Increased jejunal intraepithelial lymphocytes bearing gamma/delta T-cell receptor in dermatitis herpetiformis.

T-cell receptor 1 (gamma/delta) expression was studied in 19 jejunal or duodenal specimens from patients with dermatitis herpetiformis and in 16 jejunal or duodenal specimens showing normal histology. In normal specimens, gamma/delta+ cells represented 10.8% of intraepithelial CD3+ lymphocytes. Around 50% of these cells were recognized by the A13 monoclonal antibody, which detects products of the V gamma 1/V delta 1 gene rearrangement and the non-disulfide-linked form of T-cell receptor 1. The remaining 50% reacted with the BB3 monoclonal antibody, which recognizes products of the V gamma 9/V delta 2 rearrangement and the disulfide-linked form of receptor. Very few gamma/delta+ cells were observed in the lamina propria. In jejunal specimens from patients with dermatitis herpetiformis, a significant increase in the prevalence of gamma/delta+ intraepithelial lymphocytes was observed (P less than 0.001). This finding was largely accounted for by an increase in those cells recognized by the A13 monoclonal antibody, thus possibly expressing the V gamma 1/V delta 1 rearrangement and the nondisulfide-linked form of receptor. These data suggest that similar pathogenetic mechanisms may be active in determining the jejunal damage in celiac disease and dermatitis herpetiformis.

Gastric histology and function tests in Italian patients with dermatitis herpetiformis.

Gastric mucosal histology and function were evaluated in 57 Italian subjects with dermatitis herpetiformis (DH), by means of multiple endoscopic biopsies, gastrin and pepsinogen I (Pg I) serum levels, and parietal cell antibodies (PCA). One hundred and forty-nine patients with nonulcer dyspepsia served as reference population for the prevalence of atrophic gastritis of the body. Seventeen DH patients (30%) and 23 controls (15.4%) showed atrophic gastritis of the body mucosa (p less than 0.05). Nine of the DH patients with atrophic gastritis of the body also had atrophic changes in the antrum. Six patients, all with severe atrophic gastritis, had high gastrin levels and PCA; five of these six also had low Pg I levels. We found an increased prevalence of abnormal indirect function tests among patients with atrophic gastritis is due to the younger age of the patients in our series. Thus, atrophic gastritis can be detected early on a histologic basis, but functional impairment occurs later, as the mucosal damage increases in severity.

Evidence of altered structural and secretory glycoconjugates in the jejunal mucosa of patients with gluten sensitive enteropathy and subtotal villous atrophy.

The pattern of lectin histochemistry in formalin fixed, paraffin embedded normal jejunal and subtotal villous atrophy specimens from patients with gluten sensitive enteropathy were compared. There was no significant difference in the binding pattern of five lectins (Arachis hypogaea, Canavalia ensiformis, Lens culinaris, Phaseolus vulgaris and Triticum vulgaris) between normal and abnormal specimens. There were significant changes in the binding pattern of three lectins (Dolichos biflorus, Ulex europaeus, Ricinus communis), with special reference to goblet cells staining. These changes were present in all the specimens studied, regardless of the clinical diagnosis of dermatitis herpetiformis or coeliac disease. Dolichos biflorus reactive goblet cells were significantly decreased (p less than 0.001) in abnormal tissue and confined to the luminal edge of the mucosa. Strong reactivity of goblet cells in abnormal tissue was recorded with Ricinus communis and Ulex europaeus, lectins that bind to few or no goblet cells in normal tissue. These findings show that modifications of structural and secretory glycoconjugates occur in the jejunal mucosa of patients with gluten sensitive enteropathy.

Pancreatic enzyme replacement therapy in post-pancreatectomy patients.

The occurrence of malnutrition and maldigestion was studied in nine patients who underwent pancreatoduodenectomy and sclerosis of the residual pancreatic stump with neoprene. The operation causes a complete loss of exocrine pancreatic function, but spares islet cell function. Upon discharge from the hospital, patients received pancreatin powder as a dietary enzyme supplement (18,000 lipase U/meal). Patients were again hospitalized 2 y after surgery for evaluation of nutritional status and digestive function (hospital checkup). Nutritional status was evaluated by measuring serum albumin, total iron binding capacity, and total lymphocytes. Digestive function was assessed by the D-xylose tolerance test and determination of fecal fat excretion. Patients were then discharged with pancrelipase enteric-coated microspheres (ECM) as a dietary enzyme supplement (16,050 lipase U/meal). Malnutrition, defined as the occurrence of at least two abnormal nutritional parameters, was observed in three patients at the time of the hospital checkup. Upon reevaluation of nutritional status after 6 mo on pancrelipase ECM, all patients were well nourished. The mean body weight, which had been 52.8 Kg immediately after surgery, increased to 54.9 Kg at the time of the hospital checkup (p less than 0.01) and to 58.0 Kg after six months of pancrelipase ECM therapy (p less than 0.05). At the hospital checkup, the D-xylose test was normal in all patients and steatorrhea had decreased from a mean of 32.8 g/d without enzyme supplementation to 16.7 g/d with pancrelipase therapy (16,050 lipase U/meal). The complete loss of exocrine pancreatic function following surgery was well tolerated. In fact, when patients were on pancrelipase therapy, much of the original body weight was recovered and the biochemical indices of malnutrition were normalized.

Correction of malnutrition and maldigestion with enzyme supplementation in patients with surgical suppression of exocrine pancreatic function.

We studied the occurrence and extent of malnutrition and maldigestion in 13 patients who underwent pancreatoduodenectomy (PD) and injection of Neoprene (polychloroprene) (NI) into the duct of Wirsung, which results in sclerosis of hte acinar pancreatic tissue, but spares the endocrine function. At discharge, patients under took an enzyme supplementation regimen with pancreatin (18, 00 United States Pharmacopoeia units of lipase per meal). Patients were rehospitalized 24.9 months after PD plus NI to undergo nutritional and metabolic evaluation (hospital control). Nutritional status was evaluated by measuring the serum albumin level, total iron binding capacity and total lymphocyte count. Digestive function was assessed by the D-xylose tolerance test and determination of fecal fat excretion. Patients were then discharged with pancrelipase, enteric-coated microspheres (ECM) supplementation (16,050 United States Pharmacopoeia units of lipase per meal). Malnutrition, defined as the occurrence of at least two abnormal nutritional parameters, was observed in six patients at hospital control. After six months on pancrelipase ECM, the nutritional status was re-evaluated in nine patients (three previously malnourished) who were all well nourished. The mean body weight was 84.7 per cent of usual body weight at discharge after PD plus NI and raised to 88.0 per cent at the hospital control (p less than 0.01) and to 93.7 per cent )p less than 0.05) after six months on pancrelipase ECM. At hospital control, results from the D-xylose test were normal in all patients, and steatorrhea dropped from 33.6 grams per day without enzyme supplementation to 15.3 grams per day with pancrelipase ECM (16,050 United States Pharmacopoeia units of lipase per meal). Steatorrhea was incompletely but satisfactorily corrected by pancrelipase ECM. On supplementation therapy with pancrelipase ECM, patients recover a good deal of the body weight and normalize the biochemical indices of malnutrition.

Eradication of esophageal varices by endoscopic sclerotherapy: how much is enough?

To clarify if complete eradication of varices from the lower esophagus by endoscopic sclerotherapy is really essential to prevent rebleeding, or if reduction of varices below a certain size can be considered a sufficient result, we compared the fate of 72 patients in whom sclerotherapy was stopped after one of the following endoscopic endpoints was reached: complete eradication (15 patients, group 1), partial eradication with residual small white varices (32 patients, group 2), and partial eradication with residual small blue varices (25 patients, group 3). The incidence of variceal recurrences and recurrent bleeding over a median follow-up of 17 months after stopping sclerotherapy did not differ significantly in the three groups. Analysis of the time course of variceal recurrences showed that the recurrence-free interval was almost identical in group 1 and group 2 patients (13 and 14 months, respectively). Group 3 patients had a shorter recurrence-free interval (8.3 months), but the difference was not statistically significant. We conclude that sclerotherapy can be stopped safely when either complete eradication or reduction of varices to small white columns is obtained.

Activation of coagulation in cirrhotics after endoscopic variceal schlerotherapy.

To investigate the occurrence and extent of activation of coagulation after endoscopic variceal sclerotherapy (EVS), we performed serial measurements of conventional coagulation tests [prothrombin time (PT), partial thromboplastin time (PTT), platelets, and fibrinogen], and of plasma fibrinopeptide A (FPA) in 39 cirrhotic patients undergoing 55 sessions of elective EVS. Thrombin (20 U/ml) and sodium morrhuate 5% were used in sequence as sclerosants on 34 occasions. In the remaining 21 sessions, sodium morrhuate 5% alone was used. Conventional coagulation tests did not change significantly after EVS, regardless of the type of treatment. Basal plasma FPA levels were abnormally high in about 50% of patients. After EVS, plasma FPA increased sharply in 37/39 patients (95%), returning to baseline values in most of them within 24 h. We conclude that transient systemic activation of blood coagulation occurs after EVS. Such activation can be detected only by sensitive methods such as FPA assay, and has no effect on conventional coagulation tests. This, and the absence of any clinical EVS-related coagulation disorder in our patients, suggests that activation of coagulation should not be a major concern for patients undergoing EVS.

Prevalence of duodenal and jejunal lesions in dermatitis herpetiformis.

Sixty-eight patients with dermatitis herpetiformis underwent jejunal suction biopsies and/or multiple endoscopic duodenal biopsies to evaluate the incidence of small bowel mucosal atrophy and to compare the diagnostic yield of the two methods. Small bowel function tests were also performed to evaluate the extent of functional impairment. Small bowel lesions were observed in 89.4% of jejunal suction biopsies and in 100% of endoscopic duodenal biopsies. Of the 10 patients who underwent both procedures, one had lesions only in the duodenum, one had more severe lesions in the duodenum than in the jejunum, while the remaining 8 patients showed identical lesions at both sites. The 1-h blood d-xylose test after a dose of 5 g proved more sensitive than xylosuria or serum folic acid assay in detecting subclinical malabsorption. Finally, histological features of gluten-sensitive enteropathy can be found in nearly 100% of patients with dermatitis herpetiformis. Upper gastrointestinal endoscopy with duodenal biopsies is at least as sensitive as jejunal suction biopsy in assessing small bowel involvement in dermatitis herpetiformis.

Evaluation of structural and secretory glycoconjugates in normal human jejunum by means of lectin histochemistry.

The labelling pattern of eight lectins was studied in jejunal samples from ten normal subjects, in order to define the normal distribution of structural and secretory glycoconjugates in the small bowel. The following lectins were studied by means of a peroxidase technique on formalin-fixed samples: Arachis hypogaea, Ricinus communis, Canavalia ensiformis, Lens culinaris, Phaseolus vulgaris, Triticum vulgaris, Ulex europaeus, Dolichos biflorus. Phaseolus vulgaris reacted with goblet cell mucus throughout the villus-crypt axis. Conversely Ulex europaeus, Dolichos biflorus and Triticum vulgaris lectin labelling of goblet cells appeared to be confined to the upper part of the villi. This finding suggests that during cell migration from crypt to villus tip, the continuing maturation of goblet cells is associated with the differentiation of secretory carbohydrates, which probably parallels the cell maturation cycle. Lectin histochemistry appears to be a reliable tool for the study of structural and secretory glycoconjugates in the jejunal mucosa, and might be of value in the study of diseases in which the cell-maturation cycle in the small bowel is altered.

Nutritional status, function of the small intestine and jejunal morphology after total gastrectomy for carcinoma of the stomach.

We studied the nutritional status and the prevalence of malabsorption in 12 patients one to three years after total gastrectomy (TG) for gastric neoplasm. The Roux-en Y technique was used for reconstruction. A correct dietary regimen according to the recommended daily allowance was suggested and patients were seen quarterly on an out patient basis. The nutritional status was evaluated by measuring serum albumin levels, total iron binding capacity, cholinesterase, area muscular circumference, triceps skinfold and delayed hypersensitivity response. Work-up studies for the small intestine included: stool fat, D-xylose and glucose tolerance tests, Schilling test (phase II and III), serum iron levels, serum vitamin B12 levels and biopsy of the jejunum. Malnutrition, defined as the occurrence of two or more abnormal nutritional parameters, was observed in one patient; glucose and D-xylose tolerance tests were normal in all. A mild degree of steatorrhea was observed in four patients. The second phase of the Schilling test was abnormal in eight patients, but urinary excretion of vitamin B12 increased in three of four patients after use of antibiotics. Low serum vitamin B12 levels were common after the twentieth postoperative month. Serum iron levels were initially low and returned to normal six months after TG. All patients had normal jejunal histologic findings. These data indicate that malnutrition after TG is not common if an adequate dietary intake is maintained. Malabsorption, possibly due to bacterial overgrowth, is not a major clinical problem.

In situ identification of immune competent cells in gastrointestinal mucosa: an evaluation by immunoelectronmicroscopy.

The in situ identification of lymphocyte subpopulations by means of immunopathological techniques using specific monoclonal antibodies provides a tool for the study of the gastrointestinal-associated lymphoid tissue (GALT) in health and disease. In this field, monoclonal antibodies have been applied previously using light microscopy and either immunofluorescence or immunoperoxidase; however, these techniques are not sensitive enough to allow precise evaluation of localization of labelling. We describe an immunoelectronmicroscopic method, which defines labelling specificity, since it allows the identification of cells by immunophenotype labelling and ultrastructural markers simultaneously. This in turn allows a better evaluation of the labelled cells and of the relationship between labelled and unlabelled cells. The main features of the method are the use of fresh tissue samples, fixing in paraformaldehyde CaCl2, and the coupling of the immune reaction to an amplification system (avidin-biotin-peroxidase complex). The technique yields a good preservation of cellular ultrastructure, together with a strong and specific immunolabelling. Our results confirm the high specificity of monoclonal antibodies when applied to immunopathology techniques. We confirm the pattern of distribution of various lymphocyte subsets in the jejunal mucosa described by other authors by light microscopy.

Antibodies to gliadin in adult coeliac disease and dermatitis herpetiformis.

Antibodies to gliadin, searched for by indirect immunofluorescence and a micro-ELISA, were detected in 16 (64%) of 25 sera from patients with adult coeliac disease and in 13 (45%) of 29 with dermatitis herpetiformis. Although the sensitivity of the two tests was relatively low in the whole groups, it increased when only cases with severe jejunum abnormalities were considered (93% for coeliac disease and 81% for dermatitis herpetiformis). A significant correlation was found between antigliadin antibodies and the severity of jejunum damage in both diseases. Moreover, most coeliac and dermatitis herpetiformis patients with antigliadin antibodies were on normal diet. The specificity of the tests was 100% for the immunofluorescence and fairly good for the micro-ELISA, as only 5 (11%) of the 46 disease control patients (Crohn's disease, ulcerative colitis) were positive for antigliadin antibodies. R1-reticulin antibody test was equally specific but less sensitive in both groups. We conclude that antigliadin antibodies are useful in the diagnosis of patients with active adult coeliac disease and dermatitis herpetiformis with gluten-sensitive enteropathy. Moreover, the two tests make it possible to monitor the compliance to gluten-free diet in both diseases.

Small-bowel involvement in dermatitis herpetiformis and in linear-IgA bullous dermatosis.

In 23 patients with dermatitis herpetiformis (DH) and five patients with linear-IgA bullous dermatosis (BD), we evaluated the occurrence of histologic jejunal changes and small-bowel function abnormalities. None of the patients showed clinical signs or symptoms of malabsorption. Morphological jejunal changes consistent with gluten-sensitive enteropathy were found in 82% of DH patients and in 60% of BD patients. However, BD patients showed only mild jejunal histologic abnormalities, whereas more severe jejunal lesions were found in most patients with DH. Functional tests showed a rough correlation with the severity of the jejunal lesions, being almost completely normal in BD patients and DH patients with mild intestinal damage, whereas most of DH patients with subtotal or total villous atrophy showed abnormal d-xylose tests and folic acid assays. Lactose tolerance tests (H2 breath test and blood glucose after oral lactose load) showed no correlation with the degree of jejunal damage.