These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Pseudomembranous colitis leading to toxic megacolon associated with antineoplastic chemotherapy  

Microsoft Academic Search

Pseudomembranous colitis and toxic megacolon are rare complications of antineoplastic chemotherapy. Twelve cases of pseudomembranous colitis and four cases of toxic megacolon, both occurring as complications of chemotherapy, have been reported in the medical literature. These diseases occurred as separate and distinct entities. Fulminating pseudomembranous colitis leading to toxic megacolon in the setting of chemotherapy has not been previously reported.

Vic Velanovich; Anthony J. LaPorta; Wayne L. Garrett; Timothy B. Richards; Patricia A. Cornett

1992-01-01

2

Ultrastructural and Histochemical Studies of Murine Megacolon  

PubMed Central

The myenteric plexus of the colon was studied ultrastructurally in a colony of an Ls Ls strain of mice manifesting a piebald coat color mutation associated with a high incidence of genetically determined aganglionic megacolon. Ultrastructural studies were histochemically supplemented by the Maillet technic and stains for acetylcholinesterase and catecholamines. The development of megacolon did not appear to require total aganglionosis, since ostensibly aganglionic areas contained rare ganglion cells. In the distal narrowed segment, both cholinergic and adrenergic fibers in the muscularis, submucosa and mucosa were somewhat reduced. In the mouse, the dilated portion showed an abrupt increase in adrenergic fibers. These findings are related to the pathophysiology of the disorder. The increasing degenerative changes seen in myenteric plexus structures from the fetus to adult suggest that aganglionic megacolon may be an abiotrophy, wherein the congenitally deficient myenteric plexus may be unusually predisposed to postnatal injury and degeneration. ImagesFig 7Fig 8Fig 9Fig 10Fig 11Fig 12Fig 13Fig 14Fig 15Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:5080702

Bolande, Robert P.; Towler, William F.

1972-01-01

3

Unusual complication of toxic megacolon in typhoid colitis.  

PubMed

Colitis is a rare manifestation of enteric fever in children. Toxic megacolon complicating typhoid colitis is even rarer and requires early recognition and aggressive management due to the high mortality associated with this condition. The authors report a rare case of Toxic megacolon secondary to typhoid colitis in a seven-year-old girl. PMID:23900751

Arun Babu, Thirunavukkarasu; Ananthakrishnan, Shanthi; Jayakumar, P; Kullu, Poonam

2014-05-01

4

Partial, selective survival of nitrergic neurons in chagasic megacolon.  

PubMed

One frequent chronic syndrome of Chagas' disease is megacolon, an irreversible dilation of a colonic segment. Extensive enteric neuron loss in the affected segment is regarded as key factor for deficient motility. Here, we assessed the quantitative balance between cholinergic and nitrergic neurons representing the main limbs of excitatory and inhibitory colonic motor innervation, respectively. From surgically removed megacolonic segments of four patients, each three myenteric wholemounts (from non-dilated oral, megacolonic and non-dilated anal parts) was immunohistochemically triple-stained for choline acetyltransferase, neuronal nitric oxide synthase (NOS) and the panneuronal human neuronal protein Hu C/D. Degenerative changes were most pronounced in the megacolonic and anal regions, e.g. bulked, honeycomb-like ganglia with few neurons which were partly enlarged or atrophic or vacuolated. Neuron counts from each 15 ganglia of 12 megacolonic wholemounts were compared with those of 12 age- and region-matched controls. Extensive neuron loss, mainly in megacolonic and anal wholemounts, was obvious. In all three regions derived from megacolonic samples, the proportion of NOS-positive neurons (control: 55%) was significantly increased: in non-dilated oral parts to 61% (p = 0.003), in megacolonic regions to 72% (p < 0.001) and in non-dilated anal regions to 78% (p < 0.001). We suggest the chronic dilation of megacolonic specimens to be due to the preponderance of the nitrergic, inhibitory input to the intestinal muscle. However, the observed neuronal imbalance was not restricted to the dilated regions: the non-dilated anal parts may be innervated by ascending, cholinergic axons emerging from less affected, more anally located regions. PMID:21184236

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

2011-01-01

5

Partial, selective survival of nitrergic neurons in chagasic megacolon  

PubMed Central

One frequent chronic syndrome of Chagas’ disease is megacolon, an irreversible dilation of a colonic segment. Extensive enteric neuron loss in the affected segment is regarded as key factor for deficient motility. Here, we assessed the quantitative balance between cholinergic and nitrergic neurons representing the main limbs of excitatory and inhibitory colonic motor innervation, respectively. From surgically removed megacolonic segments of four patients, each three myenteric wholemounts (from non-dilated oral, megacolonic and non-dilated anal parts) was immunohistochemically triple-stained for choline acetyltransferase, neuronal nitric oxide synthase (NOS) and the panneuronal human neuronal protein Hu C/D. Degenerative changes were most pronounced in the megacolonic and anal regions, e.g. bulked, honeycomb-like ganglia with few neurons which were partly enlarged or atrophic or vacuolated. Neuron counts from each 15 ganglia of 12 megacolonic wholemounts were compared with those of 12 age- and region-matched controls. Extensive neuron loss, mainly in megacolonic and anal wholemounts, was obvious. In all three regions derived from megacolonic samples, the proportion of NOS-positive neurons (control: 55%) was significantly increased: in non-dilated oral parts to 61% (p = 0.003), in megacolonic regions to 72% (p < 0.001) and in non-dilated anal regions to 78% (p < 0.001). We suggest the chronic dilation of megacolonic specimens to be due to the preponderance of the nitrergic, inhibitory input to the intestinal muscle. However, the observed neuronal imbalance was not restricted to the dilated regions: the non-dilated anal parts may be innervated by ascending, cholinergic axons emerging from less affected, more anally located regions. PMID:21184236

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

2010-01-01

6

Campylobacter colitis complicated by toxic megacolon: prevalence, characteristics and outcome  

Microsoft Academic Search

IntroductionCampylobacter gastroenteritis is usually a self limiting infection; the development of colitis and toxic megacolon are rare complications that may mimic inflammatory bowel disease (IBD). This study aimed to define the prevalence, characteristics and outcome of patients with campylobacter colitis and toxic megacolon in our institution.MethodsA retrospective review of medical notes, laboratory data, imaging and endoscopic records for adult inpatients

E L Culver; E Morris; P Trivedi; A J Ellis

2011-01-01

7

Observations on the immunocytes and macrophages in megacolon.  

PubMed

An immunoperoxidase staining method was used to study specific immunoglobulin-containing cells in the intestinal mucosa of children who presented with features suggestive of Hirschsprung's disease. No evidence was found to substantiate the hypothesis of an immunologic component in the etiology of Hirschsprung's disease. The megacolon in this condition had an increased proportion of IgG-containing cells and a reduced proportion of IgA-containing cells when compared with normal and unobstructed colon; this may be a reflection of an abnormal mucosal immune defense leading to susceptibility to the enterocolitis found in Hirschsprung's disease. Numerous lipofuscin-bearing macrophages were seen in the colonic mucosa of children with anal stenosis who were given anthraquinone laxatives for varying periods. The possibility that this represents an early stage of melanosis coli, as well as the likelihood of anthraquinones contributing to the pathogenesis of acquired megacolon, are considered. PMID:7044725

Wijesinha, S S; Steer, H W

1982-01-01

8

Clinical Features: Goldberg-Shprintzen megacolon syndrome (GOSHS, OMIM #609460) is a multiple malformation disorder  

E-print Network

malformation disorder characterized by Hirschsprung megacolon, microcephaly, hypertelorism, submucous cleft:185-189. 2. Hurst, JA., et al. Unknown syndrome: Hirschsprung's disease, microcephaly, and iris coloboma

Ober, Carole

9

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

PubMed

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

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

2013-12-01

10

Toxic megacolon in ulcerative colitis: a continuing challenge.  

PubMed Central

The incidence, predisposing factors, management and outcome of toxic megacolon (TM) has been reviewed in 65 cases of severe ulcerative colitis (UC) and compared in 2 successive 6-year periods before and after January, 1973. Nineteen episodes of TM occurred in 18 patients. Despite a conscious aim towards earlier surgery in recent years this was not achieved, and despite more intensive medical therapy the incidence of TM was unchanged. Emergency operative mortality in UC fell from 36% to 21% but the mortality of TM remained at 30%. The chief cause of death was colonic perforation. Mortality was associated with increased age, longer pre-operative hospital stay and lower levels of serum albumin. These findings reemphasize the need for earlier surgery if TM is to be prevented, but such a policy must result in some unnecessary emergency colectomies. Images Fig. 1 PMID:7291100

Muscroft, T. J.; Warren, P. M.; Asquith, P.; Montgomery, R. D.; Sokhi, G. S.

1981-01-01

11

Intestinal microvillous atrophy in a patient with Down syndrome and aganglionic megacolon.  

PubMed

Intestinal microvillous disorders are an uncommon cause of severe diarrhea, with very poor prognosis. The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy. The patient condition improved after a colostomy performed in the setting of the treatment of Hirschprung disease. PMID:12028658

Martínez, Miguel A; Egea, Anastasio Serrano; López, Javier Manzanares; Benítez, Enrique Medina

2002-01-01

12

Clinical Features: Goldberg-Shprintzen megacolon syndrome (GOSHS, OMIM #609460) is a multiple malformation disorder  

E-print Network

Sequencing for Goldberg-Shprintzen megacolon syndrome #12;12/11 Prenatal testing for a known mutation with GOSHS but is a genetically distinct disorder caused by mutations in the ZEB2 gene [5]. Distinctive of or underdeveloped thymus and parathyroid glands [7] Molecular Genetics: Mutations in the KIAA1279 gene (OMIM #609367

Gilad, Yoav

13

Enteroglial cells act as antigen-presenting cells in chagasic megacolon.  

PubMed

Chagas disease is one of the most serious parasitic diseases of Latin America, with a social and economic impact far outweighing the combined effects of other parasitic diseases such as malaria, leishmaniasis, and schistosomiasis. In the chronic phase of this disease, the destruction of enteric nervous system components leads to megacolon development. Besides neurons, the enteric nervous system is constituted by enteric glial cells, representing an extensive but relatively poorly described population within the gastrointestinal tract. Several lines of evidence suggest that enteric glial cells represent an equivalent of central nervous system astrocytes. Previous data suggest that enteric glia and neurons are active in the enteric nervous system during intestinal inflammatory and immune responses. To evaluate whether these cells act as antigen-presenting cells, we investigated the expression of molecules responsible for activation of T cells, such as HLA-DR complex class II and costimulatory molecules (CD80 and CD86), by neurons and enteric glial cells. Our results indicate that only enteric glial cells of chagasic patients with megacolon express HLA-DR complex class II and costimulatory molecules, and hence they present the attributes necessary to act as antigen-presenting cells. PMID:21208643

da Silveira, Alexandre Barcelos Morais; de Oliveira, Enio C; Neto, Salustiano G; Luquetti, Alejandro O; Fujiwara, Ricardo Toshio; Oliveira, Rodrigo Correa; Brehmer, Axel

2011-04-01

14

Regenerative process evaluation of neuronal subclasses in chagasic patients with megacolon.  

PubMed

Chagas' disease is one of the most serious parasitic diseases of Latin America, with a social and economic impact far outweighing the combined effects of other parasitic diseases such as malaria, leishmaniasis and schistosomiasis. In the chronic phase of this disease, the destruction of enteric nervous system (ENS) components leads to megacolon development. Previous data presented that the regeneration tax in the ENS neurons is augmented in chagasic patients. Although, there are several neuronal types with different functions in the intestine a detailed study about the regeneration of every neuronal type was never performed before. Therefore, the aim of this study was to evaluate the regeneration tax of every neuronal cell type in the ENS from chagasic patients with megacolon and non-infected individuals. A neuronal regeneration marker (GAP-43) was used in combination with a pan-neuronal marker (Peripherin) and several neuropeptides markers (cChat, Substance P, NPY, VIP and NOS), and it was considered as positive just with the combination of these markers. Our results demonstrated that the regeneration levels of cChat, Substance P, and NPY were similar in chagasic patients and non-infected individuals. However, levels of VIP and NOS neuropeptides were increased in chagasic patients when compared with non-infected individuals. We believe that the augment in the regeneration occur due to an increased destruction of selective neuronal types. These results corroborates with previous studies that pointed out to selective destruction of VIP and NOS neurons in chagasic patients. PMID:23220499

Moreira, Milena Dionízio; Brehmer, Axel; de Oliveira, Enio Chaves; Neto, Salustiano Gabriel; Luquetti, Alejandro O; Bueno, Lilian Lacerda; Fujiwara, Ricardo Toshio; de Freitas, Michelle Aparecida Ribeiro; da Silveira, Alexandre Barcelos Morais

2013-02-01

15

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

PubMed

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

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

2014-01-01

16

Pathophysiological and functional aspects of the megacolon-syndrome of homozygous spotted rabbits.  

PubMed

The Megacolon-Syndrome is a hereditary disease of homozygous spotted rabbits (En En). Investigations have been performed on some special traits related to functional aspects of the gut in comparison to vital heterozygous spotted rabbits (En en). It was found that En En rabbits showed significantly reduced sodium absorption rates across the wall of the cecum. Consequently, the dry matter content of the ingesta was reduced at this location, whereas the content of the ashes was increased. These results indicate that a further important pathogenetic aspect of this hereditary disease is an undue liquification of ingesta in proximal parts of the large intestine. Severe clinical problems, however, resulted from obstipation. This is concluded to be a late complication due to and modified by different stressors of endogenic and exogenic origin. Thus, there are some indications that an early site of spot-gene related effects might be the small intestine. This segment of the bowel was shorter and had an increased dry matter proportion of its wall when compared with heterozygous spotted rabbits. But a decreased proportion of dry matter within the wall of the large intestine was found. The latter could be an effect of the hypothyreotic state of metabolism in En En rabbits. PMID:8822192

Bödeker, D; Türck, O; Lovén, E; Wieberneit, D; Wegner, W

1995-11-01

17

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

PubMed

The English spotting coat color locus in rabbits, also known as Dominant white spotting locus, is determined by an incompletely dominant allele (En). Rabbits homozygous for the recessive wild-type allele (en/en) are self-colored, heterozygous En/en rabbits are normally spotted, and homozygous En/En animals are almost completely white. Compared to vital en/en and En/en rabbits, En/En animals are subvital because of a dilated ("mega") cecum and ascending colon. In this study, we investigated the role of the KIT gene as a candidate for the English spotting locus in Checkered Giant rabbits and characterized the abnormalities affecting enteric neurons and c-kit positive interstitial cells of Cajal (ICC) in the megacolon of En/En rabbits. Twenty-one litters were obtained by crossing three Checkered Giant bucks (En/en) with nine Checkered Giant (En/en) and two en/en does, producing a total of 138 F1 and backcrossed rabbits. Resequencing all coding exons and portions of non-coding regions of the KIT gene in 28 rabbits of different breeds identified 98 polymorphisms. A single nucleotide polymorphism genotyped in all F1 families showed complete cosegregation with the English spotting coat color phenotype (?=0.00 LOD ?=75.56). KIT gene expression in cecum and colon specimens of En/En (pathological) rabbits was 5-10% of that of en/en (control) rabbits. En/En rabbits showed reduced and altered c-kit immunolabelled ICC compared to en/en controls. Morphometric data on whole mounts of the ascending colon showed a significant decrease of HuC/D (P<0.05) and substance P (P<0.01) immunoreactive neurons in En/En vs. en/en. Electron microscopy analysis showed neuronal and ICC abnormalities in En/En tissues. The En/En rabbit model shows neuro-ICC changes reminiscent of the human non-aganglionic megacolon. This rabbit model may provide a better understanding of the molecular abnormalities underlying conditions associated with non-aganglionic megacolon. PMID:24736498

Fontanesi, Luca; Vargiolu, Manuela; Scotti, Emilio; Latorre, Rocco; Faussone Pellegrini, Maria Simonetta; Mazzoni, Maurizio; Asti, Martina; Chiocchetti, Roberto; Romeo, Giovanni; Clavenzani, Paolo; De Giorgio, Roberto

2014-01-01

18

Systematic Review of Surgical Options for Idiopathic Megarectum and Megacolon  

PubMed Central

Objective: A subgroup of patients with intractable constipation has persistent dilatation of the bowel, which in the absence of an organic cause is termed idiopathic megabowel (IMB). The aim of this systematic review was to evaluate the published outcome data of surgical procedures for IMB in adults. Methods: Electronic searches of the MEDLINE (PubMed) database, Cochrane Library, EMBase, and Science Citation Index were performed. Only peer-reviewed articles of surgery for IMB published in the English language were evaluated. Studies of all surgical procedures were included, providing they were performed on 3 or more patients, and overall success rates were documented. Studies were critically appraised in terms of design and methodology, inclusion criteria, success, mortality and morbidity rates, and functional outcomes. Results: A total of 27 suitable studies were identified, all evidence was low quality obtained from case series, and there were no comparative studies. The studies involved small numbers of patients (median 12, range 3–50), without long-term follow-up (median 3 years, range 0.5–7). Inclusion of subjects, methods of data acquisition, and reporting of outcomes were extremely variable. Subtotal colectomy was successful in 71.1% (0%–100%) but was associated with significant morbidity related to bowel obstruction (14.5%, range 0%–29%). Segmental resection was successful in 48.4% (12.5%–100%), and recurrent symptoms were common (23.8%). Rectal procedures achieved a successful outcome in 71% to 87% of patients. Proctectomy, the Duhamel, and pull-through procedures were associated with significant mortality (3%–25%) and morbidity (6%–29%). Vertical reduction rectoplasty (VRR) offered promising short-term success (83%). Pelvic-floor procedures were associated with poor outcomes. A stoma provided a safe alternative but was only effective in 65% of cases. Conclusions: Outcome data of surgery for IMB must be interpreted with extreme caution due to limitations of included studies. Recommendations based on firm evidence cannot be given, although colectomy appears to be the optimum procedure in patients with a nondilated rectum, restorative proctocolectomy the most suitable in those with dilatation of the colon and rectum, and VRR in those patients with dilatation confined to the rectum. Appropriately designed studies are required to make valid comparisons of the different procedures available. PMID:15798457

Gladman, Marc A.; Scott, S Mark; Lunniss, Peter J.; Williams, Norman S.

2005-01-01

19

Clinical Features: Polymicrogyria (PMG) is a cortical brain malformation which is characterized by an excessive number of small irregular  

E-print Network

) is an autosomal recessive multiple malformation disorder characterized by Hirschsprung megacolon, microcephaly include early onset seizures, severe microcephaly and developmental arrest. O'Driscoll et al. (2010

Das, Soma

20

Clinical Features: Polymicrogyria (PMG) is a cortical brain malformation which is characterized by an excessive number of small irregular  

E-print Network

disorder characterized by Hirschsprung megacolon, microcephaly, hypertelorism, submucous cleft palate include early onset seizures, severe microcephaly and developmental arrest. O'Driscoll et al. (2010

Gilad, Yoav

21

Clinical Features: Polymicrogyria (PMG) is a cortical brain malformation which is characterized by an excessive number of small irregular  

E-print Network

malformation disorder characterized by Hirschsprung megacolon, microcephaly, hypertelorism, submucous cleft include early onset seizures, severe microcephaly and developmental arrest. O'Driscoll et al. (2010

Das, Soma

22

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

PubMed

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

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

2014-10-01

23

Diagnosing and Managing IBD  

MedlinePLUS

... high-frequency sound waves, not heard by the human ear, are transmitted through body tissues using a transducer, relaying information to a computer for display. Toxic megacolon: an acute condition where ...

24

TTF-1 and RET promoter SNPs: regulation of RET transcription in Hirschsprung's disease  

Microsoft Academic Search

Single nucleotide polymorphisms (SNPs) of the coding regions of receptor tyrosine kinase gene (RET )a re associated with Hirschsprung's disease (HSCR, aganglionic megacolon). These SNPs, individually or com- bined, may act as a low penetrance susceptibility locus and\\/or be in linkage disequilibrium (LD) with another susceptibility locus located in RET regulatory regions. Because two RET promoter SNPs have been found

Raymond W. Ganster; Vincent C. H. Lui; Thomas Y. Y. Leon; Man-Ting So; Anson M. F. Lau; Ming Fu; Mai-Har Sham; Joanne Knight; Maria Stella Zannini; Pak C. Sham; Paul K. H. Tam

2005-01-01

25

Hirschsprung disease, associated syndromes, and genetics: a review  

PubMed Central

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

Amiel, J.; Lyonnet, S.

2001-01-01

26

Research on Trypanosoma cruzi and Analysis of Inflammatory Infiltrate in Esophagus and Colon from Chronic Chagasic Patients with and without Mega  

PubMed Central

To compare parasitism and inflammatory process in esophagus and colon from chronic chagasic patients, immunohistochemistry was carried out to research for T. cruzi and to evaluate the inflammatory infiltrate in the muscular and myenteric plexus in 39 esophagi (20 with and 19 without megaesophagus) and 50 colons (25 with and 25 without megacolon). The frequency of T. cruzi in megaesophagus was 20%, and in megacolon it was 4%. No amastigotes were found in organs without mega; considering the total of esophagi (with and without mega), the frequency of T. cruzi would be 10% and 2% in the colon. Myositis and ganglionitis were more frequent and intense in organs with mega compared to those without mega, and in esophagus compared to colon. Qualitatively, inflammatory infiltration in esophagus and colon, with or without mega, was similar, consisting predominantly of T lymphocytes (CD3+), scarce macrophages (CD68+), and rare B lymphocytes (CD20+). PMID:22131997

Côbo, Eliângela de Castro; Silveira, Thales Parenti; Micheletti, Adilha Misson; Crema, Eduardo; Adad, Sheila Jorge

2012-01-01

27

Strategies for the Care of Adults Hospitalized for Active Ulcerative Colitis  

PubMed Central

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

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

28

[The problems of spotted breeds of rabbits. 4. Morpho- and histometric findings in the CNS and thyroid glands and the hormone content in blood at slaughter of hybrid rabbits, and estimation of the heterosis effect].  

PubMed

Morpho- und histometric investigations of brains, pituitary and thyroid glands as well as thyroid-related functional parameters in the blood of purebred and hybrid rabbits revealed a predisposition to hypothyreotic conditions in homozygous, megacolon-prone genotypes. In addition to this also a hypoganglionotic state in different gut wall localizations was confirmed; pituitary traits however did not indicate a primary contribution of this gland to the syndrome, though some alterations were found, which are interpreted as secondary sv. symptomatic. Gender influences varied hormonal characteristics and disease manifestations too: A dramatic fall in severely diseased does with respect to T3-concentration as well as a seemingly more inactive thyroid gland compared to bucks underline hormonal influences. As a consequence of these results it is concluded, that hybridisation within spotted rabbits does not amend the inclination to megacolon in animals homozygous for the K (En) gene, though it may influence its manifestation. PMID:7895623

Flemming, K; Kühnel, C; Wieberneit, D; Wegner, W

1994-11-01

29

Review of medical and surgical management of Clostridium difficile infection  

Microsoft Academic Search

Clostridium difficile infection (CDI) has become an important area in our daily clinical practice. C. difficile is known to cause a broad spectrum of conditions ranging from asymptomatic carriage, through mild or moderately severe disease\\u000a with watery diarrhoea, to the life-threatening pseudomembranous colitis (PMC), with toxic megacolon and ileus. Peoples who\\u000a have been treated with broad-spectrum antibiotics, patients with serious

B. FarisA; A. Blackmore; N. Haboubi

2010-01-01

30

Clostridium difficile colitis.  

PubMed

Clostridium difficile enterocolitis is endemic in most modern hospitals. The spectrum of clinical presentation varies from the asymptomatic carrier state to fulminant colitis with toxic megacolon and perforation. Highly toxigenic and lethal strains of C. difficile have emerged worldwide. Medical treatment consists of discontinuing the precipitating antibiotic, supportive measures and bowel rest, and antibiotic treatment with metronidazole or vancomycin. Surgical treatment may be necessary in cases of fulminant disease. Subtotal colectomy with end ileostomy is the operation of choice. PMID:20011356

Trudel, Judith L

2007-02-01

31

Clostridium difficile  

Microsoft Academic Search

\\u000a \\u000a Clostridium difficile produces gastrointestinal infection in humans and animals, ranging from asymptomatic colonization to diarrhea, pseudomembranous\\u000a colitis, toxic megacolon, colonic perforation, sepsis, and death. C. difficile has emerged as a major cause of nosocomial diarrhea and is the most frequently identified cause of hospital-acquired infectious\\u000a diarrhea in patients.(1,2) C. difficile-associated disease (CDAD) is a general term used to describe the

Dale N. Gerding; Stuart Johnson

32

Human GFRA1: Cloning, Mapping, Genomic Structure, and Evaluation as a Candidate Gene for Hirschsprung Disease Susceptibility  

Microsoft Academic Search

Congenital aganglionic megacolon, commonly known as Hirschsprung disease (HSCR), is the most frequent cause of congenital bowel obstruction. Germline mutations in theRETreceptor tyrosine kinase have been shown to cause HSCR. Knockout mice forRETand for its ligand, glial cell line-derived neurotrophic factor (GDNF), exhibit both complete intestinal aganglionosis and renal defects. Recently, GDNF and GFRA1 (GDNF family receptor, also known as

Misha Angrist; Shuqian Jing; Stacey Bolk; Kimberly Bentley; Sudha Nallasamy; Marc Halushka; Gary M. Fox; Aravinda Chakravarti

1998-01-01

33

Involvement of SOX10 in the pathogenesis of Hirschsprung disease: report of a truncating mutation in an isolated patient  

Microsoft Academic Search

SOX10 protein is a key transcription factor during neural crest development. Mutations in SOX10 are associated with several neurocristopathies such as Waardenburg syndrome type IV (WS4), a congenital disorder characterized\\u000a by the association of hearing loss, pigmentary abnormalities, and absence of ganglion cells in the myenteric and submucosal\\u000a plexus of the gastrointestinal tract, also known as aganglionic megacolon or Hirschsprung

Avencia Sánchez-Mejías; Yuli Watanabe; Raquel M. Fernández; Manuel López-Alonso; Guillermo Antiñolo; Nadege Bondurand; Salud Borrego

2010-01-01

34

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

Microsoft Academic Search

The consequence of presence versus absence of mucosal neurons is not consistently assessed. Here, we addressed two questions.\\u000a First, based on resected gut specimens of 65 patients\\/body donors suffering from different diseases, counts of mucosal neurons\\u000a per mm2 were analysed with respect to age, gender and region. Second, we evaluated resected megacolonic specimens of four patients\\u000a suffering from chronic Chagas’

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

35

Signalling of the Ret receptor tyrosine kinase through the c-Jun NH2-terminal protein kinases (JNKs): evidence for a divergence of the ERKs and JNKs pathways induced by Ret  

Microsoft Academic Search

The RET proto-oncogene encodes a functional receptor tyrosine kinase (Ret) for the Glial cell line Derived Neurotrophic Factor (GDNF). RET is involved in several neoplastic and non-neoplastic human diseases. Oncogenic activation of RET is detected in human papillary thyroid tumours and in multiple endocrine neoplasia type 2 syndromes. Inactivating mutations of RET have been associated to the congenital megacolon, i.e.

Mario Chiariello; Roberta Visconti; Francesca Carlomagno; Rosa Marina Melillo; Cecilia Bucci; Vittorio de Franciscis; Gary M Fox; Shuqian Jing; Omar A Coso; J Silvio Gutkind; Alfredo Fusco; Massimo Santoro

1998-01-01

36

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

PubMed

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

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

2012-08-01

37

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

PubMed

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

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

2011-07-01

38

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

PubMed Central

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

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

2012-01-01

39

[Most frequent causes of constipación in our environment].  

PubMed

At the Digestive Motility Department on gastroenterology floor of the "Hospital de Clinicas Jose de San Martin", 165 patients were evaluated due to chronic constipation, underlying the most frequent causes in our environment. The use of the present diagnostic methods is suggested following a suitable clinical orientation. The most frequent causes of constipation after this test were: chronic idiopathic constipation in 112 cases (67.87%) and with megarectum, megasigma and megacolon 32 cases (19.09%), rectocele in 9 cases (5.45%), rectal prolapse in 5 cases (3.03%), enf. De Hirschprung 5 cases (3.03%) and anal estenosis 2 cases (1.21%). PMID:14708507

Curi, L A; Maldonado, Gabriela; Genoud, Teresa

2003-01-01

40

Alternative treatments for Clostridium difficile disease: what really works?  

PubMed

Vancomycin and metronidazole have been used for treating Clostridium difficile-associated disease (CDAD) for the past 25 years, but approximately 20 % of patients develop recurrent disease. The increasing incidence of nosocomial outbreaks, cases of recurrent CDAD and other complications (toxic megacolon, ileus, sepsis) has fuelled the search for different types of treatments. As the understanding of the pathogenesis of this disease has matured, newer treatment strategies that take advantage of these mechanisms have been developed. This review will describe such treatments and examine the evidence for each strategy. PMID:15673502

McFarland, Lynne V

2005-02-01

41

Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection  

NASA Astrophysics Data System (ADS)

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.

Surawicz, Christina M.

42

Adrenergic Innervation of Bowel in Hirschsprung's Disease  

PubMed Central

The adrenergic innervation of normal and aganglionic regions of bowel from patients with Hirschsprung's disease was investigated by a fluorescent histochemical technique. In normal bowel the adrenergic nerves end about intramural ganglion cells. In aganglionic bowel the adrenergic nerves form a dense varicose plexus in both muscularis externa and muscularis mucosae. It is suggested that the cause of megacolon in Hirschsprung's disease is due to a lack of nervous pathways controlling the intrinsic reflexes, which is probably congenital in origin. ImagesFig. 1Fig. 2 PMID:5800344

Gannon, B. J.; Noblet, Helen R.; Burnstock, G.

1969-01-01

43

[The problem of breeding for spots in rabbits. 2. Further results on the variation of characteristics in fattening and breeding animals].  

PubMed

The mode of inheritance of spotting in both breeds (ES and DRS) is compatible with incompletely dominant resp. intermediate segregation, though a broad variability of spotted areas exists, indicating the influence of minor genes or other ontogenetic factors. Additional findings support the conclusion, that there is a very distinct predisposition of homozygous KK animals to develop megacolon with growing age. This also has consequences for the relative organ weight of the heart and of the adrenals in this genotype. Sporadically encountered accessory adrenal cortical tissue however did not exhibit genotypic preferences. PMID:1576947

Mahdi, N; Wieberneit, D; Wegner, W

1992-03-01

44

Multiple endocrine neoplasia 2B presenting with pseudo-Hirschsprung's disease.  

PubMed Central

Multiple endocrine neoplasia type 2B (MEN 2B) is a rare syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and typical phenotypic features, such as marfanoid habitus, multiple mucosal ganglioneuromas and thickened corneal nerves. Individuals with MEN 2B may develop megacolon and pseudo-obstruction due to intestinal ganglioneuromatosis simulating Hirschsprung's (HSCR) disease. We hereby describe the clinical and genetic features of a 21-year-old male patient with MEN 2B associated with pseudo-HSCR disease. The patient had MTC, pheochromocytoma, marfanoid habitus, multiple mucosal ganglioneuromas, thickened corneal nerves and severe gastrointestinal involvement. Emergent laparotomy was performed when he was presented with acute bowel obstruction. The myenteric and submucosal nerve plexuses in the small and large intestines were composed of diffusely hyperplasic, disorganized, mature ganglion cells. Genetic testing revealed a de novo ret proto-oncogene germline mutation in codon 918 in exon 16. Megacolon and pseudo-obstruction similar to the HSCR disease may develop in patients with MEN 2B. However, the observed dysmotility is the result of an abnormal proliferation of intramural ganglion cells in contrast to the absence of enteric ganglia which were present in the HSCR disease. Attentiveness about the phenotypic characteristics and unusual findings might lead to early and correct diagnosis of the MEN 2B syndrome. This approach improves the survival rate and quality of life considerably. Images Figure 1 PMID:16749656

Erdogan, Murat Faik; Gulec, Bulent; Gursoy, Alptekin; Pekcan, Mesut; Azal, Omer; Gunhan, Omer; Bayer, Atilla

2006-01-01

45

Functional Aerophagia in Children: A Frequent, Atypical Disorder  

PubMed Central

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

Morabito, Giuliana; Romeo, Claudia; Romano, Claudio

2014-01-01

46

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

SciTech Connect

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.

Teichgraeber, Ulf Karl-Martin, E-mail: ulf.teichgraeber@charite.de; Streitparth, Florian, E-mail: florian.streitparth@charite.d [Charite Universitaetsmedizin Berlin, Institut fuer Diagnostische und Interventionelle Radiologie (Germany); Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.d [Charite Universitaetsmedizin Berlin, Klinik fuer Strahlenheilkunde (Germany); Benter, Thomas, E-mail: Thomas.Benter@klinikum-rg.d [Elblandkliniken Riesa-Grossenhain gGmbH, Klinik fuer Innere Medizin II Haematologie/Onkologie und Gastroenterologie (Germany)

2010-04-15

47

Building a brain in the gut: development of the enteric nervous system.  

PubMed

The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, is an essential component of the gut neuromusculature and controls many aspects of gut function, including coordinated muscular peristalsis. The ENS is entirely derived from neural crest cells (NCC) which undergo a number of key processes, including extensive migration into and along the gut, proliferation, and differentiation into enteric neurons and glia, during embryogenesis and fetal life. These mechanisms are under the molecular control of numerous signaling pathways, transcription factors, neurotrophic factors and extracellular matrix components. Failure in these processes and consequent abnormal ENS development can result in so-called enteric neuropathies, arguably the best characterized of which is the congenital disorder Hirschsprung disease (HSCR), or aganglionic megacolon. This review focuses on the molecular and genetic factors regulating ENS development from NCC, the clinical genetics of HSCR and its associated syndromes, and recent advances aimed at improving our understanding and treatment of enteric neuropathies. PMID:23167617

Goldstein, A M; Hofstra, R M W; Burns, A J

2013-04-01

48

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

PubMed Central

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

Pinazo, Maria-Jesus; Lacima, Gloria; Elizalde, Jose-Ignacio; Posada, Elizabeth-Jesus; Gimeno, Fausto; Aldasoro, Edelweiss; Valls, Maria-Eugenia; Gascon, Joaquim

2014-01-01

49

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

PubMed Central

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 ?-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

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

2013-01-01

50

[Giant Meckel's diverticulum in an adult].  

PubMed

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. PMID:25299124

Contreras, Tomas; Eluzen, Nasser; King, Sebastian; Molina, María Elena; Zúñiga, José Miguel; Bustamante, Carol; Spralja, Biserka

2014-01-01

51

Clostridium difficile-associated colitis.  

PubMed Central

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

Hull, Mark W.; Beck, Paul L.

2004-01-01

52

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

PubMed

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

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

2014-04-01

53

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

PubMed Central

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

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

2014-01-01

54

[The problems of breeding spotted rabbits. 3. Variability of the pigmentation grade, ganglionic intestinal wall supply, relationship to pathogenesis--animal breeding and animal welfare aspects].  

PubMed

In a total of 128 animals of the German Giant Spot und the English Spot Breed grade of pigmentation and spotting pattern were investigated by photography and planimetry. A clear cut binary distribution, representing homozygous (KK) or heterozygous spot rabbits (Kk), and a strong bilateral concordance was found as well as a broad variance within both genotypical groups. Thus only a small percentage of animals bred can be compatible with mandatory fancy breed standards. Measurements of intestinal layers and neural components in well pigmented and depigmented individuals revealed an enhancement of these histological structures but a relative hypoganglionosis in distal parts of the gut in animals with predisposition to megacolon (KK, so-called chaplins). It is not yet clear whether this is symptomatic or of primary pathogenetic relevance. There were no pleiotropic deleterious effects of the K-allele in heterozygous rabbits and no correlations between the degree of depigmentation and the severity of symptoms in homozygous spotted ones, thus indicating a mode of inheritance by an incompletely dominant gene K, acting as or being linked to a recessive semilethal when homozygous. A change in breeders' attitude and breeding practices is mandatory because neither the permanent elimination of animals not "fitting" a fancy standard nor the continuous production of defective genotypes is legal. PMID:8339710

Gerlitz, S; Wessel, G; Wieberneit, D; Wegner, W

1993-06-01

55

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

PubMed

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. PMID:808136

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

1975-07-01

56

The host immune response to Clostridium difficile infection  

PubMed Central

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

2013-01-01

57

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

PubMed Central

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

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

2013-01-01

58

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

PubMed Central

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

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

1975-01-01

59

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

PubMed Central

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

Carroll, Karen C.

2013-01-01

60

[Clostridium-difficile-associated infections].  

PubMed

C. difficile is a spore-forming anaerobic enteropathogen. This bacillus is responsible for virtually all cases of pseudomembranous colitis and for 15 to 25% of cases of antibiotic-associated diarrhoea. Clostridium difficile associated-infections (CDI) have a wide range of clinical features which vary from mild uncomplicated diarrhoea to severe debilitating disease, paralytic ileus, toxic megacolon, or even perforation and sometimes death. Risk factors for CDI include age > 65 years, previous hospitalization and recent antibiotic therapy. Main virulence factors for this pathogen are toxins A and B. A third toxin, the binary toxin, has been found in up to 10% of strains from infected patients. For some years, a new hypervirulent strain has emerged. This epidemic strain belongs to PCR-ribotype 027 and is responsible for outbreaks with increased mortality and severity in North America and Europe. The most effective antibiotics for treatment are oral metronidazole and vancomycin. Control of CDI needs to prevent the emergence of CDI by minimizing the number of patients exposed to antimicrobials and to limit cross transmission. PMID:20188046

Eckert, Catherine; Barbut, Frédéric

2010-02-01

61

Dosage Effects of Cohesin Regulatory Factor PDS5 on Mammalian Development: Implications for Cohesinopathies  

PubMed Central

Cornelia de Lange syndrome (CdLS), a disorder caused by mutations in cohesion proteins, is characterized by multisystem developmental abnormalities. PDS5, a cohesion protein, is important for proper chromosome segregation in lower organisms and has two homologues in vertebrates (PDS5A and PDS5B). Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown. To delineate genetic interactions between Pds5A and Pds5B and explore mechanisms underlying phenotypic variability, we generated Pds5A-deficient mice. Curiously, these mice exhibit multiple abnormalities that were previously observed in Pds5B-deficient mice, including cleft palate, skeletal patterning defects, growth retardation, congenital heart defects and delayed migration of enteric neuron precursors. They also frequently display renal agenesis, an abnormality not observed in Pds5B?/? mice. While Pds5A?/? and Pds5B?/? mice die at birth, embryos harboring 3 mutant Pds5 alleles die between E11.5 and E12.5 most likely of heart failure, indicating that total Pds5 gene dosage is critical for normal development. In addition, characterization of these compound homozygous-heterozygous mice revealed a severe abnormality in lens formation that does not occur in either Pds5A?/? or Pds5B?/? mice. We further identified a functional missense mutation (R1292Q) in the PDS5B DNA-binding domain in a familial case of CdLS, in which affected individuals also develop megacolon. This study shows that PDS5A and PDS5B functions other than those involving chromosomal dynamics are important for normal development, highlights the sensitivity of key developmental processes on PDS5 signaling, and provides mechanistic insights into how PDS5 mutations may lead to CdLS. PMID:19412548

Zhang, Bin; Chang, Jufang; Fu, Ming; Huang, Jie; Kashyap, Rakesh; Salavaggione, Ezequiel; Jain, Sanjay; Shashikant, Kulkarni; Deardorff, Matthew A.; Uzielli, Maria L. Giovannucci; Dorsett, Dale; Beebe, David C.; Jay, Patrick Y.; Heuckeroth, Robert O.; Krantz, Ian; Milbrandt, Jeffrey

2009-01-01

62

Clostridium difficile Spore-Macrophage Interactions: Spore Survival  

PubMed Central

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

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

2012-01-01

63

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

SciTech Connect

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.

Bolk, S.; Duggan, D.J.; Chakravarti, A. [Case Western Reserve Univ., Cleveland, OH (United States)

1994-09-01

64

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

PubMed

Ulcerative colitis (UC) is an idiopathic, inflammatory gastrointestinal disease of the colon. As a chronic condition, UC follows a relapsing and remitting course with medical maintenance during periods of quiescent disease and appropriate escalation of therapy during times of flare. Initial treatment strategies must not only take into account current clinical presentation (with specific regard for extent and severity of disease activity) but must also take into consideration treatment options for the long-term. The following review offers an approach to new-onset UC with a focus on early treatment strategies. An introduction to the disease entity is provided along with an approach to initial diagnosis. Stratification of patients based on clinical parameters, disease extent, and severity of illness is paramount to determining course of therapy. Frequent assessments are required to determine clinical response, and treatment intensification may be warranted if expected improvement goals are not appropriately reached. Mild-to- moderate UC can be managed with aminosalicylates, mesalamine, and topical corticosteroids with oral corticosteroids reserved for unresponsive cases. Moderate-to-severe UC generally requires oral or intravenous corticosteroids in the short-term with consideration of long-term management options such as biologic agents (as initial therapy or in transition from steroids) or thiopurines (as bridging therapy). Patients with severe or fulminant UC who are recalcitrant to medical therapy or who develop disease complications (such as toxic megacolon) should be considered for colectomy. Early surgical referral in severe or refractory UC is crucial, and colectomy may be a life-saving procedure. The authors provide a comprehensive evidence-based approach to current treatment options for new-onset UC with discussion of long-term therapeutic efficacy and safety, patient-centered perspectives including quality of life and medication compliance, and future directions in related inflammatory bowel disease care. PMID:24872716

Marchioni Beery, Renée; Kane, Sunanda

2014-01-01

65

Hirschsprung's disease as a model of complex genetic etiology.  

PubMed

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. PMID:23605783

Borrego, Salud; Ruiz-Ferrer, Macarena; Fernández, Raquel M; Antiñolo, Guillermo

2013-09-01

66

The developmental etiology and pathogenesis of Hirschsprung disease.  

PubMed

The enteric nervous system is the part of the autonomic nervous system that directly controls the gastrointestinal tract. Derived from a multipotent, migratory cell population called the neural crest, a complete enteric nervous system is necessary for proper gut function. Disorders that arise as a consequence of defective neural crest cell development are termed neurocristopathies. One such disorder is Hirschsprung disease (HSCR), also known as congenital megacolon or intestinal aganglionosis. HSCR occurs in 1/5000 live births and typically presents with the inability to pass meconium, along with abdominal distension and discomfort that usually requires surgical resection of the aganglionic bowel. This disorder is characterized by a congenital absence of neurons in a portion of the intestinal tract, usually the distal colon, because of a disruption of normal neural crest cell migration, proliferation, differentiation, survival, and/or apoptosis. The inheritance of HSCR disease is complex, often non-Mendelian, and characterized by variable penetrance. Extensive research has identified a number of key genes that regulate neural crest cell development in the pathogenesis of HSCR including RET, GDNF, GFR?1, NRTN, EDNRB, ET3, ZFHX1B, PHOX2b, SOX10, and SHH. However, mutations in these genes account for only ?50% of the known cases of HSCR. Thus, other genetic mutations and combinations of genetic mutations and modifiers likely contribute to the etiology and pathogenesis of HSCR. The aims of this review are to summarize the HSCR phenotype, diagnosis, and treatment options; to discuss the major genetic causes and the mechanisms by which they disrupt normal enteric neural crest cell development; and to explore new pathways that may contribute to HSCR pathogenesis. PMID:23528997

Butler Tjaden, Naomi E; Trainor, Paul A

2013-07-01

67

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

PubMed Central

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

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

2014-01-01

68

[The problems of spotted breeds of rabbits. 1. Fattening and body condition at slaughter, organ parameters].  

PubMed

Rabbits of the Giant German Spot Breed and of the English Spot Breed were bred, reared, fattened and evaluated under standardized conditions. A total of 50 animals (31 German spot = DRS; 19 English spot = ES; both derived from mating of heterozygotes) was tested, belonging to the three possible genotypes: Homozygous black (kk), heterozygous spotted (Kk, "standard animals") and homozygous spotted (KK, so-called "Chaplins"). As expected, breed differences consisted of better daily gains and higher carcass weights in DRS, but higher dressing percentages in ES. With respect to colour genotypes, only in DRS-KK depressions of daily gains and carcass weight were observed; food conversion efficiency however was even better in these animals (of both breeds), primarily because of lower feed uptake. Very distinct differences in some important organ traits could be demonstrated for those genotypes: A significantly augmented intestine (abs. and rel.) in KK-animals, specially with reference to the gross intestine--indicating a tendency to motility disturbances and/or chronic obstipation. This predisposition was underlined by the premature loss of three KK-rabbits suffering from severe corresponding symptoms. Seemingly analogous syndromes (Megacolon) in man and other species are cited, though further investigations are needed to clarify the etiology in spot rabbits. Significance of lower heart weights was stated in DRS-KK-animals, probably induced by minor activities observed in this genotype. Thus the K-gene can be classified as a subvital one when homozygous though manifestations of the symptoms obviously vary with the genetic background (breed, line) and perhaps with the environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1954863

Wieberneit, D; Mahdi, N; Zacharias, K; Wegner, W

1991-09-01

69

Nitric oxide as a modulator of intestinal water and electrolyte transport.  

PubMed

The role of nitric oxide in intestinal fluid and electrolyte secretion depends upon whether the conditions under study are physiological or pathophysiological. In physiological conditions, endogenous nitric oxide seems to be a proabsorptive molecule, based on the findings that nitric oxide synthase inhibitors reverse net fluid absorption to net secretion in mice, rats, guinea pigs, rabbits, and dogs. This proabsorptive mode involves the enteric nervous system, the suppression of prostaglandin formation, and the opening of basolateral K+ channels. However, in some pathophysiological states nitric oxide synthase may be produced at higher concentrations that are capable of evoking net secretion. Thus nitric oxide synthase contributes to the diarrheal response in trinitrobenzene sulfonic acid-induced ileitis in guinea pigs and is the mediator of the laxative action of several intestinal secretagogues including castor oil, phenolphthalein, bisacodyl, magnesium sulfate, bile salts, senna, and cascara in the rat. Corresponding with the in vivo results, nitric oxide-donating compounds or nitric oxide itself stimulate chloride secretion in the guinea pig and rat intestine in vitro. Exceptions are the diarrhea produced by bacterial enterotoxins in the rat, in which nitric oxide seems to have a proabsorptive role, and the mouse ileum in vitro, in which nitric oxide-donating compounds produce a net proabsorptive effect on basal ion transport. Several endogenous secretagogues (substance P, 5-hydroxytryptamine, interleukin-1beta), which are important mediators of the inflammatory bowel diseases, act, at least in part, through the liberation of nitric oxide. Clinical studies have shown that nitric oxide is elevated in several inflammatory bowel diseases and other secretory conditions including ulcerative colitis, Crohn's disease, toxic megacolon, diverticulitis, infectious gastroenteritis, and infantile methemoglobinemia. However, the determination of nitric oxide in secretory diarrhea per se does not give conclusive information on the nitric oxide contribution to clinical secretory diarrhea. PMID:9724140

Izzo, A A; Mascolo, N; Capasso, F

1998-08-01

70

Chagas' disease: a clinical, parasitological, immunological, and pathological study in rabbits.  

PubMed

Thirty-four rabbits were experimentally infected with trypomastigotes of either the Ernestina or the Albuquerque strains of Trypanosoma cruzi. These animals showed patent parasitemias, as demonstrated by xenodiagnosis, in the acute phases of the infections. Typical chagoma signs developed in two rabbits 1 week after parasite inoculation in the skin, although the acute phase of Chagas' disease in the rabbit model was usually asymptomatic. In the 6th month of infection the parasitemias became negative and the infections remained subpatent, as indicated by the persistence of positive serologic tests and of delayed-type skin reactions elicited in Chagas' rabbits against a microsomal T. cruzi antigen. This latent infection continued asymptomatically, in the absence of electrocardiographic (ECG) alterations. However, ECG changes consistent with enlargement and overload of cardiac chambers, alterations of ventricular repolarization, S-T changes and bundle-branch blocks were frequently recorded later in the chronic phase of Chagas' disease. The pathological manifestations of these ECG alterations were confirmed at the autopsy of each experimental rabbit. Congestive heart failure and pulmonary thromboemboli related to chronic myocarditis of Chagas' disease were frequent causes of death. Megacolon was seen in two rabbits inoculated with the Ernestina strain of the parasite. The relatively limited duration of detectable parasitemia even when xenodiagnosis is used, the lack of correlation between parasitemia and severity of pathological manifestations, and the fact that all infected animals showed histopathological evidence of myocarditis, destructive inflammatory lesions characterized by mononuclear infiltrates in skeletal muscles, as well as cutaneous delayed hypersensitivity to T. cruzi antigens, are notable observations in this animal model of the human disease. PMID:6404186

Teixeira, A R; Figueiredo, F; Rezende Filho, J; Macêdo, V

1983-03-01

71

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

PubMed Central

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

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

2011-01-01

72

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

PubMed Central

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

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

2012-01-01

73

Current approaches to the management of new-onset ulcerative colitis  

PubMed Central

Ulcerative colitis (UC) is an idiopathic, inflammatory gastrointestinal disease of the colon. As a chronic condition, UC follows a relapsing and remitting course with medical maintenance during periods of quiescent disease and appropriate escalation of therapy during times of flare. Initial treatment strategies must not only take into account current clinical presentation (with specific regard for extent and severity of disease activity) but must also take into consideration treatment options for the long-term. The following review offers an approach to new-onset UC with a focus on early treatment strategies. An introduction to the disease entity is provided along with an approach to initial diagnosis. Stratification of patients based on clinical parameters, disease extent, and severity of illness is paramount to determining course of therapy. Frequent assessments are required to determine clinical response, and treatment intensification may be warranted if expected improvement goals are not appropriately reached. Mild-to- moderate UC can be managed with aminosalicylates, mesalamine, and topical corticosteroids with oral corticosteroids reserved for unresponsive cases. Moderate-to-severe UC generally requires oral or intravenous corticosteroids in the short-term with consideration of long-term management options such as biologic agents (as initial therapy or in transition from steroids) or thiopurines (as bridging therapy). Patients with severe or fulminant UC who are recalcitrant to medical therapy or who develop disease complications (such as toxic megacolon) should be considered for colectomy. Early surgical referral in severe or refractory UC is crucial, and colectomy may be a life-saving procedure. The authors provide a comprehensive evidence-based approach to current treatment options for new-onset UC with discussion of long-term therapeutic efficacy and safety, patient-centered perspectives including quality of life and medication compliance, and future directions in related inflammatory bowel disease care. PMID:24872716

Marchioni Beery, Renee; Kane, Sunanda

2014-01-01

74

Newborn endothelin receptor type B mutant (piebald) mice have a higher resting anal sphincter pressure than newborn C57BL/6 mice.  

PubMed

Hirschsprung's disease is characterized by aganglionosis of the distal colon and hypertonicity of the anal sphincter. Endothelin receptor type B mutant (piebald) mice phenotypically resemble infants with Hirschsprung's disease in that these mice are susceptible to developing toxic megacolon because of the absence of ganglion cells in their distal colon. Therefore, we hypothesized that newborn piebald mice would have a higher resting anal sphincter pressure than would newborn wild-type mice. To test this hypothesis, we developed a reliable and reproducible technique for measuring the resting anal sphincter pressure in mice. Heterozygote breeding pairs of endothelin receptor type B mutant mice were purchased and bred in our animal facility. Pregnant, time-dated C57BL/6J mice provided control newborn mice. One-day-old newborn mice were evaluated for resting anal sphincter pressure. Under the operating microscope, a 24-gauge open-tip epidural catheter was placed into the anus until a deflection (approximately 3 to 5 mm) was noticed on a polygraph pressure monitor. Three consecutive measurements were obtained for each mouse. Mean values for each group were determined and compared using Student's t test. The resting anal sphincter pressure (mean +/- standard deviation) in newborn C57BL/6J mice was 13.3 +/- 2.6 mmHg, whereas that in piebald mice 22.7 +/- 2.5 mmHg (P < 0.0001). Therefore, because of their increased resting anal sphincter pressure, piebald mice may provide a useful animal model for the study of Hirschsprung's disease. PMID:14615959

Nadler, Evan P; Boyle, Patricia; Murdock, Alan D; Dilorenzo, Carlo; Barksdale, Edward M; Ford, Henri R

2003-11-01

75

Severe birth defects in children perinatal exposed to HIV from a "real-world" setting: Infectious Diseases National Institute, Bucharest, Romania  

PubMed Central

Introduction The shift in epidemic trends in recent years in Romania shows new problems in regard of HIV vertical transmission, firstly in intravenous drug user's mothers co-infected with hepatitis viruses and with social problems, and secondly the children of young mothers with an old HIV infection and long antiretroviral therapy history. Materials and Methods We studied all HIV perinatal exposed children routinely followed up in the Paediatric Department of the National Institute of Infectious Diseases, since January 1st 2006 till December 31st 2012. The analyses consisted of describing the birth defects and association with certain risk factors: gender, mother's age at birth and exposure to antiretrovirals in the first trimester of pregnancy. Results We analyzed 244 children born to HIV-infected mothers. The incidence of HIV infection was 16.39%. The rate of birth defects was 39.34% (96/244 cases). The most frequent findings were cardiac malformations (47/96), followed by musculoskeletal defects (24/96), neurologic defects (20/96), urogenital malformations (13/96), digestive tract defects (3/93), metabolic disorders (2/96) and genetic disorders (2/96). We found nine cases of severe congenital anomalies: complex heart defect, total congenital aganglionic megacolon, anal imperforation, Dandy-Walker syndrome, gangliosidosis, Niemann-Pick syndrome, Down syndrome, true hermaphroditism and cleft palate. Two children died during first year of life due to severe malformations. 9% of cases had associated malformations. The gender rate was in favour of males in group with birth defects (58/38) and with no birth defects (82/66). The median age at birth in mothers was 22 years, similar in both groups. The highest mean age at birth was in offspring's mothers with neurologic congenital defects 25, 15 years old, but is not statistically significant (p=0.1). In the studied period the highest number of birth defects were found in 2012, 37 children, compared with less than 15 in previous years (not statistically significant, p=0.07). In our studied patients the risk of birth defects was not statistically associated with HIV transmission or with exposure to antiretrovirals before and in first trimester of pregnancy (p=0.88). Conclusion The rate of birth defects among HIV-exposed children was not significantly associated with antiretroviral exposure, but we identify very rare and severe congenital conditions. We have noticed also a trend to increasing number of birth defects in 2012 among studied patients compared to previous years.

Maria Tudor, Ana

2014-01-01

76

Clostridium difficile associated infection, diarrhea and colitis  

PubMed Central

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

Hookman, Perry; Barkin, Jamie S

2009-01-01

77

Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4).  

PubMed

Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors involving two or more endocrine glands within a single patient. Four major forms of MEN, which are autosomal dominant disorders, are recognized and referred to as: MEN type 1 (MEN1), due to menin mutations; MEN2 (previously MEN2A) due to mutations of a tyrosine kinase receptor encoded by the rearranged during transfection (RET) protoncogene; MEN3 (previously MEN2B) due to RET mutations; and MEN4 due to cyclin-dependent kinase inhibitor (CDNK1B) mutations. Each MEN type is associated with the occurrence of specific tumors. Thus, MEN1 is characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumors; MEN2 is characterized by the occurrence of medullary thyroid carcinoma (MTC) in association with phaeochromocytoma and parathyroid tumors; MEN3 is characterized by the occurrence of MTC and phaeochromocytoma in association with a marfanoid habitus, mucosal neuromas, medullated corneal fibers and intestinal autonomic ganglion dysfunction, leading to megacolon; and MEN4, which is also referred to as MENX, is characterized by the occurrence of parathyroid and anterior pituitary tumors in possible association with tumors of the adrenals, kidneys, and reproductive organs. This review will focus on the clinical and molecular details of the MEN1 and MEN4 syndromes. The gene causing MEN1 is located on chromosome 11q13, and encodes a 610 amino-acid protein, menin, which has functions in cell division, genome stability, and transcription regulation. Menin, which acts as scaffold protein, may increase or decrease gene expression by epigenetic regulation of gene expression via histone methylation. Thus, menin by forming a subunit of the mixed lineage leukemia (MLL) complexes that trimethylate histone H3 at lysine 4 (H3K4), facilitates activation of transcriptional activity in target genes such as cyclin-dependent kinase (CDK) inhibitors; and by interacting with the suppressor of variegation 3-9 homolog family protein (SUV39H1) to mediate H3K methylation, thereby silencing transcriptional activity of target genes. MEN1-associated tumors harbor germline and somatic mutations, consistent with Knudson's two-hit hypothesis. Genetic diagnosis to identify individuals with germline MEN1 mutations has facilitated appropriate targeting of clinical, biochemical and radiological screening for this high risk group of patients for whom earlier implementation of treatments can then be considered. MEN4 is caused by heterozygous mutations of CDNK1B which encodes the 196 amino-acid CDK1 p27Kip1, which is activated by H3K4 methylation. PMID:23933118

Thakker, Rajesh V

2014-04-01

78

Comparative genetics of albinism.  

PubMed

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

Searle, A G

1990-09-01

79

[Chagasic myocardiopathy: historical perspective].  

PubMed

Considerable advances in the clinical pathological and pathogenic aspects of Chagas disease have been made since the Brazilian physician Carlos Chagas described the disease in 1909. The disease caused by the flagellate protozoon parasite Trypanosoma cruzi is transmitted to humans by a blood sucking triatomine and much less frequently by blood transfusion. It is estimated that 18 million are infected and that about 100 million people from Latin America are at risk of contracting T. cruzi infection. One of the most important contributions to the knowledge of Chagas' disease has been the recognition of the natural history of the disease, which can be divided into three well defined periods: 1. The acute stage; 2. An undetermined or undifferentiated stage and 3. The chronic stage. The primary infection (first stage) occurs mostly unrecognized and clinically apparent acute chagasic myocarditis may appear in less than 5% of the infected individuals, usually children living in endemic areas. The majority of the cases of acute myocarditis are mild and reversible. Autopsied cases of acute chagasic myocarditis are uncommon and correspond to exceptionally severe or fulminant forms showing diffuse myocardial damage with myocytolisis, degenerative changes of myocardial fibers and marked intersticial cellular infiltration. The acute clinical manifestations of the infected individuals include fever, muscular pain, sweating, swollen lymph nodes, hepatospienomegaly. Following this initial stage, all patients enter the undifferentiated or undetermined stage of the chronic period (second stage), which lasts between 10 to 20 years. Of these, 20 to 30% (depending on marked geographical differences) develop symptoms or signs of visceral damage conforming the cohort that enter the third stage. Although megaesophagous and megacolon are not uncommon (mainly in Brazil), the most frequent and important clinical manifestation is a dilated cardiomyopathy. Thus, 70% or more of the infected individuals will never show any clinical manifestation of the disease. The ajmaline test and the endomyocardial biopsy are, probably, the most sensitive methods to unmask latent forms of chagasic myocarditis during the undifferentiated stage. In the most advanced stages of chronic chagasic myocarditis, pathological findings are those of a dilated cardiomyopathy. At autopsy, the apical aneurysm with thrombus in it is a frequent and distinctive finding. The histopathological picture is that of an active and chronic microfocal and disseminated myocarditis. In some cases fibrosis may be confluent, which accounts for the electrocardiographic patterns of myocardial necrosis. The widespread distribution of cardiac lesions also constitute the substrate for atrioventricular and intraventricular conduction disturbances and for atrial and ventricular arrhythmias. The clinical diagnosis of Chagas' heart disease is based on a triad of: positive epidemiology, positive serology and a combination of clinical findings (suggestive electrocardiograhic abnormalities, apical aneurysm, cardiac enlargement). The electrocardiogram in the most advanced forms, usually shows sinus bradycardia, right bundle branch block with or without left anterior hemiblock, primary T wave abnormalities, pathological Q waves and multiform ventricular premature beats. The pathogenesis of the myocardial lesions of acute and also chronic chagasic myocarditis appears to be related in large part to autoimmune mechanisms. The lack of correlation between the location and number of parasitized fibers and the severity, type, and extension of degenerative and inflammatory lesions supports this assumption. Experimental and clinical studies have demonstrated the presence of antibodies directed against different components of T. cruzi and crossreacting with human antigens in patients with chronic chagasic myocarditis. Microvascular dysfunction, myocardial ischemia and autonomic nervous system impairment have also been implica PMID:10668240

Elizari, M V

1999-01-01