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Biomedical subjects

H A Carpenter

Publications and source records attributed to H A Carpenter.

At least 55 records · Page 3Linked to original sources
PubMed1993

The nature and prognosis of severe cryptogenic chronic active hepatitis.

BACKGROUND: Cryptogenic chronic active hepatitis may be an autoimmune or viral disease. Our aims were to determine the clinical features, human leukocyte antigen phenotype, and response to corticosteroid therapy of severe cryptogenic chronic active hepatitis and to compare it with these other diseases. METHODS: Twelve patients with cryptogenic hepatitis were compared with 94 patients with autoimmune hepatitis and 30 patients with chronic viral hepatitis. RESULTS: Patients with cryptogenic hepatitis were indistinguishable from those with autoimmune hepatitis by age, gender, and individual laboratory and histological findings. HLA B8 (75% vs. 49%, P = 0.2), DR3 (71% vs. 51%, P = 0.5), and A1-B8-DR3 (57% vs. 38%, P = 0.6) occurred as commonly in each group. Patients with cryptogenic hepatitis entered remission (83% vs. 78%, P > 0.9) and failed treatment (9% vs. 11%, P > 0.8) as frequently as those with autoimmune hepatitis during corticosteroid therapy. In contrast, patients with chronic viral hepatitis had lower biochemical abnormalities, less frequent multilobular necrosis at presentation, and different human leukocyte phenotypes than those with cryptogenic or autoimmune disease. CONCLUSIONS: Severe cryptogenic hepatitis has a clinical expression, genetic phenotype, and corticosteroid responsiveness that is similar to autoimmune hepatitis. It may be an autoimmune disorder that has escaped detection by conventional immunoserological markers.

Adult↗
PubMed1993

Sensitivity, specificity, and predictability of biopsy interpretations in chronic hepatitis.

BACKGROUND: To determine the frequency of individual histological findings in different types of chronic hepatitis and to assess the sensitivity, specificity, and predictability of histological patterns in distinguishing these types, liver biopsy specimens were examined from 86 patients with autoimmune hepatitis (43 patients), chronic hepatitis B (11 patients), chronic hepatitis C (21 patients), and cryptogenic hepatitis (11 patients). METHODS: Specimens were examined under code by a single hepatopathologist, and predefined histological features were sought. A histological diagnosis was rendered based on composite changes. RESULTS: Patients with chronic hepatitis C had a higher frequency of portal lymphoid aggregates (76% vs. 42%, P = 0.02) and steatosis (52% vs. 16%, P = 0.006) than patients with autoimmune hepatitis, whereas the latter patients more commonly had severe periportal hepatitis (23% vs. 0%, P = 0.02), moderate to severe plasma cell infiltration of the portal tracts (66% vs. 21%, P = 0.005), and lobular hepatitis (47% vs. 16%, P = 0.04). Patients with chronic hepatitis B had a higher frequency of ground-glass hepatocytes (36% vs. 0%, P = 0.001) and multinucleated giant cells (54% vs. 2%, P = 0.0001) than those with autoimmune hepatitis and chronic hepatitis C. The histological diagnoses for these clinical entities had high specificity (81%-99%) and predictability (62%-91%) but low sensitivity (36%-57%). CONCLUSIONS: Autoimmune hepatitis, chronic hepatitis B, and chronic hepatitis C have characteristic individual histological features. Histological patterns based on these features have high specificity and predictability but low sensitivity.

Adult↗
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↗
PubMed1992

Long-term nonsteroidal anti-inflammatory drug use and gastroduodenal injury: the role of Helicobacter pylori.

To evaluate the association of Helicobacter pylori infection with gastroduodenal ulceration and symptoms in rheumatoid arthritis patients chronically ingesting nonsteroidal anti-inflammatory drugs (NSAIDs), a population-based study was performed. Residents of Olmsted County, Minnesota, and surrounding counties, 40 years of age and over with active rheumatoid arthritis taking therapeutic dose of NSAIDs daily for 6 months or more were evaluated (n = 50). An endoscopic score from 0 to 5 was assigned and independently confirmed. Biopsies were obtained from the antrum and gastric body for the presence of H. pylori. A symptom score based on the frequency and severity of dyspeptic symptoms was calculated. Substantial mucosal injury (greater than or equal to grade 2) was observed at endoscopy in 33 patients (66%); 14 (28%) had chronic ulcers. Eleven of the community patients with rheumatoid arthritis (22%) were H. pylori positive; adjusting for age, the prevalence of H. pylori was not significantly different to that in 67 health controls (25%). One or more upper gastrointestinal symptoms were reported by 19 of the community patients (38%). Adjusting for age, community rheumatoid arthritis patients with H. pylori were not more likely to have visible mucosal damage or dyspepsia, but were significantly more likely to have histological gastritis (P less than 0.01). The results suggest that, in primarily asymptomatic persons from the community with rheumatoid arthritis taking daily NSAIDs for 6 months or more, H. pylori infection is not related to the severity of visible mucosal injury.

Adult↗
PubMed1992

Deposition of eosinophil granule major basic protein in eosinophilic gastroenteritis and celiac disease.

Degrees of eosinophil infiltration and eosinophil degranulation, as evidenced by localization of the eosinophil granule major basic protein (MBP), were compared in patients with eosinophilic gastroenteritis, patients with celiac disease, and healthy controls using a specific indirect immunofluorescence technique for the localization of MBP. Formalin-fixed, paraffin-embedded biopsy specimens from the mucosa of the stomach and small intestine of 11 patients with eosinophilic gastroenteritis, from the small intestine of 4 patients with celiac disease, and from the stomach and/or upper small intestine of 18 healthy asymptomatic volunteers were tested. Degrees of eosinophil infiltration and extracellular deposition of MBP were graded by two blinded observers; each section was given a score from 0 (nil) to 4 (marked). In the small bowel biopsy specimens, both eosinophil infiltration and extracellular MBP deposition scores were significantly greater in patients with eosinophilic gastroenteritis and in patients with celiac disease than in controls. In the gastric biopsy specimens, extracellular MBP deposition scores were significantly increased in patients with eosinophilic gastroenteritis compared with controls even though eosinophil infiltration scores did not differ significantly at this site. The results support the hypothesis that the eosinophil, through toxic cationic proteins such as MBP, plays a role in the pathogenesis of these diseases.

Adolescent↗
PubMed1992

Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis.

To assess the prevalence and significance of chronic ulcerative colitis in patients with severe autoimmune hepatitis and to determine the frequency of cholangiographic and histologic features of primary sclerosing cholangitis in those with colitis, 105 patients who had been screened by annual proctoscopic examination were studied. Patients with features of colitis were compared to counterparts without colitis who had been matched by age, sex, disease severity and treatment regimen. Seventeen patients (16%) had findings of chronic ulcerative colitis. Twelve of these underwent cholangiography and five (42%) had features of primary sclerosing cholangitis. Patients with and without cholangiographic abnormalities were indistinguishable by clinical, laboratory, immunoserologic, and histologic features. Fibrous obliterative cholangitis was present in only two patients, including one with normal cholangiography. Patients with colitis entered remission less frequently (59 vs. 94%, p less than 0.05), failed treatment more commonly (41 vs. 6%, p less than 0.05) and progressed to cirrhosis more frequently (75 vs. 25%, p less than 0.05) than counterparts without colitis. Patients with colitis but normal cholangiography, however, responded satisfactorily to therapy. We conclude that chronic ulcerative colitis can coexist with severe autoimmune hepatitis in the absence of primary sclerosing cholangitis or hepatitis C infection. Under such circumstances its presence does not adversely influence treatment outcome. Primary sclerosing cholangitis cannot be excluded by routine examinations and its presence is associated with a poor treatment response. Cholangiography should be considered in all patients with autoimmune hepatitis and colitis, especially in those recalcitrant to therapy.

Adult↗
PubMed1991

Gastric adenocarcinoma and Helicobacter pylori infection.

Helicobacter pylori infection, thought to be causally related to chronic gastritis, may also be associated with an increased risk of gastric cancer. To determine whether an association with gastric cancer does exist, we retrospectively evaluated serum samples from 69 patients with histologically confirmed gastric adenocarcinoma (32 with cancer at the cardia and 37 with cancer at other sites) and from 218 patients with one of three categories of nongastric cancers, with other gastric cancers, or with benign gastric neoplasms. These samples were compared with samples from 252 cancer-free control subjects, a group comprising 76 asymptomatic volunteers and 176 persons with nonmalignant disorders. Serum samples collected from cancer patients prior to surgery and from cancer-free controls were tested for antibodies to H. pylori by using a highly sensitive and specific IgG enzyme-linked immunosorbent assay. The risk of H. pylori infection in the case patients relative to the control subjects was estimated with the use of multivariate logistic regression analysis to adjust for potential confounding variables. Antibodies to H. pylori were detected in 65% of the patients with noncardia gastric cancer but in only 38% of the patients with gastric cancer located at the cardia. A significant association was found between H. pylori infection and noncardia gastric cancer (odds ratio = 2.67; 99% confidence interval = 1.01-7.06). Within the subset of patients with noncardia gastric cancer, a statistically nonsignificant tendency existed for those with the intestinal versus the diffuse histologic type of noncardia gastric cancer to have a higher risk of H. pylori infection. Our results support the hypothesis of a relationship between H. pylori infection and the development of noncardia gastric adenocarcinoma.

Adenocarcinoma↗
PubMed1991

Eosinophil infiltration and degranulation in Helicobacter pylori-associated chronic gastritis.

Eosinophil granules contain cationic proteins, including the major basic protein, which are toxic to mammalian tissue. While eosinophils have been observed to comprise part of the inflammatory reaction in acute Helicobacter pylori gastritis, the role of the eosinophil in the pathogenesis of chronic gastritis is unknown. We evaluated whether eosinophil infiltration and degranulation are associated with chronic gastritis and H. pylori infection. We studied eight patients with chronic H. pylori antral gastritis, three with chronic antral gastritis in the absence of H. pylori, 11 healthy age-matched volunteers without antral gastritis, and eight patients with H. pylori-negative chronic specific gastritis (three Crohn's antral gastritis and five Ménétrier's disease). Serial sections were stained with hematoxylin and eosin, with Giemsa, and by a specific indirect immunofluorescence technique for eosinophil granule major basic protein. Specimens were graded independently by three observers and scores of 0-3 were given for eosinophil infiltration and degranulation (0 = none to 3 = confluent infiltration and/or degranulation). In H. pylori antral gastritis, significantly greater eosinophil infiltration and degranulation were found compared to the normal group, Ménétrier's disease, and chronic H. pylori-negative gastritis. There was no significant difference between gastric Crohn's disease and H. pylori gastritis. The severity of chronic gastritis was significantly correlated with the eosinophil score. Eosinophil degranulation did not appear to be greater at or near sites of bacterial colonization in the H. pylori gastritis specimens. The results suggest that eosinophil infiltration and degranulation may be associated with H. pylori gastritis. We postulate that the release of toxic cationic proteins from eosinophils contributes to the inflammatory changes present in H. pylori gastritis.

Cell Degranulation↗
PubMed1991

Prevalence of Helicobacter pylori in specific forms of gastritis. Further evidence supporting a pathogenic role for H. pylori in chronic nonspecific gastritis.

Helicobacter pylori colonization of the gastric mucosa is strongly associated with chronic nonspecific gastritis; moreover, there is evidence to suggest that H. pylori may cause this form of gastritis. However, there is little or no information on the prevalence of H. pylori in specific forms of gastritis. Our hypothesis was that if H. pylori was pathogenic in chronic nonspecific gastritis, organisms would be found frequently in this type of gastritis but infrequently in specific forms of gastritis. Prevalence rates of H. pylori were determined independently in patients with eosinophilic and Crohn's gastritis, Menetrier's disease, and chronic nonspecific gastritis. The prevalence of H. pylori in patients with chronic nonspecific gastritis was 71%, whereas the organism was not identified in patients with any form of specific gastritis. This finding further supports the accumulating evidence that H. pylori is a primary pathogenic factor in chronic nonspecific gastritis.

Adolescent↗
PubMed1991

The effect of somatostatin 201-995 on the early course of porcine pancreaticoduodenal allotransplantation.

This study was undertaken to determine the effects of somatostatin 201-995 (SMS) on the maintenance dose of intravenous cyclosporine and on graft blood flow, exocrine secretion, and rejection after porcine pancreaticoduodenal allotransplantation (PDA). For seven days, 12 pigs (6 control, 6 SMS-treated) were studied to determine the effects of SMS on serum CsA concentrations. Twenty-six pigs (14 control, 12 SMS) with streptozocin-induced diabetes underwent PDA. Blood flow was measured through graft celiac and superior mesenteric arteries 15 and 60 min after reperfusion. SMS (75 micrograms s.c.) was given after the 15-min blood-flow measurement in the SMS group. Sixteen pigs (8 control, 8 SMS) were followed postoperatively with daily measurements of serum glucose and amylase concentrations, and urine amylase and trypsin activities. All pigs were immunosuppressed with azathioprine, prednisone, and i.v. CsA. SMS pigs also received SMS (75 micrograms s.c.) every 8 hr. SMS had no effect on maintenance dose of CsA or on serum amylase, urine amylase, or urine trypsin activities. Mean days to rejection were also not affected. Intraoperative graft blood flow was significantly decreased by SMS, but incidence of graft thrombosis was unchanged. These results suggest that in the porcine PDA model, SMS does not appear to inhibit exocrine secretion and potentially may adversely affect the early course of PDA by decreasing graft blood flow.

Animals↗
PubMed1991

Serodiagnosis of Helicobacter pylori: comparison of enzyme-linked immunosorbent assays.

Enzyme-linked immunosorbent assays (ELISAs) have been developed to diagnose Helicobacter pylori infection. However, the methods are not standardized. We therefore prospectively evaluated the sensitivities and specificities of ELISAs developed in the United States and the United Kingdom in a study population comprising 41 consecutive symptomatic outpatients and 35 volunteers. At endoscopy, multiple biopsies were obtained for histology and culture and stained sections were graded for chronic gastritis, active chronic gastritis, and density of H. pylori. Serum samples were analyzed for H. pylori by ELISA. The first set of assays for immunoglobulin G (IgG) and IgA used a pool of sonicated isolates of H. pylori from five patients in the United States (antigen A). The second set of assays, developed in the United Kingdom, used three different antigens: antigen 1, an acid-extractable surface antigen; antigen 2, an acid-extractable antigen from an aflagellate variant; and antigen 3, a urease-containing fraction. Cutoff scores for positive results were determined a priori on the basis of previous serological studies. There was close agreement between histology and culture. In the study population, 36% of the individuals were H. pylori positive. The diagnostic value of the different ELISAs were highly comparable, and the crude antigens performed as well as the more purified antigens. The antigen A IgG had a sensitivity and specificity of 96 and 94%, respectively; the values for antigen 1 were 93 and 96%, respectively. The antigen A IgA and antigen 3 assays were the least sensitive tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗