Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Liquorrhoea associated with intrapelvic meningocele resection successfully treated by conservative therapy: a case report. [Journal Article]
- J Biomed Res 2013 May; 27(3):239-41.
Asymptomatic intrapelvic meningocele is rare. Here, we report the case of a 30-year-old Chinese man who underwent sigmoidectomy due to megacolon. During the operation, an intrapelvic cyst was found and resected. Meningocele was confirmed by histological examination. The patient recovered well postoperatively with the exception of liquorrhoea. Conservative therapy was initiated, including draining, anti-infection and specific posture maintenance. During the following week, liquorrhoea was generally relieved and the patient was discharged. This is the first known report of liquorrhoea associated with intrapelvic meningocele resection successfully treated by conservative therapy. Our case indicates that conservative treatment may be considered for similar cases so that a second surgery is avoided.
- Clinical Factors Associated with Development of Severe-Complicated Clostridium difficile Infection. [JOURNAL ARTICLE]
- Clin Gastroenterol Hepatol 2013 May 20.
Aims:Clostridium difficile infection (CDI) can cause life-threatening complications. Severe complicated CDI is characterized by hypotension, shock, sepsis, ileus, megacolon, and colon perforation. We created a model to identify clinical factors associated with severe complicated CDI.
METHODS:We analyzed data from 1446 inpatient cases of CDI (48.6% female, median age 62.5 y, range 0.1-103.7 y) at the Mayo Clinic from June 28, 2007 through June 25, 2010. Patients with severe complicated CDI (n=487) were identified as those who required admission to the intensive-care unit (ICU) or colectomy, or died, within 30 days of CDI diagnosis. Logistic regression models were used to identify variables that were independently associated with the occurrence of severe complicated CDI in 2 cohorts. One cohort comprised all hospitalized patients; the other comprised a subset of these inpatients who were residents of Olmsted County, MN, to assess the association of comorbid conditions with the development of severe complicated infection in a population-based cohort. The linear combinations of variables identified using logistic regression models provided scores to predict the risk of developing severe-complicated CDI.
RESULTS:In a multivariable model that included all inpatients, increasing age, leukocyte count >15x10(9)/L, increase in serum level of creatinine >1.5-fold from baseline, and use of proton pump inhibitors or narcotic medications were independently associated with severe complicated CDI. In the secondary analysis, which included only patients from Olmsted County, comorbid conditions were not significantly associated with severe complicated CDI.
CONCLUSION:Older age, high numbers of leukocytes in blood samples, an increased serum level of creatinine, gastric acid suppression, and use of narcotic medications were independently associated with development of severe complicated CDI in hospitalized patients. Early aggressive monitoring and intervention could improve outcomes.
- Clostridium difficile Infection in Children: Current State and Unanswered Questions. [JOURNAL ARTICLE]
- J Pediatric Infect Dis Soc 2012 Sep; 1(3):230-243.
The incidence of Clostridium difficile infection (CDI) in children has increased over the past decade. In recent years, new and intriguing data on pediatric CDI have emerged. Community-onset infections are increasingly recognized, even in children who have not previously received antibiotics. A hypervirulent strain is responsible for up to 20% of pediatric CDI cases. Unique risk factors for CDI in children have been identified. Advances in diagnostic testing strategies, including the use of nucleic acid amplification tests, have raised new questions about the optimal approach to diagnosing CDI in children. Novel therapeutic options are available for adult patients with CDI, raising questions about the use of these agents in children. Updated recommendations about infection prevention and control measures are now available. We summarize these recent developments in pediatric CDI in this review and also highlight remaining knowledge gaps that should be addressed in future research efforts.
- The presence of primary sclerosing cholangitis is protective for ileal pouch from Crohn's disease. [Journal Article]
- Inflamm Bowel Dis 2013 Jun; 19(7):1483-9.
: Primary sclerosing cholangitis (PSC) has been shown to increase the risk for chronic pouchitis. However, the association between PSC and Crohn's disease (CD) of the pouch has not been studied.: Consecutive inflammatory bowel disease patients undergoing proctocolectomy with ileal pouch-anal anastomosis in our Pouchitis Registry from 2002 to 2012 were studied. Cases consisted of patients with CD of the pouch. Both univariable and multivariable analyses were performed.: A total of 1425 patients met the inclusion criteria, including 265 (18.6%) with CD of the pouch and 78 (5.5%) with PSC. In the whole cohort, 799 patients (56.1%) were male and the mean ages at the time of diagnosis of inflammatory bowel disease and at pouch surgery were 25.5 ± 12.3 years and 35.4 ± 13.9 years, respectively. Patients with PSC had a longer duration from inflammatory bowel disease diagnosis to pouch construction (P < 0.001). Fewer patients with PSC had toxic megacolon at the time of colectomy (P = 0.009), but more patients with PSC had neoplasia as the indication for colectomy (P < 0.001), concurrent autoimmune disorders (P < 0.001), and liver transplantation (P = 0.001). In the multivariate analysis, the presence of PSC was shown to be inversely associated with the risk for the development of CD of the pouch, with a hazard ratio of 0.39 (95% confidence interval: 0.16 to 0.95, P = 0.038). However, no significant difference in terms of the distribution of phenotypes of CD of the pouch between patients with and without PSC was identified (P = 0.59).: The presence of PSC is inversely associated with the development of CD of the pouch.
- Contemporary Outcomes for Ulcerative Colitis Inpatients Admitted to Pediatric Hospitals in the United Kingdom. [JOURNAL ARTICLE]
- Inflamm Bowel Dis 2013 Jun; 19(7):1434-1440.
BACKGROUND::Pediatric ulcerative colitis (UC) care is variable with a lack of appropriate guidelines to guide practice until recently.
METHODS::UC inpatients <17 years old admitted to 23 U.K. pediatric hospitals had clinical details collected between September 2010 and 2011. Comparative data for 248 patients were available from a previous audit in 2008.
RESULTS::One hundred and seventy-six patients (98 males) of median age 13 years (interquartile range, 10-13) were analyzed; 23 were elective surgical admissions, 47 new diagnoses, and 106 needed acute medical care for established UC. Median length of stay was 6 days (interquartile range, 3-10) with no deaths. Eighty-eight of 126 patients (70%) with active disease had standard stool cultures performed (3 [2%] were positive), and 57 (45%) had Clostridium difficile toxin tested (none positive). Twenty-five of 66 (38%) emergency admissions had an abdominal x-ray on admission, and 13 of 66 patients (20%) had a Pediatric Ulcerative Colitis Activity Index score. There were 3 cases of toxic megacolon and 2 thromboses. Eighty-one of 116 patients (71%) responded to steroids. Nineteen patients who did not respond adequately to steroids received rescue therapy (7 infliximab, 11 ciclosporin, and 1 both) with overall response rate of 90%; 7 patients needed surgery acutely, 5 without previous rescue therapy. Compared with the 2008 data, stool culture rates improved significantly (86 of 121 [71%] versus 76 of 147 [52%], P = 0.001) as did heparinization rates (15 of 150 [10%] versus 5 of 215 [2%], P = 0.002) and rescue therapy usage (17 of 33 [52%] versus 10 of 38 [26%], P = 0.03).
CONCLUSIONS::There were signs of improving UC care with significantly increased rates of stool culture and rescue therapy. The majority of sites, however, did not use Pediatric Ulcerative Colitis Activity Index scores.
- Hirschsprung's disease as a model of complex genetic etiology. [JOURNAL ARTICLE]
- Histol Histopathol 2013 Apr 19.
Hirschsprung disease (HSCR), or aganglionic megacolon, is a developmental disorder characterised by the absence of ganglion cells along variable length of the distal gastrointestinal tract, leading to the most common form of functional intestinal obstruction in neonates and children. Aganglionosis is attributed to a failure of neural crest cells to migrate, proliferate, differentiate or survive during enteric nervous system (ENS) development in the embryonic stage. The incidence of HSCR is estimated at 1/5000 live births and most commonly presents sporadically with reduced penetrance and male predominance, although it can be familial and may be inherited as autosomal dominant or autosomal recessive. In 70% of cases, HSCR occurs as an isolated trait and in the other 30% HSCR is associated with other congenital malformation syndromes. HSCR has a complex genetic etiology with several genes and loci being described as associated with either isolated or syndromic forms. These genes encode for receptors, ligands (especially those participating in the RET and EDNRB signaling transduction pathways), transcriptional factors or other cell elements that are usually involved in the neural crest cell development and migration that give rise to ENS. Nevertheless, the RET proto-oncogene is considered the major disease causing gene in HSCR. A common RET variant within the conserved transcriptional enhancer sequence in intron 1 has been shown to be associated with a great proportion of sporadic cases and could act as a modifier by modulating the penetrance of mutations in other genes and possibly of those mutations in the RET proto-oncogene itself.
- Pleiotropic effects of coat colour-associated mutations in humans, mice and other mammals. [JOURNAL ARTICLE]
- Semin Cell Dev Biol 2013 Apr 9.
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.
- The developmental etiology and pathogenesis of Hirschsprung disease. [JOURNAL ARTICLE]
- Transl Res 2013 Mar 22.
The enteric nervous system is the part of the autonomic nervous system that directly controls the gastrointestinal tract. Derived from a multipotent, migratory cell population called the neural crest, a complete enteric nervous system is necessary for proper gut function. Disorders that arise as a consequence of defective neural crest cell development are termed neurocristopathies. One such disorder is Hirschsprung disease (HSCR), also known as congenital megacolon or intestinal aganglionosis. HSCR occurs in 1/5000 live births and typically presents with the inability to pass meconium, along with abdominal distension and discomfort that usually requires surgical resection of the aganglionic bowel. This disorder is characterized by a congenital absence of neurons in a portion of the intestinal tract, usually the distal colon, because of a disruption of normal neural crest cell migration, proliferation, differentiation, survival, and/or apoptosis. The inheritance of HSCR disease is complex, often non-Mendelian, and characterized by variable penetrance. Extensive research has identified a number of key genes that regulate neural crest cell development in the pathogenesis of HSCR including RET, GDNF, GFRα1, NRTN, EDNRB, ET3, ZFHX1B, PHOX2b, SOX10, and SHH. However, mutations in these genes account for only ∼50% of the known cases of HSCR. Thus, other genetic mutations and combinations of genetic mutations and modifiers likely contribute to the etiology and pathogenesis of HSCR. The aims of this review are to summarize the HSCR phenotype, diagnosis, and treatment options; to discuss the major genetic causes and the mechanisms by which they disrupt normal enteric neural crest cell development; and to explore new pathways that may contribute to HSCR pathogenesis.
- Treatment of Aganglionic Megacolon Mice via Neural Stem Cell Transplantation. [JOURNAL ARTICLE]
- Mol Neurobiol 2013 Mar 20.
To explore a potential methodology for treating aganglionic megacolon, neural stem cells (NSCs) expressing engineered endothelin receptor type B (EDNRB) and glial cell-derived neurotrophic factor (GDNF) genes were transplanted into the aganglionic megacolon mice. After transplantation, the regeneration of neurons in the colon tissue was observed, and expression levels of differentiation-related genes were determined. Primary culture of NSCs was obtained from the cortex of postnatal mouse brain and infected with recombinant adenovirus expressing EDNRB and GDNF genes. The mouse model of aganglionic megacolon was developed by treating the colon tissue with 0.5 % benzalkonium chloride (BAC) to selectively remove the myenteric nerve plexus that resembles the pathological changes in the human congenital megacolon. The NSCs stably expressing the EDNRB and GDNF genes were transplanted into the benzalkonium chloride-induced mouse aganglionic colon. Survival and differentiation of the implanted stem cells were assessed after transplantation. Results showed that the EDNRB and GDNF genes were able to be expressed in primary culture of NSCs by adenovirus infection. One week after implantation, grafted NSCs survived and differentiated into neurons. Compared to the controls, elevated expression of EDNRB and GDNF was determined in BAC-induced aganglionic megacolon mice with partially improved intestinal function. Those founding indicated that the genes transfected into NSCs were expressed in vivo after transplantation. Also, this study provided favorable support for the therapeutic potential of multiple gene-modified NSC transplantation to treat Hirschsprung's disease, a congenital disorder of the colon in which ganglion cells are absent.
- [Genetic, population and phenotypic characteristics of patients with Hirschsprung disease]. [English Abstract, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't]
- Cir Pediatr 2012 Jul; 25(3):135-9.
Hirschsprung disease (HSCR) is caused by the absence of ganglion cells in the intestine due to defects in the migration of enteric nervous system cells during embryologic development. The incidence is one in every 5000 births, more common in men than women. There are two main phenotypes according to the aganglionic segment length: Short (S-HSCR, (80% of patients) and Long (L-HSCR, 20%). Variations have been detected in the coding sequence of the RET proto-oncogene in patients with HSCR, suggesting a genetic predisposition to the disease. Our aim is to find and analyze polymorphisms (SNPs) associated with the disease. We are interested also in stablish an association between sex and type of aganglionic segment. We analyzed the RET promoter as well a polymorphism in exon 13 strongly associated to the disease. The populations for the study were a group of 56 patients with sporadic HSCR and 178 healthy controls. The results obtained show that the disease is more common in men than in women (3:1). The RET genotype shows that alleles A and G of the promoter (c.-200A > G and c.-196C > A) and G of exon 13 (c.2307T > G) are associated with the affected population. Our data suggest neither association between the disease phenotype and the distribution of the polymorphisms analyzed nor with the sex of the patients. The presence of certain polymorphisms in the RET sequence indicates a genetic predisposition (combined with other genetic or environmental factors) to the disease.