Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection.

BACKGROUND: Long-term outcome of atrophic body gastritis has not yet been defined. AIM: To investigate at long-term follow-up the behaviour of atrophy and intestinal metaplasia and the occurrence of neoplastic lesions in atrophic body gastritis patients. METHODS: Overall 106 atrophic body gastritis patients with > or = 4-year follow-up were studied; 38 were Helicobacter pylori-positive at histology + serology and cured of infection (group A), 36 were positive at serology and not treated (group B) and 32 were H. pylori-negative (group C). Patients underwent gastroscopy with antral (n = 3) and body (n = 3) biopsies for histology according to the Sydney System. RESULTS: At 6.7-year follow-up body atrophy and intestinal metaplasia remained unchanged in all 106 patients irrespective of H. pylori status. Antral atrophy was significantly increased at follow-up only in group C, whereas antral intestinal metaplasia was unchanged in all three groups. During follow-up eight (8%) patients developed neoplastic lesions (one adenocarcinoma, one adenoma with low-grade dysplasia and six low-grade dysplasia without endoscopic lesions). Antral atrophic gastritis was present at baseline in all but one (88%) of the eight patients with neoplastic lesions, but only in 15 (15%) of the 98 patients without (P < 0.0001, RR = 26.7). CONCLUSIONS: Atrophy and intestinal metaplasia persist at 6.7-year follow-up and atrophic body gastritis patients with panatrophic gastritis are at increased risk of developing neoplastic lesions.

Azathioprine or methotrexate in the treatment of patients with steroid-dependent or steroid-resistant ulcerative colitis: results of an open-label study on efficacy and tolerability in inducing and maintaining remission.

BACKGROUND: The role of azathioprine and methotrexate in inducing and maintaining remission in patients with ulcerative colitis is still controversial. AIM: To evaluate the efficacy and tolerability of these two drugs in a series of patients with steroid-dependent or steroid-resistant active ulcerative colitis. METHODS: Forty-two patients were treated with a daily dose of azathioprine (2 mg/kg) and, if intolerant or not responding, with methotrexate (12.5 mg/week intramuscularly), and their efficacy was established by clinical, endoscopic and histological examinations at 6 months. Patients achieving clinical remission continued with treatment and were followed up. RESULTS: Of the 42 patients on azathioprine, 10 experienced early side-effects requiring withdrawal from treatment, 22 (69%) achieved complete remission, six (19%) achieved improvement and four (12%) obtained no substantial benefit. Methotrexate, administered to eight patients intolerant to and two patients resistant to azathioprine, induced complete remission in six patients (60%) and improvement in four (40%). During follow-up, a larger number of patients on azathioprine relapsed in comparison with patients on methotrexate [16/28 (57%) vs. 2/10 (20%), respectively; P < 0.05]. Only minor side-effects were observed on both treatments. CONCLUSIONS: Azathioprine is effective in patients with steroid-dependent or steroid-resistant ulcerative colitis. Methotrexate seems to be a good alternative in patients intolerant to or not responding to azathioprine.

Expression of nerve growth factor-like polypeptides and immunoreactivity related to the two types of neurotrophin receptors in earthworm tissues.

Nerve growth factor (NGF) belongs by sequence homology to the neurotrophins, a family of proteins binding the same p75 receptor and closely related members of the Trk family of receptor tyrosine kinases. Fundamental in the vertebrate nervous system, neurotrophin signals have also been suggested as essential for relatively complex nervous systems occurring in invertebrate species that live longer than Caenorhabditis elegans and Drosophila melanogaster. Mammalian neurotrophins have been found to influence invertebrate neuronal growth. However, there are only a few data on the presence of molecules related to neurotrophin signalling components in invertebrates. Our studies provide evidence that analogues of neurotrophins and neurotrophin receptors are expressed in Eisenia foetida earthworms. In particular, NGF-like and Trk-like immunoreactive proteins are both expressed in the nervous system, whereas p75-like positivity identifies tubular structures associated with dorsal pores that are involved in the earthworm response to mechanical irritation or stress.

Efficacy of gluten-free diet alone on recovery from iron deficiency anemia in adult celiac patients.

OBJECTIVE: Iron deficiency anemia has been reported as the most frequent extraintestinal symptom in adult celiac disease. Prospective studies on the effect of gluten-free diet on recovery from iron deficiency anemia are lacking. The aim of this study was to verify in adult patients with celiac disease the efficacy of and the time course of recovery from iron deficiency anemia by a gluten-free diet alone. METHODS: We studied 190 consecutive adult patients with iron deficiency anemia, screened for celiac disease by duodenal biopsies. New diagnosed celiac patients were invited to follow a gluten-free diet alone without iron supplementation. After 6 months of diet, duodenal biopsies were performed and hematological tests were repeated at 6, 12, and 24 months. RESULTS: Celiac disease was diagnosed in 26 (24 women, 2 men; 13.7%) adult patients. After 6 months of gluten-free diet 14 of 18 (77.8%) female patients recovered from anemia, but only 5 of 18 (27.8%) reversed from iron deficiency. At 12-month control all but one patient (94.4%) recovered from anemia and 9 patients (50%) from iron deficiency. After 24 months of diet, only the patient who did not recover from anemia at 12-month control was still anemic, whereas 10 patients (55.5%) reversed from iron deficiency. A significant inverse correlation (r = -0.7141, p = 0.0003) between increase of Hb concentrations and decrease of individual histological scores of duodenitis was observed. CONCLUSIONS: A screening for celiac disease should be carried out in adult patients with iron deficiency anemia. Recovery from anemia occurs between 6 and 12 months on a gluten-free diet alone as a consequence of normalization of histological alterations of the intestinal mucosa.

Does pretreatment with omeprazole decrease the chance of eradication of Helicobacter pylori in peptic ulcer patients?

OBJECTIVE: It has been reported that pretreatment with omeprazole could decrease the efficacy of Helicobacter pylori eradication. Our aim was to compare the efficacy, safety, and tolerability of the eradicating regimen, omeprazole/amoxicillin/metronidazole. The two antibiotics were scheduled either during the first or during the last 2 wk of omeprazole administration. METHODS: In this prospective controlled study conducted in a single center, 78 symptomatic peptic ulcer patients were treated for 4 wk with omeprazole 40 mg o.m.; the patients were randomly assigned to receive amoxicillin 1 g t.i.d. postprandially and metronidazole 250 mg t.i.d. postprandially, either during the first 2 wk (group A, n = 40) or the last 2 wk of therapy with omeprazole (group B, n = 38). H. pylori status was assessed by culture, histology, urease test, and IgG antibodies. Each patient's course was followed for 1 yr. RESULTS: H. pylori infection was cured in 97.4% of group A (95% CI: 0.84-0.99) and in 89% of group B (95% CI: 0.73-0.96, p = 0.28). Healing was achieved in 80% of the patients in group A (95% CI: 0.63-0.90) and in 75.7% of patients in group B (95% CI: 0.60-0.90, p = 0.60) At 12-month follow-up, 72 patients were evaluated: 37/38 (97%) of patients in group A and 33/33 (100%) in group B were confirmed as cured of the infection (NS). Peptic ulcer healing rate reached 100% in the two groups. Furthermore, between the two groups, there were no significant differences in symptom relief or improvement. Both regimens were well tolerated, and no patient had to be withdrawn from therapy because of an adverse event. Minor side-effects appeared to be similar in the two groups (40% vs. 38%). CONCLUSIONS: This randomized study clearly indicates that omeprazole pretreatment does not significantly reduce the efficacy of eradicating therapy for H. pylori in peptic ulcer patients.

Case report: reversal of decreased bone mass by antibiotic treatment in a patient with Whipple's disease.

Whipple's disease is a rare systemic illness, with the main clinical feature being severe malabsorption syndrome. Bone involvement in the disease has rarely been described in previous articles. The authors report a case in which an extensive skeletal evaluation was carried out. Even though osteomalacia is generally considered the most typical metabolic bone disease of malabsorption syndromes, bone biopsy demonstrated that osteoporosis was the prominent histologic feature in this patient. On the basis of serial bone mineral density measurements, antibiotic treatment was able to reverse the initial reduced bone mass.

Salivary-specific immunoglobulin G in the diagnosis of Helicobacter pylori infection in dyspeptic patients.

OBJECTIVES: Helicobacter pylori infection is arguably the most common chronic bacterial infection in humans. The high prevalence and the association with peptic ulceration and gastric cancer indicate that simple, noninvasive methods for diagnosis of the infection are needed. In this study, the accuracy of salivary diagnosis for H. pylori infection was assessed. METHODS: Saliva and serum samples of 152 dyspeptic patients were tested for H. pylori IgG and IgA by an in-house ELISA. All patients underwent gastroscopy with biopsy. RESULTS: One hundred thirty-one patients (86%) were found to be H. pylori positive on histology. Duodenal ulcer was found in 67 patients; 85 had no macroscopic lesion. Salivary and serum H. pylori IgG as well as serum H. pylori IgA titers were significantly higher in H. pylori-positive than in H. pylori-negative patients. The sensitivity and specificity of salivary H. pylori IgG were 82% and 71%, respectively; the positive and negative predictive values were 95% and 40%, respectively; and the accuracy 81%. The corresponding figures for serum H. pylori IgG were 97% and 91%; 98% and 83%; and 96%. Those for serum H. pylori IgA were 80% and 52%; 91% and 30%; and 76%. The sensitivity of salivary H. pylori IgG in detecting duodenal ulcer was 83% (56/67) that of serum H. pylori IgG was 97% (65/67) (odds ratio = 0.15; confidence interval = 0.02-0.8; p = 0.02). CONCLUSIONS: Salivary H. pylori IgG was a fairly sensitive and accurate indicator of gastric H. pylori colonization, with a high positive predictive value in our population. Data, however, suggest that salivary H. pylori IgG measurements do not compare favorably with serology.

Zollinger-Ellison syndrome and antral G-cell hyperfunction in patients with resistant duodenal ulcer disease.

We measured basal and pentagastrin-stimulated acid secretion, as well as basal and meal-stimulated plasma gastrin concentration to determine, in 67 patients affected by resistant duodenal ulcer, whether their condition could be related to gastric acid secretion and/or gastrin-related syndromes. We then compared them to 46 duodenal ulcer control patients. The outpatients were investigated consecutively. The resistant duodenal ulcer patients differed from the controls only in their higher complication rates (bleeding or perforation, P < 0.05). We identified five patients in the resistant duodenal ulcer group with Zollinger-Ellison syndrome and 12 with antral G cell hyperfunction, whereas in the control group only one patient was affected by antral G cell hyperfunction. IgG anti-Helicobacter pylori antibodies were positive for the presence of infection in 7 of the hypergastrinaemic patients. When Zollinger-Ellison syndrome or antral G cell hyperfunction were excluded, no differences could be found in gastric acid secretion, or basal and meal-stimulated plasma gastrin levels, between the resistant and control duodenal ulcer patients, except for basal acid hypersecretion (resistant duodenal ulcer 16% vs duodenal ulcer 2% P = 0.0144). In the presence of duodenal ulcer disease resistant to H2-blockers, it is mandatory to measure basal plasma gastrin concentration since it was possible to diagnose the gastrin-related syndromes, Zollinger-Ellison syndrome and antral G cell hyperfunction, in 26% of this group of patients.

Mixed type sweat gland adenoma: a case report.

We describe a case of a young woman with inguinal sweat-gland adenoma, that had histological characteristics of both hidradenoma papilliferum and clear-cell hidradenoma. The neoplastic risk potential for the 2 conditions is discussed.

Abnormalities of colonic mucin secretion and metabolic changes after internal urinary diversion for bladder exstrophy. A prospective study.

Ten patients with different types of internal urinary diversion for bladder exstrophy were studied prospectively in order to assess metabolic abnormalities and morphological, histochemical and lectin binding changes in the colorectal mucosa. The histochemical and/or lectin binding changes which were found in the majority of patients were identical to those observed in premalignant and malignant conditions of the colon. In some cases they were detectable 3 years after the initial examination but were completely absent from the colorectal mucosa of normal subjects. Metabolic disturbances (metabolic acidosis, increased anion gap, hyperchloraemia) were observed in a substantial number of asymptomatic patients. These findings stress the need for regular endoscopic, histological and metabolic follow-up in these patients and for life-long treatment with bicarbonate or citrate.

Phenotypes and spontaneous immunoglobulin production in mononuclear cells suspensions isolated from colonic biopsies of patients with mild active and quiescent ulcerative colitis.

Lamina propria mononuclear cells can be isolated from mucosal specimens of human colon. In the present study, we have explored whether both the phenotypes and functional properties can be studied in lamina propria mononuclear cell suspensions isolated from the same set of endoscopic biopsies in patients with ulcerative colitis. The counts of CD11b+ lamina propria mononuclear cells in mild active ulcerative colitis were significantly higher than those of both quiescent ulcerative colitis and controls. Similarly, the CD16+ and the CD19+ lamina propria mononuclear cells were significantly increased in mild ulcerative colitis patients in comparison to both quiescent ulcerative colitis and control lamina propria mononuclear cells. Lamina propria mononuclear cells from all the biopsy samples appeared to produce detectable amounts of immunoglobulins of the three classes. The production of IgG in mild ulcerative colitis cultures was significantly higher than that observed in quiescent ulcerative colitis and controls. In contrast, the production of IgA in active ulcerative colitis lamina propria mononuclear cell cultures appeared to be significantly lower than that of both quiescent ulcerative colitis and controls. This study shows that morphology, phenotypes, and functional properties can be assessed in lamina propria mononuclear cell suspensions obtained from the same set of endoscopic biopsy samples. We have also shown that changes in phenotypes and functional status of lamina propria mononuclear cells occurred in mild active ulcerative colitis while no significant abnormality of these parameters was found in quiescent ulcerative colitis. This indicates that a normalization of mucosal immune functions occurs in ulcerative colitis patients when complete clinical and histological remission is achieved.

Clinical and laboratory indicators of extent of ulcerative colitis. Serum C-reactive protein helps the most.

We estimated the extent of the inflammatory mucosal lesion by colonoscopy and biopsy in 60 patients with their first attack of ulcerative colitis. Proctitis was found in 12, proctosigmoiditis in 19, left-sided colitis in 10, and extensive colitis in 19. Fourteen clinical variables and laboratory measurements (bowel frequency, stool consistency, rectal bleeding, fecal mucus/pus, temperature, pulse rate, white blood cell count, hematocrit, sedimentation rate, serum iron, serum albumin, serum alpha 2-globulin, serum C-reactive protein, and seromucoids) were determined. All the variables except rectal bleeding and hematocrit were correlated (p less than 0.001) with the extent of colitis. On stepwise discriminant analysis, only C-reactive protein distinguished proctosigmoiditis from more improved the discrimination. Cross-validation by the "jack-knife method" showed that 86.7% of patients were correctly classified, the errors consisting in underestimation of disease in 8/29 patients with extensive colitis.

Campylobacter-like organisms on the human gastric mucosa. Relation to type and extent of gastritis in different clinical groups.

Three hundred and thirty-four pyloric type and 244 fundic type gastric mucosal specimens from 135 patients undergoing upper gastrointestinal endoscopy were checked for Campylobacter-like organisms (CLO) by the Warthin-Starry method. CLOs were found in 77/135 (57 p. 100) patients and in 235/578 (41 p. 100) biopsy specimens. There was no significant difference in the prevalence of CLO-positive specimens in the two types of gastric mucosa. The prevalence of CLO-positive specimens was higher in patients with duodenal ulcer than in the other patients (p less than 0.01). In the whole group, 42 p. 100 of the specimens with gastritis showed CLOs. Neither the type nor the activity of gastritis seemed to be relevant. Twenty-two per cent of the pyloric type and 36 p. 100 of the fundic type specimens classed as normal were positive for CLOs. In the normal fundic type mucosa, CLO-positive specimens were more frequent (p less than 0.01) in those patients with CLO-positive specimens from the antral area than in those without CLOs in the antrum. In 41 patients with multiple specimens from either the duodenal bulb and the stomach, chronic non specific duodenitis appeared to be more frequent in patients with CLO-positive antral specimens. The present study provided data on the frequency of gastric CLOs in a mediterranean population and confirmed that an association between CLOs and antral gastritis exists in patients with duodenal ulceration. However, data of the present investigation indicate that no relation between CLOs and the type and activity of gastritis exists and that CLOs are frequently found in the histologically normal mucosa, particularly in the body-gland area.

Abnormal patterns of colorectal mucin secretion after urinary diversion of different types: histochemical and lectin binding studies.

Clinical and experimental evidence indicates that ureterosigmoidostomy is associated with a high risk for the development of colonic cancer, while there is no reported evidence of increased risk in patients who undergo urinary diversion of other types. In the present study the histochemical and lectin binding characteristics of goblet cell mucin were investigated in biopsy specimens from patients who had undergone ureterosigmoidostomy and from patients who had undergone rectal bladder surgery. Specimens from transitional mucosa surrounding colonic cancers and from normal rectal mucosa were also studied. For histochemical studies the high iron diamine-Alcian blue method was used. FITC-conjugated Dolichus biflorus agglutinin (FITC-DBA) and Arachis hypogaea agglutinin (FITC-PNA) were used for the study of lectin binding characteristics. In contrast to the striking increase in numbers of sialomucin-containing goblet cells found in the patients who had undergone ureterosigmoidostomy, the mucin proved to be histochemically normal in the rectal bladder surgery group. Abnormal lectin binding patterns were observed in colorectal mucosa after urinary diversion of both types, with the abnormalities consisting of dramatic decreases in FITC-DBA labeling (compared with controls) and the appearance of substantial numbers of FITC-PNA-labeled goblet cells. These findings indicate that the pattern of mucin secretion is definitely abnormal in patients who have undergone urinary diversion. Whether this abnormality is an indicator of premalignant changes remains to be established. These data, however, confirm that endoscopic and histologic follow-up studies may be of value in assessing the risk for the development of cancer in these patients.

Melanosis of the rectum in patients with chronic constipation.

In patients with constipation the prevalence of melanosis in rectal biopsies was evaluated in an attempt to correlate its occurrence with laxative consumption and intestinal stasis. Melanosis was present in 58 percent of the patients and in none of a control group. Melanosis was present in 73.4 percent of patients consuming anthracene laxatives and in 26.6 percent of those not consuming anthracene laxatives (P less than 0.01). No correlation was found between the occurrence (and grading) of melanosis and pattern of transit through the large bowel, bowel movements, and duration of symptoms. Results of this study seem to indicate that intestinal stasis is not a cause of melanosis of the colon and rectum and confirm that melanosis may well be due only to the consumption of anthracene laxatives; melanosis coli does not appear to be a sensitive marker of impairment of motor function in the "cathartic colon."

Abnormal patterns of colonic mucin secretion after ureterosigmoidostomy.

Colonic epithelial mucin was investigated histochemically in biopsy specimens from a group of patients who had undergone ureterosigmoidostomy. For comparison, colonic biopsy samples from uninvolved mucosa adjacent to carcinomas from another group of patients and from a group of patients undergoing sigmoidoscopy for hemorrhoids were also studied. The high-iron diamine-alcian blue (HID-AB; pH 2.5) method was used, and the proportions of HID-positive and AB-positive cells were assessed semiquantitatively. In both ureterosigmoidostomy and cancer groups, highly significant increases in the proportions of AB-positive cells (sialomucins) were observed, particularly in the middle and lower segments of the crypts. Ureterosigmoidostomy introduces a high risk for the development of colonic carcinoma. Morphologic features that could account for such a high risk were investigated, and an abnormal pattern of colonic mucin secretion after ureterosigmoidostomy was demonstrated. Although this abnormality cannot be related specifically to ureterosigmoidostomy, data from the present investigation suggest that histochemical studies of colonic specimens from patients who have undergone ureterosigmoidostomy may provide a useful tool for follow-up studies.

Frequency and extent of bulbar duodenitis in duodenal ulcer, endoscopic and histological study.

The present prospective investigation was aimed at ascertaining the true incidence of duodenitis in the presence of duodenal ulcer, and the extent of bulbar involvement. In 54 consecutive patients 3 biopsy specimens were collected from preestablished sites during endoscopy. Endoscopic findings were defined as the presence or absence of definite inflammation. Biopsy specimens were evaluated blind, and the degree of duodenitis was classified from 0 to 3 in accordance with the criteria proposed by Whitehead; grade 1 was further classified into 1a (within the range of normal mucosa) and 1b (mild duodenitis). Only grades 1b, 2 and 3 were regarded as duodenitis. Reliable histologic evaluation of all 3 biopsies was possible in only 36 out of the 54 patients. Results show that endoscopic and histologic findings are in agreement in 82% of the patients, but endoscopic judgement of inflammation was false in 17 out of 54 (35%) observations of histologically normal mucosa. Histological duodenitis is more frequent and more severe close to the ulcer than in the mid-bulbar area, and the mucosa of the mid-bulbar area appears to be significantly more affected by the inflammatory process than the apex. Duodenitis is present predominantly in the areas of the duodenal bulb in which ulcers usually develop, and therefore it might not be merely a phenomenon induced by the presence of the ulcer.