Wilfred M. Weinstein

Human cryptosporidiosis in immunocompetent and immunodeficient persons. Studies of an outbreak and experimental transmission.

Infection with cryptosporidium occurred in 12 immunocompetent persons who had direct contact with the feces of infected calves during three unrelated outbreaks of calf cryptosporidiosis. Nine of the twelve subjects had diarrhea and abdominal cramps that lasted 1 to 10 days. Infections were diagnosed and monitored by detection of oocysts in feces, with a modified Sheathers flotation technique and phase-contrast microscopy. Oocysts of cryptosporidium were isolated from calves but not from other animals with which these subjects had been in contact. Oocysts of cryptosporidium were also detected during repeated examinations of feces from two immunodeficient patients with persistent cryptosporidiosis. An apparently identical infection was transmitted to calves and mice, using oocysts from infected calves and human beings. Oocysts from an immunodeficient person also produced infections in kittens, puppies, and goats. This study shows that cryptosporidium may produce a moderate self-limited illness in immunocompetent persons, which contrasts sharply with the prolonged severe diarrhea in immunocompromised patients who contract cryptosporidiosis. Calves with diarrhea should be considered a potential source of human infection, and immunocompromised persons should avoid contact with such animals.

Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis

The recommended approach to the increased risk of colorectal carcinoma in ulcerative colitis has been colonoscopic surveillance rather than prophylactic colectomy. This strategy is based on the assumption that dysplastic lesions can be detected before invasive cancer has developed. We have analysed published reports on dysplasia surveillance to find out whether this assumption is valid. Ten prospective studies (1225 patients) satisfied our criteria. Of 40 patients with dysplasia-associated mass or lesion (DALM) detected, 17 (43%) already had cancer at immediate colectomy. The risks of cancer at immediate colectomy were 42% (10 of 24 patients) for high-grade and 19% (3 of 16) for low-grade dysplasia. Of 47 patients found to have high-grade dysplasia after the initial colonoscopy, 15 (32%) had cancer. 16-29% of patients with untreated low-grade dysplasia progressed to DALM, high-grade dysplasia, or cancer. Of patients with indefinite results, 28% progressed to high-grade dysplasia and 9% to cancer, so continued surveillance is essential. The risk of progression to dysplasia was only 2.4% for patients whose initial result was negative, so surveillance could perhaps be less frequent for these patients. Immediate colectomy is essential for all patients diagnosed with high-grade or low-grade dysplasia. A diagnosis of dysplasia does not preclude the presence of invasive cancer. We believe that patients should be informed about the limitations of colonoscopic surveillance so that they can take part rationally in decision-making about their management.

Small intestinal biopsy

Abstract A practical approach to the interpretation of peroral small intestinal biopsy specimens is presented. Biopsy technique and tissue handling are described. Interpretation of normal and abnormal biopsy specimens is discussed. A practical classification of abnormal small intestinal biopsies is presented and illustrated.

The Normal Human Esophageal Mucosa: A Histological Reappraisal

In 19 asymptomatic subjects, a total of 95 mucosal suction biopsies were taken from multiple sites in the distal 10 cm of esophagus. The biopsies were examined for evidence of basal cell hyperplasia and elongated dermal papillae, features considered to be histological consequences of gastroesophageal reflux. Fifty-seven per cent of the biopsies in the distal 2.5 cm of the esophagus and 19% of the biopsies above 2.5 cm exhibited these histological features.

Patchiness of mucosal inflammation in treated ulcerative colitis: A prospective study

Conventional wisdom dictates that ulcerative colitis affects contiguous areas of the colon and is most severe in the rectum, and that the finding of rectal sparing or patchy involvement should raise suspicions of Crohns disease. We and others have noted occasional rectal sparing and patchy involvement in patients with ulcerative colitis. Therefore, we prospectively studied the prevalence of patchiness, including rectal sparing, in treated cases of ulcerative colitis. Consecutive patients with longstanding ulcerative colitis were studied. The left colon was divided into three zones for scoring degree of activity, and biopsy specimens from each zone were graded for histologic activity by a blinded observer. Patchiness by endoscopy or histology was defined as (1) frank rectal sparing (normal appearance endoscopically; absence of inflammation of the lamina propria and crypts histologically); (2) areas of greater inflammation proximally than distally; or (3) discrete areas of patchiness endoscopically within any one zone. Of 39 patients evaluated, 17 (44%) had endoscopic evidence of patchiness, including 5 (13%) with rectal sparing. Thirteen (33%) had histologic evidence of patchiness, including 6 (15%) with rectal sparing. Both endoscopic and histologic patchiness were seen in 9 patients (23%). The patchy and nonpatchy groups did not differ in regard to the use of rectal therapy. In patients with treated ulcerative colitis, the finding of rectal sparing or patchiness should not necessarily indicate a change in the diagnosis to Crohns disease.

Esophagitis in scleroderma: Prevalence and risk factors

Of 53 patients with scleroderma (43 women and 10 men) evaluated by esophagoscopy and biopsy, 32 (60%) had erosive esophagitis. Symptoms of heartburn and dysphagia were significantly more frequent in the patients who had erosive esophagitis but often were present in those without this condition. Abnormal motility characterized by loss of peristalsis in the distal esophagus was present in all patients with erosive esophagitis, including the 5 who were asymptomatic. No patient with normal esophageal motility had erosive esophagitis at endoscopy. The patients with erosive esophagitis also had significantly diminished lower esophageal sphincter pressures and increased frequency and duration of gastroesophageal reflux episodes. Stricture was present in 13 of 32 patients with erosive esophagitis and was absent in the other 21 patients. The duration of disease, rate of gastric emptying, and fungal smear and culture were not significantly different in those with or without esophagitis. Treatment of fungal infection for a month had little beneficial effect. The pattern of esophageal motility in scleroderma identifies high and low risk groups for esophagitis and stricture, and can be used to select those who require further investigation, irrespective of symptoms.

Interaction of NSAIDs and Helicobacter pylori on gastrointestinal injury and prostaglandin production: a controlled double‐blind trial

Background: H. pylori and nonsteroidal anti‐inflammatory drugs (NSAIDs) are major causes of gastroduodenal injury in man. We assessed the effect of daily NSAID ingestion on gastric histology and the interaction of H. pylori infection and NSAID ingestion on gross and histological injury and prostaglandin production.

Barrett's esophagus in childhood

This study describes the clinical, radiologic, esophageal function test, endoscopic, and histologic findings of Barretts esophagus in 11 children aged 6-14 yr. All had long-standing symptoms of gastroesophageal reflux, which had begun in the first year of life in 10 of the 11. Eight of the 11 patients had mid or upper esophageal strictures and 10 of the 11 required fundoplication. Most patients had low lower esophageal sphincter pressures and abnormal pH probe studies. Only 6 of the 11 children had the characteristic pink-red appearance of the mucosa at endoscopy. Fifty endoscopic biopsy specimens taken at multiple levels in the esophagus contained columnar-lined epithelium above the gastroesophageal junction. Five of the patients had specialized (intestinal-type) epithelium as part of the histologic spectrum. The clinical expression of Barretts esophagus in children is similar to that in adults except that strictures appear to be more common in children, and the endoscopic appearance of the mucosa is not always typical in color. As in adults, gastroesophageal reflux appears to be the etiology. In children beyond infancy, Barretts esophagus is the most common indication for antireflux surgery at our institution. Biopsy specimens should be taken from multiple levels in the esophagus to avoid overdiagnosis and to establish the diagnosis with certainty.

Interobserver agreement and predictive value of endoscopic findings for H. pylori and gastritis in normal volunteers

BACKGROUND Endoscopic findings such as erythema are frequently labeled as gastritis. We sought to determine interobserver agreement for specific endoscopic features and assess the diagnostic value of features with good agreement for Helicobacter pylori and histologic gastritis. METHODS Fifty-two healthy subjects without ulcers, erosions, or hemorrhages had a full endoscopy recorded on video tape. Biopsy specimens were examined for H. pylori and gastritis. Two endoscopists independently reviewed the tapes for predefined features (erythema, area gastricae, clefts, and nodularity) in the gastric body and antrum. Diagnostic value of endoscopic features with acceptable agreement (kappa > 0.40) was then determined for H. pylori and gastritis. RESULTS Kappa was greater than 0.40 only for prominent body area gastricae (0.49), body nodularity (0.65), and antral nodularity (0.68). For antral nodularity, sensitivity was 32%, specificity was 96%, and positive predictive value was 90% for H. pylori. when both antral nodularity and body area gastricae were both present, sensitivity was only 18% but specificity and positive predictive value were 100%. CIRCULATION: Interobserver agreement is poor for some features such as erythema labeled as gastritis. Antral nodularity is a fairly reproducible finding and is very specific, though not sensitive, for H. pylori gastritis.

The histologic spectrum and clinical outcome of refractory and unclassified sprue

The vast majority of patients with celiac disease respond to a gluten-free diet; yet, a small number of refractory patients do not respond and have persistent malabsorption and residual mucosal abnormalities of the small intestine. The histologic features of refractory/unclassified sprue have been published as case reports, often without long-term follow up, and no clear histologic picture has emerged. We present the results of a long-term study of the clinical and histologic features of 10 patients with refractory/unclassified sprue. The histologic features of small bowel biopsies in this group of patients were compared with those of 10 patients with responsive celiac disease and with 10 patients without malabsorption who had normal duodenal biopsies. Five of the 10 refractory patients ultimately developed collagenous sprue as a distinct histologic marker of refractory disease. Additional distinctive findings found in small bowel biopsies in the refractory group were subcryptal chronic inflammation (10 of 10) and marked mucosal thinning in three patients. Other nonspecific findings included acute inflammation and gastric metaplasia. One patient with collagenous sprue developed a B-cell lymphoma of the ileum, and in general collagenous sprue was associated with a poor prognosis. Two of five patients died whereas two others require total parenteral nutrition for survival. Pathologists evaluating small bowel biopsies in the setting of malabsorption should be aware of the subtle histologic changes described here that may portend a refractory course.