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H A Carpenter

Publications and source records attributed to H A Carpenter.

At least 37 records · Page 2Linked to original sources
PubMed1996

Genetic predispositions for immunological features in chronic liver diseases other than autoimmune hepatitis.

BACKGROUND/AIMS: Human leukocyte antigens DR3 and DR4 influence susceptibility for type 1 autoimmune hepatitis and affect its immunological manifestations. We aimed to determine if autoimmune features in patients with chronic liver diseases other than autoimmune hepatitis are associated with these same antigens. METHODS: One hundred and seventy-eight patients were evaluated. Class II typing was performed by restriction fragment length polymorphism in all patients and 80 normal subjects. RESULTS: One or more autoantibodies, including antinuclear antibodies (28%), smooth muscle antibodies (8%), thyroid antibodies (18%) and antimitochondrial antibodies (13%), were found in 92 patients (52%). Concurrent clinical diseases of an immunological nature were recognized in 53 patients (30%). Patients with antinuclear antibodies had a higher frequency of the A1-B8-DR3 haplotype than patients without these antibodies (27% versus 12%, p = 0.04) and patients with concurrent immunological diseases had a higher frequency of HLA DR4 than patients without this antigen (51% versus 26%, p = 0.003). Patients with antinuclear antibodies were more commonly DR3 positive than normals (35% versus 16%, p = 0.03) and patients with concurrent immunological diseases were more commonly HLA DR4 positive than normals (51% versus 30%, p = 0.02). CONCLUSIONS: We conclude that the clinical expression of antinuclear antibodies is associated with the A1-B8-DR3 haplotype and the presence of concurrent immunological diseases is related to the DR4 antigen. These clinical manifestations have a genetic basis that is not disease-specific.

Adult↗
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

Immunolocalization of transforming growth factor-alpha in normal and diseased human gastric mucosa.

Roles for transforming growth factor-alpha (TGF alpha) in the stomach include cell migration and proliferation, inhibition of acid secretion, and cytoprotection. The authors have previously shown increased TGF alpha expression in rat gastric mucosa in response to acute gastric injury. They also have shown that TGF alpha immunoreactivity is increased in the gastric mucosa of four patients with Ménétrier's disease. To further characterize TGF alpha immunoreactivity in human gastric mucosa, the authors have performed immunohistochemical analysis with an anti-TGF alpha monoclonal antibody on human gastric biopsies (n = 25) showing either normal (n = 8), mild reactive/reparative change in common conditions with or without associated gastritis (n = 13), and exaggerated mucosal change in proliferative conditions (Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic polyps) (n = 17). All normal biopsies showed a predictable pattern of TGF alpha immunostaining, with significant positivity found only in foveolar cells at the luminal surface and parietal cells, sparing foveolar cells in the gastric pits, mucous neck cells and chief cells of the gastric glands. Three patients with mild foveolar hyperplasia without associated inflammation did not deviate from the normal pattern except in foci of reactive epithelial change. Ten of 11 patients with chronic active gastritis, in addition to this normal staining pattern, demonstrated significant immunoreactivity in deeper foveolar cells and mucous neck cells showing reactive epithelial changes, defined as the presence of nuclear enlargement and nucleolar prominence with or without mucin depletion. Three cases of ulceration with associated reactive epithelial changes also showed increased immunoreactivity. Furthermore, five cases of Ménétrier's disease with massive foveolar hyperplasia and minimal inflammation (MFH) and six cases with hypertrophic lymphocytic gastritis (HLG) have been studied, and both show full-thickness TGF alpha immunoreactivity restricted to the gastric epithelium. This pattern of staining is indistinguishable from that observed in two cases of hyperplastic polyps but differs significantly from that observed in cases of mild foveolar hyperplasia. These results further define patterns of TGF alpha immunostaining in normal, reactive/reparative and exaggerated proliferative human gastric biopsies, confirm participation of TGF alpha in the response to gastric mucosal injury, and provide additional support for a possible role for TGF alpha in the pathogenesis of proliferative gastric disorders including Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic gastric polyps.

Gastric Mucosa↗
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

Genetic predispositions for the immunological features of chronic active hepatitis.

To assess the frequency and genetic predispositions of concurrent immunological diseases and immunoserological markers in autoimmune hepatitis and chronic viral hepatitis, we assessed 185 patients prospectively, including 122 patients with autoimmune hepatitis and 63 patients with viral disease. Human leukocyte antigens were determined in all patients. Sixty patients (32%) had concurrent immunological diseases, and the majority of the diseases (68%) had known human leukocyte antigen associations. Although patients with autoimmune hepatitis had concurrent immunological diseases more commonly than those with viral disease (38% vs. 22%; p = 0.04), the nature of the diseases was similar in both groups, as were the frequencies of human leukocyte antigen-DR4 (42% vs. 39%; p = 0.7). The presence of human leukocyte antigen-DR4 was associated with the concurrence of immunological diseases in both autoimmune (62% vs. 33%; p = 0.01) and viral hepatitis (75% vs. 29%; p = 0.009). In autoimmune hepatitis, human leukocyte antigen-DR4 was also associated with the expression of smooth muscle antibodies and high-titer antinuclear antibodies. We conclude that concurrent immunological diseases and immunoserological markers are common in autoimmune and chronic viral hepatitis. Both conditions have a common genetic predisposition for concurrent immunological disease associated with human leukocyte antigen-DR4. The expression of smooth muscle antibodies and high-titer antinuclear antibodies is associated with human leukocyte antigen-DR4 in autoimmune hepatitis only, suggesting that this response is associated with triggering antigens and immune recognition systems that are different from those in viral disease.

Antibodies, Antinuclear↗
PubMed1993

Influence of pancreatic and biliary reflux on the development of esophageal carcinoma.

We previously presented an experimental model of Barrett's adenocarcinoma of the esophagus by demonstrating that esophagojejunostomy combined with subcutaneous injection of 2,6-dimethylnitrosomorpholine in Sprague-Dawley rats resulted in development of adenocarcinoma in the distal esophagus. The present study was devised to investigate the influence of pancreatic and biliary duodenal-content reflux on the induction of esophageal carcinoma. Three groups of 8-week-old Sprague-Dawley rats were controls: the first was exposed to pancreatic reflux, the second to biliary reflux, and the third to both. The other three experimental groups were similar except that a 1/100 LD50 dose of 2,6-dimethylnitrosomorpholine was injected subcutaneously weekly, starting on day 15. Carcinoma of the esophagus was induced only in animals receiving the carcinogen after exposure to either pancreatic reflux (3/22, 13%) or pancreatic and biliary reflux (9/27, 33%). Half of the carcinomas were adenocarcinoma and half were squamous cell carcinoma. These findings suggest that under these experimental conditions, in which the carcinogen is used in a low dose, esophageal carcinoma is induced only when pancreatic secretions are present in the duodenal-content reflux. Biliary reflux, however, appears to exert a cocarcinogenic effect when combined with pancreatic secretions. The clinical relevance of these findings needs further evaluation. Conceivably, the elimination of pancreatic and biliary duodenal-content reflux in patients with documented Barrett's mucosa may inhibit the progression from metaplasia to adenocarcinoma.

Adenocarcinoma↗
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

Menetrier's disease: a form of hypertrophic gastropathy or gastritis?

BACKGROUND: Menetrier's disease is characterized by giant gastric folds and foveolar hyperplasia. The extent of mucosal inflammation and glandular atrophy, however, is controversial. The aim of this study was to test the hypothesis that patients previously diagnosed with Menetrier's disease actually represent at least two diseases: (1) Hypertrophic lymphocytic gastritis (HLG) and (2) Massive foveolar hyperplasia and minimal inflammation (MFH). METHODS: All cases of possible Menetrier's disease were identified, and their clinical, laboratory, and pathological data were reviewed. In twenty-three patients with giant fundal folds, full-thickness tissue specimens (n = 19) or large suction biopsy (n = 4) tissue specimens were obtained. RESULTS: Two distinct, nonoverlapping histological patterns were found; 13 patients had HLG and 10 patients had MFH. Clinical features and frequency of Helicobacter pylori were similar in these two groups. Patients with HLG had severe inflammation with numerous intraepithelial lymphocytes and mild foveolar hyperplasia. Alternatively, patients with MFH had greater foveolar hyperplasia, significantly thicker mucosa, and greater mucosal edema. CONCLUSIONS: Patients with MFH represent a form of hypertrophic gastropathy and should be designated as having Menetrier's disease, whereas patients with HLG should be considered part of the spectrum of lymphocytic gastritis.

Adult↗
PubMed1993

Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction.

BACKGROUND: The aim of this study was to determine whether the incidence of adenocarcinoma of the esophagus and esophagogastric junction in a well-defined population was higher than previously recognized. METHODS: Clinical records and original histological slides from patients residing in Olmsted County, Minnesota, were reviewed and compared with a previous study in the same population. RESULTS: The incidence of esophageal adenocarcinoma rose from 0.13 for 1935-1971 to 0.74 for 1974-1989, and the incidence of adenocarcinoma of the esophagogastric junction rose from 0.25 to 1.34 per 100,000 person-years. Histological review of preserved surgical specimens showed associated intestinal metaplasia (Barrett's esophagus) in 2 of 2 esophageal and in 5 of 9 esophagogastric adenocarcinomas. CONCLUSIONS: The incidence of adenocarcinoma in each location increased five to sixfold compared with the earlier study. This increase could not be explained by improved diagnostic methods or classification changes. The association with Barrett's esophagus and the parallel increased incidence of cancer in each location is evidence that adenocarcinoma of the esophagus and of the esophagogastric junction are related disorders.

Adenocarcinoma↗
PubMed1993

The histological pattern and pathological involvement of the anal transition zone in patients with ulcerative colitis.

BACKGROUND: The aim was to determine whether the transitional epithelium (TE) of the anal transition zone (ATZ) was involved by chronic ulcerative colitis (CUC) and whether preserving the ATZ preserves the disease. METHODS: Proctocolectomy specimens from 50 CUC patients and 50 patients with rectal cancer serving as controls were stained with alcian-blue to map the ATZ, and biopsy specimens containing adjacent TE and rectal mucosa were examined. RESULTS: The mean inflammation score (0, none; 4, severe) in TE of controls was 0.4, whereas in CUC it was 0.5. However, the mean inflammation score of the rectal mucosa within the ATZ was 0.2 in controls and 2.6 in CUC (P < 0.001). Rectal columnar epithelium extended past half of the maximum length of TE in 75% of patients (65-83%; 95% CI) and was within 1 cm of the dentate line in 89% (81%-94%). CONCLUSIONS: Although the TE of the ATZ was not inflamed, the rectal mucosa within the ATZ was. Moreover, rectal mucosa traversed half of the length of the ATZ in 75% of patients and was within 1 cm of the dentate line in fully 89%. Preserving the ATZ may preserve the disease in the majority of patients with CUC.

Aged↗