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Biomedical subjects

C N Bernstein

Publications and source records attributed to C N Bernstein.

At least 73 records · Page 4Linked to original sources
PubMed1996

A randomized, placebo-controlled trial of calcium supplementation for decreased bone density in corticosteroid-using patients with inflammatory bowel disease: a pilot study.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high prevalence of osteoporosis. A number of studies have found that corticosteroid use is associated with the development of osteoporosis in these patients. Calcium supplementation may be of benefit in corticosteroid-induced osteoporosis and calcium may be a nutrient that patients with IBD lack. AIM: To test the benefit of calcium supplementation on bone density in a pilot study over a 1-year period, in a group of corticosteroid-using patients with IBD, in a randomized, double-blind, placebo-controlled treatment study. METHODS: Corticosteroid-using patients with IBD including males over the age of 18 years and premenopausal females, were randomized to receive either calcium carbonate 1000 mg plus vitamin D 250 IU (Oscal) or an identically matched placebo. Dual energy X-ray absorptiometry measurements of bone density were obtained at entry and at 1 year. At entry, and every 3 months thereafter, serum was collected for the measurement of haemoglobin, biochemistry and bone hormones. Simultaneously a 24-h urine collection was analysed for calcium excretion and creatinine clearance, and a 4-day food record was collected to document dietary calcium and vitamin D ingestion. RESULTS: We found a high prevalence of moderately severe decreased bone density in corticosteroid-using patients with IBD. The dose of prednisone in the year prior to study entry was inversely correlated with bone density at the hip (R = -0.67, P = 0.004). At study entry serum osteocalcin was inversely correlated with corticosteroid dose in the year prior to the study (R = -0.64, P = 0.02) and at study end, directly correlated with the percentage change in spine bone density (R = 0.59, P = 0.01). The dietary calcium intake of these patients was close to the current RDA (recommended daily intake) for premenopausal, post-adolescent adults. Calcium supplementation with small extra doses of vitamin D conferred no obvious benefit to bone density at the end of 1 year. There was no correlation between oral calcium ingestion and bone mass measurements. Both the treatment and placebo groups' bone density remained relatively stable at 1 year, suggesting that bone loss in corticosteroid-using patients may peak early into the use of the corticosteroids. CONCLUSIONS: Calcium supplementation (1000 mg/day) conferred no significant benefit to bone density at 1 year in patients with corticosteroid-using IBD patients with osteoporosis. Future investigations should explore other therapeutic avenues that may have greater effects on increasing bone density in patients who already have considerable osteoporosis.

Absorptiometry, Photon↗
PubMed1996

The differential expression of a novel intestinal epithelial glycoprotein in various forms of inflammatory bowel disease.

A13D8 is a monoclonal IgM antibody that identifies an as yet unknown antigen that is expressed intensely and ubiquitously in enterocytes. Immunohistochemically, it was shown that A13D8 has a granular supranuclear staining pattern in columnar epithelial cells of normal small intestine and the colon. In ulcerative colitis, this staining pattern was retained. However, during active inflammation, staining also was evident in goblet cells. To test whether this feature of goblet cell staining was unique to ulcerative colitis, tissue sections from a variety of colitides were examined. Crohn's disease, infectious colitis, and ischemic colitis had similar staining patterns to that seen with ulcerative colitis. There was significantly more inflammation in the biopsies from patients with ulcerative colitis and Crohn's disease with positive goblet cell staining than in the biopsies from those patients with negative goblet cell staining. Almost all positive goblet cell staining in ulcerative colitis and Crohn's disease occurred in biopsies that were actively inflamed, whereas there was rare staining in biopsies that were noninflamed (regardless of whether or not there was active inflammation elsewhere in the colon). Ileal goblet cells stained positively with A13D8 only in cases of active ileitis. In cases of collagenous colitis, with comparable degrees of inflammation to that seen in ulcerative colitis and Crohn's disease, there was rarely goblet cell staining and in graft-versus-host disease goblet cell staining of A13D8 was not observed. The binding of A13D8 to tissue sections was completely inhibited by N-acetyl-D-galactosamine. These results, in conjunction with immunochemical studies, suggest that the antibody recognizes an N-acetyl-D galactosamine-containing epitope on a glycoprotein(s). In conclusion, these data suggest that A13D8 recognizes a glycoprotein expressed by intestinal columnar epithelial cells and during specific inflammatory states, particularly those associated with a neutrophilic infiltrate, becomes evident in goblet cells. Further work is required to establish the exact nature of this molecule and whether it is a pro- or anti-inflammatory factor.

Antibodies, Monoclonal↗
PubMed1996

Beta 2-integrin/intercellular adhesion molecule (ICAM) expression in the normal human intestine.

The beta 2-integrin family of adhesion molecules and their ligands, the ICAM molecules, probably have an important role to play in the intestinal immune response. To date, any data published regarding the intestinal expression of beta 2-integrins and ICAMs have mostly described only mucosal expression. The presence in the intestine of alpha d, a newly described beta 2-integrin molecule, has not yet been determined. To understand further the expression of these molecules in all layers of the intestine, a comprehensive study was undertaken in both normal colon and normal small intestine specimens from 15 patients (colon n = 15, and ileum n = 6) who underwent surgical resections. Immunohistochemistry was performed for CD18, CD11a, CD11b, CD11c, alpha d, ICAM-1, ICAM-2, and ICAM-3. The colon and small intestine cases were grouped separately and each of the mucosal, submucosal, muscle and adventitial layers were scored for expression. The beta 2-integrin molecules were expressed by mononuclear cells in all layers of the bowel, predominantly in the mucosa and adventitia. CD11a showed the greatest mucosal expression and CD11b showed the greatest adventitial expression. alpha d exhibited expression in all bowel layers, as well, with most intense expression in the mucosa and adventitia. CD11c exhibited the least expression of all alpha subunit molecules. The expression of these alpha-chains at times appeared to be greater than that seen for CD18 (beta 2), raising the possibility of non-beta 2-containing complexes (i.e. alpha-chains associating with an alternate beta-chain). ICAM-1 was expressed on endothelium, particularly in the mucosa and rarely on mucosal mononuclear cells. ICAM-2 was predominantly on submucosal endothelium and rarely expressed in colon mucosa and never expressed in ileal mucosa. ICAM-3 was expressed by mononuclear cells throughout the bowel wall, but also on adventitial endothelium in selected cases. In summary, we are reporting a comprehensive immunohistochemical study of the differential expression of beta 2-integrins, including the newly described alpha d molecule, and the ICAM molecules in all layers of normal human colon and ileum. We raise the possibility that a second beta 2-integrin beta subunit may exist, and we report that ICAM-3 is expressed on endothelium, particularly in the adventitial layer.

Antigens, CD↗
PubMed1995

Decreased bone density in inflammatory bowel disease is related to corticosteroid use and not disease diagnosis.

Although corticosteroid therapy is associated with the development of osteopenia, it is unclear whether the cause of osteopenia in inflammatory bowel disease (Crohn's disease and ulcerative colitis) is related to corticosteroid therapy or other disease-related variables. Patients with Crohn's disease (a diffuse gastrointestinal disease) could have greater osteopenia than patients with ulcerative colitis because of small bowel disease and secondary malabsorption of calcium and vitamin D. A cross-sectional analysis of consecutive patients with Crohn's disease and ulcerative colitis was undertaken. Bone density was determined by measurements of the L2-L4 spine, the total hip, and Ward's triangle using dual energy X-ray absorptiometry (DXA). A number of clinical parameters were recorded prior to bone density evaluation and analyzed by univariate and subsequently multivariate analysis to determine possible predictors of osteopenia. Of the 26 patients with Crohn's disease, diminished bone density (a Z score of at least -1) was found at the hip in 64% and at the spine in 44%; and of the 23 patients with ulcerative colitis diminished bone density was found at the hip in 43% and at the spine in 48%. Among all the variables tested, only corticosteroid use was a statistically significant predictor of diminished bone density (p = 0.025 for the spine and hip and p = 0.005 for Ward's triangle). Disease diagnosis (Crohn's disease compared with ulcerative colitis) did not predict or correlate with diminished bone density. No obvious associations were seen between the measurements of any serum hormones or biochemistries and bone density, although the patients using corticosteroids had lower serum calcium levels than the nonusers.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

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 Crohn's 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 Crohn's disease.

Adult↗
PubMed1995

Small bowel transplantation.

The small bowel, the largest lymphoid organ in the body and host to a myriad of foreign antigens has presented a formidable challenge for transplantation. In the past 5 years, small bowel transplantation has become a viable clinical entity. Successful transplantation of the small bowel has been achieved as part of multivisceral grafting, combined small bowel and liver grafts and even as isolated small bowel grafts. Allograft rejection remains an important post-transplantation problem, although graft versus host disease has been less of a clinical problem than initially feared. Markers that may serve to predict early rejection have been identified and include: assessment of endoscopic biopsies for enterocyte Class II antigen expression and for mucosal T cell and macrophage infiltration, bowel permeability studies, and measurement of changes in transepithelial potential difference. Earlier detection of rejection and more potent therapy for rejection episodes will be necessary to further improve outcomes.

Animals↗
PubMed1995

Physicians' perceptions of dysplasia and approaches to surveillance colonoscopy in ulcerative colitis.

OBJECTIVE: Colonoscopic biopsy surveillance to detect dysplasia, defined as a neoplastic change of the epithelium without invasion into the lamina propria, in patients with ulcerative colitis has become a widespread practice. We undertook a survey study to determine physicians' perceptions of, and approaches to, dysplasia surveillance colonoscopy in ulcerative colitis. METHODS: Members of two regional gastroenterology associations in the United States, including both academic and private practice-based gastroenterologists, and a group of senior gastroenterology trainees were surveyed by means of a written questionnaire. The questionnaires were distributed at three separate meetings of practicing gastroenterologists or trainees: 1) a Gastrointestinal pathology course for second-year gastroenterology fellows from training programs around the United States (February 1993, Los Angeles, CA); 2) a meeting of the Southern California Gastroenterology Society (March 1993, Los Angeles, CA); and 3) a meeting of the Pacific Northwest Gastroenterology Society (June 1993, Seattle, Washington). The percentages of all responses were tallied and analyzed for the group as a whole as well as by subgroup analysis. Understanding of the definition of dysplasia and specific practice techniques and approaches were the main outcomes sought. RESULTS: Only 19% of respondents correctly identified the definition of dysplasia. More respondents (48%) correctly defined high grade dysplasia specifically compared with only 16% who correctly defined low grade dysplasia. The majority of respondents (69%) recommended colectomy when high grade dysplasia was diagnosed, yet nearly one-third of respondents pursued continued surveillance in this setting. Almost uniformly, respondents pursued continued surveillance and not colectomy when low grade dysplasia was diagnosed. Nearly one-half of the respondents thought that there was only < 20% chance of finding invasive cancer in patients with preoperative diagnoses of high grade dysplasia. On average, respondents performed surveillance colonoscopy every 1-2 yr and took an average of three biopsies per site, at approximately eight sites in the colon, and most respondents confidently relied on their local pathologist at making the diagnosis. There were, however, wide variations in the practice of dysplasia surveillance. CONCLUSIONS: The majority of respondents did not know the definition of dysplasia, and most viewed it as a preneoplastic lesion. Furthermore, there was a lack of appreciation that the difference between low grade and high grade dysplasia is one of degree or severity of neoplastic change and for the likelihood of finding invasive cancer at surgery if there is only a diagnosis of dysplasia preoperatively. Dysplasia surveillance colonoscopy in ulcerative colitis is not a well standardized, clearly understood screening tool, and continued education of the gastroenterology community regarding its outcomes and pitfalls is needed.

Colectomy↗
PubMed1994

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.

Colitis, Ulcerative↗
PubMed1994

Isolation, identification, and culture of normal mouse colonic glia.

We have developed a novel method of isolating and culturing murine colonic mucosal glial cells. Two morphologies are appreciated, a small flat bi or tri polar cell and a larger multipolar cell. The glial cultures have been freed of contaminating fibroblasts and epithelial cells and have been passaged by trypsinization. By intermediate filament (IF) typing, the glial cells have been further characterized as astrocyte-like. All cells expressed glial fibrillary acid protein but not neurofilament 160 protein. The glial cultures expressed the neuropeptides, substance P and substance K. Central nervous system astrocytes synthesize neuropeptides, prostaglandins and cytokines, and can express major histocompatibility class II antigens. It is likely that enteric mucosal glia will also prove to have varied functions. These cultures can now be used to define the role of enteric mucosal glia and to further study their complex interaction with other cells of the colonic mucosa.

Animals↗
PubMed1994

Low-dose 6-mercaptopurine in inflammatory bowel disease is associated with minimal hematologic toxicity.

A feared complication of therapy with 6-mercaptopurine (6-MP) is myelosuppression. To evaluate whether rigorous blood count monitoring is necessary, we prospectively followed the hematologic profiles of 57 patients with inflammatory bowel disease who were treated with low-dose 6-MP. Most patients (97%) were treated initially with a single dose of 50 mg/day and 79% never used more than 50 mg/day. Blood counts were obtained at weekly intervals over the first month, every two weeks for the second month, and monthly thereafter in the first year. Sixteen (28%) developed mild leukopenia (white blood count < 4.5 x 10(3)/mm3). No patient had a white blood cell count < 2.8 x 10(3)/mm3 and no patient developed leukopenia prior to three months of treatment. In only five patients did the leukopenia prompt a change in 6-mercaptopurine dose. Very mild thrombocytopenia (platelet count of < 145 x 10(3)/mm3) developed in three (5%) and macrocytosis (mean cell volume > 101 fl) was seen in nine (16%). In conclusion, leukopenia was not uncommon in patients treated with low-dose 6-MP, but was not clinically significant. Leukopenia occurred no earlier than three months and as late as 42 months into therapy. Thrombocytopenia was uncommon, mild, and was not associated with apparent bleeding. Macrocytosis may occur in the absence of vitamin B12 and folate deficiencies. Patients can be spared from weekly blood count monitoring when using low-dose 6-mercaptopurine treatment.

Anemia, Macrocytic↗
PubMed1994

Milk tolerance in adults with ulcerative colitis.

OBJECTIVES: There has been concern in the literature and among physicians and patients that milk intolerance may contribute to disease activity in ulcerative colitis. We sought to define whether patients with ulcerative colitis have problems with milk tolerance. METHODS: 1) A questionnaire was administered to a group of gastroenterologists. 2) Consecutive unselected ulcerative colitis patients were administered a questionnaire regarding issues concerning their ingestion and tolerance of milk products. 3) Patients, and age- and ethnically matched controls, underwent lactose hydrogen breath testing at a 50-g dose, and if intolerant, returned for testing at a 12.5-g dose. RESULTS: Eighty percent of responding physicians stated that they recommend avoidance of milk products at some time to their patients. Thirteen of 29 (44%) ulcerative colitis patients were lactose intolerant compared with five of 14 (36%) controls (p = 0.57). Of 11 subjects returning for the 12.5-g test dose, only three (28%) were intolerant. Of 10 ulcerative colitis patients tested during a flare, only two (20%) were intolerant. Nineteen of 28 (66%) patients reduced or eliminated milk products from their diet, but only 10 (45%) of these patients were lactose intolerant. The discordance rate for predicting lactose tolerance status among patients was 35%. By logistic regression analysis, age (p = 0.04) and ethnicity (p = 0.006) were the only variables that were predictive of an abnormal lactose hydrogen breath test. CONCLUSIONS: There are common misperceptions among physicians and patients about lactose intolerance in ulcerative colitis. Lactose intolerance in patients with ulcerative colitis is dependent on their age and ethnicity and not any particular aspects of their disease. The proscription of milk products during flares of disease by many physicians is not supported by this study.

Adult↗