemipelvectomy offers good long-term limb function; however, its success in relieving clinical signs of constipation requires additional research. PMID:27587887

  11. 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

  12. [A Serious Case of Pseudomembranous Colitis in which Treatment with Endoscopic Vancomycin Sprinkling Got a Good Result].

    PubMed

    Takeda, Rinne; Koga, Tsunehisa; Ishimaru, Toshiyuki; Sawayama, Yasunori

    2015-05-01

    We report herein on a 71-year-old man who developed pseudomembranous colitis (PMC). He was treated with oral metronidazole and vancomycin prescription, but deteriorated, and developed a toxic megacolon. Under paralytic ileus condition, per os and enema treatment efficacy was thought to be limited. Sprinkling with vancomycin via colonoscopy was therefore performed, resulting in therapeutic success. Additionally, participation in infection control should be carried out with severe PMC cases like this. PMID:26552134

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

    PubMed Central

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

    2012-01-01

    Background Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. Methodology Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. Principal Findings The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011haplotype was associated with resistance against chronic Chagas disease. Conclusions This is the first report of HLA haplotype association with resistance to chronic Chagas disease. PMID:22448298

  14. 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.

  15. MELAS syndrome presenting as an acute surgical abdomen.

    PubMed

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

    2014-01-01

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

  16. Emergency laparotomy in patients with AIDS.

    PubMed

    Davidson, T; Allen-Mersh, T G; Miles, A J; Gazzard, B; Wastell, C; Vipond, M; Stotter, A; Miller, R F; Fieldman, N R; Slack, W W

    1991-08-01

    The presentation, operative management and final diagnosis were reviewed in 28 patients with AIDS (27 men and one woman) who underwent emergency laparotomy. On clinical and radiological examination, six patients showed features of toxic megacolon, five patients had small bowel obstruction, six patients had localized peritonitis and three had perforated viscus with generalized peritonitis. The most common disease processes were acute colitis in seven patients (associated with cytomegalovirus (CMV) infection in six), intra-abdominal lymphoma in five patients, acute appendicitis in five patients (associated with CMV infection in two), and atypical mycobacterial (MAI) infection in four patients. Two perioperative deaths occurred; one in a patient with acute pancreatitis and a second with generalized peritonitis. Later deaths were due to progression of AIDS, and patient survival at 1 month, 3 months and 6 months was 89 per cent, 64 per cent and 48 per cent, respectively. Lower operative mortality than in previously reported series may be due to earlier intervention in CMV toxic megacolon. Surgery, however, conferred less benefit in patients with acute abdominal pain from MAI infection or lymphoma. With careful patient selection, emergency laparotomy may achieve worthwhile palliation in patients with AIDS. PMID:1655153

  17. Fulminant ulcerative colitis in a healthy pregnant woman.

    PubMed

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

    2015-05-21

    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

  18. Complications of inflammatory bowel disease.

    PubMed

    Gasche, C

    2000-01-01

    Complications in inflammatory bowel disease determine the severity of disease as well as the complexities of medical or surgical treatment opportunities. Therefore, in known inflammatory bowel disease, the prevention, the early detection and the adequate therapeutic response to certain complications are important goals in the follow-up of inflammatory bowel disease patients. Disease complications are separated into intestinal and extraintestinal complications. Intestinal complications are somewhat disease specific, which means that they occur exclusively in either Crohn's disease or ulcerative colitis (e.g., enteric fistulas are particularly found in Crohn's disease and toxic megacolon in ulcerative colitis). Most extraintestinal complications occur in both forms of inflammatory bowel disease (e.g., anemia, thromboembolic events or osteoporosis). The current knowledge on pathogenesis, diagnostic tools, prevention and treatment of certain intestinal and extraintestinal complications is reviewed. PMID:10690585

  19. Slow Transit Constipation.

    PubMed

    Wald, Arnold

    2002-08-01

    The diagnosis of slow transit functional constipation is based upon diagnostic testing of patients with idiopathic constipation who responded poorly to conservative measures such as fiber supplements, fluids, and stimulant laxatives. These tests include barium enema or colonoscopy, colonic transit of radio-opaque markers, anorectal manometry, and expulsion of a water-filled balloon. Plain abdominal films can identify megacolon, which can be further characterized by barium or gastrografin studies. Colonic transit of radio-opaque markers identifies patients with slow transit with stasis of markers in the proximal colon. However, anorectal function should be characterized to exclude outlet dysfunction, which may coexist with colonic inertia. Because slow colonic transit is defined by studies during which patients consume a high-fiber diet, fiber supplements are generally not effective, nor are osmotic laxatives that consist of unabsorbed sugars. Stimulant laxatives are considered first-line therapy, although studies often show a diminished colonic motor response to such agents. There is no evidence to suggest that chronic use of such laxatives is harmful if they are used two to three times per week. Polyethylene glycol with or without electrolytes may be useful in a minority of patients, often combined with misoprostol. I prefer to start with misoprostol 200 mg every other morning and increase to tolerance or efficacy. I see no advantage in prescribing misoprostol on a TID or QID basis or even daily because it increases cramping unnecessarily. This drug is not acceptable in young women who wish to become pregnant. An alternative may be colchicine, which is reported to be effective when given as 0.6 mg TID. Long-term efficacy has not been studied. Finally, biofeedback is a risk-free approach that has been reported as effective in approximately 60% of patients with slow transit constipation in the absence of outlet dysfunction. Although difficult to understand

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

    PubMed

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

    2010-04-01

    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.

  1. 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

  2. [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.

  3. Pre-Columbian Chagas disease in Brazil: Trypanosoma cruzi I in the archaeological remains of a human in Peruaçu Valley, Minas Gerais, Brazil.

    PubMed

    Fernandes, Alexandre; Iñiguez, Alena M; Lima, Valdirene S; Souza, Sheila M F Mendonça de; Ferreira, Luiz Fernando; Vicente, Ana Carolina P; Jansen, Ana M

    2008-08-01

    We evaluated the presence and distribution of Trypanosoma cruzi DNA in a mummy presenting with megacolon that was dated as approximately 560 +/- 40 years old. The mummy was from the Peruaçu Valley in the state of Minas Gerais, Brazil. All samples were positive for T. cruzi minicircle DNA, demonstrating the presence and broad dissemination of the parasite in this body. From one sample, a mini-exon gene fragment was recovered and characterized by sequencing and was found to belong to the T. cruzi I genotype. This finding suggests that T. cruzi I infected humans during the pre-Columbian times and that, in addition to T. cruzi infection, Chagas disease in Brazil most likely preceded European colonization.

  4. 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.

  5. 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

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

    PubMed Central

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

    2012-01-01

    Aim: To analyse the clinicopathological features of neonatal mucormycosis Materials and Methods: Retrospective analysis of cases of neonatal gastrointestinal mucormycosis. Results: There were six neonates with male: female ratio of 1:1. Except one all were preterm babies. The clinical presentation was abdominal distension in the majority. All were clinically diagnosed as either NEC or toxic megacolon with perforation. Neonatal gastrointestinal mucormycosis was not suspected clinically in any. All the children were explored immediately. Biopsy revealed transmural hemorrhagic necrosis/infarction of the intestinal wall with fungal hyphae. Conclusions: The physicians should have a high index of suspicion for gastrointestinal tract mucormycosis in neonates with metabolic disturbances who present with abdominal distension and pneumoperitoneum. Early diagnosis and aggressive medical and surgical treatment may improve the outcome of neonates with this potentially lethal invasive disease. PMID:23243366

  7. Analysis of Enteric Neural Crest Cell Migration Using Heterotopic Grafts of Embryonic Guts

    PubMed Central

    Soret, Rodolphe; Pilon, Nicolas

    2016-01-01

    Hirschsprung disease (HSCR), also named aganglionic megacolon, is a severe congenital malformation characterized by a lack of enteric nervous system (ENS) in the terminal regions of the bowel (Bergeron et al., 2013). As the ENS notably regulates motility in the whole gastrointestinal track, the segment without neurons remains tonically contracted, resulting in functional intestinal obstruction and accumulation of fecal material (megacolon). HSCR occurs when enteric neural progenitors of vagal neural crest origin fail to fully colonize the developing intestines. These “enteric” neural crest cells (ENCCs) have to migrate in a rostro-caudal direction during a fixed temporal window, which is between embryonic day (e) 9.5 and e14.5 in the mouse (Obermayr et al., 2013). Recently, our group generated a new HSCR mouse model called Holstein in which migration of ENCCs is impaired because of increased collagen VI levels in their microenvironment (Soret e al., 2015). Here, we describe the method that allowed us to demonstrate the cell-autonomous nature of this migration defect. In this system adapted from a previously described heterotopic grafting approach (Breau et al., 2006), the donor tissue is a fully colonized segment of e12.5 midgut while the host tissue is an aneural segment of e12.5 hindgut. Extent of ENCC migration in host tissue is assessed after 24 h of culture and is greatly facilitated when donor tissue has a transgenic background such as the Gata4-RFP (Pilon et al., 2008) that allows endogenous labeling of ENCCs with fluorescence. Depending of the genetic background of donor and host tissues, this approach can allow evaluating both cell-autonomous and non-cell-autonomous defects of ENCC migration.

  8. Analysis of Enteric Neural Crest Cell Migration Using Heterotopic Grafts of Embryonic Guts

    PubMed Central

    Soret, Rodolphe; Pilon, Nicolas

    2016-01-01

    Hirschsprung disease (HSCR), also named aganglionic megacolon, is a severe congenital malformation characterized by a lack of enteric nervous system (ENS) in the terminal regions of the bowel (Bergeron et al., 2013). As the ENS notably regulates motility in the whole gastrointestinal track, the segment without neurons remains tonically contracted, resulting in functional intestinal obstruction and accumulation of fecal material (megacolon). HSCR occurs when enteric neural progenitors of vagal neural crest origin fail to fully colonize the developing intestines. These “enteric” neural crest cells (ENCCs) have to migrate in a rostro-caudal direction during a fixed temporal window, which is between embryonic day (e) 9.5 and e14.5 in the mouse (Obermayr et al., 2013). Recently, our group generated a new HSCR mouse model called Holstein in which migration of ENCCs is impaired because of increased collagen VI levels in their microenvironment (Soret e al., 2015). Here, we describe the method that allowed us to demonstrate the cell-autonomous nature of this migration defect. In this system adapted from a previously described heterotopic grafting approach (Breau et al., 2006), the donor tissue is a fully colonized segment of e12.5 midgut while the host tissue is an aneural segment of e12.5 hindgut. Extent of ENCC migration in host tissue is assessed after 24 h of culture and is greatly facilitated when donor tissue has a transgenic background such as the Gata4-RFP (Pilon et al., 2008) that allows endogenous labeling of ENCCs with fluorescence. Depending of the genetic background of donor and host tissues, this approach can allow evaluating both cell-autonomous and non-cell-autonomous defects of ENCC migration. PMID:27642615

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

    PubMed Central

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

    2014-01-01

    Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels. PMID:24676665

  10. 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

  11. 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

  12. 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

  13. Proteomic profile of circulating immune complexes in chronic Chagas disease.

    PubMed

    Ohyama, K; Huy, N T; Yoshimi, H; Kishikawa, N; Nishizawa, J E; Roca, Y; Revollo Guzmán, R J; Velarde, F U G; Kuroda, N; Hirayama, K

    2016-10-01

    Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0·046 for human, 1/11, P = 0·0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease.

  14. 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.

  15. Clostridium difficile infection: a review of current and emerging therapies

    PubMed Central

    Ofosu, Andrew

    2016-01-01

    Clostridium difficile (C. difficile) infection (CDI) is the most common cause of ­healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value. PMID:27065726

  16. 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.

  17. 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

  18. A Tetraspecific VHH-Based Neutralizing Antibody Modifies Disease Outcome in Three Animal Models of Clostridium difficile Infection.

    PubMed

    Schmidt, Diane J; Beamer, Gillian; Tremblay, Jacqueline M; Steele, Jennifer A; Kim, Hyeun Bum; Wang, Yaunkai; Debatis, Michele; Sun, Xingmin; Kashentseva, Elena A; Dmitriev, Igor P; Curiel, David T; Shoemaker, Charles B; Tzipori, Saul

    2016-09-01

    Clostridium difficile infection (CDI), a leading cause of nosocomial infection, is a serious disease in North America, Europe, and Asia. CDI varies greatly from asymptomatic carriage to life-threatening diarrhea, toxic megacolon, and toxemia. The incidence of community-acquired infection has increased due to the emergence of hypervirulent antibiotic-resistant strains. These new strains contribute to the frequent occurrence of disease relapse, complicating treatment, increasing hospital stays, and increasing morbidity and mortality among patients. Therefore, it is critical to develop new therapeutic approaches that bypass the development of antimicrobial resistance and avoid disruption of gut microflora. Here, we describe the construction of a single heteromultimeric VHH-based neutralizing agent (VNA) that targets the two primary virulence factors of Clostridium difficile, toxins A (TcdA) and B (TcdB). Designated VNA2-Tcd, this agent has subnanomolar toxin neutralization potencies for both C. difficile toxins in cell assays. When given systemically by parenteral administration, VNA2-Tcd protected against CDI in gnotobiotic piglets and mice and to a lesser extent in hamsters. Protection from CDI was also observed in gnotobiotic piglets treated by gene therapy with an adenovirus that promoted the expression of VNA2-Tcd. PMID:27413067

  19. 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.

  20. 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

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

    PubMed

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

    2014-04-01

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

  2. Use of laparoscopy in the diagnosis and treatment of patients with surgical abdominal sepsis.

    PubMed

    Geis, W P; Kim, H C

    1995-02-01

    Patients often present to the surgeon with abdominal pain, tenderness, and fever. Many exhibit progressive sepsis due to abdominal pathology. Delay in diagnosis and treatment often occurs due to the use of multiple, time-consuming, expensive diagnostic studies. We delineate the use of diagnostic laparoscopy in subsets of patients in whom confusion exists as to the cause of abdominal sepsis--i.e., females in child-bearing years, elderly patients, obese patients, immunosuppressed patients, and patients with suppression of physical findings. The methodical assessment of the entire abdominal cavity is performed utilizing manipulation of the patient's position (Trendelenburg, supine, reverse Trendelenburg, left side up, right side up) and meticulous inspection of the entire small bowel. Diagnoses included acute appendicitis, gangrenous appendicitis, perforated appendicitis with peritonitis or abscess, gangrenous cholecystitis, ischemic bowel disease, perforating carcinoma of the colon, perforating diverticulitis with abscess or peritonitis, tubo-ovarian abscess, closed-loop small-bowel obstruction, megacolon, and perforation of the colon. Laparoscopic treatment of 96% of the patients was performed successfully and a laparoscopic-assisted approach was used in the remainder. There was one mortality (cardiac) and no major morbidity. The development of a Formal Diagnostic Exploratory Laparoscopic (FDEL) approach has aided in the assessment of each of the diagnoses of sepsis in the abdominal cavity. The diagnostic and therapeutic approach laparoscopically avoids extensive preoperative studies, avoids delay in operative intervention, and appears to minimize morbidity and shorten the postoperative recovery interval.

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. Telomere length in non-neoplastic colonic mucosa in ulcerative colitis (UC) and its relationship to the severe clinical phenotypes.

    PubMed

    Tahara, Tomomitsu; Shibata, Tomoyuki; Okubo, Masaaki; Kawamura, Tomohiko; Sumi, Kazuya; Ishizuka, Takamitsu; Nakamura, Masakatsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Ohmiya, Naoki; Arisawa, Tomiyasu; Hirata, Ichiro

    2015-08-01

    Telomere shortening occurs with human aging in many organs and tissues and is accelerated by rapid cell turnover and oxidative injury. To clarify the clinical importance of telomere shortening in colonic mucosa in ulcerative colitis (UC), we measured average telomere length using quantitative real-time PCR in non-neoplastic colonic mucosa in UC patients and assessed its relationship to various clinical subtypes. Relative telomere length in genomic DNA was measured in colonic biopsies obtained from rectal inflammatory mucosa from 86 UC patients as well as paired non-inflammatory proximal colonic mucosae from 10 patients. Data were correlated with various clinical phenotypes. In paired samples, average relative telomere length of rectal inflammatory mucosa was shortened compared to normal appearing proximal colon in eight out of ten cases (p = 0.01). Telomere length shortening was significantly associated with more severe Mayo endoscopic subscore (p < 0.0001) and cases needing surgery due to toxic megacolon or cancer occurrence (p = 0.043). When the severe clinical phenotype was defined as having at least one of following phenotypes, more than two times of hospitalization, highest Mayo endoscopic subscore, steroid dependent, refractory, or needing operation, average relative telomere length was significantly shortened in the same phenotypes than the others (p = 0.003). Telomere shortening is associated with more severe clinical phenotypes of UC, reflecting severe inflammatory state in the colonic mucosa.

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

    PubMed

    Sun, Xingmin; Hirota, Simon A

    2015-02-01

    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 C. 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.

  7. 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.

  8. Volvulus of the Sigmoid Colon Associated With Rectal Cancer: A Case Report

    PubMed Central

    Lee, Seung-Hyun; Ahn, Byung-Kwon; Baek, Sung-Uhn

    2015-01-01

    Sigmoid volvulus is one of the three most common causes of acute colonic obstruction. Predisposing factors include chronic constipation, adhesion from a prior abdominal surgery, and megacolon. However, concomitant presentation of volvulus of the sigmoid colon and rectal cancer is extremely rare. We report a case of a 50-year-old woman with coexisting volvulus of the sigmoid colon and rectal cancer. The patient presented with abdominal distension and pain for 2 days. On computed tomography, the whole colon was dilated with gas and feces. A whirl sign with rotation of the inferior mesenteric vessel was identified. The rectum had irregular wall thickening. Colonoscopy showed a circumscribed, ulcerofungating mass approximately 6 cm from the anal verge. The sigmoid colon was obstructed at a point approximately 25 cm from the anal verge. The mucosa was hyperemic and edematous with the pathognomonic spiral pattern. Endoscopic reduction was not successful. On laparotomy, the sigmoid colon was rotated around its mesentery. It was severely distended with edematous, hyperemic serosa. A tumor of the rectum was identified in the mid-rectum. The patient underwent low anterior resection and protective ileostomy. Pathologic findings confirmed adenocarcinoma of the rectum. The postoperative course was complicated by an ileus, which was managed with conservative treatment.

  9. 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.

  10. [NONSPECIFIC ULCERATIVE COLITIS COMPLICATED WITH MULTIPLE REPETITIVE PERFORATIONS AND DIFFUSE FECALIC PERITONITIS (CASE REPORT)].

    PubMed

    Antadze, A; Mukhashavria, G; Lekvtadze, N; Tomadze, G; Chikobava, G

    2016-06-01

    Nonspecific ulcerative colitis is disease with complicated and not fully studied etiology and pathogenesis, and treatment of its complications is very difficult. Especially complicated is disease course with repetitive bleeding, toxic megacolon and perforation. We present a quite rare case of complication with multiple, especially repetitive perforations of transverse colon. After 13 days from the performance of subtotal colectomy, the patient underwent to the relaparotomy because of secondary perforation of sygmoid colon 2-3 cm lower from its cult and iliac intestine 0.2-0.3 cm distance from nearby ileostoma. The full eventration took place on the 6th day and was performed repetitive laparotomy. On the 8th day patient was released from artificial ventilation of lungs and on the 66th day from hospitalization patient was discharged from the hospital with satisfactory status. Such kind of serious course of the treatment process was determined by the late hospitalization and developed serious complications. Situation mentioned above more impressively underlines the value of the positive result of presented case. PMID:27441530

  11. 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

  12. A Tetraspecific VHH-Based Neutralizing Antibody Modifies Disease Outcome in Three Animal Models of Clostridium difficile Infection

    PubMed Central

    Beamer, Gillian; Tremblay, Jacqueline M.; Steele, Jennifer A.; Kim, Hyeun Bum; Wang, Yaunkai; Debatis, Michele; Sun, Xingmin; Kashentseva, Elena A.; Dmitriev, Igor P.; Curiel, David T.; Shoemaker, Charles B.

    2016-01-01

    Clostridium difficile infection (CDI), a leading cause of nosocomial infection, is a serious disease in North America, Europe, and Asia. CDI varies greatly from asymptomatic carriage to life-threatening diarrhea, toxic megacolon, and toxemia. The incidence of community-acquired infection has increased due to the emergence of hypervirulent antibiotic-resistant strains. These new strains contribute to the frequent occurrence of disease relapse, complicating treatment, increasing hospital stays, and increasing morbidity and mortality among patients. Therefore, it is critical to develop new therapeutic approaches that bypass the development of antimicrobial resistance and avoid disruption of gut microflora. Here, we describe the construction of a single heteromultimeric VHH-based neutralizing agent (VNA) that targets the two primary virulence factors of Clostridium difficile, toxins A (TcdA) and B (TcdB). Designated VNA2-Tcd, this agent has subnanomolar toxin neutralization potencies for both C. difficile toxins in cell assays. When given systemically by parenteral administration, VNA2-Tcd protected against CDI in gnotobiotic piglets and mice and to a lesser extent in hamsters. Protection from CDI was also observed in gnotobiotic piglets treated by gene therapy with an adenovirus that promoted the expression of VNA2-Tcd. PMID:27413067

  13. Clinical and morphofunctional features of idiopathic myenteric ganglionitis underlying severe intestinal motor dysfunction: a study of three cases.

    PubMed

    De Giorgio, Roberto; Barbara, Giovanni; Stanghellini, Vincenzo; De Ponti, Fabrizio; Salvioli, Beatrice; Tonini, Marcello; Velio, Pietro; Bassotti, Gabrio; Corinaldesi, Roberto

    2002-09-01

    Ganglionitis, i.e., the inflammatory neuropathy characterized by a marked lymphoplasmacellular infiltrate in the myenteric plexus, may underlie a variety of paraneoplastic, infectious, or neurological disorders, although occasional cases are idiopathic in origin. We report clinical, manometric, morphofunctional, and immunological features of three cases of idiopathic ganglionitis. All patients had megacolon and underwent surgery for repeated episodes of intestinal subocclusion. Esophageal, GI, and colonic manometry performed in one patient showed dysmotility of the whole gut. Histological examination of colonic and ileum specimens identified a prominent lymphoplasmacellular infiltrate within the myenteric plexus along with a marked decrease of a wide array of neuronal peptides/transmitters. In one patient, tissue analysis revealed progressive neuronal changes up to marked myenteric neuron damage. The inflammatory infiltrate in all patients comprised CD4+ and CD8+ T lymphocytes. Abundance of both subclasses of lymphocytes suggests that immune-mediated mechanisms were responsible for neuronal degeneration. In one patient, systemic steroid therapy brought a significant clinical improvement. The immunosuppressive approach deserves further investigation in patients with severe gut motor abnormalities attributable to idiopathic myenteric ganglionitis.

  14. Clostridium difficile colitis.

    PubMed

    Trnka, Y M; Lamont, J T

    1984-01-01

    Clostridium difficile has become one of the commonest pathogens of the lower intestinal tract. This organism appears unique in that infection almost always occurs during or after antibiotic therapy, suggesting that some component of the normal microflora prevents colonization by C. difficile. Once it has overgrown in the colon, C. difficile releases several toxins which cause tissue damage and diarrhea. Infection can range from a simple self-limited diarrheal illness to fulminant colitis with perforation and megacolon. Assay of stool filtrates reveals the presence of cytotoxin in nearly all patients with antibiotic-associated pseudomembranous colitis, and in approximately one third to one half of those with less severe infections. Effective therapy is available in the form of oral vancomycin, although the expense of this antibiotic has led to the use of oral metronidazole or bacitracin, which appear to be equally efficacious and considerably cheaper. Although we have learned a great deal about C. difficile in the past decade, a number of fascinating puzzles remain. We know very little about the immune response to this organism or its toxin, or whether a vaccine might someday be feasible. Similarly, we have very little insight into what effects antibodies exert on the normal colonic flora and how these effects allow C. difficile infection in a small percentage of patients. Studies of this pathogen will undoubtedly lead to a fuller understanding of the enormously complex and still mysterious microbial ferment which lives within our gastrointestinal tract. PMID:6369936

  15. The burden of Chagas disease: estimates and challenges.

    PubMed

    Stanaway, Jeffrey D; Roth, Gregory

    2015-09-01

    Chagas disease, caused by infection with the protozoa Trypanosoma cruzi is transmitted most often by Triatominae insect vectors, but also through blood transfusion, organ transplant, and congenital transmission. Between 5 and 18 million people are currently infected and the infection is estimated to cause more than 10,000 deaths annually. The disease has 3 phases: acute, indeterminate, and chronic. The acute phase immediately follows infection. It is typically asymptomatic but produces fever and malaise in up to 5% of people. The indeterminate phase is asymptomatic. More than one-half of those infected will remain in this phase for life and never experience long-term sequelae. After a decade or more, 20% to 30% of people will experience chronic cardiovascular Chagas disease with sequelae including heart failure, arrhythmias, and thromboembolism. Another 15% to 20% will experience chronic digestive sequela including megaesophagus and megacolon. A complete accounting of the burden of Chagas disease requires estimating the prevalence of the infection, the prevalence of each of its sequelae among those with the infection, and the number of deaths attributable to the infection. Attempts to estimate Chagas disease prevalence are complicated by several challenges imposed by the disease's extreme spatial heterogeneity, quickly evolving temporal trends, the decades-long lag between infection and symptomatic disease, biased prevalence data, incomplete recognition of Chagas-attributable deaths, limited data on sequela, and a near total absence of data outside of endemic countries. Even though researchers have found methodological approaches to dealing with these challenges, there is a need for better data.

  16. Severe acute ulcerative colitis: the pediatric perspective.

    PubMed

    Turner, Dan

    2009-01-01

    Many features of pediatric ulcerative colitis (UC) are similar to adult-onset disease, but the rate of extensive disease is doubled in children. It is, therefore, not surprising that the admission rate for severe UC is higher in childhood-onset UC, reaching 28% by the age of 16 years. Approximately 30-40% of children will fail corticosteroids and require second-line medical therapy or colectomy. A pediatric UC activity index (PUCAI) score of >65 indicates severe disease and the index can assist in determining the need and timing of second-line medical therapy or colectomy early during the admission. A PUCAI score of >45 points on day 3 identify patients likely to fail corticosteroids (negative predictive value 90-95%), and a score >70 points on day 5 identify patients who will require short-term treatment escalation (positive predicting value 95-100%). Data in children are limited, but it seems that cyclosporine, tacrolimus and infliximab achieve a similar short-term response rate, in the range of 60-80%. Infliximab has the advantage that it may be given for a prolonged period of time while calcineurin inhibitors should not be used for more than 3-4 months, bridging to a thiopurine regimen. Colectomy is indicated in toxic megacolon or in cases refractory to one salvage therapy. The choice of colectomy in other cases should carefully consider its effect on the patient's quality of life, its impact on the physical and emotional development at a critical age of personality development, and its association with a high infertility rate in females undergoing pouch procedure before childbearing age.

  17. Clostridium difficile Spore-Macrophage Interactions: Spore Survival

    PubMed Central

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

    2012-01-01

    Background Clostridium difficile is the main cause of nosocomial infections including antibiotic associated diarrhea, pseudomembranous colitis and toxic megacolon. During the course of Clostridium difficile infections (CDI), C. difficile undergoes sporulation and releases spores to the colonic environment. The elevated relapse rates of CDI suggest that C. difficile spores has a mechanism(s) to efficiently persist in the host colonic environment. Methodology/Principal Findings In this work, we provide evidence that C. difficile spores are well suited to survive the host’s innate immune system. Electron microscopy results show that C. difficile spores are recognized by discrete patchy regions on the surface of macrophage Raw 264.7 cells, and phagocytosis was actin polymerization dependent. Fluorescence microscopy results show that >80% of Raw 264.7 cells had at least one C. difficile spore adhered, and that ∼60% of C. difficile spores were phagocytosed by Raw 264.7 cells. Strikingly, presence of complement decreased Raw 264.7 cells’ ability to phagocytose C. difficile spores. Due to the ability of C. difficile spores to remain dormant inside Raw 264.7 cells, they were able to survive up to 72 h of macrophage infection. Interestingly, transmission electron micrographs showed interactions between the surface proteins of C. difficile spores and the phagosome membrane of Raw 264.7 cells. In addition, infection of Raw 264.7 cells with C. difficile spores for 48 h produced significant Raw 264.7 cell death as demonstrated by trypan blue assay, and nuclei staining by ethidium homodimer-1. Conclusions/Significance These results demonstrate that despite efficient recognition and phagocytosis of C. difficile spores by Raw 264.7 cells, spores remain dormant and are able to survive and produce cytotoxic effects on Raw 264.7 cells. PMID:22952726

  18. 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.

  19. 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

  20. MANAGEMENT OF ACUTE SEVERE ULCERATIVE COLITIS: A CLINICAL UPDATE

    PubMed Central

    SOBRADO, Carlos Walter; SOBRADO, Lucas Faraco

    2016-01-01

    ABSTRACT Introduction: Acute severe colitis is a potentially lethal medical emergency and, even today, its treatment remains a challenge for clinicians and surgeons. Intravenous corticoid therapy, which was introduced into the therapeutic arsenal in the 1950s, continues to be the first-line treatment and, for patients who are refractory to this, the rescue therapy may consist of clinical measures or emergency colectomy. Objective: To evaluate the indications for and results from drug rescue therapy (cyclosporine, infliximab and tacrolimus), and to suggest a practical guide for clinical approaches. Methods: The literature was reviewed using the Medline/PubMed, Cochrane library and SciELO databases, and additional information from institutional websites of interest, by cross-correlating the following keywords: acute severe colitis, fulminating colitis and treatment. Results: Treatments for acute severe colitis have avoided colectomy in 60-70% of the cases, provided that they have been started early on, with multidisciplinary follow-up. Despite the adverse effects of intravenous cyclosporine, this drug has been indicated in cases of greater severity with an imminent risk of colectomy, because of its fast action, short half-life and absence of increased risk of surgical complications. Therapy using infliximab has been reserved for less severe cases and those in which immunosuppressants are being or have been used (AZA/6-MP). Indication of biological agents has recently been favored because of their ease of therapeutic use, their good short and medium-term results, the possibility of maintenance therapy and also their action as a "bridge" for immunosuppressant action (AZA/6-MP). Colectomy has been reserved for cases in which there is still no response five to seven days after rescue therapy and in cases of complications (toxic megacolon, profuse hemorrhage and perforation). Conclusion: Patients with a good response to rescue therapy who do not undergo emergency

  1. 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

  2. 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

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

    PubMed

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

    2015-08-01

    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

  4. 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

  5. Hirschsprung disease associated with Mowat-Wilson syndrome: report of a case.

    PubMed

    Ferris Villanueva, Elena; Guerrero Bautista, Rocío; Chica Marchal, Amelia

    2015-04-01

    Introducción: La enfermedad de Hirschsprung (EH) o megacolon agangliónico es un trastorno congénito que se caracteriza por la ausencia de células ganglionares intramurales de los plexos mioentéricos submucosos (de Auerbach y Meissner, respectivamente) en tramos distales del intestino, debido al fracaso de la migración de los precursores de estas células desde la cresta neural durante el desarrollo embrionario y asociada a otras anomalías en el 18% restante de los casos, en ocasiones formando parte de síndromes polimalformativos específicos. Objetivo: Este artículo tiene como objetivo presentar la evolución clínica y nutricional de un paciente pediátrico de 14 meses diagnosticado de EH al nacer asociado a MWS, así como evaluar los resultados clínicos de este paciente. Métodos: A través de la revisión de la historia clínica, se estudió la evolución de los datos antropométricos (peso y talla) así como los parámetros analíticos para su valoración. Adicionalmente, se evaluaron las complicaciones asociadas al soporte nutricional y la estrategia terapéutica en el contexto multidisciplinar. Resultados: Paciente de 16 meses, sexo masculino, hijo de padres sanos no consanguíneos inmigrantes de Colombia acude al servicio de urgencias de nuestro hospital por presentar distensión abdominal y vómitos con ausencia de deposiciones espontáneas. Descripción de la composición de la nutrición parenteral recibida durante los 28 días que duró su ingreso hospitalario. Conclusión: La asociación de la enfermedad de Hirschsprung y el síndrome de Mowat-Wilson puede conducir a la necesidad de nutrición parenteral de manera prolongada y presentar con mayor frecuencia desvío del estoma produciéndose un mayor número de complicaciones postoperatorias en estos pacientes, tal y como es el caso de nuestro paciente.

  6. Functional characterization of three mutations of the endothelin B receptor gene in patients with Hirschsprung's disease: evidence for selective loss of Gi coupling.

    PubMed Central

    Fuchs, S.; Amiel, J.; Claudel, S.; Lyonnet, S.; Corvol, P.; Pinet, F.

    2001-01-01

    BACKGROUND: Hirschsprung's disease (HSCR) is one the most common congenital intestinal disease. It leads to aganglionic megacolon in the early childhood. Several susceptibility genes have been identified : RET protooncogene and its ligand, glial cell derived neutrophic factor (GDNF), Sox 10, Endothelin-3 (EDN3) and its receptor B (EDNRB). EDNRB mutations are found in 5% of familial or sporadic HSCR. Only few EDNRB mutations found in HSCR have been explored and some of them seem to be non fonctional variants. MATERIALS AND METHODS: The properties of three mutant human endothelin B receptor (hETB) (G57S, R319W and P383L) in isolated HSCR were analyzed. Stable recombinant cells expressing the three mutants and the wild-type (WT) were established. The hETB receptors were characterized for 125I ET-1 binding, ET-1 induced signaling: calcium transient, AP-1 transcriptional factor activation and cAMP accumulation. RESULTS: Immunofluorescence experiments showed normal cellular distributions of the mutant G57S, R319W and WT hETB receptors. In contrast, the P383L hETB mutant receptor was concentrated near the nucleus and essentially no ET-1 binding was detected. The two other mutants (G57S and R319W) bound ET-1 normally, induced calcium transients and activated the AP-1 pathway in the same way as wild type, but did not inhibit adenylate cyclase. The G57S hETB mutant even stimulated cAMP accumulation which was blocked by pertussis toxin. CONCLUSION: The absence of the P383L mutant receptor from the membrane clearly indicates that this mutation could be involved in HSCR. The G57S and R319W mutant receptors, despite their normal coupling to Gaq, have a defect in the Galphai signaling pathway and the G57S mutation couples to Galphas. These observations allow us to hypothesize that cAMP signaling might be involved in the differenciation of neural cells in the bowel. PMID:11471546

  7. Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era

    PubMed Central

    Polage, Christopher R.; Gyorke, Clare E.; Kennedy, Michael A.; Leslie, Jhansi L.; Chin, David L.; Wang, Susan; Nguyen, Hien H.; Huang, Bin; Tang, Yi-Wei; Lee, Lenora W.; Kim, Kyoungmi; Taylor, Sandra; Romano, Patrick S.; Panacek, Edward A.; Goodell, Parker B.; Solnick, Jay V.; Cohen, Stuart H.

    2016-01-01

    IMPORTANCE Clostridium difficile is a major cause of health care–associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment. OBJECTIVE To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox−/PCR+) for CDI. DESIGN, SETTING, AND PARTICIPANTS Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015. MAIN OUTCOMES AND MEASURES Patients undergoing C difficile testing were grouped by US Food and Drug Administration–approved toxin and PCR tests as Tox+/PCR+, Tox−/PCR+, or Tox−/PCR−. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days. RESULTS Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox−/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients (P < .001 for all). The median duration of diarrhea was shorter in Tox−/PCR+ patients (2 days; interquartile range, 1-4 days) than in Tox+/PCR+ patients (3 days; interquartile range, 1-6 days) (P = .003) and was

  8. [Recent epidemiology of Clostridium difficile infection in Japan].

    PubMed

    Yamagishi, Yuka; Mikamo, Hiroshige

    2015-12-01

    Clostridium difficile (C. difficile) is a major pathogen for diarrhea in hospitalized patients and because of outbreak of highly virulent strain in EU and US, increased length of hospital stay and increased numbers of severe patients and deaths have become major challenges. In recent years, transmissions through community-acquired or food-borne infections are reported. National surveillance has been already performed overseas. Guidelines for preventing C. difficile infection (CDI) is available, and education activities are promoted for preventing the infection spread. Meanwhile, in Japan, medical hospitals are reporting individual CDI incidence, however, a large-scale research has not been conducted up to the present date and therefore the entire status of CDI including infection of the highly virulent strain has yet to be revealed. This time, we performed a questionnaire-based survey at 2,537 hospitals nationwide between April 15, 2013 and May 31, 2013 to investigate CDI incidence, diagnosis and treatment. Valid responses were obtained from 321 hospitals. Regarding the annual number of CDI patients at all the hospitals, the highest group of hospitals responding "1 to 5 patients a year" was 17.8%, and the second highest group of hospitals responding "no patients a year" was 13.1%. In contrast, there was a group of hospitals with "more than 101 patients a year", which was 3.1%. This indicates that there was the difference in the CDI incidences among hospitals. According to the questionnaire results, a highest group of hospitals responding "0-20%" for CDI patients with serious complication such as toxic megacolon, gastrointestinal perforation, ileus paralytic, bacteremia, sepsis, crohn's disease, and ulcerative colitis was 62.6%, and for CDI patients with recurrence more than one, a group of hospitals answering "0 to 20%" was 56.4%, which was the highest. This suggested that there was only a small number of serious CDI patients and recurrence CDI patients in Japan