Serum transforming growth factor-beta1 levels increase in response to successful anti-inflammatory therapy in ulcerative colitis.

OBJECTIVE: To investigate serum levels of transforming growth factor-beta1 and interferon-gamma in active ulcerative colitis and to assess changes during treatment. METHODS: We prospectively evaluated serum from 25 patients with untreated active ulcerative colitis and 19 healthy controls. Disease activity score (DAI), serum transforming growth factor-beta1 and interferon-gamma levels were measured at baseline and after 7 days of conventional treatment. Disease activity score and transforming growth factor-beta1 were also assessed at 42 days. RESULTS: Baseline transforming growth factor-beta1 levels were significantly higher in patients than in controls (P < 0.02). On the 7th day, transforming growth factor-beta1 levels increased only in patients who responded (P < 0. 01); variations in transforming growth factor-beta1 levels and disease activity score were inversely correlated (r=- 0.72, P < 0. 001). At day 42, serum transforming growth factor-beta1 decreased significantly compared with the 7th day (P < 0.05). While in controls, interferon-gamma was undetectable; untreated patients had higher, widely variable, levels. At day 7, responders had higher interferon-gamma values than unresponsive cases. Variations in interferon-gamma correlated moderately with changes in transforming growth factor-beta1 (r=0.53, P < 0.05). Cytokine response did not depend upon the type of treatment. CONCLUSIONS: Both transforming growth factor-beta1 and interferon-gamma may play a role in the injury-repair process in active ulcerative colitis. Variations in circulating transforming growth factor-beta1 levels in the first week of treatment seem to be related to the therapeutic response.

Long-term effect of gluten restriction on bone mineral density of patients with coeliac disease.

AIM: To assess the long-term effect of a gluten-free diet on bone mineral density of adults with untreated coeliac disease. METHODS: Bone mineral density was assessed at baseline and after a mean duration of 37 months of treatment in 25 unselected newly diagnosed coeliac patients. RESULTS: At baseline, osteopenia (> -1 s.d. below normal) was evident in the lumbar spine and total skeleton in 18 (72%) and 21 (84%) patients, respectively. At the end of the study, bone density had increased (mean bone mass Z-score increase: Z-score +1.0 for the lumbar spine and +1.1 for total skeleton) in 22 and 23 patients, respectively. Patients who adhered to strict gluten restriction (n = 15) demonstrated a similar bone remineralization in the spine than those patients with partial compliance (n = 10) (mean Z-score increase: +1.0, in both areas). A greater mean annual change in Z-score in the total skeleton was noted in patients who followed strict gluten restriction (0.4 +/- 0.1) respect to those with partial compliance (0.3 +/- 0.1); however, this difference was not statistically significant. Pre-menopausal women had significantly greater remineralization that post-menopausals (P > 0.05). Remineralization showed an inverse correlation with the degree of basal osteopenia (r = -0.525; P < 0.002). CONCLUSIONS: Long-term treatment with gluten-free diet produces a significant improvement in bone density in coeliac patients. Remineralization was more pronounced in patients who better comply with gluten-free diet, in pre-menopausal women and in patients with the lowest baseline bone mineral density.

Budesonide enema in pouchitis--a double-blind, double-dummy, controlled trial.

BACKGROUND: Pouchitis has been suggested to be a recurrence of ulcerative colitis in a colon-like mucosa. Topical steroids are a valid therapeutic alternative for distal forms of ulcerative colitis. AIM: To investigate the efficacy and tolerability of budesonide enema in the treatment of pouchitis compared with oral metronidazole. MATERIALS AND METHODS: Twenty-six patients with an active episode of pouchitis (defined as a pouchitis disease activity index score >or= 7) and no treatment during the previous month were randomized to receive either budesonide enema (2 mg/100 mL at bedtime) plus placebo tablets or oral metronidazole (0.5 g b.d.) plus placebo enema in a prospective, double-blind, double-dummy, 6-week, controlled trial. RESULTS: Based on the intention-to-treat principle, we detected a significant improvement in disease activity at the end of the first week with both drugs (P < 0.01). After that, improvement was moderated until stabilization at 4 weeks in both treatments. The per protocol analysis showed that both drugs had similar efficacy in terms of disease activity, clinical and endoscopic findings. Fifty-eight per cent and 50% of patients improved (decrease in pouchitis disease activity index >or= 3) with budesonide enema and metronidazole, respectively (odds ratio, 1.4; confidence interval, 0.2-8.9). Adverse effects were observed in 57% of patients given metronidazole and in 25% of patients given budesonide. CONCLUSIONS: Budesonide enemas are an alternative treatment for active pouchitis, with similar efficacy but better tolerability than oral metronidazole.

Faecal alpha 1-antitrypsin concentration in the diagnosis and management of patients with pouchitis.

OBJECTIVE: To investigate the role of faecal alpha 1-antitrypsin concentration in the diagnosis and management of patients with ileal pouch-anal anastomosis. DESIGN: Prospective study. METHODS: Fifty-two measurements of faecal alpha 1-antitrypsin concentration were taken from 33 patients operated on for ulcerative colitis. RESULTS: Patients with active pouchitis (44.4 +/- 7.1 mg%) had a three-fold higher mean faecal alpha 1-antitrypsin concentration than patients in remission (13.7 +/- 1.3 mg%; P < 0.0001), than patients who had never had pouchitis (14.4 +/- 2.3 mg%; P < 0.003) and than patients with incontinent ileostomies (12.7 +/- 1.3 mg%; P < 0.004). Faecal alpha 1-antitrypsin measurements were 80% sensitive and 97% specific for active pouchitis. A significant positive correlation between the pouchitis disease activity index and faecal protein loss was observed (r = 0.702; P < 0.0001). The correlations between protein loss and other parameters were weaker (protein loss versus clinical score, r = 0.309; versus endoscopic score, r = 0.583; and versus histologic score, r = 0.558). CONCLUSION: Faecal alpha 1-antitrypsin concentration is a good indicator of the degree of intestinal inflammation in pouchitis and may be useful as a quantitative index of disease activity in prospective studies.

Gynaecological and obstetric disorders in coeliac disease: frequent clinical onset during pregnancy or the puerperium.

BACKGROUND AND AIM: While gynaecological and obstetric disorders have been reported among women with coeliac sprue, their true prevalence and relationship to the coeliac disease process has not been completely elucidated. Our aims were to determine: (1) the prevalence of gynaecological and obstetric problems in patients with coeliac disease and the influence of strict gluten restriction on their occurrence, (2) the effect of pregnancy on the clinical course of coeliac disease and (3) the clinical features of those patients with onset of coeliac disease during pregnancy and the puerperium. PATIENTS AND METHODS: The gynaecological and obstetric history of 130 coeliac patients and 130 age-matched healthy female controls were compared in a case-control study. RESULTS: In comparison to the controls, untreated coeliac disease patients exhibited significantly later menarche, an earlier menopause, an increased prevalence of secondary amenorrhoea and a greater incidence of spontaneous abortions. Patients who had adhered, in the long term, to a gluten-free diet had gynaecological and obstetric history indistinguishable from controls. Clinical deterioration of coeliac disease was observed in untreated patients during 17% of their pregnancies. In 14% of those untreated patients who were pregnant symptoms related to coeliac disease were manifested for the first time during either pregnancy (n = 7) or the puerperium (n = 4). Nine of these patients had underestimated features suggestive of coeliac disease. CONCLUSION: The early diagnosis and treatment of coeliac disease may avoid significant gynaecological and obstetric complications in affected women. Celiac sprue must always be borne in mind among patients who develop diarrhoea and weight loss during pregnancy and/or the puerperium.

Increased mucosal levels of leukotriene B4 in pouchitis: evidence for a persistent inflammatory state.

DESIGN AND METHODS: In order to evaluate its possible role in the pathogenesis of pouchitis we measured the release, into the incubation medium of leukotriene B4 from mucosal samples from patients with ileal pouch-anal anastomosis and correlated release with clinical, endoscopic and histological features. RESULTS: Leukotriene B4 release was significantly elevated in patients with active pouchitis in comparison to those with a normal pouch mucosa (P < 0.007). No overlap was observed between leukotriene B4 levels from patients with active pouchitis samples and those obtained from individuals without pouchitis. Effective treatment of pouchitis was associated with a significant reduction in leukotriene B4 mucosal release to the incubation medium (P < 0.03). However, even in remission, levels of leukotriene B4 release remained significantly increased in these patients in comparison to people who never experienced pouchitis (P < 0.003). A modest correlation was observed between pouchitis disease activity index and leukotriene B4 release (r = 0.596; P < 0.01). CONCLUSION: These results suggest that the increased production of leukotriene B4 may be implicated in the pathogenesis of pouchitis. The persistence of an increased mucosal release of leukotriene B4 in pouchitis patients during clinical remission suggests the presence of a chronic, ongoing, underlying inflammatory process.

Serological markers identify histologically latent coeliac disease among first-degree relatives.

BACKGROUND AND AIM: Serological markers detect asymptomatic coeliac disease among first-degree relatives of patients with sprue. However, some relatives with coeliac disease-related antibodies have 'normal' jejunal mucosa by conventional histology. Whether these serological abnormalities represent false-positives or are consequences of gluten sensitivity is not known. Our aim was to evaluate, through quantitative histology, intestinal biopsies of asymptomatic relatives of probands seeking abnormalities consistent with latent coeliac disease. MATERIALS: Fifty-nine intestinal biopsies obtained from asymptomatic relatives were evaluated; 40 samples were suitable for histological quantification. Seven samples showed severe mucosal atrophy (coeliac disease) and 33 were considered as 'normals'. In the 'normal' group, nine samples were obtained from patients with one or more positive serological tests and 24 from those with negative tests. Morphometry was compared for samples obtained from healthy control individuals (n = 10) and for those from coeliac patients (n = 7). METHODS: Serological tests used were: antigliadin antibodies type immunoglobulin (Ig)A and IgG (enzyme-linked immunosorbent assay), antirrecticulin antibody (immuno-fluorescence) and endomysial antibody (immunofluorescence). Biopsy samples were obtained with endoscopic forceps from the distal duodenum (second portion). Quantitative histology of duodenal biopsies was performed with a computerized image analysis system. RESULTS: Relatives with positive serology showed shorter villi (P < 0.05) and higher number (P < 0.01) and numerical density (P < 0.01) of intraepithelial lymphocytes in crypts than healthy controls. Numerical density of intraepithelial lymphocytes in crypts in antibody-positive patients was significantly higher than that observed in relatives with negative serology (P < 0.03). Four of nine (44%) relatives with positive serology had a number of intraepithelial lymphocytes in crypts within the range of coeliac disease patients. However, only one patient with negative serology (4%) was in this range. CONCLUSION: Our study shows quantitative histological evidence that relatives of probands with positive coeliac disease-related serology are not false-positives, and that they should be considered as individuals with latent coeliac sprue.

Chromosome instability in untreated adult celiac disease patients.

Spontaneous chromosome aberrations (CAs) and induced fragile sites (FSs) were analysed in 12 untreated adult coeliac disease (CD) patients and 8 healthy controls. Blood lymphocytes from each individual were cultured for 72 h at 37 degrees C in F-10 medium with 5% fetal calf serum and 0.1 ml phytohemagglutinine. FSs were induced by FudR (10 micrograms/ml, 24 h before harvesting) and caffeine (2.2 mM. 6 h before harvest). Spontaneous CAs and FSs were analysed on 30-50 Giemsa-stained and G-banded metaphases. The mean frequencies of spontaneous CAs (abnormal cells, gaps/cell and breaks/cell) of CD patients (0.24 +/- 0.02, 0.21 +/- 0.02 and 0.13 +/- 0.02, respectively) were significantly higher than those of controls (0.04 +/- 0.01, 0.02 +/- 0.01 and 0.02 +/- 0.01, respectively) (p < 0.001). Fourteen spontaneous CAs and 5 FSs specific for CD patients presented a strong coincidence (70%) with bands involved in T- and B-cell malignant lymphoma rearrangements. These findings suggest that CD has chromosome instability affecting specific points that could be related to the high prevalence of malignancies in this disorder.

[Hyposplenism in celiac disease. Role of a gluten-free diet]. / Hipoesplenia en la enfermedad celíaca. Rol de la dieta libre de glúten.

Hyposplenism is a common complication of adult celiac disease. A study of splenic function in 17 adult patients with celiac disease was performed both before and during treatment with a gluten-free diet. Splenic hypofunction was assessed evaluating morphological changes in red cells (Howell-Jolly bodies, spherocytosis, achantocytosis). The hyposplenic changes were compared with: age of patients, duration of symptoms previous to diagnosis, severity of the clinical picture and histological response to treatment. We concluded that 82.4% of patients had hyposplenic changes and that there was a non significant tendency to improve such changes by a strict adherence to gluten-free diet.

[Effect of acute irradiation on small bowel morphometry and D-xylose absorption in rats]. / Efecto de la irradiación aguda sobre la morfometría del intestino delgado y la absorción de D-xilosa en ratas.

UNLABELLED: In previous study in our laboratory, we had shown the effect of radiation on morphometry of small bowel of rats after 7 days of a single external doses of 1,000 rads with liver protection. Our aim was to determine the effect of the same procedure of gamma radiation in rats on the morphometry and D-Xylose absorption 7, 14 and 21 days after injury and compared with a control group matched by weight. The D-Xylose absorption was measured by plasmatic D-Xylose, 60' after an intragastric doses of the pentose (0.5 grs/kg of body weight). RESULTS: In the control group the mucosal thickness was 880 +/- 40 mu (X +/- SD), the vellous height was 640 +/- 37.6 mu and the xylosemia 15.91 +/- 11.39 mg%. At 7 days in the irradiated group (n: 11) the weight decreased 33.36 +/- 6.29% (Vs. control p less than .001), the mucosal thickness and the vellous height were 666 +/- 97 (p less than .001) and 466 +/- 66.9 mu (p less than .001) and the xylosemia 6.16 +/- 2.3 (p less than .05). The figures at 14 days (n: 16) showed improving and completed recovery at 21 days (n: 14). Irradiated rats were shown to be affected in weight, morphology and D-Xylose absorption, they began recovering after 7 days, and completed recovery at 21 days.

[Botulinum toxin is effective in the short-term treatment of esophageal achalasia. Preliminary results of a randomized trial]. / La toxina botulínica es efectiva en el tratamiento a corto plazo de acalasia esofágica. Resultados preliminares de un estudio randomizado.

UNLABELLED: Botulinum toxin (BoTox) is a potent inhibitor of the release of acetylcholine from terminal nerves and has been used successfully in spastic disorders of skeletal muscle. Its used for the treatment of disorders of gastrointestinal smooth muscle has recently been explored. In this study we evaluated the efficacy of transendoscopic injection of BoTox in 13 symptomatic patients with achalasia G II (Siewert classification) without previous treatment of an ongoing randomized-controlled trial. Patients were blindly randomized to administrate: a) 8OU of BoTox were injected in four quadrants (1 ml in each quadrant-20 U/ml) (n = 8), b) normal saline solution as placebo injected in the same way (n = 5). Patients who did not respond were retreated in an open design with the same schedule of BoTox. BoTox or placebo were injected directly into the lower esophageal sphincter (LES), located by manometric and endoscopic procedures, via sclerotherapy injector. Response to treatment was assessed by changes in symptoms score, weight, LES pressure, barium esophagograms and endoscopy. All determinations were repeated at basal and after 7-30-60 and 90 days of treatment. Post treatment response was considered positive if at one month, 3 of 4 parameters were improved. No evidence of response to BoTox were assessed in 3 patients. At 90 days, 10 patients remain well and data are as follows: (mean +/- SD) symptoms score: (Pre: 3.23 +/- 0.44) (Post: 1.31 +/- 0.95); LES pressure (mmHg) (Pre: 53, 15 +/- 66.31 +/- 7.49); % reduction of esophageal diameter 55% (p < 0.0001) (pair T-test). Relaxation of LES did not change after treatment. There were no side effects related to BoTox injection. CONCLUSIONS: Endoscopic intrasphincteric BoTox injection is safe, simple and effective in the short term treatment for achalasia. Further studies are necessary for evaluation of long term effects.

[Osteoarthropathies of inflammatory diseases of the colon]. / Osteo-artropatías de las enfermedades inflamatorias del colon.

Fifteen patients suffering from inflamatory diseases of the colon (14 nonspecific ulcerous recto colitis and 1 Crohn disease) were complicated with involvement of large joints and spine (ankylosing spondelytis). The clinic, radiology, pathology, seriology and evolution of ankylosing spondylitis were considered in relation-ship with inflamatory disease of colon.

[Pyoderma gangrenosum in Crohn's diseases of the colon]. / Pioderma gangrenoso en enfermedades de Crohn del colon.

A case of much less frequent association of the pyoderma gangrenosum and granulomatous disease of the colon (Crohn's disease of the colon) is presented. A literature review is made about the association of the same with other gastrointestinal affections. It is brought up to date the possible atiopathogenical mechanisms and therapeutical effects.

[Protein loss in gastrectomized patients with or without steatorrhea]. / Pérdida de proteínas en operados gástricos con y sin esteatorrea.

Intestinal protein loss was determined in a group of patients with gastric resection by measuring the faecal radioactivity in the stools of 4 days, after intravenous administration of Cl3Cr51. The patients studied were divided in three groups: a) 10 healthy control subjects, b) 5 patients with gastrectomy BII without steatorrhoea, c) 15 patients with gastrectomy BII with steatorrhoea. In group (a) faecal radioactivity was 0.36 +/- 0.26% of the administrated dosis; in group (b) the value was 1.24 +/- 1.07% and in group (c) the activity was 1.40 +/- 1%. Statistically significative difference between groups (a) and (b) ((p less than 0.05) was found between groups (a) and (c) the difference was highly significative (p less than 0.001). However there was no significative difference between groups (b) and (c) (p less than 0.8). We think that serum protein intestinal loss may be, one of the causes of the hipoalbuminemia present in some patients who underwent partial gastrectomy because of gastroduodenal ulcer. Otherwise we did not find a relation between protein loss and steatorrhoea.

Fecal alpha 1-antitrypsin clearance in the differential diagnosis of steatorrhea.

We reviewed the fecal fat excretion and alpha 1-antitrypsin clearance results of 160 patients with steatorrhea in whom a final diagnosis was obtained, based on history, physical examination, and radiological, functional and morphological tests. Twenty-two patients had pancreatic diseases and 138 had steatorrhea due to gastrointestinal diseases. alpha 1-antitrypsin clearance was invariably normal in chronic pancreatitis, but there was only a 23 to 50% of correct etiological classification when the combination of steatorrhea and normal alpha 1-antitrypsin clearance was present. However, none of our patients diagnosed of chronic pancreatitis had abnormal alpha 1-antitrypsin clearance. The combination of steatorrhea and normal clearance of alpha 1-antitrypsin was a modest clue for diagnosis of pancreatic malabsorption.

[Primary lymphoma of the small bowel and malabsorption]. / Linfoma primario de intestino delgado y malabsorción.

Between 1974 and 1984 we saw 69 patients with lymphoma that involved the gastrointestinal tract. In ten patients the lymphoma compromised the small bowel and were associated to malabsorption. Seven patients fulfilled the criteria to be considered as primary small bowel lymphoma. We presumed the intestinal origin in the other 3 patients, but it was impossible to confirm it. The peroral small bowel biopsy showed histological findings compatible with celiac disease in 7 patients. Other particular histological signs were patchy alterations, inconstant epithelial pseudo-stratification and ulcerations. In 2 cases we found findings that suggested the diagnosis of lymphoma. In 50% of patients we found unspecific malabsorption signs in the small bowel radiology. We found giant ulcers and stenosis too. The gluten-free diet or the steroid therapies resulted in temporary or inconstant improvement. The laparotomy was the most effective diagnostic approach. It was performed electively in 6 patients and in 1 because of a small bowel perforation. The primary small bowel lymphoma is an entity of difficult diagnosis. The most important trouble is to differentiate it with celiac disease.

Impaired monocyte function in patients successfully treated for Whipple's disease.

Peripheral blood mononuclear cells (monocytes) from patients with Whipple's disease in long-term remission were tested for their ability to handle intracellular microorganisms. Phagocytosis and lysis of Candida tropicalis by monocytes of patients (n = 12) and controls (n = 8) were quantified after 30 min of incubation. Phagocytosis was similar in both groups but intracellular killing of Candida tropicalis was significatively lower in patients (p < 0.001). We concluded that our study showed an in vitro defect in the intracellular killing function of monocytes in subjects in remission many years after diagnosis of Whipple's disease. The defective function did not seem to be related to relapse or to the susceptibility to other infections.

Abnormal colonic transit time in untreated celiac sprue.

Motility disorders of the digestive tract have long been implicated in the pathophysiology of diarrhea in patients with celiac sprue. However, the contribution of the colon to the intestinal transit of celiac sprue has not been reported. Our aim was to determine whether sprue alters gut transit and whether differences in the clinical status of the disease influences colonic transit. We prospectively studied 25 patients with untreated celiac sprue, 15 treated patients and 15 healthy controls. Oro-cecal transit time, measured by the lactulose breath H2 test, was significantly delayed in untreated patients compared with treated patients and controls (p < 0.001 and p < 0.01 respectively). The delayed transit through the stomach and small bowel was not related to the presence of the steatorrhea. Transit of radiopaque makers, a measure of total colonic transit, was significantly faster in untreated patients (p < 0.05). The major finding was that this abnormal colonic behavior was principally due to a subpopulation of untreated patients with very fast transit times (< 18 hours). A weakly significant inverse correlation between transit and fecal weight (r: -0.55, p < 0.01), and between transit and steatorrhea (r: -0.38, p < 0.05), was observed. We confirm previous descriptions of delayed oro-cecal transit time in untreated patients, and also provide the first evidence that disordered colonic transit contributes to the pathophysiology of the diarrhea in sprue.

[Absence of bleeding recurrence of peptic ulcer after long term follow-up of successful eradication of Helicobacter pylori]. / Ausencia de recidiva de sangrado por úlcera péptica en el largo plazo luego de una erradicación exitosa del Helicobacter pylori.

Helicobacter pylori (HP) eradication reduces dramatically the peptic ulcer relapse rate, but information regarding recurrence of peptic ulcer bleeding after eradication is still scanty. Available data show rebleeding rates of 0-3% per year in successfully eradication patients, compared with figures between 12 and 33% among the non eradicated ones. The aim of this study was to determine the rebleeding rate among successfully eradicated patients with a prior history of rebleeding peptic ulcer. 42 patients (34 male, mean age 49, range 18-74) hospitalised for Hp positive bleeding peptic ulcer undergoing conservative treatment, were given as soon as oral route was re-established, a one-week eradication treatment, followed by the same proton pump inhibitor for three or five weeks for duodenal and gastric ulcer healing respectively. No maintenance antiulcer therapy was indicated. Patients were advised not to take nonsteroideal anti-inflammatory drug. Ulcer healing and Hp eradication was confirmed in all 42 patients by means of endoscopy and biopsies for urease rapid test and histology four weeks after completion of the treatment. After this patients were invited to enter a long-term follow-up program with periodical visits. End point of the study was occurrence of rebleeding. Further endoscopies were planned when rebleeding or symptomatic relapse. Median follow-up time was 24.02 months, ranging from 3 up to 27 months. All patients were compliant with the follow-up visits. None of the patients presented with symptoms suggestive of ulcer relapse or upper gastrointestinal bleeding. Our data suggest, that Hp eradication can prevent bleeding relapses in patients with Hp positive bleeding peptic ulcers.

[Value of the breath test with cholylglycine C14 in the diagnosis of bacterial contamination in patients with gastric surgery]. / Valor del test del aire espirado con colilglicina 14C en el diagnóstico de contaminación bacteriana en operados gástricos.

The TAE C14 has been evaluated as a diagnostic method of small bowel contamination in a group of patients operated for gastric disturbances. It has been compared with bacterial culture and bile salts chromatogrpahy of jejunum liquid and therapeutic response. 36 patients have been studied and divided in 3 groups: a) negative control: 8 subjects without pathology; b) positive control: 6 patients with intestinal resection and 1 with intestinal scleroderma, all of them with steatorrhea; c) gastric operated patients: 16 BII with and without vagotomy, 3 gastroenteroanastomosis and vagotomy, 1 superselective vagotomy and pyloroplasty and 1 B I, all the patients had steatorrhea, except one with BII. The period elapsed between the operation and the studies varied from 1 to 17 years (X: 4.9 +/- 4.1). The average value of steatorrhea was 23.9 +/- 10.2 g/24 hs. 100% of group b and 80% of group c had abnormal TAE C14. In 80% of the patients of the group c chromatogrpahy was performed and it agreed with TAE C14 in 80% of the studies. Bacteriology was positive in 100% of 18 studies, coinciding with TAE C14 in 70% patients. Therapeutic control of 100% of group c was positive in 90%.