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Sample records for megacolon

  1. Megacolon in a collagen vascular overlap syndrome.

    PubMed

    Ferreiro, J E; Busse, J C; Saldana, M J

    1986-02-01

    Mixed connective tissue disease is a syndrome having clinical features of scleroderma, systemic lupus erythematosus, and polymyositis with a unique combination of clinical and laboratory findings. Not all patients with clinical features of more than one connective tissue disease fit the mixed connective disorders category; therefore, the term "overlap syndrome" is applied to patients with features of two or more connective tissue diseases. Gastrointestinal involvement in progressive systemic sclerosis is common, with the esophagus being the usual site, followed by the small bowel, colon, and stomach. Colonic involvement is reported to occur in 10 to 50 percent of cases and is typically manifested radiographically as wide-mouthed diverticular saculations. Symptoms secondary to colonic involvement are rare but occasionally serious, such as impaction of barium or feces. A case is described in which systemic lupus erythematosus coexisted with previously undiagnosed scleroderma involving predominantly the gastrointestinal tract and resulting in megacolon. PMID:3946449

  2. [Anesthetic management of a patient with diaphragmatic relaxation and megacolon].

    PubMed

    Suematsu, Rie; Sugi, Yasuyuki; Higa, Kazuo; Katori, Kiyoshi; Kikuta, Toshihiro

    2013-12-01

    We managed an 87-year-old man with diaphragmatic relaxation under general anesthesia. He had dyspnea and severe constipation. The chest X-ray revealed that two thirds of the left chest cavity were compressed by the megacolon gas. The Spo2 before the operation was 93%. The colon gas was deflated before and after the induction of anesthesia. There was no significant improvement in the tidal volume and the arterial oxygen tension. The postoperative chest X-ray showed that the shift of the left diaphragm was improved. He was able to walk 100 meters and the severe constipation disappeared after the operation. PMID:24498779

  3. A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.

    PubMed Central

    Hatano, M; Aoki, T; Dezawa, M; Yusa, S; Iitsuka, Y; Koseki, H; Taniguchi, M; Tokuhisa, T

    1997-01-01

    The Ncx/Hox11L.1 gene, a member of the Hox11 homeobox gene family, is mainly expressed in neural crest-derived tissues. To elucidate the role of Ncx/Hox11L.1, the gene has been inactivated in embryonic stem cells by homologous recombination. The homozygous mutant mice were viable. These mice developed megacolon with enteric ganglia by age 3-5 wk. Histochemical analysis of the ganglia revealed that the enteric neurons hyperinnervated in the narrow segment of megacolon. Some of these neuronal cells degenerated and neuronal cell death occurred in later stages. We propose that Ncx/Hox11L.1 is required for maintenance of proper functions of the enteric nervous system. These mutant mice can be used to elucidate a novel pathogenesis for human neuronal intestinal dysplasia. PMID:9259577

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

    PubMed

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

    2014-05-22

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

  5. Treating congenital megacolon by transplanting GDNF and GFR?-1 double genetically modified rat bone marrow mesenchymal stem cells.

    PubMed

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

    2015-01-01

    We studied the survival and gene expression of glial cell line-derived neurotrophic factor (GDNF) and GDNF receptor ?-1 (GFR?-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 GFR?-1 were extracted and ligated into pEGFP-N1. Eukaryotic fluorescent expression vectors carrying the GDNF and GFR?-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-GFR?-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 GFR?-1 mRNA in the stem cell transplantation group increased gradually. The double-genetically modified BMSCs colonized and survived in the intestinal wall of the experimental megacolon rat model and expressed related genes, partially recovering the colonic neuromuscular regulatory functions and thus providing an experimental basis for treating congenital megacolon by cellular transplantation. PMID:26345878

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

    PubMed Central

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

    2015-01-01

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

  7. 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

  8. 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.

  9. Treatment Options in IBD

    MedlinePLUS

    ... Clinical trials have not shown that antibiotics have value in treating severe ulcerative colitis. The exception is toxic megacolon, a condition that places people at high risk for perforation. This life- ...

  10. Hypertrophy of colonic smooth muscle: structural remodeling, chemical composition, and force output

    E-print Network

    Trinkle-Mulcahy, Laura

    Hypertrophy of colonic smooth muscle: structural remodeling, chemical composition, and force output muscle lengths. In megacolon the following occur: 1) structural remodeling expressed as a greater Narayan, William S. Stirewalt, and Barry C. Starcher. Hypertro- phy of colonic smooth muscle: structural

  11. 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.

  12. Fulminant ulcerative colitis in a healthy pregnant woman

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-04-21

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

  14. RET-deficient mice: an animal model for Hirschsprung's disease and renal agenesis.

    PubMed

    Schuchardt, A; D'Agati, V; Larsson-Blomberg, L; Costantini, F; Pachnis, V

    1995-10-01

    Receptor tyrosine kinases play a critical role in transducing signals involved in cell growth and differentiation. The c-ret proto-oncogene is a member of the receptor tyrosine kinase gene superfamily originally identified by its transforming ability. Somatic mutations of c-ret are responsible for a large proportion of thyroid papillary carcinomas, while germ-line mutations are responsible for multiple endocrine neoplasia types 2A and 2B, dominantly inherited cancer syndromes characterized by multiple tumours of neuroectodermal origin. In addition to its role in tumour formation. c-ret is thought to have a developmental role since mutations of the gene have been implicated in the aetiology of Hirschsprung's syndrome (congenital megacolon). A targeted mutation in the murine c-ret locus shows that the ret receptor is required for normal development of two lineally unrelated systems, the excretory system and the enteric nervous system. PMID:7595168

  15. 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

  16. 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.

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

    PubMed

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

    2015-12-01

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

  18. Chagas disease and gynecologic neoplasias.

    PubMed

    Dominical, Venina Marcela; Cavellani, Camila Lourencini; Rocha, Laura Penna; Corręa, Rosana Rosa Miranda; Pereira, Gilberto de Araújo; Teixeira, Vicente de Paula Antunes

    2010-10-01

    The inflammation caused by Trypanosoma cruzi produces irritation and cell proliferation and may contribute to the development of cancer. The objective was to determine the occurrence of gynecologic neoplasia (GN) and demographic characteristics in patients with Chagas disease (CD). We used protocols of 671 autopsies between 1976 and 2008. The patients were divided into 3 groups: with GN and CD, only with CD, and only with GN. The 2 diseases were observed in 4.5% of patients with a mean age of 47.6 years and who were predominantly white. The megaesophagus and megacolon were more frequent in the group with only CD. The most common benign neoplasm was uterine leiomyoma, and malignant, carcinoma of the cervix. We conclude that the epidemiological profile of patients with CD and GN was similar to the other groups, and the CD was found not to be a risk factor or protective against the development of GN. PMID:20850696

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

    PubMed

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

    1996-01-01

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

  20. Can colonic migrating motor complexes occur in mice lacking the endothelin-3 gene?

    PubMed

    Barnes, Kyra J; Spencer, Nick J

    2015-05-01

    In mammals, colonic migrating motor complexes (CMMC) are a major propulsive contraction responsible for the expulsion of faecal content. Mice with a mutation of the endothelin-3 gene raised on a 129SL background strain have ~70% colonic aganglionosis, lack CMMC, and are lethal within 12 days postpartum. In contrast, endothelin-3 mutant mice raised and maintained on a C57BL6 background strain (lethal-spotted (ls/ls) mice) can live for much longer, but it is unclear whether CMMC generation is preserved in these mice also lacking the endothelin-3 gene. The aim of this study was to determine whether CMMC exist in ls/ls mouse colon and, if so, whether their existence and frequency are related to the length of aganglionosis. Spatiotemporal mapping and mechanical recordings of colonic wall movements were made from isolated whole colons obtained from wild-type and ls/ls mice. Although ls/ls mice had a megacolon, they still generated CMMC in the ganglionic segment, which on some occasions could propagate short distances into the aganglionic region. There was large variability in aganglionosis length, which showed a weak correlation with the existence or frequency of CMMC. Interestingly, CMMC propagation velocity was slower in ls/ls mice when evoked by intraluminal fluid. A myogenic motor pattern was identified in the aganglionic region that was maintained under tonic inhibition. We show that despite megacolon, ls/ls mice still generate CMMC in the ganglionic region. These offspring have sufficient propulsive motility in the ganglionic segment to live a normal murine lifespan and rarely die of bowel obstruction. PMID:25708159

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    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

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

    PubMed

    Sergi, Consolato

    2015-11-01

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

  4. 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

  5. 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.

  6. The host immune response to Clostridium difficile infection

    PubMed Central

    2013-01-01

    Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

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

    PubMed Central

    Sergi, Consolato

    2015-01-01

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

  8. Diagnosis of Clostridium difficile infection: an ongoing conundrum for clinicians and for clinical laboratories.

    PubMed

    Burnham, Carey-Ann D; Carroll, Karen C

    2013-07-01

    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

  9. Clostridium difficile-associated colitis.

    PubMed Central

    Hull, Mark W.; Beck, Paul L.

    2004-01-01

    OBJECTIVE: To review the basic microbiology, pathogenesis of disease, and diagnosis of the nosocomial pathogen Clostridium difficile and to examine therapies recommended by the Canadian Task Force on Preventive Health Care. QUALITY OF EVIDENCE MEDLINE: was searched using MeSH headings. Controlled trials for therapy were sought, but case-control studies and observational reviews were included. MAIN MESSAGE: Clostridium difficile causes approximately 20% of cases of diarrhea associated with antibiotics, including clindamycin and the second- and third-generation cephalosporins. Diarrhea is usually mild, but can be severe; extreme cases develop toxic megacolon. Diagnosis is dependent on demonstrating presence of clostridial toxin in stool specimens or of pseudomembranes through sigmoidoscopy. First-line therapy for C. difficile diarrhea is restricted to metronidazole. Second-line therapy for treatment failure is vancomycin. For relapse, a second course of metronidazole is recommended; tapering courses of vancomycin and probiotics are used for multiple recurrences. CONCLUSION: Clostridium difficile is an important nosocomial pathogen requiring prudent use of antibiotics and strict infection-control policies to prevent large health care costs. PMID:15597970

  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. 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.

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

    PubMed

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

    2015-08-01

    Telomere shortening occurs with human aging in many organs and tissues and is accelerated by rapid cell turnover and oxidative injury. To clarify the clinical importance of telomere shortening in colonic mucosa in ulcerative colitis (UC), we measured average telomere length using quantitative real-time PCR in non-neoplastic colonic mucosa in UC patients and assessed its relationship to various clinical subtypes. Relative telomere length in genomic DNA was measured in colonic biopsies obtained from rectal inflammatory mucosa from 86 UC patients as well as paired non-inflammatory proximal colonic mucosae from 10 patients. Data were correlated with various clinical phenotypes. In paired samples, average relative telomere length of rectal inflammatory mucosa was shortened compared to normal appearing proximal colon in eight out of ten cases (p = 0.01). Telomere length shortening was significantly associated with more severe Mayo endoscopic subscore (p < 0.0001) and cases needing surgery due to toxic megacolon or cancer occurrence (p = 0.043). When the severe clinical phenotype was defined as having at least one of following phenotypes, more than two times of hospitalization, highest Mayo endoscopic subscore, steroid dependent, refractory, or needing operation, average relative telomere length was significantly shortened in the same phenotypes than the others (p = 0.003). Telomere shortening is associated with more severe clinical phenotypes of UC, reflecting severe inflammatory state in the colonic mucosa. PMID:24925640

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

    PubMed

    Reissmann, Monika; Ludwig, Arne

    2013-01-01

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

  15. [Long-term prognosis of ulcerative colitis].

    PubMed

    Kaminaga, N; Satake, Y

    1999-11-01

    Despite its intermittent course of activity and remission, the good response to salazopyridine and steroids makes the long-term prognosis of ulcerative colitis favorable. The number of non-active type ulcerative colitis is increasing and consequently, the rate of active disease and relapse is decreasing every year. More than 90% of the patients even with disease of 10 or more years are able to work almost with no limits for the daily living. The colectomy rate in Japan is 4.1% after one year of the onset of the disease and 6.8% after 2 years. Thereafter approximately 1% of the patients undergo surgery yearly. The most common reasons of surgery are complications such as massive bleeding, perforation or toxic megacolon. Other indications are chronic continuous disease and cases with frequent relapses. Considering the extension of the disease, about one-third of the total colitis type and 10% of the left-sided type undergo surgery. The risk of colonic cancer is higher in patients with total colitis type and when has had the disease for more than 10 years. Most of the them are flat type poor-differentiated adenocarcinomas. Therefore patients with total colitis type for more than 10 years should undergo colonoscopic surveillance. PMID:10572407

  16. [Conception and course of eight pregnancies in five women on TNF blocker etanercept treatment].

    PubMed

    Rump, J-A; Schönborn, H

    2010-12-01

    The introduction of tumor necrosis factor (TNF)-? inhibitors s in the late 1990s considerably broadened the treatment options for, and essentially contributed to the successful management of, rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. Nevertheless, their use during pregnancy is still controversially discussed since it remains unclear whether the benefits of treatment might be outweighed by potential teratogenicity or adverse effects on the course of pregnancy. In this case series report we describe the course and outcome of eight pregnancies in five women (four with RA and one with ankylosing spondylitis) at our private clinical practice treated with the TNF-? inhibitor etanercept at the time of conception and during pregnancy. The course was inconspicuous in six of the eight pregnancies; in one case a megacolon congenitum was diagnosed 2 weeks after birth, while one spontaneous abortion occurred in the 10th week of pregnancy after a disease flare following treatment discontinuation with etanercept in the 5th week of pregnancy. Based on our experience to date and the currently available literature data, we believe that continuation of treatment with TNF-? blockers is justified in pregnant patients with otherwise high disease activity and disease progression. PMID:20532789

  17. NAP1 Strain Type Predicts Outcomes from Clostridium difficile Infection

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    1994-09-01

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

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

    PubMed

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

    2015-11-01

    BACKGROUND Conflicting reports have been published on the association between Clostridium difficile ribotypes and severe disease outcomes in patients with C. difficile infection (CDI); several so-called hypervirulent ribotypes have been described. We performed a multicenter study to assess severe disease presentation and severe outcomes among CDI patients infected with different ribotypes. METHODS Stool samples that tested positive for C. difficile toxin were collected and cultured from patients who presented to any of 7 different hospitals in Houston, Texas (2011-2013). C. difficile was characterized using a fluorescent PCR ribotyping method. Medical records were reviewed to determine clinical characteristics and ribotype association with severe CDI presentation (ie, leukocytosis and/or hypoalbuminemia) and severe CDI outcomes (ie, ICU admission, ileus, toxic megacolon, colectomy, and/or in-hospital death). RESULTS Our study included 715 patients aged 61±18 years (female: 63%; median Charlson comorbidity index: 2.5±2.4; hospital-onset CDI: 45%; severe CDI: 36.7%; severe CDI outcomes: 12.3%). The most common ribotypes were 027, 014-020, FP311, 002, 078-126, and 001. Ribotype 027 was a significant independent predictor of severe disease (adjusted odds ratio [aOR], 2.24; 95% confidence interval [CI], 1.53-3.29; P<.001) and severe CDI outcomes (aOR, 1.71; 95% CI, 1.02-2.85; P=.041) compared with all other ribotypes in aggregate. However, in an analysis using all common ribotypes as individual variables, ribotype 027 was not associated with severe CDI outcomes more often than other ribotypes. CONCLUSION Ribotype 027 showed virulence equal to that of other ribotypes identified in this endemic setting. Clinical severity markers of CDI may be more predictive of severe CDI outcomes than a particular ribotype. Infect. Control Hosp. Epidemiol. 2015;36(11):1318-1323. PMID:26288985

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

    PubMed Central

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

    2015-01-01

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

  1. Clostridium difficile associated infection, diarrhea and colitis

    PubMed Central

    Hookman, Perry; Barkin, Jamie S

    2009-01-01

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

  2. Comparative genetics of albinism.

    PubMed

    Searle, A G

    1990-09-01

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