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Biomedical subjects

F Shanahan

Publications and source records attributed to F Shanahan.

At least 145 records · Page 8Linked to original sources
PubMed1996

MALTectomy (appendectomy/tonsillectomy) does not influence the occurrence or mode of presentation of adult celiac disease.

OBJECTIVE: Recent reports suggest that appendectomy may protect against the development of ulcerative colitis. Depletion of mucosal helper T-cells is the suggested mechanism. Because mucosal T-cell activity has an even more critical role in the pathogenesis of celiac disease, our objective was to determine whether the development or mode of presentation of this disorder is influenced by appendectomy and/or tonsillectomy. METHODS: One hundred fifty consecutive adult celiac patients were compared with 138 consecutive patients examined at orthopedic clinics. One hundred twenty consecutive patients with ulcerative colitis from the same ethnogeographic population were included as positive disease control. RESULTS: Contrary to the previous findings in ulcerative colitis, which were again confirmed in this study, appendectomy and/or tonsillectomy did not influence the occurrence of celiac disease. In addition, presenting features, predefined in the study protocol, did not differ significantly in the appendectomy and nonappendectomy celiac patients. CONCLUSION: Resection of mucosa-associated lymphoid tissue (MALT) does not influence the occurrence or the mode of presentation of adult celiac disease. Therefore, in this classical example of a T-cell-mediated disorder, the hypothesis that surgical depletion of mucosal T-cells has a protective effect or influences the clinical manifestations cannot be supported.

Adult↗
PubMed1996

Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis.

The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, c1, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF c1 alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 "shared epitope" (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF c1 and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, c1, d1, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.

Arthritis, Rheumatoid↗
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

Non-linkage of a T-cell receptor gamma chain microsatellite (D7S485) to rheumatoid arthritis in multiplex families.

A highly informative microsatellite marker, D7S485, from the T-cell receptor gamma (TCRG) locus, has been used to study segregation of TCRG genes in 26 multiplex rheumatoid arthritis (RA) families. We used the sib-pair method to assess excess identity-by-descent sharing among affected members in these families and the LINKAGE package of programs was used to calculate two-point lod scores for the D7S485 marker. There was no evidence for segregation of TCRG genes with RA in affected siblings and significantly negative lod scores were obtained from linkage analyses using both autosomal dominant and recessive models of inheritance.

Adolescent↗
PubMed1995

Micrometastases in bone marrow of patients undergoing "curative" surgery for gastrointestinal cancer.

BACKGROUND & AIMS: Immunohistochemical detection of bone marrow micrometastases has been reported as a prognostic marker in colorectal cancer. The aims of this study were to evaluate the potential advantage of flow cytometry as an objective method of identifying and quantifying micrometastatic deposits within bone marrow and to determine the prevalence and quantity of micrometastases in patients undergoing surgery for gastrointestinal cancers. METHODS: Flow cytometry was first validated by a controlled "spike" experiment in which varying numbers of neoplastic epithelial cells were added to bone marrow, and cytometry was performed in a blinded fashion. Three neoplastic cell lines (colonic and esophageal) with varying degrees of expression of cytokeratin-18 were used. Epithelial cells were detected by dual staining with fluorescence-labeled, monoclonal anti-cytokeratin, and propidium iodide. RESULTS: Cytometry reproducibly detected the presence of > or = 10 neoplastic cells per 10(5) marrow cells. Micrometastases were found in 20%-30% of patients undergoing potentially curative resection of colorectal and gastroesophageal adenocarcinomas. There was a trend toward increasing positivity for marrow deposits with advanced Dukes' staging of colorectal cancer. CONCLUSIONS: Flow cytometric assessment of bone marrow is a reliable, objective, and quantitative method of detecting micrometastatic deposits found in a substantial subset of patients undergoing surgery for gastrointestinal adenocarcinomas.

Adenocarcinoma↗
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

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↗
PubMed1995

A prospective comparison of laparoscopy and imaging in the staging of esophagogastric cancer before surgery.

OBJECTIVE: To carry out a prospective comparison of laparoscopy and combined imaging (CT and ultrasound) in the preoperative staging of distal esophageal and gastric cancer in patients who were selected for surgery. METHODS: Patients with clinically overt metastases or a contraindication to major surgery were excluded. One hundred and forty-five patients underwent chest radiography, CT of mediastinum and abdomen, and ultrasonography of abdomen and laparoscopy. The primary diagnoses were adenocarcinoma of the esophagogastric region in 110 cases, squamous cell carcinoma of the distal esophagus in 30 patients, and five miscellaneous. RESULTS: Thirty nine (27%) patients had metastatic disease outside the potential field of resection. Metastases were detected preoperatively by laparoscopy in 30 patients (sensitivity 77%) and by combined imaging in 15 (sensitivity 38%) (p < 0.01). Twenty four patients with adenocarcinoma had metastases to the peritoneal cavity, which were detected preoperatively by laparoscopy in 23 (sensitivity 96%) and by combined imaging in five (sensitivity 21%) (p < 0.01). Peritoneal metastases were not seen in patients with squamous cell carcinoma. Fifteen patients had hepatic metastases, which were detected preoperatively by laparoscopy in nine (sensitivity 60%) and by combined imaging in seven (sensitivity 47%). Laparoscopy was more sensitive than combined imaging in detecting metastases in patients with adenocarcinoma [laparoscopy 28, combined imaging 10 (p < 0.01)]. CONCLUSION: Addition of laparoscopy to the staging protocol prevented unbeneficial thoraco-abdominal exploration in 20 patients with adenocarcinoma. Thus, laparoscopy should be used in the assessment of patients with adenocarcinoma of the esophagogastric region before performing excisional surgery.

Adult↗
PubMed1994

Epstein-Barr virus SM protein.

The protein products of the Epstein-Barr virus (EBV) BMLF1 open reading frame have been characterized in the early productive cycle in B95-8 and Akata cells. The SM protein derived from the spliced RNA joining BSLF2 to BMLF1 is much the most abundant protein. SM is a phosphoprotein in EBV-infected cells and can be phosphorylated in vitro with casein kinase II (CKII). Computer analysis of the SM protein sequence showed a C terminal section of SM to be related to genome positional homologues of four other herpesviruses and revealed consensus CKII sites near the N termini of the EBV SM protein, the herpes simplex virus (HSV) ICP27 protein and the herpesvirus saimiri (HVS) open reading frame 57 protein. Site-directed mutagenesis of the consensus CKII site in EBV SM greatly reduced the in vitro phosphorylation of SM by CKII. The mechanism of transactivation by BMLF1 proteins has been controversial but SM was shown to transactivate gene expression from a CAT reporter construct by increasing the amount of cytoplasmic CAT mRNA. Mutagenesis of the CKII site in SM made no difference to the transactivation in this transient transfection assay.

Amino Acid Sequence↗