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Biomedical subjects

H A Carpenter

Publications and source records attributed to H A Carpenter.

At least 19 recordsLinked to original sources
PubMed1995

Significance of human leukocyte antigens DR3 and DR4 in chronic viral hepatitis.

Immune mechanisms have been implicated in chronic viral hepatitis, and these may be influenced by genetic factors. To determine if disease severity in chronic viral hepatitis is associated with the human leukocyte antigens DR3 and/or DR4, 109 patients were evaluated prospectively. The frequencies of DR3 and DR4 in these patients were compared to those in 80 normal subjects. Patients with DR3 and/or DR4 had the same occurrence of severe disease as patients with other DR antigens (21% versus 30%, P = 0.3). Patients with DR3, however, had higher serum gamma globulin and immunoglobulin G levels than patients with DR4 and a greater frequency of severe disease (36% vs 12%, P = 0.046). Patients with DR4 had concurrent immunologic diseases more commonly than patients with DR3 (44% vs 9%, P = 0.005) and patients with other DR antigens (44% vs 9%, P = 0.0002). Patients with DR4 but not DR3 had severe disease less frequently than other patients (9% vs 31%, P = 0.02). The frequencies of DR3 in patients with severe disease (37% vs 18%, P = 0.06) and DR4 in patients without severe disease (44% vs 30%, P = 0.07) were different than those in normal subjects but not to a statistically significant level. We conclude that patients with DR3 and DR4 have different clinical and laboratory findings and disease severity. Patients with DR4 have milder disease than patients with other DR antigens. Disease severity, however, is not closely associated with DR3 or DR4.

Autoimmune Diseases↗
PubMed1995

Immunologic features and HLA associations in chronic viral hepatitis.

BACKGROUND/AIMS: Chronic viral hepatitis may have immunologic manifestations, and such features may reflect genetic predispositions. The aim of this study was to assess associations between immune manifestations and HLA-DR antigens. METHODS: Ninety-five patients were evaluated prospectively for immunologic features. A microlymphocytotoxicity technique was used to determine DR3, DR4, and A1-B8-DR3 phenotypes. DR antigens were also determined by restriction fragment length polymorphism in 76 patients with chronic viral hepatitis and 80 normal subjects. RESULTS: Autoantibodies were found in 59 patients (62%), and concurrent immunologic diseases were found in 22 patients (23%). Patients with antinuclear antibodies had the A1-B8-DR3 phenotype more commonly than seronegative counterparts (26% vs. 6%; P = 0.02) and had DR3 positivity more frequently than normal subjects (41% vs. 18%; P = 0.03). In contrast, patients with concurrent immunologic diseases had DR4 positivity more commonly than patients without these findings (68% vs. 27%; P = 0.001) and normal subjects (68% vs. 30%; P = 0.003). CONCLUSIONS: Patients with chronic viral hepatitis commonly have autoantibodies and/or concurrent immunologic diseases. The expression of antinuclear antibodies is associated with the A1-B8-DR3 phenotype, and the presence of concurrent immunologic diseases is associated with the DR4 phenotype. In these instances, autoimmune expression may reflect a genetic predisposition that is facilitated by viral infection or is coincidental with it.

Biomarkers↗
PubMed1995

Adenocarcinoma of the esophagogastric junction and Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus is associated with adenocarcinoma of the esophagus. The aim of this study was to find the prevalence of Barrett's esophagus in patients with adenocarcinoma of the esophagogastric junction. METHODS: Consecutive, freshly resected surgical esophagogastrectomy specimens were examined, and multiple histological sections were made around the tumor periphery. Barrett's esophagus was defined as specialized columnar epithelium above the esophagogastric junction. Tumors centered < or = 2 cm from the junction were defined as junction cancers. RESULTS: Barrett's esophagus was found in 9 of 9 (100%) esophageal adenocarcinomas compared with 0 of 8 (0%) squamous carcinoma controls (P < 0.001). Ten of 24 (42%) junction adenocarcinomas had a Barrett's esophagus. A Barrett's esophagus was found in 8 of 12 (67%) junction cancers < or = 6 cm in length but only 2 of 12 (17%) larger tumors (P < 0.05). Barrett's esophagus was significantly associated with junction tumors < 6 cm compared with squamous carcinoma controls (P < 0.02). In 5 specimens with junction cancer, the length of Barrett's esophagus was < 3 cm, and in 5 specimens it was > or = 3 cm. Specialized epithelium was often found below the esophagogastric junction in controls. CONCLUSIONS: Adenocarcinomas of the esophagogastric junction are associated with short and long segments of Barrett's esophagus. Larger cancers probably overgrow and conceal the underlying specialized columnar epithelium from which they arise.

Adenocarcinoma↗
PubMed1995

Changes in the site- and histology-specific incidence of gastric cancer during a 50-year period.

BACKGROUND & AIMS: In contrast to the dramatic decrease in the overall incidence of gastric cancer, there has been a reported increase in the incidence of cases located in the gastric cardia. The aim of this study was to identify changes in site- and histology-specific incidence rates of gastric adenocarcinoma during a 50-year period. METHODS: The Rochester Epidemiology Project medical records linkage system was used to identify all cases of gastric adenocarcinoma among residents of Olmsted County, Minnesota, between 1941 and 1990 (n = 342). Each patient's complete (inpatient and outpatient) medical records were reviewed and tumor location determined from pathological, surgical, endoscopic, and radiological reports. All available histological specimens (n = 246) were reviewed independently. RESULTS: The overall incidence of gastric cancer decreased from 48.8 per 100,000 person-years in the 1940s to 11.6 per 100,000 in the 1980s, whereas the incidence of adenocarcinoma of the cardia did not change significantly during the 50-year period. The incidence of adenocarcinoma of the esophagogastric junction increased from 0.0 to 1.9 per 100,000 person-years, but the number of cases was small. CONCLUSIONS: The incidence of adenocarcinoma of the gastric cardia has not increased in this population. The reported increase in cardia cancer in other populations may be due to an increasing incidence of adenocarcinoma of the esophagogastric junction.

Adenocarcinoma↗
PubMed1995

Collagenous colitis: mucosal biopsies and association with fecal leukocytes.

OBJECTIVE: To determine the frequency of patchy colonic involvement, fecal leukocytosis, and association with celiac sprue in a large cohort of patients with collagenous colitis. DESIGN: We conducted a retrospective review of the medical records of 172 consecutive Mayo Clinic patients in whom collagenous colitis had been diagnosed between 1982 and 1993. METHODS: For each of the 172 patients, the medical record was reviewed to determine the frequency of (1) fecal leukocytosis; (2) characteristic histologic findings in the rectum and the sigmoid, descending, and ascending colon; and (3) small bowel biopsy findings consistent with celiac sprue. RESULTS: The presence of fecal leukocytes was noted in 64 of 116 patients (55%) who had undergone assessment for fecal leukocytosis. On analysis of histologic findings, 113 of 123 rectal, 116 of 121 sigmoid, and 68 of 70 descending colon biopsy specimens were diagnostic of collagenous colitis. Small bowel biopsies were performed in 45 patients who did not have a history of small intestinal disease: 1 had celiac sprue and 44 had normal findings. Two other patients had previously diagnosed celiac sprue. CONCLUSION: The finding of fecal leukocytes in 55% of patients with collagenous colitis confirms the inflammatory basis of this disease. Biopsy specimens obtained by flexible sigmoidoscopy seem sufficient to establish the diagnosis in most patients, and colonoscopic biopsy of the more proximal area of the colon is usually unnecessary. Celiac sprue infrequently accompanies collagenous colitis; thus, routine small bowel biopsy is not warranted.

Adolescent↗
PubMed1994

Cytomegalovirus as an exacerbating factor in ulcerative colitis.

Cytomegalovirus (CMV) colitis has been reported infrequently in patients with underlying inflammatory bowel disease, and usually in those who are taking long-term corticosteroid drugs and who are potentially immunosuppressed. We report a 39-year-old man with long-standing ulcerative colitis, taking only sulfasalazine, who developed a viral prodrome followed by bloody diarrhea. Severe colitis was noted on endoscopy. He worsened with intravenous steroid and antibiotic drugs. Flexible sigmoidoscopy with biopsy before a contemplated colectomy revealed a moderately active colitis with large cells containing intranuclear inclusions scattered throughout the biopsies, characteristic of CMV colitis. Serologic and immunologic studies suggested recent CMV infection. The patient improved with intravenous ganciclovir and a steroid taper, and colectomy was avoided. CMV colitis is a potentially treatable cause of fulminant colitis.

Adult↗
PubMed1994

Epidemiology of celiac sprue: a community-based study.

OBJECTIVE: To address the frequency and outcome of celiac disease in a United States community. METHODS: We identified all Olmsted County, Minnesota, residents diagnosed with this condition during the period, 1960 through 1990, using the resources of the Rochester Epidemiology Project. Twenty-eight incident cases (19 women, nine men) were identified. RESULTS: The overall age- and gender-adjusted incidence of celiac disease in the community was 1.2 per 100,000 person-yr (95% CI 0.7, 1.6). There were no significant changes in incidence over time, although rates did increase; the incidence was similar in men and women and rose with age in both genders (p < 0.05). Survival in this inception cohort was 100% at 6 months and 96% at 5 yr, which was not significantly different from expected. The estimated prevalence on January 1, 1991, was 21.8 per 100,000. CONCLUSION: This study provides the first epidemiologic data on celiac disease in the United States.

Adult↗
PubMed1993

Significance of HLA DR4 in type 1 autoimmune hepatitis.

BACKGROUND: HLA DR3 and DR4 have been recognized as independent risk factors for autoimmune hepatitis. We compared the clinical features and prognosis of patients with HLA DR4 to those with HLA DR3 and other phenotypes to determine if subclassification by HLA is a valid consideration. METHODS: Forty-four patients with HLA DR4; 41 patients with HLA DR3; and 16 patients with neither allele were studied. Ninety patients were treated with corticosteroids. RESULTS: Patients with HLA DR4 were older (51 +/- 2 years vs. 38 +/- 3 years, P = 0.0001) and more commonly women (89% vs. 68%, P = 0.04) than counterparts with HLA DR3. Additionally, these patients had higher serum immunoglobulin G levels (3300 +/- 216 mg/dL vs. 2732 +/- 192 mg/dL, P = 0.05) and a greater frequency of concurrent immunologic diseases (59% vs. 27%, P = 0.005). Similar differences in clinical presentation distinguished the patients with HLA DR4 from those with other phenotypes. Remission during corticosteroid therapy (85% vs. 63%, P = 0.05) occurred more commonly in the patients with HLA DR4 than in those with HLA DR3 and treatment failure (10% vs. 32%, P = 0.03) occurred less frequently. CONCLUSIONS: Patients with HLA DR4 have a different clinical profile than counterparts with other phenotypes, and they have a better response to corticosteroid therapy than patients with HLA DR3. Subclassification of patients by HLA DR phenotype may have clinical and prognostic value.

Adrenal Cortex Hormones↗
PubMed1993

Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis.

BACKGROUND: Antibodies to soluble liver antigen, P450IID6, and the E2 subunits of mitochondrial dehydrogenase complexes occur in autoimmune liver diseases, but their specificities and implications are uncertain. The aims of the present study were to assess the importance of these autoantibodies in different types of chronic hepatitis. METHODS: Sera from 62 patients with autoimmune hepatitis, 37 patients with cryptogenic hepatitis, and 19 patients with chronic hepatitis C were assessed under code by enzyme immunoassay. RESULTS: Antibodies to soluble liver antigen were found in 7 patients with autoimmune hepatitis (11%) and 5 patients with cryptogenic disease (14%). Patients with antibodies to soluble liver antigen were indistinguishable from seronegative counterparts with autoimmune hepatitis. Seropositive patients with cryptogenic hepatitis had autoimmune features, and they responded to corticosteroid therapy. Five patients (8%) with autoimmune hepatitis were seropositive for antibodies to mitochondrial complexes. Three lacked antimitochondrial antibodies. None of the patients had antibodies to P450IID6, and patients with chronic hepatitis C were seronegative for all markers. CONCLUSIONS: Antibodies to soluble liver antigen do not define a distinct subgroup of patients with autoimmune hepatitis. They may be found in some patients with corticosteroid-responsive cryptogenic hepatitis. Antibodies to E2 subunits and P450IID6 are uncommon in adults with chronic hepatitis.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1993

Evidence against hepatitis viruses as important causes of severe autoimmune hepatitis in the United States.

To determine if the hepatitis viruses are important etiologic factors in autoimmune hepatitis, the clinical, immunoserologic, virologic and HLA phenotypes of 105 of the latter patients were assessed prospectively and compared to 45 patients with chronic viral hepatitis. Patients with autoimmune hepatitis were more often women with higher serum aspartate aminotransferase and immunoglobulin levels than patients with viral disease. Only eight patients (8%) were seropositive for anti-HBc and anti-HBs (four patients) or anti-HCV (four patients) and none with anti-HCV were reactive by second generation immunoassay or recombinant immunoblot assay. Smooth muscle (90 vs. 22%, P < 0.001) and antinuclear (70 vs. 22%, P < 0.001) antibodies were more common in patients with autoimmune hepatitis and the titers more frequently exceeded 1:80 (84 vs. 11%, P < 0.0001). Patients with autoimmune hepatitis were more often positive for HLA B8 (48 vs. 20%, P < 0.01) and DR3 (49 vs. 20%, P < 0.003) and they more frequently had the HLA A1-B8-DR3 phenotype (38 vs. 10%, P < 0.003). Only one of the 120 patients tested for anti-LKM1 was seropositive. We conclude that in an American referral population autoimmune hepatitis usually lacks virologic markers and has a distinctive clinical, immunoserologic and HLA phenotype. Hepatitis viruses are not important immunogenic stimuli for non-organ specific antibodies and they are unlikely to be important causes of this form of autoimmune hepatitis.

Adult↗
PubMed1992

Expression of p53 and 17p allelic loss in colorectal carcinoma.

Mutations in the p53 gene are the most common genetic changes in cancer thus far. Many p53 mutations result in a protein product having a prolonged half-life compared to wild-type p53. The mutant protein is frequently detectable immunohistochemically, whereas the wild-type p53 present in normal cells is not. We examined 90 colorectal carcinomas for increased expression of p53 using 3 p53 specific monoclonal antibodies, PAb1801, PAb421, and PAb240. Overall, 70% of the colorectal carcinomas stained for p53. Each tumor's DNA was also assessed for loss of heterozygosity on chromosome 17p, the location of the p53 gene. Of those tumors that reacted with the anti-p53 antibodies, 76% showed loss on chromosome 17p. Tumors with loss of heterozygosity on 17p generally stained with all 3 antibodies, whereas those without loss tended to stain with just one antibody, typically PAb240. Fifteen tumors were examined for the presence of specific p53 mutations. A total of 10 mutations were found, 6 were missense and 2 were deletions, and all but one of the tumors with missense mutations stained for p53.

Alleles↗
PubMed1992

Early gastric cancer.

Early gastric cancer comprises more than 30 per cent of gastric carcinomas treated in Japan but remains an uncommon entity in the western hemisphere. A retrospective review of 48 patients with early gastric cancer undergoing operative treatment between 1965 and 1984 was carried out. The mean patient age was 70 years, in 31 men and 17 women. Preoperative diagnosis was made in 88 per cent of patients undergoing oesophagogastroduodenoscopy with biopsy but upper gastrointestinal radiography was diagnostic in only 20 per cent. Surgical management consisted of subtotal gastrectomy (86 per cent), total gastrectomy (10 per cent) and wide local excision (4 per cent). The operative mortality and morbidity rates were 0 and 38 per cent, respectively. Mean follow-up was 7.7 years, with 44 per cent of patients still alive. Multivariate analysis disclosed only a healthy Eastern Cooperative Oncology Group score (P = 0.002) and a diploid DNA tumour pattern (P = 0.05) as significant prognostic variables of survival. The overall survival rate of patients with early gastric cancer (70 per cent at 5 years) was equivalent to that of an age- and sex-matched control population.

Aged↗
PubMed1992

Sequential histologic evaluations in collagenous colitis. Correlations with disease behavior and sampling strategy.

To evaluate the histologic manifestations of collagenous colitis and correlate histologic changes with disease behavior, 14 patients who had undergone sequential evaluations during 33 +/- 6 months of follow-up were studied. Two hundred twelve tissue specimens from all anatomic regions of the colon (mean, 15 +/- 3 samples per patient) were interpretated independently under code by two pathologists. Eight patients (57%) had histologic resolution after 14 +/- 4 months of empiric therapy and in only one of these (12%) did symptoms persist. Four patients (29%) had sequential histologic examinations from the same anatomic region that varied from classical collagenous colitis to inflamed mucosa without a thickened collagen band to normal mucosa. Eight patients (57%) had varying histologic findings from different anatomic regions during the same examination that ranged from classical collagenous colitis to increased inflammation with resolution of the collagen band to normal mucosa. Normal mucosa was found mainly in specimens from the rectosigmoid, and proctosigmoidoscopic examinations alone would have missed the diagnosis of collagenous colitis in 40% of cases. Pathologic interpretations were concordant in 171 of 212 instances (81%). We conclude that histologic resolution of collagenous colitis can occur and it is associated with loss of symptoms. The histologic features of collagenous colitis are distinctive, but they may be patchy and inconsistently sampled. Rectosigmoid biopsies underestimate the diagnosis.

Adult↗
PubMed1992

Dysplasia in chronic ulcerative colitis: implications for colonoscopic surveillance.

Mucosal dysplasia has been used as a marker for patients with chronic ulcerative colitis considered to be most at risk of developing cancer, and its identification is the basis for colonoscopic surveillance programs. To evaluate the reliability of this premise, colectomy specimens from two groups of patients who had undergone surgery for chronic ulcerative colitis (50 with cancer and 50 without) were retrieved. The groups were matched by age, sex, duration of disease, disease extent, and symptoms at the time of surgery. Using a standard technique of multiple random biopsies, we utilized the standard colonoscopic biopsy forceps to obtain four biopsies from mucosa that was not macroscopically suspicious for dysplasia or cancer in eight defined regions in each of the 100 colon specimens. This technique mimicked exactly the methods used in our clinical surveillance program. All 3,200 biopsies were evaluated blindly by one pathologist for presence and grade of dysplasia. Twenty-six percent of colons with an established cancer harbored no dysplasia in any biopsy from any region in the colon. While an overall association between the presence of cancer and high-grade dysplasia was detected (relative risk = 9.00; 95 percent CI of 2.73-29.67), the sensitivity and specificity of random colonic biopsies to detect concomitant carcinoma were 0.74 and 0.74, respectively. These findings prompt concern that reliance on random biopsies, obtained during colonoscopic surveillance, may be misplaced.

Adult↗
PubMed1992

Barrett's esophagus with high-grade dysplasia: an indication for esophagectomy?

Between 1982 and 1991, 19 patients (17 men and 2 women) with Barrett's esophagus, 10 of whom were in a surveillance program, were found to have high-grade dysplasia without evidence of invasive carcinoma. Median age was 66 years (range, 30 to 79 years). Heartburn was the most common presenting symptom. Esophagoscopy at the time of high-grade dysplasia diagnosis demonstrated normal Barrett's mucosa in 10 patients (53%), shallow ulcers in 3, slight mucosal irregularities in 2, small mucosal nodules in 2, stricture in 1, and shallow ulcer with stricture in 1. Eighteen patients underwent esophagectomy. There were no operative deaths. Nine patients (50%) had invasive carcinoma. Postsurgical stage was stage 0 in 9 patients, stage I in 6, stage IIA in 2, and stage IIB in 1. Median follow-up was 34 months (range, 2 to 116 months). Recurrent cancer developed in 2 patients. Overall 5-year survival was 66.7%; 5-year survival for patients with stage 0 disease was 100% and for stage I and II disease, 35.7%. We conclude that high-grade dysplasia in an indication for esophageal resection because of the high rate of associated early invasive carcinoma and that resection can be done safely with the expectation of excellent long-term survival. Because of these findings, we continue to recommend endoscopic surveillance in all patients with Barrett's esophagus.

Adenocarcinoma↗