Brief report: non-corticosteroid-associated osteonecrosis of the femoral heads in two patients with inflammatory bowel disease.
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Publications and source records attributed to H J Freeman.
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Lymphocytic gastritis is a recently described lesion which occurs in a significant proportion of patients with celiac sprue. This paper describes two patients with lymphocytic gastritis and no evidence of celiac sprue. Both patients had markedly enlarged gastric folds and serum hypoproteinemia, which were clinically suggestive of Ménétrier's disease. These cases indicate that lymphocytic gastritis may cause a protein-losing gastropathy and should be considered in the differential diagnosis of Ménétrier's disease.
We conducted a double-blind, randomized, parallel group study in 169 patients with acute duodenal ulcers to compare omeprazole, 20 mg daily, with cimetidine, 600 mg twice daily. After 2 wk, 58% of the omeprazole-treated patients and 46% of the cimetidine-treated patients were completely healed (p = 0.056). After 4 and 6 wk 84% and 88% healed with omeprazole, and 80% and 89% healed with cimetidine (p = NS). After 2 wk, pain was completely gone in 62% of the omeprazole-treated patients versus 46% of the cimetidine-treated patients (p = 0.04). Clinical or laboratory adverse events were reported in 6 (7%) of the omeprazole-treated patients and 11 (13%) of the cimetidine-treated patients (p = NS). An adverse event caused withdrawal of 1 patient on omeprazole (anxiety and depression) and 2 patients on cimetidine (diarrhea and fall in hemoglobin). We conclude that omeprazole (20 mg daily) resulted in a trend toward more rapid ulcer healing compared with a relatively high dose of cimetidine (600 mg b.i.d.), and was preferred by patients for relief of ulcer pain.
Current and widely used methods for the isolation and purification of brush-border membranes involve the aggregation of non-brush-border membranes with the divalent cations Ca2+ or Mg2+ with or without subsequent exposure to chaotropic agents (e.g., KSCN). Evidence suggests that these techniques yield morphologically distinct and heterogeneous populations of membranes and that functional differences exist between membrane vesicles prepared by the different procedures, presumably reflecting this heterogeneity. To investigate the effect of the various isolation techniques on the kinetic parameters of D-glucose transport, rat intestinal brush-border vesicles were prepared by each of the following four methods: (i) Ca2+ precipitation; (ii) Ca2+ precipitation with KSCN treatment; (iii) Mg2+ precipitation; and (iv) Mg2+ precipitation with KSCN treatment. Membrane purity as indicated by the enrichment of the enzyme membrane markers sucrase and alkaline phosphatase did not differ between isolation procedures. The Mg-Na-K ATPase activity showed an enrichment factor of less than 1.0 for each of the isolation techniques. D-Glucose uptake was measured with a rapid filtration method under conditions of a zero-trans, 100 mM cis-NaSCN gradient. The membrane preparations yielded similar Hofstee transformations displaying the curvilinear relationship thought to be consistent with the existence of multiple transporters for D-glucose. The average kinetic parameters calculated from the Hofstee plots for each technique were similar. It was concluded that D-glucose transport into rat jejunal membrane vesicles was unaffected by the variation in morphology arising from the technique used to purify the membranes.
Massive small intestinal resection results in both structural and functional changes in the residual small bowel. Sodium-dependent D-glucose transport was examined in brush-border membrane vesicles derived from the terminal 20-30 cm of ileal mucosa of male Sprague-Dawley rats, 2 and 6 wk after 66% proximal jejunoileal resection or jejunoileal transection. Kinetic characteristics for sodium-dependent D-glucose transport were investigated with rapid filtration under conditions of a zero-trans, 100 mM cis-NaSCN gradient. Mucosal weight, protein, and DNA content were increased in the residual terminal intestinal segment compared with transected controls, whereas morphometric studies revealed increased villus and crypt heights as well as an increased mitotic index. Mean kinetic transport parameters at 6 wk after proximal small bowel resection revealed two saturable systems in the distal residual ileum: first, a low-affinity, high-capacity system with a Km of 0.19 +/- 0.03 mM and a Vmax of 0.48 +/- 0.04 nmol.mg protein-1.min-1; and second, a high-affinity, low-capacity system with a Km of 0.009 +/- 0.001 mM and a Vmax of 0.105 +/- 0.016 nmol.mg protein-1.min-1. In contrast, negligible sodium-dependent D-glucose transport was detected in the most distal ileum in control animals or animals 2 wk after resection or 2 and 6 wk after transection. Thus adaptational changes including mucosal hyperplasia and the appearance of two sodium-dependent D-glucose brush-border membrane vesicle transport systems occur in the residual distal intestine after massive proximal small bowel resection.
Massive small intestinal resection in the rat results in both structural and functional changes in the residual small bowel. Sodium-dependent D-glucose transport was examined in brush-border membrane vesicles derived from the proximal small bowel mucosa of male Sprague-Dawley rats 2 and 6 wk after a 66% distal jejunoileal resection or jejunoileal transection. Kinetic characteristics for the low-affinity, high-capacity system and high-affinity, low-capacity system were defined with rapid filtration under conditions of a zero-trans, 100 mM cis-NaSCN gradient. Mucosal weight, protein, and deoxyribonucleic acid content were increased in the residual intestinal segment compared to transected controls and morphometric studies revealed increased villus and crypt heights as well as an increased mitotic index. Postresection mean kinetic parameters for D-glucose transport at 2 wk (low-affinity system: Km, 177.5 +/- 45.1 microM; Vmax, 3.73 +/- 0.99 nmol X mg protein-1 X min-1; and high-affinity system: Km, 6.2 +/- 1.9 microM; Vmax, 0.12 +/- 0.06 nmol X mg protein-1 X min-1) and 6 wk (low-affinity system: Km, 267.8 +/- 83.1 microM; Vmax, 0.06 +/- 0.01 nmol X mg protein-1 X min-1; and high-affinity system: Km, 6.5 +/- 1.1 microM; Vmax, 0.06 +/- 0.01 nmol X mg protein-1 X min-1) were similar to values post-transection at 2 wk (low-affinity system: Km, 280.4 +/- 53.7 microM; Vmax, 3.05 +/- 0.32 nmol X mg protein-1 X min-1; and high-affinity system: Km, 9.1 +/- 1.3 microM; Vmax, 0.17 +/- 0.01 nmol X mg protein-1 X min-1) and 6 wk (low-affinity system: Km, 271.7 +/- 17.5 microM; Vmax, 4.69 +/- 0.23 nmol X protein-1 X min-1; and high-affinity system: Km, 10.6 +/- 4.2 microM; Vmax, 0.16 +/- 0.09 nmol X mg protein-1 X min-1). These kinetic data suggest that the hyperplastic response in adapting proximal small bowel after distal resection is accompanied by a persistence of the membrane functional characteristics for both sodium-dependent D-glucose transport systems despite an altered pattern of enterocyte proliferation and differentiation.
Yersinia enterocolitica was cultured from feces of 122 symptomatic adults in a single facility using selective culture media; all isolates were confirmed in an independent reference laboratory. Of 128 isolates, multiple serotypes were defined and all were biochemically typical for Yersinia enterocolitica. Other agents were seen in 20 patients; of these, seven were Yersinia fredriksenii and six were Clostridium difficile. Diarrhea (80%) and abdominal pain (64%) were common, whereas other features such as fever (9%) and bloody stools (8%) were unusual. Use of antibiotics (24%) or opiates (28%) in the month before culture was common. The terminal ileum was seen radiographically in 20 patients, but only two barium studies showed abnormalities. Fiberoptic endoscopy and biopsy studies, done in greater than 50% of the cases, showed minimal or no changes in most patients. However, 3 patients had pseudomembranous colitis with concomitant Clostridium difficile cytotoxin and 7 had diffuse severe colitis. New culture techniques, and possibly geographic differences, have contributed to the high isolation rates of this organism. Yersinia enterocolitica occurs sporadically, involves a variety of serotypes, and is associated with a broader clinical spectrum than was formerly appreciated.
A retrospective chart review was performed on 100 patients infected with Blastocystis hominis (Bh) and 50 randomly selected age and sex matched controls to examine the clinical and epidemiologic features associated with this organism. The finding of greater than 5 Bh per oil immersion field (1,000 X) was significantly associated with acute presentation of symptoms but was not predictive of the presence of gastrointestinal symptoms. Of patients infected with Bh, 57.5% had recently travelled to the tropics or had consumed untreated water as compared to 12.2% of controls (p less than 0.001). Forty Bh-positive patients were assessed on more than one occasion. No significant differences appeared to exist in the clinical responses of those treated with Metronidazole (14/18; 77.8%) or with dietary management (6/6; 100%) as compared with those not receiving treatment (13/16:81.2%). Patients tended to become less symptomatic with time and in the absence of specific treatment, and therefore treatment with Metronidazole may not be warranted in light of the natural history of Bh infection.
During the 42-month period from June 1982 through December 1985, 215 fecal specimens from 171 patients were found to be positive for yersiniae by using a combination of CIN agar and cold enrichment. Isolates were tested for markers of virulence including carriage of a plasmid 42 megadaltons in size, calcium dependence, autoagglutination, Congo red uptake, pyrazinamidase activity, fermentation of salicin, and hydrolysis of esculin. The results were correlated to symptoms in patients. A total of 80 Yersinia enterocolitica and 52 Y. enterocolitica-like strains (42 Y. frederiksenii, 8 Y. intermedia, and 2 Y. kristensenii) were examined. Positive virulence-related tests were as follows (for Y. enterocolitica, Y. frederiksenii, Y. intermedia, and Y. kristensenii, respectively): pyrazinamidase negativity, 12.5, 0, 0, and 50%; Congo red positivity, 5, 7.1, 87.5 and 0%; calcium dependence, 3.8, 0, 0, and 0%; autoagglutination positivity, 8.8, 0, 0, and 0%; carriage of the 42-megadalton plasmid, 28.6, 73.2, 5.7, and 0; salicin and esculin negativity, 12.5, 0, 0, and 50%. The isolates recovered from symptomatic patients were characterized in relation to the presenting symptoms. Isolates from 12 of 32 (37.5%) patients with acute-onset diarrhea and 9 of 30 (30.0%) patients with chronic symptoms expressed at least one virulence feature. No individual test or group of tests was consistently associated with onset or either type of symptoms. Routine testing of plasmid carriage, uptake of Congo red, calcium dependence, autoagglutination, and pyrazinamidase activity did not appear to provide information that would link the presence of symptoms with the virulence potential of fecal isolates of yersiniae.
A commercially available latex agglutination test for Clostridium difficile was compared with a cell culture cytotoxin assay and bacteriological culture for the laboratory diagnosis of C. difficile-associated diarrhea and colitis (CAD). Stool specimens from 626 patients were tested by the three methods, and specimens from 118 patients (19%) were positive by at least one of the methods. The results of the three tests agreed in 88% of the specimens tested, overall, but they agreed in only 34% of the 118 positive specimens. Ninety-three patients were evaluated to assess the significance of positive and negative results for each assay. Of 40 patients found to have CAD, 70% were positive by the cytotoxin assay, 78% were positive by the latex agglutination test, and 90% were culture positive. Of 53 patients who did not have CAD, 2% were positive by the cytotoxin assay, 8% were positive by the latex test, and 4% were culture positive. The detection of CAD was improved by using the tests in combination, and 97% of specimens positive by two or three methods were from patients who had CAD. Testing of multiple specimens from individual patients also increased the sensitivity of detection of CAD. The results suggest that the latex agglutination test may be useful for rapid diagnosis of CAD, especially in laboratories that lack cell culture facilities. However, the accuracy of CAD detection is improved when the latex test is used in combination with culture or the cytotoxin assay.
Differentiation and maturation of enterocytes occur with migration from the crypt to villus compartments. To investigate the effect of epithelial cell differentiation on sodium-dependent D-glucose transport, brush-border membrane vesicles were prepared from small intestinal epithelial cell suspensions selectively isolated from villus and crypt populations. Enterocytes were isolated with a morphologically monitored sequential cell dissociation method. Thymidine kinase, sucrase, and alkaline phosphatase activities were measured as differentiation markers of specific cell populations. Brush-border membrane vesicles were purified and their kinetic characteristics defined with a rapid filtration method under conditions of a zero-trans, 100 mM cis-NaSCN gradient. Typical "overshoot" phenomena characteristic of sodium D-glucose cotransport were observed for both villus (five- to eight-fold equilibrium values) and crypt brush-border membrane vesicles (two- to four-fold equilibrium values). Kinetics analyses of the initial D-glucose flux in brush-border membrane vesicles suggested the presence of at least two sodium-dependent D-glucose carriers in the villus and only a single carrier in the crypt compartments. These data indicate that sodium D-glucose cotransport occurs in brush-border membranes of both villus and crypt populations. Moreover, quantitative and qualitative differences between these two membrane populations suggest that epithelial D-glucose transport processes are differentiation dependent and reflect the degree of enterocyte development.
Renal brush-border membrane D-glucose transport was studied in vesicles prepared from early proximal tubules (outer cortical tissue) and late proximal tubules (outer medullary tissue). Kinetics of sodium-dependent D-glucose uptake, determined with zero trans sodium gradient of 200 mM at 21 degrees C demonstrated a curvilinear Woolf-Augustinsson-Hofstee plot in both cortical and medullary vesicles. Three sodium-dependent systems were discerned in the cortex, possessing Km values of 12.35 +/- 2.2 mM, 520 +/- 39 microM, and 12 +/- 1 microM, respectively. In contrast, only the high-affinity, low-capacity systems were present in the medullary tissue; with respective Km values of 484 +/- 95 microM and 11 +/- 1 microM and mean Vmax values of 2.4 +/- 0.1 and 0.44 +/- 0.08 nmol X mg protein-1 X min-1. The high-affinity systems were more abundant in the medulla than in the cortex. These studies support the notion of multiple transport processes for sodium-dependent D-glucose transport in the pig kidney. Further, they provide evidence for a third, high-affinity system located principally in the medullary tissue, perhaps the late proximal tubule.
The effects of increasing amounts of differing single-fiber sources in chemically-defined and nutritionally-equivalent diets on morphometric measurements of the rat small and large intestinal mucosa were examined. Male Wistar rats received a fiber-free diet, or diets containing 4.5% or 9.0% cellulose, pectin, or hemicellulose. Cellulose and pectin increased jejunal (but not ileal) villus and crypt heights, whereas hemicellulose increased ileal (but not jejunal) mucosal height. Moreover, cellulose and pectin (but not hemicellulose) increased crypt heights in cecum and proximal (but not distal) colon. Parallel increases in the mitotic index were seen with cellulose and pectin diets, but there was a decrease with hemicellulose, suggesting different mechanisms for altered patterns of cell renewal induced by orally-administered single-fiber sources. These changes indicate that differing single-fiber sources exert differential structural effects along the length of the small and large intestine in the rat.
Malignant small intestinal lymphoma may complicate or antedate clinical recognition of celiac sprue, a disorder becoming increasingly diagnosed as a subclinical or occult disease. A 73-yr-old woman with previously resected jejunoileal lymphoma and normal proximal small bowel biopsy specimens was given a high-gluten diet containing 40 g of added gluten daily for 4 wk. This caused small intestinal biopsy abnormalities typical of celiac sprue; the abnormalities resolved 6 wk later with a gluten-free diet. This indicates that latent celiac sprue may be present in some patients with lymphoma and suggests that the association of celiac sprue and lymphoma may be more frequent than is currently appreciated.
Malignant small intestinal lymphoma may complicate or antedate clinical recognition of celiac sprue. However, histologic diagnosis of lymphoma is made especially difficult in the presence of small bowel ulceration. A 70-yr-old man with celiac sprue and a history of dermatitis herpetiformis was initially seen for recurrent diarrhea; panmalabsorption with steatorrhea and protein-losing enteropathy were documented. Subsequent studies showed ectopic gastric mucosa in the small bowel, hyposplenism with mesenteric lymph node cavitation, and small bowel erosions and ulceration. Despite strong clinical suspicion for more than 2 yr, only 1 of 88 small bowel biopsy specimens was positive for lymphoma. At autopsy, shortly after histologic diagnosis of lymphoma, extensive small bowel involvement and infiltration were observed. This is the first report of lymphoma complicating the recently described nonneoplastic lymphoreticular syndrome associated with celiac sprue characterized by splenic atrophy and mesenteric lymph node cavitation.
The incidence, distribution, size, and histopathology of small and large bowel tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats given 1% or 2% sodium butyrate dissolved in drinking water. Although previous in vitro reports on colon cancer cell lines have suggested that sodium butyrate might have a role to play as a chemotherapeutic "differentiating agent," the results of this in vivo study indicate that sodium butyrate treatment enhanced the development of colonic neoplasia and was associated with increased fecal butyric acid concentrations. In contrast, no changes were seen in the incidence of small bowel tumors, luminal butyric acid concentrations, mucosal morphology, or brush-border enzyme activities (i.e., sucrase, alkaline phosphatase). This study suggests that dietary butyrate has an important, possibly indirect, regulatory role in carcinogenesis associated with an experimental animal model of colonic neoplasia.
A 35-year-old man developed leg edema, marked hypoalbuminemia, and proteinuria. Subsequent renal biopsy revealed a diffuse membranoproliferative glomerulonephritis and, on electron microscopy, typical electron-dense deposits characteristic of an immune complex pathogenesis. Although protein wasting might have readily been explained on the basis of his nephrotic syndrome, the concomitant symptom of diarrhea led to the diagnosis of celiac sprue, another disorder with a possible immune-mediated pathogenesis. While reports of immune complex glomerulonephritis in celiac sprue are rarely recorded, the potential significance of gastrointestinal symptoms in patients with the nephrotic syndrome may have important nutritional implications, especially if underlying occult celiac sprue is recognized.
Diarrhea and a small bowel lesion similar to that reported in celiac sprue were observed in a patient who had been taking sulindac. Symptoms and biopsy abnormalities resolved completely after discontinuation of the medication and promptly recurred upon its re-administration. This report emphasizes the need to consider possible drug-related small bowel disease in the growing list of causes of the "flat" small intestinal mucosal lesion.