[Phenotypic characterisation of 35 Colombian children with an imaging diagnosis of schizencephaly]. / Caracterización fenotípica de 35 niños colombianos con diagnóstico imaginológico de esquisencefalia.

INTRODUCTION: Schizencephaly is the most frequent neuronal migration disorder. It is classified according to the type of lip (closed or open). Clinical features vary from the asymptomatic patient to severe neurological compromise. AIM: To describe the clinical characteristics of children who have been diagnosed with schizencephaly and their correlation with radiological findings. PATIENTS AND METHODS: Thirty-five Colombian children (17 males and 18 females) with a neuroimaging diagnosis at a mean age of 20.2 months were characterised phenotypically. RESULTS: A history of perinatal events such as neonatal asphyxia (21.6%) and meconium-stained amniotic fluid (10.8%) were detected, together with maternal histories of failure to attend prenatal check-ups (34.3%), risk of preterm labour (10.8%) and smoking (10.8%). Familial histories of neurological diseases included epilepsy (14.3%) and mental retardation (5.7%). The open-lip type was predominant (60%) and was twice a common as the closed-lip type. Unilateral cases accounted for 62.9% of the total number, with a distribution between the two hemispheres in the same proportion, and 37.1% of cases were bilateral. The frontal lobe that was the most commonly involved. The most frequent manifestations were delayed psychomotor development (80%) and infantile cerebral palsy (80%). Epilepsy was present in 37.1% of cases and the predominant type of seizure was complex focal. CONCLUSIONS: Tendencies similar to those reported in other series were observed, although with some differences, such as the higher mean age at the time of diagnosis and the lower incidence of resistant epilepsy. Limited access to prenatal check-ups, open-lip presentation, associated malformations and poor response to treatment seem to exacerbate the prognosis.

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)

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.

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...

Evaluación de ingesta en pacientes con hepatopatías crónicas / Evaluation of ingestion in patients with chronic liver diseases

La malnutrición calórico-protéica (MCP) es frecuente entre los pacientes con hepatopatías crónicas (HC) estableciéndose hasta en un 80 por ciento. El problema es multifactorial, siendo la disminución de la ingesta una de las causas más relevantes. Objetivo: evaluar la ingesta calórico-protéica en pacientes con HC. Se evaluaron prospectivamente 60 pacientes (26 mujeres, 43,3 por ciento) con una edad media de 54,1 años, con los siguientes diagnósticos: cirrosis biliar primaria 11 (18,3 por ciento), cirrosis alcohólica 26 (46,3 por ciento), hepatopatías autoinmunes 12 (20 por ciento), cirrosis criptogenética 6 (10 por ciento), Budd-Chiari 1 (1,7 por ciento), Hemocromatosis 1 (1,7 por ciento), cirrosis viral 3 (5 por ciento). Se utilizó el recordatorio de 3 días para la recolección de datos de ingesta, la evaluación global subjetiva EGS) para evaluación nutricional y la clasificación de Child-Pugh para evaluar severidad de la hepatopatía...

Evaluación de ingesta en pacientes con hepatopatías crónicas / Evaluation of ingestion in patients with chronic liver diseases

La malnutrición calórico-protéica (MCP) es frecuente entre los pacientes con hepatopatías crónicas (HC) estableciéndose hasta en un 80 por ciento. El problema es multifactorial, siendo la disminución de la ingesta una de las causas más relevantes. Objetivo: evaluar la ingesta calórico-protéica en pacientes con HC. Se evaluaron prospectivamente 60 pacientes (26 mujeres, 43,3 por ciento) con una edad media de 54,1 años, con los siguientes diagnósticos: cirrosis biliar primaria 11 (18,3 por ciento), cirrosis alcohólica 26 (46,3 por ciento), hepatopatías autoinmunes 12 (20 por ciento), cirrosis criptogenética 6 (10 por ciento), Budd-Chiari 1 (1,7 por ciento), Hemocromatosis 1 (1,7 por ciento), cirrosis viral 3 (5 por ciento). Se utilizó el recordatorio de 3 días para la recolección de datos de ingesta, la evaluación global subjetiva EGS) para evaluación nutricional y la clasificación de Child-Pugh para evaluar severidad de la hepatopatía...(AU)

Antibodies to human recombinant tissue transglutaminase may detect coeliac disease patients undiagnosed by endomysial antibodies.

BACKGROUND: The screening and diagnosis of coeliac disease have been simplified by the advent of new serological tools. AIM: To assess the clinical utility of a newly developed kit for antibodies to human recombinant tissue transglutaminase (hu-anti-tTG) in a large population of patients undergoing intestinal biopsy for suspected intestinal disorders. METHODS: We evaluated 426 serum samples from consecutive adult patients (250 from untreated coeliac disease patients and 176 from individuals in whom a diagnosis of coeliac disease had been excluded), obtained at the time of intestinal biopsy. Samples were tested for immunoglobulin A (IgA) hu-anti-tTG by enzyme-linked immunoabsorbent assay, IgA endomysial antibodies (EmA) by indirect immunofluorescence and IgA and IgG antigliadin antibodies by enzyme-linked immunoabsorbent assay. A sub-group of samples was also assessed for a guinea-pig-based anti-tissue transglutaminase. RESULTS: According to the cut-off for hu-anti-tTG, the sensitivity, specificity and positive and negative predictive values were 91%, 96%, 97% and 87%, respectively. Simultaneous determination of EmA showed values of 86%, 100%, 100% and 83% for the same parameters. Although 19 coeliac disease patients (7.6%) were negative for EmA and hu-anti-tTG, both tests rendered superior statistical values to antigliadin antibody tests. At diagnosis, IgA deficiency was detected in 11 patients, but both assays were able to detect samples with mild to moderate deficiency. The comparison of hu-anti-tTG with EmA showed excellent concordance between the tests (kappa statistic, 0.85). Discordance was observed in 20 samples from coeliac disease patients (8%) and in nine samples from controls (5%). Fifteen samples had an EmA-negative but hu-anti-tTG-positive serology, and five showed the converse pattern. Comparison of human recombinant and guinea-pig tests showed concordant results in 96% of cases. CONCLUSIONS: The quantitative determination of hu-anti-tTG type IgA using a commercial enzyme-linked immunoabsorbent assay kit was highly sensitive and specific for the detection of coeliac disease. Our results in a large population of patients with a clinical condition suggestive of the disorder demonstrated that the test can be used to detect a substantial number of patients otherwise unrecognized by IgA EmA.

Is it necessary to screen for celiac disease in postmenopausal osteoporotic women?

Decreased bone mass is a frequent finding in celiac patients, and subclinical celiac disease (CD) appears to be unusually overrepresented among patients with idiopathic osteoporosis. Since silent CD may be more common than previously believed, it has been suggested that all osteoporotic patients should be checked for occult CD. The aim of this study was to explore the prevalence of CD in a well-defined population of postmenopausal osteoporotic women. We evaluated 127 consecutive postmenopausal patients (mean age: 68 years; range: 50-82 years) with verified osteoporosis. The observed prevalence of CD in this group was compared to that observed in a group of 747 women recruited for a population-based study. The screening algorithm used to diagnose CD was based on a 3-level screening using type IgA and IgG antigliadin antibodies (AGA) in all the patients (1st level) followed by antiendomysial antibodies (EmA) and total IgA (2nd level) of samples testing positive, and intestinal biopsy of positive cases (3rd level). At the end of the serological screening, only 1 of 127 osteoporotic women was eligible for jejunal biopsy showing a characteristic celiac flat mucosa (prevalence 7.9 x 1,000; 95% CI 0.2-43.1). In addition, CD was diagnosed in 6 of 747 women of the population-based study (prevalence: 8.0 x 1,000; 95% CI 3.3-18.3). There was no significant difference between the two groups. Therefore, our study showed that the prevalence of CD in postmenopausal osteoporotic women was lower than that reported in previous studies and similar to that of the general population. In conclusion, although the relatively small size of the group tested does not allow us to be conclusive, the results suggest that a case finding policy in postmenopausal osteoporosis would have a high cost/benefit ratio except for patients not responding to conventional therapies, or presenting borderline laboratory results.

Prevalence of celiac disease in Argentina: screening of an adult population in the La Plata area.

OBJECTIVES: Up to now, the epidemiological characteristic of celiac disease among adults in South America remains unknown. The present prospective screening was designed to determine the prevalence of celiac disease in adults from the general population in an urban area of Argentina. METHODS: Between January. 1998, and May, 2000, all couples attending a centralized laboratory for an obligatory prenuptial examination in the La Plata area were offered participation in a screening program for celiac disease. The study included 2000 subjects (996 women; median age 29 yr, range 16-79 yr). All individuals completed a clinical questionnaire at the time that serum samples were obtained. A three-step screening protocol was used, as follows: 1) all samples were tested for antigliadin antibodies (AGAs) (type IgA and IgG); 2) samples that were IgA AGA positive were tested for antiendomysial antibody (EmA type IgA); samples that were positive for AGA-G but negative for IgA AGAs were tested for total IgA serum levels and EmA type IgG; and 3) subjects who were EmA-positive were referred for intestinal biopsy. RESULTS: At the end of the screening we detected 10 subjects who were EmA-A positive and two others who were IgA-deficient (both were EmA-G positive). Up to now, 11 of the 12 subjects (including nine EmA-positive and two IgA-deficient subjects) had endoscopic intestinal biopsies showing the characteristic celiac histology. The remaining EmA-positive individual was considered to be affected by celiac disease. The overall prevalence assessed was 1:167 (6.0 x 1000 subjects; 95% CI = 3.1-10.5). Eight of the 12 (67%) subjects were female (1:124; 8.0 x 1000; 95% CI = 3.5-15.8) and four (33%) were male (1:251; 4.0 x 1000; 95% Cl = 1.1-10.2). Although eight new patients were considered to be asymptomatic, three presented with a subclinical course and one was classically symptomatic. Only one patient had been previously diagnosed with celiac disease. CONCLUSIONS: Our screening protocol showed a very high prevalence of celiac disease for an urban area of Argentina that is ethnically similar to 90% of the general population of the country. The prevalence among women was double that for men, and the heterogeneous clinical picture of new patients showed predominance of asymptomatic cases.

High frequencies of telomeric associations, chromosome aberrations, and sister chromatid exchanges in ulcerative colitis.

OBJECTIVE: Chromosome instability provides a predisposing background to malignancy, contributing to the crucial genetic changes in multistep carcinogenesis. The aim of this work was to analyze chromosome instability in patients with ulcerative colitis (UC) to achieve a better understanding of the increased risk for colorectal cancer. METHODS: Peripheral blood lymphocyte cultures from 20 untreated UC patients and 24 controls were used to study chromosome instability by assessing telomeric associations (TAS), chromosome aberrations (CA), and sister chromatid exchanges (SCE). RESULTS: Mean frequencies of TAS and CA were significantly increased in UC patients compared to controls (p < 0.001). Chromosomes 10, 11, 21, 16, and 19 were the most frequently involved in TAS. A total of 104 CA clustered in 66 breakpoints could be exactly localized. Seven nonrandom bands significantly affected in UC patients were found (p < 0.004), showing a significant correlation with the location of cancer breakpoints (p < 0.003), particularly with colorectal carcinoma rearrangements. SCE analysis showed higher levels in patients compared to controls (p < 0.006), but no differences were observed in cell cycle kinetics. CONCLUSIONS: Our results demonstrate the presence of an unstable genome in UC patients that could be related to the cancer development observed in this disease.

Tissue transglutaminase antibodies in celiac disease: assessment of a commercial kit.

OBJECTIVE: Tissue transglutaminase was identified as the autoantigen eliciting endomysial antibody. A homemade enzyme-linked immunosorbent assay (ELISA)-based test was recently developed to determine quantitative titers of IgA antitissue transglutaminase antibody. Our objective in this study was to assess the suitability of a newly developed commercial kit for quantitative determination of antibody in patients with untreated celiac disease. MATERIALS: We tested serum samples from 79 untreated celiac patients, 42 healthy blood donors, and 18 patients with nonceliac intestinal disorders evaluated in two different centers. Samples were tested for antitissue transglutaminase, and antiendomysial and antigliadin antibodies in the center where diagnosis was performed. To assess interlaboratory variability of methods, 24 samples randomly selected were blindly tested in both centers. Antitissue transglutaminase antibodies were determined using a commercial kit (INOVA Diagnostics, Inc., San Diego, CA). RESULTS: Untreated celiac patients had significantly higher titers of antitissue transglutaminase than healthy and disease controls (p < 0.00001). According to the cut-off provided by the manufacturers (20 AU/mL), overall sensitivity was 92% (85% for one center and 100% for the other) and specificity was 98% (100% and 95%, respectively). Antiendomysial antibody was 86% sensitive and 100% specific. Discordance between antitissue transglutaminase and antiendomysial antibodies was detected in 13% of patients. Although two antitissue transglutaminase-negative cases had a positive antiendomysial antibody, the inverse situation was found in eight cases. A blind determination of antitissue transglutaminase on the same samples evidenced a good agreement (kappa statistic: 0.66) between both centers when assessment was qualitative (based on the decision of positive or negative). Although correlation of titers for both determinations was highly significant (r: 0.902, p < 0.00001), a very wide interlaboratory variability (median: 50%) was detected when absolute values were considered. CONCLUSIONS: The quantitative determination of antitissue transglutaminase using a commercial kit was highly sensitive and specific for detection of celiac disease. We observed an incomplete overlapping with antiendomysial antibody. The very high variability of values between laboratories still remains to be solved so as to propose the commercial ELISA assay for the screening of celiac disease.

Balance nitrogenado en el paciente crítico con nutrición enteral / Nitrogen balance in critical patients with enteral feeding

La evaluación del balance nitrogenada en pacientes criticos y en aquellos que reciben soporte nutricional se realiza con la estimación de las pérdidas de nitrógeno en orina midiendo en nitrogeno ureico urinario (NUU), el que representa la mayor parte de las plérdidas nitrogenadas. Dado que contamos con la posibilidad de realizar la determinación de nitrógeno total urinario (NTU) quisimos evaluar el impacto del soporte nutricional en el balance nitrogenado de los pacientes críticos. Objetivos: 1. evaluar el balance nitrogenado de los pacientes internados en terapia intensiva (UTI). 2. estudiar la evaluación del balance nitrogenado en pacientes ayunados y su evolución en el curso del soporte nutricional ...

Balance nitrogenado en el paciente crítico con nutrición enteral / Nitrogen balance in critical patients with enteral feeding

La evaluación del balance nitrogenada en pacientes criticos y en aquellos que reciben soporte nutricional se realiza con la estimación de las pérdidas de nitrógeno en orina midiendo en nitrogeno ureico urinario (NUU), el que representa la mayor parte de las plérdidas nitrogenadas. Dado que contamos con la posibilidad de realizar la determinación de nitrógeno total urinario (NTU) quisimos evaluar el impacto del soporte nutricional en el balance nitrogenado de los pacientes críticos. Objetivos: 1. evaluar el balance nitrogenado de los pacientes internados en terapia intensiva (UTI). 2. estudiar la evaluación del balance nitrogenado en pacientes ayunados y su evolución en el curso del soporte nutricional ... (AU)

Evidence of chromosome instability in chronic pancreatitis.

In the current study we analyzed chromosome instability on peripheral blood lymphocytes cultured from 7 untreated patients with chronic pancreatitis (CP) by assessing telomeric associations (TAS), chromosome aberrations (CA) and sister chromatid exchanges (SCE). Seven healthy individuals were also analyzed. Mean frequencies of TAS were significantly higher in CP patients (X +/- SE: 11.00 +/- 2.37) compared to controls (1.00 +/- 0.30) (p<0.001). Chromosomes preferentially involved in TAS were: 9, 20, 16 and 21, being the most affected arms: 9p, 20q, 16p, 9q and 21q. All these terminal bands were coincident with cancer breakpoints (p<0.03), two of them (40%) were specifically associated to pancreatic carcinoma rearrangements. Three bands (60%) were coincident with oncogene location. The mean frequency of CA was significantly higher in patients (3.88 +/- 0.80) compared to controls (0.63 +/- 0.49) (p<0.001). Chromosomes 1, 2 and 13 were the most damaged. No specifically affected breakpoints were found. SCE analysis showed higher levels in patients (8.33 +/- 0.70) than in controls (6.62 +/- 0.34) (p<0.025), but no differences were observed in cell cycle kinetics. Our results clearly indicate that CP patients exhibit chromosome instability, showing the presence of an unstable genome that could be related to the cancer development observed in this disease.

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.

Chromosome instability in lymphocytes from patients with celiac disease.

Cytogenetic studies were performed in celiac disease (CD) patients to determine if the presence of chromosome instability is related to the predisposition to cancer. Chromosome aberrations (CA) and sister chromatid exchange (SCE) frequencies in peripheral blood lymphocyte cultures from untreated CD patients and healthy controls were analyzed. Patients showed aberrations in 23% of cells, while only 3% were detected in the control group (p < 0.0001). The mean frequencies of gaps, breaks and total CA were found to be higher in CD patients compared to controls (p < 0.0001). Breakpoint distribution was nonrandom among chromosomes from celiac patients (p = 0.01), but not among controls (p = 0.04). The frequency of SCE/cell showed a mean value of 6.9 +/- 0.6 in CD patients and 7.3 +/- 0.2 in controls. No statistical differences were found. Breakpoints involved in CD patients presented a strong coincidence with the location of fragile sites (78.6%) and sites of cancer chromosome rearrangements (57.1%), most of them (75%) associated with malignant non-Hodgkin lymphomas. These results suggest that CD is a condition with increased chromosome instability characterized by a high level of CA and normal SCE frequencies, probably related to the increased incidence of cancer.