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PubMed1995

Clostridium difficile colitis: an efficient clinical approach to diagnosis.

OBJECTIVE: To define clinical and laboratory variables that suggest the presence of Clostridium difficile colitis and to establish the number of stool specimens needed to reasonably exclude the diagnosis of C. difficile colitis. DESIGN: Prospective study of consecutive inpatients whose stool specimens were sent to be evaluated for the presence of C. difficile toxin. SETTING: University teaching hospital. PATIENTS: 268 hospital inpatients in medical, surgical, and gynecology units. MEASUREMENTS: Structured history and physical examination; detection of C. difficile toxin by cytotoxin tissue-culture assay with anti-C. difficile antiserum neutralization and by enzyme-linked immunoassay (EIA) for C. difficile toxins A and B; and detection of fecal leukocytes by microscopic examination and by latex agglutination lactoferrin assay. RESULTS: 43 of 268 consecutive inpatients were positive for C. difficile toxin by EIA or tissue-culture assay. Although toxin was detected by EIA alone in 39 of the 43 patients, it was detected in an additional 4 patients (10%) by tissue-culture assay alone. Univariate and multivariate logistic regression analysis showed that the following clinical and laboratory features were associated with C. difficile toxin positivity: the onset of diarrhea 6 or more days after the administration of antibiotics (odds ratio, 1.38 [95% CI, 1.10 to 3.79]); hospital stay longer than 15 days (odds ratio, 1.33 [CI, 1.09 to 3.95]); the presence of fecal leukocytes determined by microscopy (odds ratio, 2.39 [CI, 1.05 to 5.42]) or lactoferrin assay (odds ratio, 3.74 [CI, 1.80 to 7.76]); the presence of semiformed (as opposed to watery) stools (odds ratio, 2.33 [CI, 1.10 to 4.90]); and cephalosporin use (odds ratio, 2.36 [CI, 1.10 to 5.09]). Toxin-positive patients were no more likely than controls to have had fever, abdominal pain or cramps, leukocytosis, green-colored diarrhea, or blood in the stool or to have received clindamycin or penicillin derivatives. Of the 43 patients with C. difficile toxin, 34 (79%) had positive results for the toxin on the first stool specimen, 5 (cumulative, 91%) had positive results on the second specimen, and 4 had positive results on the third specimen. Overall, the negative predictive value of the first stool specimen was 97%. All patients who had two or more clinical or laboratory predictors were diagnosed with C. difficile disease when either the first or the second stool specimen was positive for toxin. CONCLUSIONS: Clinicians at the bedside can use readily available clinical and laboratory information to decide which patients are likely to have C. difficile disease and when it is appropriate and useful to order specific diagnostic tests for C. difficile toxin. Such data are also useful in determining the number of stool samples that reasonably excludes the diagnosis of C. difficile colitis.

Aged↗
PubMed2004

Eosinophilia in a patient with cyclical vomiting: a case report.

BACKGROUND: Eosinophilic gastritis is related to eosinophilic gastroenteritis, varying only in regards to the extent of disease and small bowel involvement. Common symptoms reported are similar to our patient's including: abdominal pain, epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema, dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of eosinophilic infiltration usually occur in the lamina propria or submucosa with perivascular aggregates. The disease is likely mediated by eosinophils activated by various cytokines and chemokines. Therapy centers around the use of immunosuppressive agents and dietary therapy if food allergy is a factor. CASE PRESENTATION: The patient is a 31 year old Caucasian female with a past medical history significant for ulcerative colitis. She presented with recurrent bouts of vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of vomiting had been reoccurring every 7-10 days, with each episode lasting for 1-3 days. This was associated with extreme weakness and cachexia. Gastric biopsies revealed intense eosinophilic infiltration. The patient responded to glucocorticoids and azathioprine. The differential diagnosis and molecular pathogenesis of eosinophilic gastritis as well as the molecular effects of glucocorticoids in eosinophilic disorders are discussed. CONCLUSIONS: The patient responded to a combination of glucocorticosteroids and azathioprine with decreased eosinophilia and symptoms. It is likely that eosinophil-active cytokines such as interleukin-3 (IL-3), granulocyte macrophage colony stimulating factor (GM-CSF) and IL-5 play pivotal roles in this disease. Chemokines such as eotaxin may be involved in eosinophil recruitment. These mediators are downregulated or inhibited by the use of immunosuppressive medications.

Journal Article↗
PubMedDate not supplied

[Comparative study of the evolution of inflammatory colitis treated with an elemental diet, glutamine and 5-ASA. An experimental study in rats].

The objective of the present investigation was to study the evolution of untreated inflammatory disease of the colon as compared to disease treated with an elemental diet plus glutamine, with 5-ASA and with a combination of the three. A total of 120 female Wistar-Tecpar rats aged 180 days and weighing on average 290 g were studied. Inflammatory disease of the colon was induced with 10% acetic acid and the animals were divided at random into four groups of 30 rats each. Group A, which received a standard diet and no type of treatment, was used as control. Group B received an elemental diet supplemented with glutamine. Group C received a standard diet and daily 5-ASA enemas, 15 mg/ml. Group D received an elemental diet supplemented with glutamine plus daily 5-ASA enemas. Ten animals were picked at random from each group and sacrificed on the 7th, 14th and 21st days of treatment after intravenous injection of Evans blue for visualization of the damaged areas. Changes in weight and the macroscopic aspects of the abdominal cavity and the colon were evaluated and the involved segment was resected for macroscopic and microscopic analysis. The highest weight loss occurred in group D animals on the 14th and 21st days. The number of complications was larger in group A animals, with intestinal perforation, peritonitis and death (P = 0.0053). Complications were of equal intensity in groups B and C and no complications were detected in group D. Macroscopic evaluation showed a lower frequency of ulcers on the 7th day in group B (P = 0.0113) and D (P = 0.0294). Group D animals showed a significantly reduced frequency of ulcers on the 14th day (P = 0.0140). Microscopic examination showed a better evolution in groups B (P = 0.0113) and D (P = 0.0294) on the 7th day and in group D on 14th day (P = 0.0105) compared to A. We conclude that the combination of an elemental diet containing glutamine and treatment with 5-ASA leads to more rapid healing of the colon lesions induced by 10% acetic acid in rats.

Animals↗
PubMed1988

[Aspiration cytology. New method in the diagnosis of cancer of the colon].

The method of cytologic samples by aspirative punction was successfully used in lesions that are accessible with common needles. The digestive tract's lesions are of more difficult access, and that is the reason why we do not known any antecedent with this method in the literature. Since 1978 we have thought about some way of taking the sample by fiberoptic devices in endoscopic explorations, adjusting to a polyethylene tube of suitable measure, as to exceed the colonoscopy, in the distal extreme, a little trocar and on its proximal extreme the adjustable part of the trocar for the adaptation of the syringe that makes the aspiration. It crosses through the biopsy channel of the colonoscope, puncturing the lesion and extracting the material by aspiration to prepare the cytologic smear, and fixing it for its further coloration and microscopic observation. We present the result of the aspirative cytology in 100 cases of tumoral or elevated lesions detected in the course of a colonoscopy, performing a comparative study with the exfoliative cytology and biopsy of the same cases, to compare the diagnostic positivity index between all the tree methods. We have studied 77 adenocarcinomas, 9 villous adenomas or polyps, 5 elevated lesions in long-evolution idiopathic ulcerative colitis and 3 inflammatory lesions. The aspirative cytology had greater positivity than the exfoliative one, complementing the judgement of biopsy studies in cases of malign neoplasia with great necrotic component. It must be underlined the utility of aspirative cytology method due to its simplicity, innocuousness and diagnostic security.

Adenocarcinoma↗
PubMedDate not supplied

[Antibodies anti granulocytic antigens in IBD: from microscopic morphology to antigenic specificity].

OBJECTIVE: ANCA (p-ANCA and x-ANCA) have been documented to occur in many inflammatory disorders. The specific ANCA antigens and the clinical correlation of a positive ANCA test in these disorders are still for the most part obscure. The aim of the present study was to investigate the prevalence of and the target antigens for ANCA in patients with IBD. METHODS: 104 patients (67 age between 3-18 years, mean age 8+/-3 and 37 age between 25-70 years, mean age 48+/-15) clinically and hystopathologically diagnosed as: 67 ulcerative colitis, 16 Crohn' disease, 21 other colitis (7 indeterminate colitis) were enrolled in our study. ANCA were determined by ELISA and IIF methods. RESULTS: We observed a good performance in terms of sensibility and specificity of ANCA, and a good correlation between the two methods used; as regard ELISA determination the antigen frequently found in our cases was lactoferrin (60%). CONCLUSIONS: Is still unclear the role of these "minor antigens" in the diagnosis and pathogenesis of IBD, but is clear that only morphologic evaluation is no more sufficient.

Adolescent↗
PubMed1994

IL-11, a pleiotropic cytokine: exciting new effects of IL-11 on gastrointestinal mucosal biology.

Recombinant human interleukin 11 (rhIL-11) is a pleiotropic cytokine that stimulates bone marrow stem cells to proliferate and decreases intestinal mucosal injury produced by cytoablative drugs and radiation in animals. The effects of rhIL-11 were studied in a hamster model of oral mucositis and in two rat models of inflammatory bowel disease (IBD). Oral mucositis was induced in male Golden Syrian hamsters with 5-fluorouracil 60 mg/kg intraperitoneal, days 0 and 2. Peak mucositis occurred by day 10 in vehicle treated animals. rhIL-11, given twice daily subcutaneously, decreased the mucositis in a dose-dependent manner and increased animal survival at all doses tested. In two models of IBD, the acetic acid-induced acute colonic injury model in Sprague-Dawley rats and the transgenic Fischer 344 rats expressing human HLA-B27 and beta 2-microglobulin, rhIL-11 decreased the gross and microscopic damage in the colons of these animals. These data suggest that rhIL-11 exerts effects on the gastrointestinal mucosa which ameliorate responses to injurious stimuli.

Acetates↗
PubMed2006

Diagnostic methods for differentiation of Entamoeba histolytica and Entamoeba dispar in carriers: performance and clinical implications in a non-endemic setting.

Unpreserved faecal samples, suspected to contain Entamoeba histolytica/Entamoeba dispar cysts or trophozoites on the basis of microscopic examination, and serum samples from 416 patients were collected in a prospective study to determine whether stool antigen assays and detection of antibodies in serum are reliable methods to distinguish between carriers of E. histolytica and E. dispar in comparison to the reference test: real-time PCR. In 283 patients (68%) DNA of E. histolytica or E. dispar was amplified by real-time PCR: 6 patients with amoebic colitis (2%), 19 carriers of E. histolytica (6.7%), and 258 carriers of E. dispar (91.2%). In 133 patients (31%) no DNA of E. histolytica or E. dispar could be amplified in the stool samples. This patient group was used as control for the evaluation of diagnostic tests. Using real-time PCR as a reference test, the sensitivity and specificity of (1) the Entamoeba test for the diagnosis of E. histolytica/E. dispar carrier were 59% and 98%, (2) E. histolytica II for the diagnosis of E. histolytica carrier was 71% and 100%, and (3) serology for the diagnosis of E. histolytica infection was 83.3% and 95.2%, respectively. Applied to carriers that did not originate from an endemic country the sensitivity of serology for E. histolytica infection was 90% and specificity was 98.8%. In comparison to real-time PCR the performances of Entamoeba test and E. histolytica II lacked sensitivity for a reliable diagnosis of E. histolytica/E. dispar infection in a non-endemic setting. In carriers of E. histolytica/E. dispar from non-endemic countries the high specificity of serology can be used to establish the diagnosis of E. histolytica infection if antibodies are present.

Adolescent↗
PubMed2003

Mesenteric phlebosclerosis: a new disease entity causing ischemic colitis.

PURPOSE: Nonthrombotic stenosis or occlusion of the mesenteric veins is a rare cause of intestinal ischemia. The aim of this study was to describe a new disease entity causing chronic ischemic colitis. METHODS: Seven patients were diagnosed as having mesenteric phlebosclerosis. All seven patients had calcifications in the small mesenteric veins and their intramural branches. No evidence of vasculitis or portal hypertension was recognized. None of the patients had a history of gastrointestinal disease or of prolonged drug use. We report clinical, laboratory, radiographic, endoscopic, and histopathologic findings. RESULTS: Clinical findings included abdominal pain and diarrhea of a gradual onset and chronic course. A positive fecal occult blood test and mild anemia were often found. The patients had linear calcifications and stenosis in the right colon, which were discovered by plain abdominal radiography and barium enema, respectively. Endoscopic findings included edematous, dark colored mucosa and ulcerations. Four patients underwent a subtotal colectomy because of persistent abdominal pain or ileus. The histopathologic findings were macroscopically characterized by a dark purple or dark brown colored colonic surface, the swelling and disappearance of plicae semilunares coli, and marked thickening of the colonic wall, while they were microscopically characterized by marked fibrous thickening of the venous walls with calcifications, marked submucosal fibrosis, deposition of collagen in the mucosa, and foamy macrophages within the vessel walls. CONCLUSIONS: These peculiar lesions have not previously been fully described. The cause and pathogenesis still remain unknown. We conclude that such lesions represent a new clinicopathologic disease entity and propose the term "idiopathic mesenteric phlebosclerosis."

Adult↗
PubMed1995

Obstructive colitis: an analysis of 50 cases and a review of the literature.

Obstructive colitis is an ulcero-inflammatory and necrotizing condition that occurs in the colon proximal to benign or malignant stenosing lesions. it is the result of ischemia due to impairment of blood supply secondary to elevation of the endoluminal pressure, distension of the colonic wall and other factors which impair adequate perfusion. The incidence among patients with colonic obstruction is reported at between 1 and 7%. Of 50 patients with this condition in this series, 30 female and 20 male, 2/3rds were well over 70 yrs of age. Obstruction was most common in the rectosigmoid. In half the patients this was due to adenocarcinoma, 24 were due to benign obstruction and 15 were caused by diverticular disease. Type, extent and depth of ischemic lesions were highly variable and comprised early mucosal hemorrhage and edema, ulcero-hemorrhagic lesions and transmural necrosis. There was always an abrupt transition between affected and normal bowel. A segment of preserved mucosa was usually present on the proximal side of the stenosis. In 16 patients massive dilatation with stretching and thinning of the bowel wall, associated with a blow-out type of perforation or with transmural necrosis, was observed and was considered to have resulted from a rapid rise of endoluminal pressure to high levels. The microscopic and macroscopic features are described in detail and histological factors discussed in relation to the pathological lesions encountered. Emphasis is placed upon the range of appearances and similarities are shared with other inflammatory colonic diseases, particularly idiopathic inflammatory bowel disease. The importance of recognition of this disease entity, not only by pathologists but by surgeons dealing with the disease at operation, is stressed.

Aged↗
PubMed1995

Rapid diagnosis of Entamoeba infection by using Entamoeba and Entamoeba histolytica stool antigen detection kits.

Humans are infected by two morphologically identical species of Entamoeba: Entamoeba histolytica causes amebic colitis and liver abscess, and Entamoeba dispar is noninvasive. Several weeks of culture and isoenzyme (zymodeme) analysis are required to differentiate E. histolytica from E. dispar. Here we report a field trial of commercial antigen detection kits designed to rapidly detect and differentiate E. histolytica from E. dispar in stool specimens. Stool specimens from 202 patients with diarrhea were examined for E. histolytica and E. dispar by microscopy, culture, and antigen detection. Compared with culture, microscopic identification of the E. histolytica-E. dispar complex was 60% sensitive and 79% specific, while the screening antigen detection test for the E. histolytica-E. dispar complex was 80% sensitive and 99% specific. Differentiation of E. dispar from E. histolytica by the E. histolytica-specific test was 95% sensitive and 93% specific compared with zymodeme analysis. We conclude that the antigen detection test for the E. histolytica-E. dispar complex is more sensitive and specific than microscopy and that the E. histolytica-specific antigen detection test is as reliable and much more rapid than zymodeme analysis for the differentiation of E. histolytica from E. dispar.

Animals↗
PubMed1991

Peripheral blood neutrophils in inflammatory bowel disease: morphological evidence of in vivo activation in active disease.

Morphological evidence of activation in vivo of circulating neutrophils in patients with inflammatory bowel disease (IBD) was sought by quantitative light microscope examination of toluidine blue-stained preparations made from peripheral venous bloods that had been fixed immediately ex vivo. The proportion of spherical (unactivated) circulating neutrophils was reduced in active Crohn's disease (73%; 46-96 (median; range), n = 11) compared with inactive Crohn's (90%; 45-99; n = 18, P less than 0.01) and normal subjects (94%; 44-98; n = 13, P less than 0.05). There tended to be fewer spherical neutrophils in active ulcerative colitis (77%; 13-96; n = 17) than in quiescent colitis (88%; 57-99, n = 13, P less than 0.1) or normal subjects (P less than 0.05). Activated neutrophils occur in the circulating pool of patients with active IBD and can be detected by light microscopy of peripheral venous blood leucocyte preparations.

Adult↗
PubMed2006

Pathological analysis of lesions within intestines resected due to ulcerative colitis.

INTRODUCTION: Ulcerative colitis (UC) and Lesniowski-Crohn's disease together constitute a type of intestinal pathology known as Inflammatory Bowel Disease. The etiology of UC still remains unknown, however some epidemiological data suggest the role of bacteria and viruses and also some habitual as well as environmental factors like smoking, diet, drugs, geographical and social status, as well as stress. The genetic predisposition is also suggested. UC affects young people in 2nd - 4th decades of life. Exacerbations of the disease may result in the necessity of surgical treatment, typically in the form of total proctocolectomy accompanied by the subsequent formation of ileo-pouch-anal anastomosis. The aim of our study was to analyze morphological pictures of resected specimens. MATERIAL AND METHODS: We analyzed 67 cases (40 women and 27 men) of UC with the special interest being focused at macro- as well as microscopic features of the intestines resected. We reviewed macroscopic characteristics of intestines (i.e. the length of resected fragments, localization, shape and diameter of the ulcers, polyps, number of resected lymph nodes), as well as microscopic descriptions concerning, among others the character and localization of inflammatory infiltrate, the architecture of glands, the presence of crypt abscesses and Paneth's metaplasia. Special attention was paid to the morphology of intestinal wall vasculature. RESULTS: In 42% of the cases macroscopically the inflammation covered the whole length of the resected colon. In 58% macroscopically detected inflammatory changes were segmental in distribution. In four cases the disease had clinically the fulminant course and the inflammation was transmural. There were 3 cases, in which histological assessment revealed the presence of malignancy (2 cases of mucus producing adenocarcinoma and one case of carcinoma in situ situated in the anal canal). Generally, microscopic findings were typical for the active phase of UC. We found intensive vascularization and hyperemia of the intestinal wall to be the common features accompanying the inflammation. CONCLUSIONS: Young people in the 3rd and 4th decades of life constitute the group being relatively commonly affected by the UC, and undergo the surgical proctocolectomy. Some of the cases present with the fulminant course of the disease. A rich vascular network is a common finding in the inflamed intestinal wall. We hypothesize, that intensive vascularization may play a significant role in the pathogenesis of UC.

Adolescent↗
PubMed1986

Technique for measuring 50% end points in cytotoxicity assays for Clostridium difficile toxins.

Serial dilutions of Clostridium difficile culture filtrates were incubated overnight with HeLa cell monolayers. Cells were fixed in formalin, stained with crystal violet, rinsed, and drained. Cell rounding could be observed microscopically in the stained monolayers. Absorbance of the retained dye on monolayers in the drained wells was measured at 595 nm-405 nm. End points could also be estimated visually. The dilution at which dye absorbance was reduced by 50% agreed with that determined by microscopic observations. Five replicate dilution series showed high reproducibility. Specificity was verified by neutralisation with crude rabbit antibody to C difficile toxins. Cytotoxicity in faecal specimens was assayed in the same way, allowing reporting of titres, comparison with standard toxin preparations, and determination of the extent of neutralisation to be made. This novel assay technique has proved effective and reliable in a clinical setting and should allow the gathering of more information on the epidemiology of antibiotic associated colitis.

Bacterial Toxins↗
PubMed1990

Hybridomas using athymic nude mouse injected with Crohn's disease (CD) tissue filtrate. Immunoreactivity of the hybridomas with CD sera.

Injections of Crohn's disease (CD) tissue filtrates produce lymphoma and hyperplastic lymph nodes from plasma cell hyperplasia (PCH) in athymic nude (nu/nu) mice; these lymphoid tissue contain an antigen(s) recognized by CD serum/gamma G immunoglobulin (IgG). To immortalize the "CD-reactive antigen(s)," the authors fused the lymphoid cells from a CD tissue filtrate primed nu/nu mouse with nonsecretory mouse myeloma cells. Hybrids were screened and selected based on their reactivity with CD serum IgG, but not with control serum IgG in an indirect immunofluorescence assay (IF). Two CD-positive hybridomas were examined by IF with sera from 47 CD, 38 ulcerative colitis (UC), 13 controls with other gastrointestinal diseases, 19 with autoimmune diseases, and 21 normal subjects. Sera from 16 CD patients (34%) reacted with the two hybridomas, but only one of 38 UC sera and none of the 53 other disease or normal control sera reacted. The immunoreactivity of CD sera was significantly higher than UC sera (P less than 0.01) and each of the other groups (P less than 0.007). Using immunoperoxidase techniques at light and electron microscopic levels, the authors localized CD-associated antigen(s) in the plasma membrane of the two hybridomas. Further characterization of these hybridomas and the immunoreactive protein(s) may provide an important probe(s) for the diagnosis and the understanding of the pathogenesis of CD.

Animals↗
PubMed2002

Lamina propria plasma cells in inflammatory bowel disease: intracellular detection of immunoglobulins using flow cytometry.

This is the first application of flow cytometry for the detection of lamina propria plasma cells and their intracellular immunoglobulins in patients with inflammatory bowel disease compared to healthy controls. The study has been focused on the distribution of IgA, IgG, IgM and the four IgG subclasses. Plasma cells were detected as high CD38 positive cells. For fixation and permeabilisation a single step reagent, Ortho Permeafix, was used. By flow cytometry, in patients with inflammatory bowel disease compared to healthy controls, a higher percentage of IgG+ cells can be observed, in Crohn's disease also a higher percentage of IgM+ cells. Regarding the IgG subclass distribution, patients with Crohn's disease show an increase in IgG2+ cells, patients with ulcerative colitis an increase in IgG1+ and IgG3+ cells. These results do agree with and expand the results of earlier immunohistochemical and functional studies, which are favoured today. For the determination of lymphocyte subset proportions and the detection of intracellular antigens, flow cytometry provides a useful alternative to well-established immunohistochemical methods. By analysing a larger number of cells, this method is more reproducible and less prone to interobserver variations than immunohistochemistry, which needs the pre-selection of a mucosal area, the microscopic scoring of a limited number of cells and the circumvention of high background staining. The optimized flow cytometric protocol used in this study might be a promising tool for further investigations of various purposes.

ADP-ribosyl Cyclase↗
PubMedDate not supplied

[Angiodysplasias or vascular ectasias of the intestine. Report on 8 personal cases].

Angiodysplasia or vascular ectasia of the intestine is a new pathological entity which was initially revealed by arteriography. More recently it has been found by coloscopy and is considered to be responsible for many cases of intestinal bleeding, especially in older patients The present study is based on eight patients including 2 cases of microscopic bleeding, 4 of massive hemorrhage, and 2 asymptomatic cases. There is a clear difference between intestinal angiodysplasia and other forms of vascular malformations, even though its pathogenesis is still in question. Whereas in older patients it is acquired, typically in the caecum. It can also exist congenitally in younger patients and in other locations. However, identical lesions may be observed at all levels of the digestive tract in association with certain diseases, most often vascular atheroma, but also diverse intestinal diseases (diverticulitis, colitis, polyps, cancer) and even iatrogenic diseases. Even though these malformations are frequent, the lesions often go unrecognized because special histological technics are required to reveal the arteriovenous fistulas. The major circumstance leading to this diagnosis is anemia due either to occult intestinal bleeding or massive hemorrhage (after exclusion of prevalent associated disease such as diverticulosis). Occasionally latent angiodysplasia is revealed during studies undertaken for associated disease. Positive diagnosis is based on selective angiography during massive bleeding and on endoscopic examination in case of anemia from occult bleeding. Surgical treatment should be undertaken in case of major blood loss. This usually consists of resection of the ascending colon, the most frequent site of the lesion. It is recommended that an even longer colonic segment be resected in case of associated diverticulosis. The preferred treatment of limited forms with few symptoms depends on more recent technics such as endoscopic electrocoagulation. In conclusion, many cases if occult intestinal bleeding can be explained by angiodysplasia which thus deserves better understanding and recognition.

Aged↗
PubMed2002

Abnormal motility in patients with ulcerative colitis: the role of inflammatory cytokines.

HYPOTHESIS: Interleukin 1 beta (IL-1 beta) levels are elevated in the colonic mucosa of patients with ulcerative colitis (UC). We propose that IL-1 beta may also be elevated in the circular muscle layer of the colon and may be partially responsible for the motility dysfunction observed in patients with UC. DESIGN: Cohort analytic study. SETTING: Research laboratory in a tertiary academic medical center. PARTICIPANTS: Normal smooth muscle was obtained from the disease-free margins of human sigmoid colon specimens resected from patients with cancer and compared with specimens from patients with UC. INTERVENTIONS: An enzyme-linked immunosorbent assay was used to measure IL-l beta. Standard muscle chambers were used to measure force changes. Single muscle cells were isolated by enzymatic digestion, and cell shortening in response to neurokinin A (NKA) and thapsigargin was measured under a microscope. Cytosolic Ca(2+) (calcium) concentrations were measured by standard techniques. MAIN OUTCOME MEASURE: Effects of IL-1 beta on smooth muscle function in normal and UC colons. RESULTS: In patients with UC, IL-1 beta was elevated in the muscularis propria, and sigmoid circular smooth muscle contractions in response to NKA and thapsigargin were significantly reduced. In fura-2-loaded cells from patients with UC, the NKA-induced Ca(2+) signal was also significantly reduced in Ca(2+)-free medium, indicating the reduced intracellular Ca(2+) stores after UC. Exposure of normal cells to IL-1 beta mimicked the changes observed in patients with UC. An IL-1 beta-induced reduction in contraction and release of intracellular Ca(2+) in response to NKA was partially restored by the hydrogen peroxide scavenger catalase. CONCLUSION: In patients with UC, IL-1 beta was increased in colonic circular muscles and may contribute to motor dysfunction after UC through production of hydrogen peroxide.

Adenosine Triphosphate↗
PubMed1996

Systemic necrotizing vasculitides in severe alpha1-antitrypsin deficiency.

We describe the clinical presentation and outcome in a series of eight patients with systemic necrotizing vasculitis and severe alpha1-antitrypsin (AAT) deficiency followed up at three Swedish hospitals during 1968-92. We also review six other cases reported in the literature during the same period. Diagnosis of severe AAT deficiency was based on the presence of the PiZZ phenotype, or low plasma total trypsin inhibitory capacity, or a low plasma AAT concentration (10-40% of the normal mean value) and presence of the PiSZ or PiFZ phenotype. The diagnosis of systemic vasculitis was biopsy-verified in all eight patients. Pretreatment laboratory findings, treatment protocol, and outcome were reviewed in each of the 14 patients. Of the eight patients in the Swedish series, six had systemic vasculitis of the microscopic polyangiitis form, one had Wegener's granulomatosis, and another had Henoch-Schönlein purpura. In the series as a whole (n = 14), median age at diagnosis was 48 years (range 44-84), the median number of affected organs was eight, and all 14 patients had skin involvement, and either renal or joint involvement (in most cases both); 71% (10/14) had emphysema; 57% (8/14) had hepatic abnormalities (two having cirrhosis, two fibrosis, and one multiple aneurysms in hepatic arteries); one patient who presented with acute ulcerative colitis developed manifest vasculitic syndrome three years later; and 64% (9/14) died, the major cause of death being renal failure. This syndrome, characterized by multiple organ involvement and fatal outcome, has been underdiagnosed. Physicians should be alert to the presence of the PiZ AAT deficiency gene in patients with systemic vasculitis, especially when the course is progressive or when the patient also has emphysema or cirrhosis. Awareness of those features may aid prompt recognition and enable early treatment.

Adult↗