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PubMed2004

Exacerbation of protracted-relapsing experimental allergic encephalomyelitis in DA rats by gluten-free diet.

The observation of neurological dysfunctions resembling multiple sclerosis (MS) seen clinically and/or by MRI in patients with celiac disease has focused attention on the possibility that cryptic gluten sensitivity may be involved in the pathogenesis of MS. Here we study the effects of a gluten-free diet on the course of protracted-relapsing EAE in DA rats, serving as a preclinical model of human MS. The data show not only that this nutritional approach failed to ameliorate development of the disease but rather that it exacerbated the course.

Animals↗
PubMed1989

Scanning electron microscopy of histological relapse after gluten-challenge in coeliac disease.

The steps of the morphological relapse occurring during gluten-challenge in coeliac children were for the first time investigated by scanning electron microscopy and compared with the morphological changes observed in untreated and treated coeliac patients, in pathological and normal controls. Some peculiar morphological changes, not reported up to now, were observed in treated and relapsed coeliac patients. No relationship was found among the degrees of mucosal atrophy observed by SEM and the duration of the challenge performed by an uncontrolled ingestion of gluten.

Celiac Disease↗
PubMed1987

Compliance with gluten free diet in coeliac disease.

Fifty two children in whom coeliac disease was confirmed by persistent enteropathy while they were taking gluten were monitored to assess the effects of compliance with a gluten free diet (GFD). Between the ages of 17.8 and 18.5 years height (in 45 patients followed up for a mean of 14.9 years) and weight (in 43 followed up for a mean of 15.2 years) were significantly lower in those complying poorly with a GFD compared with those complying well. Of the 37 patients still attending the clinic after a mean of 25 years, having been followed up for a mean of 18.4 years, 16 who had complied well with the diet had normal or only slightly abnormal mucosal morphology whereas all 10 who had not complied had abnormal morphology. In these 10 lactase, sucrase, and alkaline phosphatase activities were significantly less than values in those who complied well. Mucosal sucrase and alkaline phosphatase activities in those who complied well were no different from those in a control population, whereas lactase activity was significantly lower. It is concluded that failure to comply with a GFD during childhood results in decreased adult stature and in persisting active enteropathy with depressed brush border enzyme activity.

Body Height↗
PubMed1969

Prognosis in early adult life of coeliac children treated with a gluten-free diet.

Long-term follow up of 57 young adults with coeliac disease diagnosed in childhood showed that 13 had relapsed clinically and had resumed a gluten-free diet Of the remainder, who were taking a normal diet and were apparently normal, 19 had low serum folate levels and 11 low serum iron levels. Pregnancy was found particularly likely to provoke an overt relapse.Only six patients were found to be stunted in height, while the menarche had occurred within the average range. The study also confirmed the very low present-daymortality rate of coeliac disease in childhood, which at the Hospital for Sick Children in London has been 0.4% between 1951 and 1968. In view of the finding that childhood coeliac disease usually persists, even though not causing symptoms, it is suggested that the use of a gluten-free diet should be lifelong.

Adolescent↗
PubMed1969

Results of treatment of dermatitis herpetiformis with a gluten-free diet after one year.

Twenty-one patients with dermatitis herpetiformis initially controlled by dapsone or sulphonamides have been treated with a gluten-free diet and reassessed at intervals for up to 15 months (mean 11.9 months). According to routine histological and dissecting microscope criteria the small-bowel lesion improved in 10, but when mean epithelial cell height was used as a measure 15 patients improved. Five of the patients with diarrhoea improved after withdrawing gluten from the diet but none reverted to completely normal bowel habit. The tests for malabsorption showed little improvement in the treatment period. Twelve patients needed less dapsone to control their skin complaint, the mean dose falling from 144 mg. to a mean of 70 mg. per day; of these three stopped using this drug altogether.

Adolescent↗
PubMed1974

Identifying toxic fractions of wheat gluten and their effect on the jejunal mucosa in coeliac disease.

THE TOXICITY OF THREE FRACTIONS (A, B, AND C) OBTAINED BY ULTRAFILTRATION OF A PEPTIC: tryptic digest of gluten has been assessed by serial feeding experiments in patients with treated coeliac disease. The first fraction (A), which contains amino acids and oligopeptides, produced no damage to the jejunal mucosa. The other two fractions (B and C) both caused mucosal damage. Fraction B, which contains the products of digestion of smaller molecular weight, consists of polypeptides which are concentrated in the region of 8000 molecular weight. It contains no gliadin (molecular weight 50 000) or gluten. Ultrastructural evidence of damage was visible six hours after challenge with fraction B and by 10 hours histological abnormalities were also present. Ultrastructural abnormalities occurred early in the epithelial cells and preceded changes in the basement membrane and capillaries. The disaccharidases showed a pronounced depression in all three subjects by 24 hours. The rapid onset of damage after challenge, coupled with the evidence of recovery as soon as 72 hours later, is more in keeping with a direct action on the surface epithelial cells rather than an immune mechanism.

Amino Acids↗
PubMed1976

Coeliac disease, gluten-free diet, and malignancy.

Two hundred and two patients with coeliac disease or idiopathic steatorrhoea previously reported from this unit have been reviewed after a further 10 years of follow-up. Of 20 more deaths, 10 were due to malignancy. A separate study was made of all patients with histologically confirmed coeliac disease seen to the end of 1972 and followed up to the end of 1974. Twenty-one of the 43 deaths in this series were due to malignant tumours, of which 13 were reticulum cell sarcomas. There was no evidence that patients showing sub-optimal clinical response to gluten withdrawal or persisting falt jejunal biopsies were more prone to die of cancer. A gluten-free diet did not appear to be effective in preventing malignant complications, but a longer follow-up of patients will be necessary to provide a final answer to this question.

Adult↗
PubMed1977

Jejunal villous atrophy and granulomatous inflammation responding to a gluten--free diet.

A 48 year old female patient with intestinal malabsorption and subtotal to total jejunal villous atrophy also had granulomatous inflammation characterised by numerous epitheloid and giant cell granulomas in the stomach, the jejunum, and the liver, On a gluten-free diet a complete remission was achieved that included disappearance of the granulomatous inflammation. It is suggested that the granulomas in this case were manifestations of the gluten intolerance.

Celiac Disease↗
PubMed1978

Response of the skin in dermatitis herpetiformis to a gluten free diet, with reference to jejunal morphology.

Twenty-one patients with dermatitis herpetiformis have been on a gluten free diet regularly followed up for at least one year (mean four years). Eighteen patients had a 'flat' mucosal appearance (grade III), one patient had moderately severe mucosal abnormality (grade II), one patient had mild mucosal abnormality (grade I), and one patient had a normal mucosal appearance (grade O). On the diet, 10 patients had no skin rash and took no dapsone, seven patients controlled the skin rash on a lower dose of dapsone, and four noticed no improvement. There was no correlation between pre-diet jejunal morphology and response of the skin. A repeat jejunal biopsy, on the gluten free diet, was possible in 15 patients. While all those with skin improvement showed some improvement in jejunal morphology, there was no association between the degree of skin improvement and the degree of recovery of the jejunal mucosa.

Adolescent↗
PubMed1981

Early or pre-coeliac mucosa: development of gluten enteropathy.

Duodenal mucosa showed normal morphology, interepithelial lymphocytes, alkaline phosphatase, and sucrase in a girl with growth retardation and iron deficiency, but normal absorption of lactose and xylose after two years of abnormal stools. Mucosal lactase was low. Fourteen months later mucosal damage consistent with coeliac disease was evident, and gluten intolerance was subsequently confirmed by gluten challenge. It is probable that, in some children, the mucosal lesion occurs very gradually, so that at an early stage with normal morphology, suppression of lactase activity and possibly interference with iron absorption may be the only abnormalities.

Anemia, Hypochromic↗
PubMed1981

Changes in N-terminal glucagon-like immunoreactivity and insulin during short-term gluten challenge in childhood coeliac disease.

Sixteen patients (aged 3.5-14.3 years) with normal jejunal mucosa, originally diagnosed as having coeliac disease at least 18 months before, were started on gluten challenge. The 'end point' of challenge was significant deterioration in jejunal mucosa morphologically and morphometrically. Studies carried out both before and after challenge included intestinal absorption of D-xylose and glucose, and release of insulin and N-terminal glucagon-like immunoreactivity (N-GLI). After gluten challenge, there were significant increases in plasma N-GLI at both 45 (P less than 0.05) and 120 minutes (P less than 0.03) after oral glucose. Significant reduction occurred in glucose absorption at 45 minutes (P less than 0.04), in one-hour D-xylose absorption (P less than 0.01) and fasting serum cholesterol (P less than 0.01). Plasma N-GLI showed significant negative correlations with D-xylose absorption (P less than 0.003) and serum cholesterol (P less than 0.004).

Adolescent↗
PubMed1987

Postheparin plasma diamine oxidase increases in patients with coeliac disease during gluten free diet.

An intravenous injection of heparin releases diamine oxidase (DAO) from villous tip enterocytes. In a previous study, we found that postheparin plasma DAO (PHD) values were significantly lower in patients with malabsorption syndrome and small bowel atrophy at jejunal biopsy than in normal subjects. In this study we performed the PHD test in 14 coeliac patients before and after three and six months of gluten free diet to show whether the enterocytes maturing processes induced by the diet joined with enhanced PHD values and to assess the clinical usefulness of this test. In all subjects jejunal biopsy carried out after six months showed a partial but consistent histological recovery. The clinical status, xylosuria and daily faecal fat excretion improved progressively and there was a significant increase (p less than 0.001) in mean PHD activity that reached the normal range after three months. After six months a further slight increase of the mean PHD value was recorded. These data indicate that PHD values rise together with the improved intestinal absorptive functions of coeliac patients on gluten free diet and that this test is a useful tool in monitoring recovery of the small bowel mucosa.

Adult↗
PubMed1989

Malignancy in coeliac disease--effect of a gluten free diet.

Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up. The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short. The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period. Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas. Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin's lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4). The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population. The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p < 0.001), and also of lymphoma (RR = 77.8, p < 0.001). A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found. The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.

Celiac Disease↗
PubMed1991

Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet.

This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal.

Adolescent↗
PubMed1996

Effect of a gluten free diet on osteopenia in adults with newly diagnosed coeliac disease.

BACKGROUND/AIMS: Calcium and vitamin D malabsorption in coeliac disease predispose to skeletal demineralisation. This study aimed to determine bone mineral density in patients studied in the first year after diagnosis of coeliac disease, and to detect changes in bone mineral density over the subsequent year. METHODS: Lumbar spine and femoral neck bone mineral density was measured in 21 adults with coeliac disease, diagnosed and started on a gluten free diet during the preceding year, with dual energy x ray absorptiometry and repeated after 12 months. RESULTS: Bone mineral density was significantly lower in patients than in paired controls (matched for age and sex), at lumbar spine (0.819 g/cm2 compared with 1.021 g/cm2, p < 0.001 Wilcoxon signed rank test) and femoral neck (0.663 g/cm2 compared with 0.794 g/cm2, p < 0.001). Repeat measurement after 12 months demonstrated that patients had a significant gain in bone mineral density at lumbar spine (16.6%/year), and femoral neck (15.5%/year, p < 0.002, Wilcoxon signed rank test at both sites), whereas no significant change in bone mineral density was detected in controls. CONCLUSIONS: Treatment of coeliac disease with a gluten free diet is associated with a significant increase in bone mineral density, although patients still had lower bone mineral density than controls.

Adult↗
PubMed1996

Celiac disease: small-bowel enteroclysis findings in adult patients treated with a gluten-free diet.

PURPOSE: To correlate the radiologic, histopathologic, and clinical findings in patients with celiac disease after treatment with a glutenfree diet. MATERIALS AND METHODS: Pretreatment and follow-up enteroclysis radiographs from 15 adult patients with known celiac disease were reviewed. Diagnosis of celiac disease was made at adult age. Changes in small-bowel morphology were determined by comparing enteroclysis findings before and after treatment with a gluten-free diet and were correlated with histopathologic and clinical findings. RESULTS: Eight of 15 patients (group I) showed increased small-bowel abnormalities. All patients had increased symptoms, and all but one, whose condition had deteriorated, showed stable disease at biopsy. Group II patients (five of 15) showed improvement at follow-up enteroclysis. Biopsy findings showed improvement in small-bowel morphology in four patients and no change in one. Clinically, four patients showed improvement, and one had stable disease. Group III patients (two of 15) showed no change from initial to follow-up enteroclysis. Both showed partial atrophy, which was consistent with biopsy findings. In all patients, clinical symptoms correlated better with enteroclysis results (r = .48; P < .005) than they did with follow-up biopsy results (r = .18). True celiac disease-related malignancies and coexisting tumors occurred in 10 of 15 patients. CONCLUSION: Enteroclysis appears to be more reliable than does biopsy in evaluation of response to a gluten-free diet in adults with celiac disease.

Adult↗
PubMed2006

Gluten intolerance: sex and age-related features.

OBJECTIVE: Gluten intolerance is an immune-mediated enteropathy associated with gluten-containing foods in genetically susceptible patients. The typical form mainly affecting children shows failure to thrive and/or gastrointestinal symptoms. The adult form is less typical, presenting vague gastrointestinal symptoms, iron deficiency (with or without anemia) or nonspecific serum chemistry abnormalities. The present study aims to analyze clinical and biochemical differences of celiac disease (CD) according to sex and age. PATIENTS AND METHODS: The present study reviewed clinical and biochemical features of patients with suspected CD admitted to the Hospital General of Móstoles (Madrid, Spain) between July 2001 and June 2005. Two hundred fifty-two patients were analyzed, in whom intestinal biopsy was performed due to clinical and/or biochemical abnormalities suggestive of CD. One hundred seventy-eight asymptomatic relatives of the affected patients were also included. Overall, 125 patients showed diagnostic features of CD in the intestinal biopsy. RESULTS: The results confirmed higher prevalence of typical forms of CD in children (67% in children compared with only 14.3% in adults). CD seemed to be more frequent in adult women than in men (ratio of women to men 4:1), but it is worth noting that men diagnosed were most often referred with a typical clinical picture, so atypical forms of the disease in men may have been underdiagnosed. CONCLUSIONS: CD shows atypical features in adults, and physicians must include this disorder in the differential diagnosis of adults with iron deficiency or slight hypertransaminasemia. Increased awareness of the disease and extensive availability of accurate sero-logical tests will lead to improved diagnosis of this disorder, both in children and adults.

Adolescent↗
PubMed2006

Gluten-free diet impact on leptin levels in asymptomatic coeliac adolescents: one year of follow-up.

Coeliac disease, daily more frequently diagnosed in our population, involves many organs also in oligosymptomatic patients and with an adequate nutritional regime. Possible endocrine implications include failure to thrive, pubertal delay and reproduction diseases due to deregulation of GH, FSH and LH secretion. Leptin, an adipose tissue hormone, can be decreased as well and its deficiency could be related to growth and puberty anomalies. We studied 14 asymptomatic coeliac patients in peripubertal age (7.5-13.8 years) and tested their leptin levels in order to correlate them with endocrine and anthropometric data. Before the diet was started leptinaemia (M+/-DS) was: 4.94+/-5.53 ng/ml. In 10/14 patients (71%) leptinaemia was<or=2 DS for gender and age. In all the patients, after a period of 6-12 months of gluten-free diet, Leptin levels appreciably raised to 10.8+/-7.9 ng/ml, with a significant correlation to the time of the diet. Leptinaemia was actually lower in patients with a severe mucosal atrophy, and in these patients it increased more significantly after the diet was started. The removal of gluten itself may reduce immunological hit to adipose tissue and the 'malnutrition' of adipocytes: leptin can hence increase despite no significant increase of body mass index occurs. This study could partially explain the correlation between body mass index, Coeliac disease and the deregulation of puberty and fertility, mainly in patients who started the diet late. It could also explain the reversibility of this alteration if the cause is removed.

Adolescent↗