Clinical utility of counting intraepithelial lymphocytes in celiac disease intestinal mucosa / Utilidad clínica del recuento de linfocitos intraepiteliales en la mucosa intestinal para el diagnóstico de enfermedad celíaca

BACKGROUND/AIMS: Our aims were to establish the clinical utility of assessing the intraepithelial lymphocyte (IEL) density in intestinal biopsies from a large series of individuals and to determine the best threshold discriminating celiac disease (CD) patients and controls in two populations with different pre-test prevalence. METHODS: We prospectively performed intestinal biopsy and CD-related serology in 349 subjects undergoing upper GI endoscopy. While 116 had symptoms suggestive of a small bowel disorder (high prevalence), 233 individuals were randomly selected from patients referred to endoscopy because upper GIsymptoms (low prevalence). Diagnosis of CD was based on the concordance of classical histological features and a positive CD serology. RESULTS: While 58 patients had a newly diagnosed CD (52 in the high and 6 in the low prevalence groups), 291 subjects did not meet diagnostic criteria of the disorder. Patients had a highly significant greater IEL density than controls (p < 0.00001). Based on the ROC curve, a count of 22.8 IEL/100 epithelial cells had the highest performance for diagnosing CD in the overall population and for subjects in the high pre-test probability subgroup and 22.5% was ,he best cut-off for those diagnosed in the low risk population (area under the curves: 0.979, 0.979 and 0.993, respectively). An abnormal CD serology confirmed the diagnosis of CD in all the four patients with counts below 22.8%. CONCLUSIONS: Our study confirms that an IEL density of 22.8% is an adequate threshold to discriminate CD patients and controls in individuals irrespective of the prevalence of the disorder.(AU)

Introducción: El recuento elevado de linfocitos intraepiteliales (LIEs) es un rasgo destacado aunque inespecífico de la enteropatía de la enfermedad celíaca (EC). Un recuento mayor a 40 LIEs/100 células epiteliales ha sido considerado por mucho tiempo esencial para el diagnóstico. Sin embargo, estudios recientes con escaso número de muestras han cuestionado este valor de corte. Objetivos: Determinar el rango normal de LIEs en biopsias intestinales y establecer su capacidad diagnóstica de EC en dos poblaciones con diferente prevalencia. Métodos: Realizamos prospectivamente biopsias de duodeno distal y serología para EC en 349 pacientesconsecutivos a quienes se les realizó una videoendoscopia digestiva alta. El grupo A consistió en 116 pacientes derivados a biopsia intestinal por síntomas sugestivos de malabsorción (considerados de alta prevalencia de EC) y el grupo B consistió en 233 pacientes randomizados entre quienes fueron derivados a endoscopía alta por síntomas gastrointestinales no sugestivos de EC (baja prevalencia de EC). El diagnóstico de EC se basó en criterios histológicos clásicos y serología positiva. Resultados: Cincuenta y ocho pacientes tuvieron EC (52 en el grupo de alto riesgo y 6 en el de baja prevalencia) y 291 individuos no tuvieron criterios de la enfermedad. Los pacientes tuvieron una densidad de LIEs significativamente mayor que los controles (p<0.00001). Basado en las curvas ROC, el conteo de 22.8 LIEs/100 células epiteliales tuvo la mejor sensibilidad y especificidad para el diagnóstico de EC en la población general y entre los sujetos con alta probabilidad y 22.5% fue el mejor valor de corte para la población de bajo riesgo (áreas bajo las curvas: 0.979, 0.979 y 0.993, respectivamente). Todos aquellos pacientes celíacos con recuento de LIEs por debajo de 22% (n=4), tuvieron serología positiva para EC. El clásico valor de 40% tuvo una sensibilidad del 55%. Conclusiones: Nuestro estudio confirma que una...(AU)

Significance of smooth muscle/anti-actin autoantibodies in celiac disease

BACKGROUND/AIM: Smooth muscle antibody (SMA) specific for the protein actin, a major component of the cytoskeleton of epithelial cells, is one of the most prevalent non-organ specific autoantibodies in the serum of celiac disease (CD) patients. Our aim was to explore the clinical relevance of the presence of IgA type anti-actin antibody (AAA) and SMA in a series of patients with CD. METHODS: We evaluated frozen serum samples collected at diagnosis from 92 adult patients with CD and 52 control individuals in whom CD was excluded. Patients were re-evaluated a median time of 5 yr after treatment. IgA type AAA was detected using a modified commercial ELISA assay and IgA SMA was detected using indirect immunofluorescence on primate esophagus substrate. RESULTS: At diagnosis, samples from CD patients had significantly higher AAA values than controls (p<0.00001). While all active CD patients had serum AAA values over the cut-off for healthy controls, we observed a very significant reduction of these antibodies after treatment (p>0.0001). AAA had a highly significant correlation with both, tissue, transglutaminase (r=0.62) and antigliadin (r=0.60, p<0.00001) antibodies as well as the severity of the intestinal injury (p<0.05). SMA was detected in sera of 35 consecutive CD patients. At diagnosis, SMA positive patients had significantly higher values of AAA (p<0.0002), increased number of autoimmune disorders (p<0.04), delayed menarche (p<0.04), lower hemoglobin levels (p<0.01), increased fecal a-I antitrypsin clearance (p<0.01) and more severe diarrhea (p<0.06). We also detected a trend to more severe complications at follow-up (p=0.059). CONCLUSIONS: Based on our findings we suggest that the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients with a potential relevance to diagnosis and follow-up. The presence of SMA seems to define a distinct subset of CD patients with ...(AU)

Introduccion/objetivo: El anticuerpo anti-musculo liso (SMA) dirigido contra la proteína actina, un componente mayor del citoesqueleto de las células epiteliales, es el anticuerpo no-órgano específico más prevalente en enfermedad celíaca (EC). Nuestro objetivo fue explorar la importancia clínica de los anticuerpos anti-actina (AAA) y SMA en una serie de pacientes con EC. Métodos: Evaluamos 92 muestras serológicas de pacientes celíacos adultos recolectadas al momento del diagnóstico y la de 52 individuos controles no celíacos. Los pacientes fueron re-evaluados luego de un tiempo medio de 5 años en tratamiento. Evaluamos AAA tipoIgA mediante ELISA empleando un equipo commercial modificado y SMA IgA por inmunofluorescencia indirecta sobre sustrato de esófago de mono. Resultados: Al momento del diagnóstico, los pacientes celíacos tuvieron valores de AAA significativamente más elevados que los controles (p<0.00001). Todos los pacientes con EC activa presentaron niveles de AAA por encima del valor de corte determinado para el grupo control sano y se evidenció una reducción significativa de los nivelesluego del tratamiento (p>0.0001). Los AAA presentaron una correlación significativa con los anticuerpos anti-transglutaminasa tisular (r=0.62) y anti-gliadina (r=0.60) (p<0.00001), de igual modo que con la severidad del daño intestinal (p<0.05). Al momento del diagnóstico, se detectó SMA en el suero de 35 pacientes no controles. Los pacientes SMA positivos tuvieron valores significativamente mayores de AAA (p<0.002), un incremento del número de enfermedades autoinmunes asociadas (p<0.04), menarca tardía (p<0.04), niveles bajos de hemoglobina (p<0.01), incremento del clearance de a-1 antitripsina fecal (p<0.01) y mayor severidad de la diarrea (p<0.06).En ellos se evidenció una tendencia al desarrollo de complicaciones más severas durante el seguimiento (p=0.059). Conclusiones: Sugerimos que la presencia de un valor sérico aumentado de AAA tipo IgA...(AU)

Osteo-artropatias de las enfermedades inflamatorias del colon. / Osteoarthropathies of inflammatory diseases of the colon

Se presentan 15 pacientes portadores de enfermedades inflamatorias del colon (14 rectocolitis ulcerosas inespecificas y 1 enfermedad de Crohn) que se complicaron con afectacion de grandes articulaciones y columna vertebral (espondilitis anquilosante). Se comenta la incidencia de estas manifestaciones, la clinica, la radiologia, la patologia, la serologia y evolucion con relacion a la enfermedad inflamatoria

Manifestaciones cutaneo-mucosas de la enfermedad de Crohn. / Mucocutaneous manifestations of the Crohns disease

Se presenta un caso de la infrecuente asociacion de pioderma gangrenoso y enfermedad granulomatosa del colon (enfermedad de Crohn del colon). Se realiza una revision de la literatura acerca de la asociacion del mismo con otras afecciones gastrointestinales. Se actualizan los probables mecanismos etiopatogenicos y resultados terapeuticos

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

Botulinum toxin (BoTox) is a potent inhibitor of the release of acetylcholine from terminal nerves and has been used succesfully 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 angoing randomized-controlled trial. Patients were blindy randomized to administrate: a) 8OU of BoTox were injected in four quadrants (1 ml in each quadrant-20 U/ml) (n=8) normal saline solution as placebo injected in the same way (n=5). Patientes who did not respond were retreated in an open design with the same schedule of BoTox. BoTox or placebe 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: (X + SD) symptoms score: (Pre: 3.23 + 0.44) (Post: 1.31 + 0.95); LES pressure (mmHg) (Pre: 53,15 + 66.31 + 7.49); per cent reduction of esophageal diameter 55 per cent (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. (AU)

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

A case of much less frequent association of the pyoderma gangrenosum and granulomatous disease of the colon (Crohns 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.

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

Pioderma gangrenoso en enfermedades de Crohn del colon. / Pyoderma gangrenosum in Crohns diseases of the colon

Se presenta un caso de la infrecuente asociacion de pioderma gangrenoso y enfermedad granulomatosa del colon (enfermedad de Crohn).Se realiza una revision de la literatura acerca de las asociaciones del mismo con otras afecciones gastrointestinales. Se actualizan los probables mecanismos etiopatogenicos y resultados terapeuticos

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

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 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

Recuperación de la absorción de vitamina B12 en el postoperatorio alejado, en ratas sujetas a la resección del 50 / distal del intestino delgado / [Recovery of vitamin B12 absorption in the late postoperative period in rats subjected to resection of 50of the distal small intestine]

Vitamin B12 Co57 intestinal absorption was evaluated in rats, determining the

whole body retention, 12 and 28 weeks after resection of 50

distal small intestine with preservation of ileocecal valve. At week 12th, a statistical significative difference in vitamin B12 absorption was found between rats submitted to surgery and the control group (p less than 0.01). On the other hand, at week 28th vitamin B12 absorption values were very close in both groups of rats. This last fact supports the evidence of recovery of vitamin B12 absorption in ilectomized rats.

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

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.

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 tansit, 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. (AU)

Fecal *1-antitripsyn clearance in the differential diagnosis of steatorrhea

Efectuamos la revisión de la excreción de grasa fecal y el Clearance de alfa1-antitripsina (CLalfa1-AT) de 160 pacientes con esteatorrea en quienes el diagnóstico final se obtuvo basado en la historia clínica, examen físico, estudios radiológicos, funcionales y morfológicos. Veintedós pacientes tenían enfermedades pancreáticas y 138 tuvieron esteatorrea debido a enfermedades gastrointestinales. La combinación de esteatorrea y CL alfa1-AT normal fue una guía de utilidad para el diagnóstico de malabsorción pancreática. El CL alfa1-AT fue normal en todos nuestros pacientes con pancreatitis crónica. Sin embargo, cuando la combinación de esteatorrea y CL alfa1-AT normal estuvo presente, el diagnóstico etiológico correcto fue posible en el 23 al 50% de los casos (AU)

Ulcera necrotica de cavidad bucal en colitis ulcerosa. / Necrotic ulcer of the bucal cavity in ulcerative colitis

Los autores presentan un caso de asociacion de ulcera necrotica de cavidad bucal durante un brote agudo de rectocolitis ulcerosa inespecifica que evoluciono hacia la curacion con el tratamiento de la enfermedad de base. Se realiza una revision de las enfermedades gastrointestinales que pueden asociarse a ulceras bucales, y se detalla su diagnostico diferencial con otras ulceras bucales especificas e inespecificas

Impaired monocyte function in patients succesfully treated for Wipples disease

Peripheral blood mononuclear cells (monocytes) from patients with Whipples 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) andcontrols (n=8) were quantified after 30 min of incubation. Phagocytosis was similar in both groups but intracellular Killing of Candida tropicalis was significativily 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 Whipples disease. The defective function did not seem to be related to relapse or to the susceptibility to other infections. (AU)

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

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.

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.

Enfermedad celíaca, antígenos de histocompatibilidad y estado inmunitario. / [Celiac disease, histocompatibility antigens and immunologic status]

Researched from immunologic and genetic point of view, 40 patients with Celiac Diseases confirmed and under-treatment. The results were compared with a group of 257 healthy people. The immunologic studies: leucocytes and lymphocytes in blood, the subpopulation of lymphocytes T and B, The immune-reaction studies of immunoglobulin Ig G, Ig M, Ig A and component C III complement didnt show difference between the comparative groups justified perhaps because the group of patients were under-treatment. In the antigen erythrocyte A B O and RHO (A), we can only in those assert that there is an increase of A and B group between the patients than who have O, and they were less exposed to get the disease. Between the histocompatibility antigen, the low presence of A9 B5 B7 BW16 antigen in Celiac patients could be a sign of protection against the disease, contrarily the presence of A1 B8 Dr3 Dr7 could indicate the high risk to get the disease. These finding confirm that the antigen group connected with the major System of histocompatibility, showed the susceptibility to suffer the disease.

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

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

.

Recuperación de la absorción de vitamina B12 en el postoperatorio alejado, en ratas sujetas a la resección del 50 / distal del intestino delgado. / [Recovery of vitamin B12 absorption in the late postoperative period in rats subjected to resection of 50 / of the distal small intestine]

Vitamin B12 Co57 intestinal absorption was evaluated in rats, determining the

whole body retention, 12 and 28 weeks after resection of 50

distal small intestine with preservation of ileocecal valve. At week 12th, a statistical significative difference in vitamin B12 absorption was found between rats submitted to surgery and the control group (p less than 0.01). On the other hand, at week 28th vitamin B12 absorption values were very close in both groups of rats. This last fact supports the evidence of recovery of vitamin B12 absorption in ilectomized rats.