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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. 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.

  3. [Myotonic dystrophy with marked megacolon: report of a case].

    PubMed

    Kawai, T; Kobari, M; Ohkubo, K; Itoh, H; Kikuchi, M

    1997-11-01

    A 45-year-old woman was incidentally suspected to have megacolon. Chest X-rays showed elevated left diaphragm due to colonic gas, and the heart was deviated to the midline. Barium enema revealed marked dilation of the sigmoid colon, confirming the diagnosis of megacolon. Maximal diameter of the sigmoid colon was 23 cm, but she had no gastrointestinal symptoms. During the work up for megacolon, the presence of myotonic dystrophy was suspected. She had hatchet face, but was not bald. Muscles of the neck and extremities were slightly atrophic. There was percussion myotonia of the tongue and both hands, and grip myotonia of the hands. Laboratory examinations showed impaired glucose tolerance and low level of serum IgG. EMG showed myotonic discharges and myopathic units in the limbs. Brain CT imaging revealed a thick skull. Cases of myotonic dystrophy associated with marked megacolon are rare in Japan. Megacolon presents a high risk for ileus, volvulus, and rupture, and myotonic dystrophy is associated with a high operative and anesthesic risk. Megacolon, therefore, is an important complication to look for in the management of myotonic dystrophy.

  4. Fatal Toxic Megacolon in a Child of Hirschsprung Disease

    PubMed Central

    Sathe, Pragati A; Taware, Annapurna C; Surve, Ketaki M

    2016-01-01

    Hirschsprung disease (HD) in late childhood is uncommon and often undiagnosed or misdiagnosed. However, in a patient with Hirschsprung disease, of greater significance is the occurrence of life threatening enterocolitis. In its more severe form, this is associated with gross dilatation of the colon and profound toxaemia, the combination being termed toxic megacolon. Because of its relative rarity, we report a case of 10-year-old child who had a history of chronic constipation for nine years. He later developed complications and presented to the emergency department with toxic megacolon, a rare occurrence due to neglected constipation. Though patient’s condition was unstable, laparotomy with right transverse colostomy was performed after appropriate intravenous rehydration. The dilated bowel loops were decompressed and intraoperatively multiple site biopsies were done. Histopathological examination of transition zone biopsy revealed absence of ganglion cells suggestive of Hirschsprung disease. But few hours later patient’s condition worsened and he succumbed. PMID:28208866

  5. Relation between mast cells concentration and serotonin expression in chagasic megacolon development.

    PubMed

    de Freitas, Michelle Aparecida Ribeiro; Segatto, Nathália; Tischler, Natália; de Oliveira, Enio Chaves; Brehmer, Axel; da Silveira, Alexandre Barcelos Morais

    2017-01-23

    Chagas' disease still reaching about 10 million people in the world. In South America, one of the most severe forms of this disease is the megacolon, characterized by severe constipation, dilated sigmoid colon and rectum and severe malnutrition. Previous data suggested that mast cells and serotonin (5-HT) expression could be involved in intestinal homeostasis control, avoiding the chagasic megacolon development. The aim at this study was to characterize the presence of mast cells and expression of serotonin in chagasic patients with and without megacolon and evaluate the relation between mast cells, serotonin and megacolon development. Our results demonstrated that patients without megacolon feature a large amount of serotonin and few mast cells, while patients with megacolon feature low serotonin expression and a lot of mast cells. We believe that serotonin may be involved in the inflammatory process control, triggered by mast cells, and the presence of this substance in large quantities of the intestine could represent a mechanism of megacolon prevention. This article is protected by copyright. All rights reserved.

  6. Toxic megacolon during pregnancy in ulcerative colitis: A case report

    PubMed Central

    Quddus, Ayyaz; Martin-Perez, Beatriz; Schoonyoung, Henry; Albert, Matthew; Atallah, Sam

    2015-01-01

    Introduction Ulcerative colitis is an idiopathic inflammatory bowel condition whose peak incidence coincides with fertility in female patients. In pregnancy, acute fulminant colitis is rare, and, when it becomes refractory to maximum medical therapy, emergency colectomy is mandated. Over the past quarter century, there have been few reports of this rare event in the literature. Presentation of case We report a 26 year old primigravida female who presented with toxic megacolon during the third trimester of pregnancy, unresponsive to medical therapy. She subsequently underwent an urgent low transverse caesarean section with a total colectomy. Both mother and child made a satisfactory recovery post operatively. Discussion Although the fetus is at higher risk than the mother in such a circumstance, morbidity and mortality rates are still noticeably high for both, and therefore, prompt diagnosis is key. Conclusion It is imperative that female patients planning to conceive with a known diagnosis of ulcerative colitis liaise with their obstetricians and gastroenterologists early to optimise medical treatment to prevent the development of a toxic megacolon and that conception is planned during a state of remission. Should surgical intervention become required, this can be performed with favourable outcomes for mother and child, as demonstrated in this report. PMID:25942749

  7. Blowhole Colostomy for Clostridium difficile-Associated Toxic Megacolon

    PubMed Central

    Kerstens, Jeroen; de Gheldere, Charles; Vanclooster, Patrick

    2016-01-01

    We present the case of a 58-year-old man who underwent urgent blowhole colostomy for toxic megacolon (TM) secondary to Clostridium difficile infection (CDI). This infection occurred under antibiotic coverage with amoxicillin-clavulanic acid, four days after laparoscopic sigmoidectomy in our hospital. Although prospective clinical research regarding the surgical management of TM is lacking, decompressive procedures like blowhole colostomy are reported to carry a high risk of postoperative morbidity and mortality and are widely regarded as obsolete. Subtotal or total colectomy with end ileostomy is currently considered the procedure of choice. After presenting our case, we discuss the literature available on the subject to argue that the scarce evidence on the optimal surgical treatment for TM is primarily based on TM associated with inflammatory bowel diseases (IBD) and that there might be a rationale for considering minimally invasive procedures like blowhole colostomy for CDI-associated TM. PMID:28097034

  8. [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.

  9. Trypanosomiasis-Induced Megacolon Illustrates How Myenteric Neurons Modulate the Risk for Colon Cancer in Rats and Humans

    PubMed Central

    Kannen, Vinicius; de Oliveira, Enio C.; Motta, Bruno Zene; Chaguri, Annuar Jose; Brunaldi, Mariângela Ottoboni; Garcia, Sérgio B.

    2015-01-01

    Background Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to megacolon. Very little is known about the risk for colon cancer in chagasic megacolon patients. To clarify whether chagasic megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi) infected patients and rats. Methods Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards. Results No colon tumors were found in chagasic megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas’ megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2nd wk onward, which ensued having the colon myenteric denervation significantly induced. Conclusion/Significance Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research. PMID:25884710

  10. Oesophageal manometric studies in patients with chronic Chagas disease and megacolon

    PubMed Central

    Heitmann, Peter; Espinoza, Julio

    1969-01-01

    Intraluminal manometric studies performed on 12 patients with chronic Chagas disease and megacolon without clinical or radiological abnormalities of the oesophagus showed no alteration in oesophageal physiology under basal conditions when compared with a control group of 30 healthy subjects. Oesophageal peristalsis was unimpaired. Patients with chronic Chagas disease and megacolon differed from normals in their reaction to a small dose of a cholinergic drug. This agent induced an isolated but significant increase in resting pressure at the level of the oesophagogastric sphincter, accompanied in most cases by an increase in spontaneous activity but not by a change in resting pressure in the body of the oesophagus. This is interpreted as a subclinical expression of oesophageal pathology related to Chagas disease. PMID:4981710

  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. A case of toxic megacolon caused by clostridium difficile infection and treated with fecal microbiota transplantation.

    PubMed

    Gweon, Tae Geun; Lee, Kyung Jin; Kang, Dong Hoon; Park, Sung Soo; Kim, Kyung Hoon; Seong, Hyeon Jin; Ban, Tae Hyun; Moon, Sung Jin; Kim, Jin Su; Kim, Sang Woo

    2015-03-01

    Clostridium difficile infection. The mortality rate of fulminant C. difficile infection is reported to be as high as 50%. Fecal microbiota transplantation is a highly effective treatment in patients with recurrent or refractory C. difficile infection. However, there are few published articles on the use of such transplantation for fulminant C. difficile infection. Here, we report on a patient with toxic megacolon complicated by C. difficile infection who was treated successfully with fecal mi-crobiota transplantation. (Gut Liver, 2015;9:247-250).

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

    PubMed

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

    2015-08-14

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

  14. Toxic megacolon from fulminant Clostridium difficile infection induced by topical silver sulphadiazine.

    PubMed

    Tan, Christopher B; Rajan, Dhyan; Shah, Mitanshu; Ahmed, Shadab; Freedman, Lester; Rizvon, Kaleem; Mustacchia, Paul

    2012-08-08

    Pseudomembranous colitis and toxic megacolon (TM) are well-known complications of Clostridium difficile infections. Systemic antibiotic is considered as the major risk factor for the development of C difficile colitis. However, topical antibiotics are rarely associated with the infection. As previously thought, the use of topical antibiotic is capable of systemic absorption in damaged and denuded skin; sufficient enough to suppress the normal bowel flora. Here, we present an unusual case of TM from C difficile infection induced by topical silver sulphadiazine in a 60-year-old man with immune-bullous pemphigus vulgaris. The diagnosis is further complicated by the absence of diarrhoea as the initial presentation. Despite adequate medical and surgical intervention, the patient had an unfavourable outcome.

  15. Severe hyponatremia and repeated intestinal resections for intestinal dysmotility mimicking congenital aganglionic megacolon due to delay in the diagnosis of congenital hypothyroidism

    PubMed Central

    Buyukyilmaz, Gonul; Baltu, Demet; Soyer, Tutku; Tanyıldız, Murat

    2016-01-01

    Congenital hypothyroidism (CH) may present with nonspecific signs and symptoms, though, majority of infants can be asymptomatic. Therefore, understimation and delay in diagnosis may result in severe complications. A 5-month-old female admitted to our clinic with the history of repeated surgical operations due to the diagnosis of congenital aganglionic megacolon. Investigations performed in our clinic revealed the diagnosis of congenital (primary) hypothyroidism due to thyroid agenesis. Histopathologic evaluation of previously resected colon sample revealed normal ganglionic cell included colon. During follow-up she developed severe hyponatremia with a plasma sodium level of 106 mEq/L. Eunatremia was maintained following achievement of euthyroid state. In conclusion, since presenting symptoms can be variable and nonspecific, hypotyhroidism should be kept in mind in the differential diagnosis of patients with persistent abdominal distention mimicking aganglionic megacolon and severe hyponatremia of unknown origin. PMID:28164077

  16. Severe hyponatremia and repeated intestinal resections for intestinal dysmotility mimicking congenital aganglionic megacolon due to delay in the diagnosis of congenital hypothyroidism.

    PubMed

    Buyukyilmaz, Gonul; Baltu, Demet; Soyer, Tutku; Tanyıldız, Murat; Demirbilek, Huseyin

    2016-12-01

    Congenital hypothyroidism (CH) may present with nonspecific signs and symptoms, though, majority of infants can be asymptomatic. Therefore, understimation and delay in diagnosis may result in severe complications. A 5-month-old female admitted to our clinic with the history of repeated surgical operations due to the diagnosis of congenital aganglionic megacolon. Investigations performed in our clinic revealed the diagnosis of congenital (primary) hypothyroidism due to thyroid agenesis. Histopathologic evaluation of previously resected colon sample revealed normal ganglionic cell included colon. During follow-up she developed severe hyponatremia with a plasma sodium level of 106 mEq/L. Eunatremia was maintained following achievement of euthyroid state. In conclusion, since presenting symptoms can be variable and nonspecific, hypotyhroidism should be kept in mind in the differential diagnosis of patients with persistent abdominal distention mimicking aganglionic megacolon and severe hyponatremia of unknown origin.

  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. 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

  19. 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

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

    PubMed

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

    2015-03-01

    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.

  1. 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.

  2. Types of Ulcerative Colitis

    MedlinePlus

    ... total) Colitis Affects the entire colon. Symptoms include diarrhea, severe abdominal pain, cramps, and extensive weight loss. Potentially serious complications include massive bleeding and acute dilation of the colon (toxic megacolon), which may ...

  3. Hirschsprung disease

    MedlinePlus

    ... megacolon References Bass LM, Wershil BK. Anatomy, histology, embryology, and developmental anomalies of the small and large ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  4. 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

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

    PubMed Central

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

    2016-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

  7. 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.

  8. 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

  9. Anatomic modifications in the enteric nervous system of piebald mice and physiological consequences to colonic motor activity.

    PubMed

    Ro, Seungil; Hwang, Sung Jin; Muto, Melodie; Jewett, William Keith; Spencer, Nick J

    2006-04-01

    It has been assumed that in piebald lethal mice that develop megacolon, impaired colonic motor activity is restricted to the aganglionic distal colon. Peristaltic mechanical recordings, immunohistochemistry, and quantitative PCR were used to investigate whether regions of the colon, other than the aganglionic segment, may also show anatomical modifications and dysfunctional colonic motor activity. Contrary to expectations, colonic migrating motor complexes (MMCs) were absent along the whole colon of piebald lethal homozygote mice and severely impaired in heterozygote siblings. Aganglionosis was detected not only in the distal colon of piebald homozygote lethal mice (mean length: 20.4 +/- 2.1 mm) but also surprisingly in their heterozygote siblings (mean length: 12.4 +/- 1.1 mm). Unlike homozygote lethal mice, piebald heterozygotes showed no signs of megacolon. Interestingly, mRNA expression for PGP 9.5 was also dramatically reduced (by 71-99%) throughout the entire small and large bowel in both homozygote lethal and heterozygous littermates (by 67-87%). Histochemical staining confirmed a significant reduction in myenteric ganglia along the whole colon. In summary, the piebald mutation in homozygote lethal and heterozygote siblings is associated with dramatic reductions in myenteric ganglia throughout the entire colon and not limited to the distal colon as originally thought. Functionally, this results in an absence or severe impairment of colonic MMC activity in both piebald homozygote lethal and heterozygote siblings, respectively. The observation that piebald heterozygotes have an aganglionic distal colon (mean length: 12 mm) but live a normal murine life span without megacolon suggests that aganglionosis >12 mm and the complete absence of colonic MMCs may be required before any symptoms of megacolon arise.

  10. Intra-Abdominal Hypertension Causes Bacterial Growth in Lungs: An Animal Study

    PubMed Central

    Papakrivou, Eleni; Manoulakas, Efstratios; Mitroudi, Magda; Tepetes, Konstantinos; Papazoglou, Konstantinos; Zakynthinos, Epaminondas

    2017-01-01

    To study the effect of intra-abdominal hypertension (IAH) on the frequency of pneumonia with an experimental study, thirteen Sprague-Dawley rats were included. Eight out of thirteen animals were randomly assigned to receive 10 ml of benzalkonium chloride 0.2% (megacolon group) and five animals received 10 ml NaCl 0.9% (controls). Animals were anaesthetized by intramuscular delivery of ketamine. The incidence of positivity for bacteria lung tissue cultures and mesenteric lymph node cultures was assessed at the 21st day after animals' sacrification, or before in case of death. All megacolon group animals presented progressive increase of the abdomen and increased IAP (≥10 mmHg) whereas the frequency of their evacuations was almost eliminated. Controls presented normal evacuations, no sign of abdominal distention, and normal IAP. In megacolon group animals, there was evidence of significant amount of bacteria in lung cultures. In contrast, no bacteria were found in control animals. PMID:28357400

  11. Successful Treatment of Clostridium difficile Bacteremia with Aortic Mycotic Aneurysm in a Patient with Prior Endovascular Aortic Aneurysm Repair

    PubMed Central

    Brauch, Rebecca; Cherabuddi, Kartikeya

    2017-01-01

    The clinical spectrum of Clostridium difficile infection can range from benign gastrointestinal colonization to mild diarrhea and life threatening conditions such as pseudomembranous colitis and toxic megacolon. Extraintestinal manifestations of C. difficile are rare. Here, we report a patient with a history of an endovascular aortic aneurysm repair (EVAR) presenting with an endovascular leak complicated by C. difficile bacteremia and a mycotic aneurysm. He was successfully treated with an explant of the EVAR, an aorto-left renal bypass, and aorto-bi-iliac bypass graft placement along with a six-week duration of intravenous vancomycin and oral metronidazole. PMID:28348903

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

    NASA Astrophysics Data System (ADS)

    Surawicz, Christina M.

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

  13. Elective and emergent operative management of ulcerative colitis.

    PubMed

    Metcalf, Amanda M

    2007-06-01

    Surgical therapy of ulcerative colitis is effective, safe, and provides an improved quality of life in those whose disease cannot be managed medically. In the elective setting, widespread acceptance of restorative proctocolectomy has made surgical therapy an attractive option in the overall management of ulcerative colitis. Enthusiasm for this procedure should be tempered by the acknowledgment of the significant incidence of pouchitis in the long term, however. Proctocolectomy with ileostomy remains a good surgical option for patients who are unsuitable for restorative procedures. The standard therapy for fulminant colitis or toxic megacolon remains subtotal colectomy with ileostomy. Patients undergoing subtotal colectomy are candidates for conversion to restorative procedures.

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

    PubMed Central

    Morabito, Giuliana; Romeo, Claudia; Romano, Claudio

    2014-01-01

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

  15. 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.

  16. [Xipho-omphalopagus--Siamese twins with multiple abnormalities of the gastrointestinal tract].

    PubMed

    Janec, M; Vojtko, M; Kubíková, E

    1989-09-01

    The authors describe a case of xiphoomphalpagus; one infant was dead, the other alive. They had a common umbilical cord and omphalocele, joined liver, only one gallbladder and common duodenum in the shape of a wide sac. From this originated two thin guts, one was wide and belonged to the dead foetus, the gut of the live foetus beneath the duodenum was atretic. Already six hours after delivery the authors separated the infants and in the live infant they not only resected the liver and reinserted the choledochus but also repaired the wide duodenum and atresia. The second infant died on the 4th day after operation from congenital heart disease incompatible with life. The stillborn infant has, as revealed by necropsy and histological examination, a congenital megacolon. The authors analyze the scope of diagnostic and surgical possibilities.

  17. William Arbuthnot Lane (1856-1943): Surgical Innovator and His Theory of Autointoxication.

    PubMed

    Morris, Mackenzie; Price, Thea; Cowan, Scott W; Yeo, Charles J; Phillips, Benjamin

    2017-01-01

    William Arbuthnot Lane contributed to the advancement of many fields of orthopedics, otolaryngology, and general surgery. He is credited for his "no-touch technique" and the invention of long-handled instruments, some of which are still in use today, to minimize tissue handling. He is most well known for his hypothesis that slowing of gastric contents could cause a variety of ailments and this became known as Lane's disease. Although his surgical treatment of Lane's disease is now defunct, it advanced the surgical technique in colorectal surgery. It seems likely that some of Lane's "autointoxication" patients would be classified today as patients with colonic inertia, diverticulitis, colonic volvulus, and megacolon or, which are all treated with colectomy. Lane was a pioneer in multiple fields and a true general surgeon. He advanced colorectal surgery immensely and propelled the field of surgery into a new era.

  18. [Management of severe ulcerative colitis: An up-to-date].

    PubMed

    Hernández-Rocha, Cristian; Ibáñez, Patricio; Molina, María Elena; Klaassen, Julieta; Valenzuela, Andrea; Candia, Roberto; Bellolio, Felipe; Zúñiga, Álvaro; Miguieles, Rodrigo; Miquel, Juan Francisco; Chianale, José; Álvarez-Lobos, Manuel

    2017-01-01

    Ulcerative Colitis (UC) is a chronic inflammatory disease involving the colon, with alternating periods of remission and activity. Exacerbations can be severe and associated with complications and mortality. Diagnosis of severe UC is based on clinical, biochemical and endoscopic variables. Patients with severe UC must be hospitalized. First line therapy is the use of intravenous corticoids which achieve clinical remission in most patients. However, 25% of patients will be refractory to corticoids, situation that should be evaluated at the third day of therapy. In patients without response, cytomegalovirus infection must be quickly ruled out to escalate to second line therapy with biological drugs or cyclosporine. Total colectomy must not be delayed if there is no response to second line therapy, if there is a contraindication for second line therapies or there are complications such as: megacolon, perforation or massive bleeding. An active management with quick escalation on therapy allows to decrease the prolonged exposure to corticoids, reduce colectomy rates and its perioperative complications.

  19. Characterization of T cell clones from chagasic patients: predominance of CD8 surface phenotype in clones from patients with pathology.

    PubMed

    Cuna, W R; Cuna, C R

    1995-01-01

    Human Chagas' disease, caused by the protozoan Trypanosoma cruzi, is associated with pathological processes whose mechanisms are not known. To address this question, T cell lines were developed from chronic chagasic patients peripheral blood mononuclear cells (PBMC) and cloned. These T cell clones (TCC) were analyzed phenotypically with monoclonal antibodies by the use of a fluorescence microscope. The surface phenotype of the TCC from the asymptomatic patient were predominantly CD4 positive (86%). On the contrary, the surface phenotype CD8 was predominant in the TCC from the patients suffering from cardiomegaly with right bundle branch block (83%), bradycardia with megacolon (75%) and bradycardia (75%). Future studies will be developed in order to identify the antigens eliciting these T cell subpopulations.

  20. 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.

  1. Direct regulation of the Microphthalmia promoter by Sox10 links Waardenburg-Shah syndrome (WS4)-associated hypopigmentation and deafness to WS2.

    PubMed

    Lee, M; Goodall, J; Verastegui, C; Ballotti, R; Goding, C R

    2000-12-01

    The transcription factor Sox10 is genetically linked with Waardenburg syndrome 4 (WS4) in humans and the Dominant megacolon (Dom) mouse model for this disease. The pigmentary defects observed in the Dom mouse and WS4 are reminiscent of those associated with mutations in the microphthalmia (Mitf) gene, which encodes a transcription factor essential for the development of the melanocyte lineage. We demonstrate here that wild type Sox10 directly binds and activates transcription of the MITF promoter, whereas a mutant form of the Sox10 protein genetically linked with WS4 acts as a dominant-negative repressor of MITF expression and can reduce endogenous MITF protein levels. The ability of Sox10 to activate transcription of the MITF promoter implicates Sox10 in the regulation of melanocyte development and provides a molecular basis for the hypopigmentation and deafness associated with WS4.

  2. [Giant Meckel's diverticulum in an adult].

    PubMed

    Rivas, Tomas Contreras; Gallardo, Nasser Eluzen; Valenzuela, Sebastian King; Pezoa, María Elena Molina; Zúñiga, José Miguel; Muñoz, Carol Bustamante; Saralic, Biserka Spralja

    2014-10-07

    Meckel's diverticulum results from a partial persistence of the omphalomesenteric duct and is the most common congenital anomaly of the gastrointestinal tract, affecting about 2% of the general population. Its presentation as a giant Meckel's diverticulum (>5 cm) is rare and is associated with major complications. We report a case of a 53 year-old woman with constipation for at least ten years. A colonoscopy from eight years ago suggested megacolon. The patient consults in the last month for abdominal pain associated with anorexia. The computed tomography scan image suggested an ileal megadiverticulum. An exploratory laparotomy revealed a saccular dilatation of the distal ileum of 6 x 15.5 cm, located 20 cm away from the ileocecal valve. We resected the involved segment of distal ileum and performed a manual ileo-ascendo anastomosis. The biopsy showed a saccular dilatation of the wall, lined by small intestinal mucosa with areas of gastric metaplasia, supporting the diagnosis of giant Meckel's diverticulum.

  3. 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

  4. 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

  5. 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.

  6. Giant Fecaloma Causing Small Bowel Obstruction: Case Report and Review of the Literature.

    PubMed

    Mushtaq, Mosin; Shah, Mubashir A; Malik, Aijaz A; Wani, Khurshid A; Thakur, Natasha; Q Parray, Fazl

    2015-04-01

    Fecaloma is a mass of hardened feces being impacted mostly in rectum and sigmoid. The most common sites of the fecaloma is the sigmoid colon and the rectum. There are several causes of fecaloma and have been described in association with Hirschsprung's disease, psychiatric patients, Chagas disease, both inflammatory and neoplastic, and in patients suffering with chronic constipation. Up to now several cases of giant fecaloma has been reported in the literature most of them presenting with megacolon or urinary retention. We herein report a case of giant fecaloma leading to bowel obstruction who was successfully treated by surgery. A 30-yrar-old man presented with sign and symptoms of acute bowel obstruction. He underwent exploratory laparotomy and enterotomy. He was found to have a giant fecaloma causing bowel obstruction in the jejunum. He was discharged after the operation with good condition. Jejunal fecaloma is extremely rare condition.

  7. [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.

  8. Characterization of clinical Clostridium difficile isolates by PCR ribotyping and detection of toxin genes in Austria, 2006-2007.

    PubMed

    Indra, A; Schmid, D; Huhulescu, S; Hell, M; Gattringer, R; Hasenberger, P; Fiedler, A; Wewalka, G; Allerberger, F

    2008-06-01

    In order to assess the lethality of Clostridium difficile-associated disease (CDAD) and the PCR ribotypes prevalent in Austria, the Austrian Agency for Health and Food Safety requested isolates of C. difficile from patients in a structured but arbitrary sampling scheme. In the allocated period from February 2006 to January 2007, local hospital laboratories within each of the nine provinces were asked to submit C. difficile isolates from at least ten cases of CDAD. Confirmation of species identification, toxin detection, susceptibility testing against four antimicrobial agents and typing using a PCR ribotyping method were performed at the reference laboratory. In total, 149 isolates of putative C. difficile were submitted, from which 142 were included for study. Antimicrobial susceptibility patterns revealed resistance to clindamycin in 57% and high-level resistance to moxifloxacin in 38% of isolates tested. CDAD manifested as diarrhoea (including eight cases of bloody diarrhoea) in 126 cases (88.7%), as pseudomembranous colitis in 15 cases (10.6%) and as toxic megacolon in one case. Twelve of the 142 patients died within 30 days of specimen collection (8.45% lethality). A lethal outcome occurred in 2/15 cases (13.3%) when pseudomembranous colitis was present and in 10/126 cases (7.9%) in the absence of pseudomembranous colitis or toxic megacolon. Among the 142 isolates from 25 health-care facilities, 41 PCR ribotype patterns were found. The most frequent ribotypes were AI-5 (including six lethal cases out of 26 patients), 014 (two out of 24) and 053 (one out of 24). The typing patterns demonstrated the occurrence of clusters in hospitals.

  9. Inflammation and glandular duct dilatation of the tongue from patients with chronic Chagas disease.

    PubMed

    de Lima Pereira, Sanívia Aparecida; Rodrigues, Denise Bertulucci Rocha; da Fonseca Ferraz, Mara Lúcia; da Cunha Castro, Eumenia Costa; dos Reis, Marlene Antonia; de Paula Antunes Teixeira, Vicente

    2006-01-01

    The purpose of this study was to evaluate morphologically the tongue of individuals with chronic Chagas disease (CD) in comparison to the non-chagasic ones. Twenty-four protocol cases of autopsies were selected. They were subdivided into CD patients (10 cases) and non-chagasic ones (14 cases). The morphometric analysis was accomplished for the tongue muscle and salivary glands duct lumen area. In three CD patients, perineuritis was found, and two of them showed megaesophagus and megacolon. The intensity of the inflammation in the von Ebner's glands, the tongue muscles, and the salivary glands duct lumen area was significantly higher in the CD patients. We concluded that the CD patients show salivary glands duct dilatation, which probably would have a relation with alterations in the autonomic nervous system. The inflammation found in CD patients is in accordance with that described in comparative studies on the digestive tract and heart. These morphological findings suggest that the histopathological analysis of the tongue associated with other organs, or even in an isolated manner, can add in the diagnosis and pathogenesis of the CD chronic phase.

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

    PubMed

    Reissmann, Monika; Ludwig, Arne

    2013-01-01

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

  11. Structural Basis of Proline-Proline Peptide Bond Specificity of the Metalloprotease Zmp1 Implicated in Motility of Clostridium difficile.

    PubMed

    Schacherl, Magdalena; Pichlo, Christian; Neundorf, Ines; Baumann, Ulrich

    2015-09-01

    Clostridium difficile is a pathogenic bacterium causing gastrointestinal diseases from mild diarrhea to toxic megacolon. In common with other pathogenic bacteria, C. difficile secretes proteins involved in adhesion, colonization, and dissemination. The recently identified Zmp1 is an extracellular metalloprotease showing a unique specificity for Pro-Pro peptide bonds. The endogenous substrates of Zmp1 are two surface proteins implicated in adhesion of C. difficile to surface proteins of human cells. Thus, Zmp1 is believed to be involved in the regulation of the adhesion-motility balance of C. difficile. Here, we report crystal structures of Zmp1 from C. difficile in its unbound and peptide-bound forms. The structure analysis revealed a fold similar to Bacillus anthracis lethal factor. Crystal structures in the open and closed conformation of the S-loop shed light on the mode of binding of the substrate, and reveal important residues for substrate recognition and the strict specificity of Zmp1 for Pro-Pro peptide bonds.

  12. Severe hypercalcaemia and colon ischaemia: dehydration as an unusual cause?

    PubMed Central

    Fernandes, Liliana Gil; Ferreira, Nuno Ribeiro; Cardiga, Rosa; Póvoa, Pedro

    2015-01-01

    Hypercalcaemia is an emergency with severe consequences. Dehydration can be an uncommon cause of hypercalcaemia, as seen in this case. A 63-year-old woman with type 2 diabetes mellitus, hypothyroidism and osteoporosis, was admitted to the emergency room with abdominal distension and vomiting for 24 h. Initial evaluation was Hg 18.5 g/dL, Htc 56.2%, creatinine 2 mg/dL, metabolic acidaemia, lactate 8.3 mmol/L, anion gap 19, total Ca2+ 17.7 mg/dL and PO4+ 6.6 mg/dL. CT revealed colonic distension without obstruction or ischaemia. Renal replacement therapy and pamidronate were initiated. The patient's clinical condition deteriorated with septic shock in the context of toxic megacolon and she underwent an emergency subtotal colectomy (10 kg). Hypercalcaemia was corrected in 24 h with aggressive fluid replacement (8 L NaCl 0.9% first 12 h), with a reduction of total Ca2+ to 8.2 mg/dL. Other causes of hypercalcaemia were excluded. ‘Hypercalcaemic crisis’ secondary to severe acute dehydration is not mentioned in the literature. PMID:25809432

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

    PubMed Central

    Carroll, Karen C.

    2013-01-01

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

  14. 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. Clinical approach to severe Clostridium difficile infection: update for the hospital practitioner.

    PubMed

    Pant, Chaitanya; Sferra, Thomas J; Deshpande, Abhishek; Minocha, Anil

    2011-12-01

    The rising incidence of Clostridium difficile (C. difficile) infection or CDI is now a problem of pandemic proportions. The NAP1 hypervirulent strain of C. difficile is responsible for a majority of recent epidemics and the widespread use of fluoroquinolone antibiotics may have facilitated the selective proliferation of this strain. The NAP1 strain also is more likely to cause severe and fulminant colitis characterized by marked leukocytosis, renal failure, hemodynamic instability, and toxic megacolon. No single test suffices to diagnose severe CDI, instead; the clinician must rely on a combination of clinical acumen, laboratory testing, and radiologic and endoscopic modalities. Although oral vancomycin and metronidazole are considered standard therapies in the medical management of CDI, recently it has been demonstrated that vancomycin is the more effective antibiotic in cases of severe disease. Moreover, early surgical consultation is necessary in patients who do not respond to medical therapy or who demonstrate rising white blood cell counts or hemodynamic instability indicative of fulminant colitis. Subtotal colectomy with end ileostomy is the procedure of choice for fulminant colitis. When applied to select patients in a judicious and timely fashion, surgery can be a life-saving intervention. In addition to these therapeutic approaches, several investigational treatments including novel antibiotics, fecal bacteriotherapy and immunotherapy have shown promise in the care of patients with severe CDI.

  17. 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

  18. 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.

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

    PubMed Central

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

    2015-01-01

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

  20. Defecatory disorders, anorectal and pelvic floor dysfunction: a polygamy? Radiologic and manometric studies in 41 patients.

    PubMed

    Siproudhis, L; Ropert, A; Lucas, J; Raoul, J L; Heresbach, D; Bretagne, J F; Gosselin, M

    1992-06-01

    A consecutive series of 41 patients with defecatory disorders was prospectively studied by anal manometry and evacuation proctography to determine the relationship between abnormalities and symptoms. The patients (29 female, 12 male, aged 41 +/- 2.3 years) all complained of difficulty in evacuation. All had normal colonoscopy and biochemistry. There was no evidence of megacolon or megarectum, and no symptoms had been previously treated by pelvic floor surgery. All subjects completed detailed questionnaires related to gastrointestinal symptoms with special reference to excessive straining and discomfort, digital manipulations during defecation, a sense of pelvic heaviness and incomplete evacuation. Each patient underwent clinical examination, anal manometry and defecography during a single outpatient visit. Rectocele (16 patients) was significantly associated with vaginal digitation, lower stool frequency, delayed rectal emptying and decreased rectal sensation to distension. Increased anal pressure on straining (14 patients) was also related to a poor rectal emptying in 13 patients. Neither perineal descent (24 patients) nor external rectal prolapse (12 patients) was related to objective obstruction. Nevertheless there was an association with pelvic heaviness and lower anal manometric recordings. Five among 16 patients with rectocele had manometric anismus. Forty percent of patients with intussusception also had a paradoxical sphincter response during defaecation. Furthermore, associated abnormalities were extremely common (34 of 41 patients), accurate interpretation of which was necessary for planning effective therapy.

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

    PubMed Central

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

    2014-01-01

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

  2. Clinical forms of Trypanosoma cruzi infected individuals in the chronic phase of Chagas disease in Puebla, Mexico.

    PubMed

    Sánchez-Guillén, María Del Carmen; López-Colombo, Aurelio; Ordóñez-Toquero, Guillermo; Gomez-Albino, Isidoro; Ramos-Jimenez, Judith; Torres-Rasgado, Enrique; Salgado-Rosas, Hilda; Romero-Díaz, Mónica; Pulido-Pérez, Patricia; Pérez-Fuentes, Ricardo

    2006-11-01

    In Mexico, despite the relatively high seroprevalence of Trypanosoma cruzi infection in humans in some areas, reported morbidity of Chagas disease is not clear. We determined clinical stage in 71 individuals seropositive to T. cruzi in the state of Puebla, Mexico, an area endemic for Chagas disease with a reported seroprevalence of 7.7%. Diagnosis of Chagas disease was made by two standardized serological tests (ELISA, IHA). Individuals were stratified according to clinical studies. All patients were submitted to EKG, barium swallow, and barium enema. Groups were identified as indeterminate form (IF) asymptomatic individuals without evidence of abnormalities (n = 34 cases); those with gastrointestinal alterations (12 patients) including symptoms of abnormal relaxation of the lower esophageal sphincter and absent peristalsis in the esophageal body, grade I megaesophagus, and/or megacolon; patients with clinical manifestations and documented changes of chronic Chagas heart disease who were subdivided as follows: mild (8 patients)--mild electrocardiographic changes of ventricular repolarization, sinus bradychardia); moderate (6 patients)--left bundle branch block, right bundle branch block associated with left anterior fascicular block); severe (8 patients)--signs of cardiomegaly, dilated cardiomyopathy); and the associated form (3 cases) that included presence of both cardiomyopathy and megaesophagus. These data highlight the importance of accurate evaluation of the prevalence and clinical course of Chagas disease in endemic and non-endemic areas of Mexico.

  3. Outcomes in patients tested for Clostridium difficile toxins

    PubMed Central

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

    2012-01-01

    Clostridium difficile testing is shifting from toxin detection to C. difficile detection. Yet, up to 60% of patients with C. difficile by culture test negative for toxins and it is unclear if they are infected or carriers. We reviewed medical records for 7,046 inpatients with a C. difficile toxin test from 2005–2009 to determine the duration of diarrhea and rate of complications and mortality among toxin-positive (toxin+) and toxin− patients. Overall, toxin− patients had less severe diarrhea, fewer diarrhea days and lower mortality (P<0.001, all comparisons) than toxin+ patients. One toxin− patient (n=1/6,121; 0.02%) was diagnosed with pseudomembranous colitis but there were no complications such as megacolon or colectomy for fulminant CDI among toxin− patients. These data suggest that C. difficile-attributable complications are rare among patients testing negative for C. difficile toxins and more studies are needed to evaluate the clinical significance of C. difficile detection in toxin− patients. PMID:23009731

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

    PubMed

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

    2015-02-01

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

  5. 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.

  6. [Selected aspects of Clostridium difficile infection].

    PubMed

    Mehlich, Agnieszka; Górska, Sabina; Gamian, Andrzej; Myc, Andrzej

    2015-05-05

    Clostridium difficile pathogen is a cause of the most frequent nosocomial infection, which is antibiotic-associated diarrhea. Antibiotic treatment causes disruption of the microbiome balance, which makes the gut a friendly environment for the pathogen. It leads to pseudomembranous colitis, toxic megacolon and even death. Clostridium difficile infection (CDI) is particularly dangerous to elderly patients, leading to the highest mortality rate. C. difficile is equipped with many virulence factors such as toxin A and B, binary toxin CDT, flagellum, S-layer proteins, Cwp66 and GroEL proteins, protease Cwp84, fibronectin-binding protein and the ability to form biofilm and spores. Problems with anti-CDI therapy prompt researchers and clinicians to seek alternative ways of therapy. Identification of immunological epitopes in outer layer proteins and the use of them as antigens for anti-CDI vaccines would be a rational approach to prevent the disease, but unfortunately such vaccines are not available yet. In this article we review the course of the disease, virulence and risk factors. We summarize briefly epidemiological data and the latest achievements in CDI treatment.

  7. Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

    PubMed

    Martins, Patrícia Rocha; Nascimento, Rodolfo Duarte; Lopes, Júlia Guimarães; Santos, Mônica Morais; de Oliveira, Cleida Aparecida; de Oliveira, Enio Chaves; Martinelli, Patrícia Massara; d'Ávila Reis, Débora

    2015-05-01

    Megacolon is frequently observed in patients who develop the digestive form of Chagas disease. It is characterized by dilation of the rectum-sigmoid portion and thickening of the colon wall. Microscopically, the affected organ presents denervation, which has been considered as consequence of an inflammatory process that begins at the acute phase and persists in the chronic phase of infection. Inflammatory infiltrates are composed of lymphocytes, macrophages, natural killer cells, mast cells, and eosinophils. In this study, we hypothesized that mast cells producing tryptase could influence the migration and the activation of eosinophils at the site, thereby contributing to the immunopathology of the chronic phase. We seek evidence of interactions between mast cells and eosinophils through (1) evaluation of eosinophils, regarding the expression of PAR2, a tryptase receptor; (2) correlation analysis between densities of mast cells and eosinophils; and (3) ultrastructural studies. The electron microscopy studies revealed signs of activation of mast cells and eosinophils, as well as physical interaction between these cells. Immunohistochemistry and correlation analyses point to the participation of tryptase immunoreactive mast cells in the migration and/or survival of eosinophils at the affected organ.

  8. 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

  9. The immunology of experimental Chagas' disease. IV. Production of lesions in rabbits similar to those of chronic Chagas' disease in man.

    PubMed Central

    Teixeira, A. R.; Teixeira, M. L.; Santos-Buch, C. A.

    1975-01-01

    Eight rabbits that received a single inoculation of trypomastigotes of a virulent strain of Trypanosoma cruzi first developed a transient acute illness associated with parasitemia; later, 4 of these rabbits died with chronic myocarditis and/or with megacolon in the absence of demonstrable parasitemia or encysted parasites in tissues. Two of these rabbits with chronic myocarditis died unexpectedly. Three of the inoculated rabbits that survived the infection were sacrificed 18 months later and showed similar but less severe microscopic lesions. The remaining rabbit is alive and well at the time of writing (26 months) with negative blood cultures but high hemagglutinating antibody titers to T. cruzi antigens. The natural course of T. cruzi infection in rabbits and the lesions observed postmortem are similar to those recorded for humans with chronic Chagas' disease. Multiple injections of particulate subcellular antigens of T. cruzi in rabbits resulted in microscopic lesions similar to those observed in rabbits that survived protozoan infection. Sera of rabbits inoculated with T. cruzi have antibodies to striated and smooth muscle structures. However, evidence provided in this and in other experiments strongly suggest that the lesions of chronic Chagas' disease are produced by delayed hypersensitivity to T. cruzi antigens. Images Figure 1 Figure 2 Figures 3-4 Figure 5 Figure 6 Figure 7 PMID:808136

  10. 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

  11. Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis.

    PubMed

    Chan, Khee-Siang; Lee, Wen-Ying; Yu, Wen-Liang

    2016-12-01

    Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients with human immunodeficiency virus infection, organ transplantation, and malignancy receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents. However, CMV colitis is increasingly recognized in immunocompetent hosts. Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in apparently healthy individuals has been published in recent years, which could result in high morbidity and mortality. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with abdominal pain, watery, or especially bloody diarrhea, which could be refractory to standard treatment for CDI. As a characteristic of CDI, however, pseudomembranous colitis may be only caused by CMV infection. Real-time CMV-polymerase chain reaction (PCR) for blood and stool samples may be a useful and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal biopsies may increase the diagnostic yield of traditional histopathology. CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon, and colonic perforation, so that may necessitate pre-emptive antiviral treatment for those who are positive for CMV-PCR in blood and/or stool samples while pending histological diagnosis.

  12. Balloon expulsion from the rectum in constipation of different types.

    PubMed

    Barnes, P R; Lennard-Jones, J E

    1985-10-01

    The defaecatory mechanism using a balloon model with simultaneous measurement of intrarectal pressure has been studied in 15 control subjects with normal bowel habit and in 39 patients with chronic constipation; 31 with a normal barium enema and eight with idiopathic megarectum. Fourteen of those with a normal barium enema had prolonged whole gut transit times as measured by radio-opaque shapes. The ability of the patient to expel a rectal balloon containing 50, 100, and 150 ml of water, lying on their side in the left lateral position was tested and if unsuccessful, in the sitting position with the knees raised. All but one of the control subjects could expel balloons in the left lateral position. Only five of 17 constipated patients with normal barium enemas and transit times could expel balloons lying on their side although a further three could do so when sitting. None of 14 patients with slow transit and normal barium enemas could expel balloons in left lateral position although three could do so when sitting. Patients with megarectum could not expel balloons in either position. Levels of intrarectal pressure with straining were not significantly different between controls, who were able to expel balloons, and constipated patients with a normal barium enema, but were greater (p less than 0.01) in patients with megacolon than in control subjects. Using the balloon model a disorder of the defaecatory mechanism is present in patients with constipation of different types, but this is not because of an inability to raise intrarectal pressure.

  13. 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

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

    PubMed

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

    2012-09-01

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

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

    PubMed

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

    2012-12-01

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

  16. 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

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

    PubMed Central

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

    2008-01-01

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

  18. 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

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

    PubMed Central

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

    2014-01-01

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

  20. 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.

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

    PubMed Central

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

    2010-01-01

    Introduction Runx1, a Runt domain transcription factor, controls the differentiation of nociceptors that express the neurotrophin receptor Ret, regulates the expression of many ion channels and receptors, and controls the lamina-specific innervation pattern of nociceptive afferents in the spinal cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. We investigated whether conditional activation of Runx1 short isoform (Runx1a), which lacks a transcription activation domain, influences differentiation of neural crest stem cells (NCSCs) in vitro and in vivo during development and whether postnatal Runx1a activation affects the sensitivity to neuropathic pain. Methods We activated ectopic expression of Runx1a in cultured NCSCs using the Tet-ON gene regulatory system during the formation of neurospheres and analyzed the proportion of neurons and glial cells originating from NCSCs. In in vivo experiments we applied doxycycline (DOX) to pregnant mice (days 8–11), i.e. when NCSCs actively migrate, and examined the phenotype of offsprings. We also examined whether DOX-induced activation of Runx1a in adult mice affects their sensitivity to mechanical stimulation following a constriction injury of the sciatic nerve. Results Ectopic Runx1a expression in cultured NCSCs resulted in predominantly glial differentiation. Offsprings in which Runx1a had been activated showed retarded growth and displayed megacolon, pigment defects, and dystrophic dorsal root ganglia. In the neuropathic pain model, the threshold for mechanical sensitivity was markedly increased following activation of Runx1a. Conclusion These data suggest that Runx1a has a specific role in NCSC development and that modulation of Runx1a activity may reduce mechanical hypersensitivity associated with neuropathic pain. PMID:20187849

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2014-12-31

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

  4. 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.

  5. 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

  6. [When is it too early or too late for surgery in Crohn's disease? ].

    PubMed

    Fernández-Blanco Hernáiz, J I; Monturiol Jalón, J M

    2008-01-01

    The surgical boarding of Crohn's disease (CD) admitted as a last effort of treatment against behavior in those the therapy prescribes it has failed, it supposes a loss on perspective that can postpone the delay in the recovery of patients and it retracts them of a better quality of life when it is considered that 50% of patients maintain inactive illness during years after selected surgical procedures; some rate no reached by the most effective treatments. The risk to specify surgical procedure in the course of CD rises to 75% of payees, more than 50% in the first year from the diagnosis, and practically 100% patients in the evolution when it is contemplated to attend perianal lesions. Therefore gastroenterologist should be trained in the selection who, when and why these patients should be operated. To retard the surgery to advanced illness phases increases morbidity, and if it is certain that the new biological therapy allow induction of remissions it is also it that to increase the duration of the process and the patient s age and contributes to face bigger surgical risk and worse perspectives in the treatment of their acute complications and also chronic manifestations often clinically inconsiderate as: Retractile mesenteritis, the states of hipercoagulability and the appearance of malignizations phenomena. Saving absolute indications for initial selective surgery in management of CD patient like: Massive intestinal bleeding, toxic megacolon or free perforation, other surgical conditions they should be reevaluated on light of our current knowledge. Patient s genotyping constitutes a clinical element that contributes to the identification of its specific risks and it facilitates the therapeutic selection. Unfortunately until these analyses can be routinely used the precocious employment of CD surgery it will be based on the consideration clinical data: The patient age, its nutritional state, smoking, and the necessities of steroids. To differ among inflammatory