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Biomedical subjects

H D Appelman

Publications and source records attributed to H D Appelman.

At least 19 recordsLinked to original sources
PubMed1995

Microallelotyping defines the sequence and tempo of allelic losses at tumour suppressor gene loci during colorectal cancer progression.

Microallelotyping of many regions from individual colorectal tumours was used to determine the sequence and tempo of allelic loss on 5q, 17p and 18q during neoplastic progression. No allelic losses were found in normal tissues surrounding colorectal neoplasms, but losses occurred abruptly on 5q at the transition from normal colonic epithelium to the benign adenoma, and on 17p at the transition from adenoma to carcinoma, indicating an essential role for these losses in tumour progression. Allelic losses were uniform throughout extensively microdissected benign adenomas and carcinomas. However, substantial allelic heterogeneity was found in high-grade dysplasia, the transition lesion between adenoma and carcinoma. Thus, allelic losses on 5q and 17p are associated with abrupt waves of clonal neoplastic expansion, and high-grade dysplasia is characterized by a high degree of allelic heterogeneity.

Adenocarcinoma↗
PubMed1995

Regression of hepatic steatosis in morbidly obese persons after gastric bypass.

Morbid obesity has been associated with hepatic steatosis and occasional cirrhosis. Despite producing weight loss, intestinal bypass procedures formerly performed to correct morbid obesity, often worsened steatosis and fibrosis, and occasionally resulted in hepatic failure. Current surgical procedures of choice for morbid obesity involve gastric bypass with gastrojejunostomy. Ninety-one liver biopsies taken at the time of gastric bypass for morbid obesity (mean body weight 125.8 kg), and 106 biopsies taken from the same patients from 2 to 61 months later (mean body weight 89.4 kg) were studied. Steatosis and perisinusoidal fibrosis were assessed in histologic sections. Serum albumin, alkaline phosphatase, aspartate aminotransferase (AST), and total bilirubin levels were measured before most biopsies were taken. Both pre- and post-gastric bypass hepatic steatosis varied directly with body weight (r = .5231, P < .001). Steatosis varied inversely with length of time after gastric bypass (r = .4590, P < .001). Of the original biopsies, 37% had lipid vacuoles in at least 26% of hepatocytes. After gastric bypass, 65 patients had reduced steatosis, 18 patients with no steatosis, and 5 patients with minimal steatosis had no change, and 3 patients had increased steatosis. Pre-gastric bypass biopsies from 13 patients had perisinusoidal fibrosis (PSF) that was marked with bridging in three patients, was moderate in one patient, and slight in nine patients. Following gastric bypass, PSF was eliminated in 10 patients, reduced in one patient, and the same in two patients. One patient developed PSF after gastric bypass. Of the three patients who had undergone previous intestinal bypass procedures, two had slight PSF in the biopsies taken at the time of gastric bypass, and one of these had slight PSF in the follow-up biopsy. Serum biochemical abnormalities tended to be slight. Before gastric bypass, serum albumin was low in 11% of cases, alkaline phosphatase was high in 14% of cases, AST was high in 11% of cases, and total bilirubin was high in 1% of cases. After gastric bypass, there was a small reduction in mean serum albumin from 43 g/L before to 41 g/L afterward (P < .05), and a slight rise in mean total bilirubin from 7.0 mumol/L before to 9.6 mu mol/L afterward (P < .01). Most hepatic fatty change and probably some PSF occurring in morbidly obese persons is reduced or eliminated with weight loss following gastric bypass surgery.

Adolescent↗
PubMed1995

Stromal tumors of the duodenum. A histologic and immunohistochemical study of 20 cases.

Using cell size, cell density, and microscopic growth pattern, 20 duodenal stromal tumors were initially separated into benign and malignant categories. The 10 histologic benign tumors had uniform spindle cells, low cellularity, and an organoid pattern. All had round eosinophilic collagen blobs scattered among the spindle cells, were 4.5 cm or less in maximum diameter, and had two or fewer mitoses per 50 high-power fields (HPF). None metastasized or recurred during a median follow-up of 7 years. In contrast, the 10 histologically malignant tumors were highly cellular, all had two or more mitoses per 50 HPF, and all but one had diameters of 4.5 cm or greater, the exception being 4 cm. Eight cases also had benign-appearing areas, usually submucosal. Eight patients died with disease a median of 31 months after resection, almost all with liver metastases. One patient is alive with metastasis at 13 years. The patient with the 4-cm malignant tumor is disease free at 49 months. All 15 cases were strongly vimentin positive, 11 had S-100 protein, and seven had the CD34 marker. None were desmin or actin positive. No immunophenotype separated benign from malignant. The proliferation marker, proliferating cell nuclear antigen, correlated with histologic diagnosis and clinical outcome, but Ki-67 did not. Based on light microscopic features alone, benign and malignant duodenal stromal tumors can be separated from each other. Tumors with large cells and an organoid pattern are predictably benign; in this study, these tumors measured 4.5 cm or less in diameter and had fewer than 2 mitoses per 50 HPF. Highly cellular tumors with small cells and little or no organoid pattern are malignant. They usually have a diameter greater than 4.5 cm and more than two mitoses per 50 HPF, and they are usually fatal. Immunostaining for cytoplasmic proteins and proliferation markers offers no additional prognostic information to the light microscopic appearances. These conclusions apply only to duodenal tumors; whether they also apply to stromal tumors of the jejunum and ileum is not known.

Adult↗
PubMed1995

Possible nizatidine-induced subfulminant hepatic failure.

Subfulminant hepatic failure has not been reported to occur with the histamine-2 receptor antagonists. We report a possible case of nizatidine-induced subfulminant hepatic failure leading to the eventual development of cirrhosis.

Adult↗
PubMed1995

Long-term follow-up of Helicobacter pylori treatment in non-ulcer dyspepsia patients.

BACKGROUND/AIMS: It remains controversial whether Helicobacter pylori infection causes symptoms in non-ulcer dyspepsia. One hundred non-ulcer dyspepsia patients were screened for H. pylori infection between November 1989 and February 1994. Forty patients entered a trial where both infected and uninfected patients were treated with H. pylori therapy, with the uninfected group serving as controls. METHODS: Non-ulcer dyspepsia was defined as unexplained epigastric discomfort lasting for at least 4 wk. From November 1989 until February 1992, all patients, regardless of H. pylori status, were treated with bismuth subsalicylate tablets (524 mg q.i.d.) for 4 wk and metronidazole (250 mg q.i.d.) for the first 2 of the 4 wk. From March 1992 until February 1994, only infected patients were treated in an attempt to obtain equal numbers in each group. H. pylori infection was diagnosed histologically at the index endoscopy and 1 month after completion of therapy. Symptoms were scored on a 0-5 scale for both frequency and severity. RESULTS: Of 100 patients screened, 33 were infected with H. pylori (mean age, 42; 10 men, 23 women), and 67 were uninfected (mean age, 38; 16 men, 51 women). Thirty-six uninfected patients were not offered treatment during the latter part of the trial. Of the remaining 31 uninfected patients, 10 dropped out; of the 33 infected patients, 14 dropped out. Twenty-one uninfected patients and 19 H. pylori-infected patients completed treatment; in 13 of 19 patients (68%), H. pylori was eradicated. Symptoms improved in eight of 13 (61%) H. pylori-eradicated patients and in four of six (66%) H. pylori-persistent patients, compared with 14 of 21 (66%) uninfected patients. Long-term follow-up (mean, 34 months) showed similar symptom outcome in the two treatment groups. CONCLUSIONS: Thirty-three percent of our non-ulcer dyspepsia patients were infected with H. pylori, a number similar to the percentage of infected age-matched controls in the U.S. Treatment with bismuth subsalicylate and metronidazole resulted in symptomatic improvement in 61-66% of non-ulcer dyspepsia patients regardless of initial or post-treatment H. pylori status. Long-term symptom follow-up in both the control and infected groups gave similar results. H. pylori infection is not related to the symptoms of non-ulcer dyspepsia.

Adult↗
PubMed1994

Gastritis: terminology, etiology, and clinicopathological correlations: another biased view.

The histological approach to gastritis, especially the chronic forms, has undergone a series of re-evaluations by different experts over the past decade, mainly because of the recognition of individual disease patterns that have specific clinical and epidemiological implications. The most spectacular of these was the discovery of Helicobacter pylori and its common gastritis, its relation to almost all duodenal peptic ulcers and to most gastric peptic ulcers, its potential as a precursor of first multifocal atrophic gastritis and later tubule-forming gastric carcinomas, and its status as a cause of gastric mucosal lymphomas. During this same decade other classes of gastric reaction and inflammations have been recognized, including chemical injury and lymphocytic gastritis. Also in the same decade the importance of non-steroidal anti-inflammatory drugs (NSAIDs) has emerged as a cause of gastric mucosal injuries. To add emphasis to all these discoveries, biopsies are being performed on stomachs in almost epidemic numbers and each biopsy specimen has the potential of having the features of one or more of these injuries as well as injuries that have yet to be described. To cope with this rapidly expanding gastric inflammatory informational extravaganza, pathologists need some way of dealing with the various entities comfortably and some method of cataloging them in ways that are understandable both to them and to the endoscopists with whom they work. However, if emerging data about the chronic gastritides are correct, it is conceivable that the need to diagnose them, from a strictly clinical standpoint, is limited. Either we may know what is in the biopsy specimen before we see it or what we see may not be important, although it may be intellectually challenging.

Acute Disease↗
PubMed1994

Achalasia. A morphologic study of 42 resected specimens.

Achalasia is characterized by failure of relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Few data are available regarding the morphologic features of achalasia, in particular its histologic progression. The esophagi of 42 patients with achalasia treated with total thoracic esophagectomy were examined histologically in order to systematically identify morphologic features of clinically unresponsive achalasia and to determine what could be learned about the disease's evolution. In all cases, myenteric ganglion cells within the esophageal body were markedly diminished, with 20 specimens having none. Twenty specimens had residual ganglion cells in the proximal esophagus, and 15 specimens had a few randomly distributed ganglion cells in the mid- and distal portions of the esophagus. Inflammation within myenteric nerves, present in all cases, generally consisted of a mixture of lymphocytes and eosinophils, occasionally with plasma and mast cells. Focal replacement of myenteric nerves by collagen occurred in all cases, and there was almost complete replacement in several cases. Actual destruction of the residual ganglion cells was not seen. The resected esophagi also shared extramyenteric morphologic features. Some features probably stemmed from physiologic obstruction, such as muscular hypertrophy, mainly of the muscularis propria (all cases), with secondary degeneration and fibrosis (29 cases), and eosinophilia of the muscularis propria (22 cases). Other changes, probably resulting from chronic stasis of ingested materials in the lumen, included diffuse squamous hyperplasia (all cases), lymphocytic mucosal esophagitis (28 cases), lymphocytic inflammation of the lamina propria and submucosa with prominent germinal centers (all cases), and submucosal periductal or glandular inflammation with complete loss of submucosal glands in half of the cases. One patient had high-grade squamous dysplasia, and another had superficially invasive squamous cell carcinoma. A third group of changes was probably due to previous esophagomyotomy, including abnormal gastroesophageal reflux, as shown by pH reflux testing (13 cases) and Barrett's mucosa (four cases). In one case of Barrett's there was low-grade dysplasia. Clinically unresponsive, surgically resected achalasia has almost total loss of ganglion cells, and widespread destruction of myenteric nerves has already occurred. The only active component is myenteric inflammation. However, it cannot be determined whether this inflammation is a manifestation of ongoing nerve destruction or whether it is a secondary phenomenon.

Adult↗
PubMed1993

Sucrase-isomaltase gene expression in Barrett's esophagus and adenocarcinoma.

BACKGROUND: Specialized Barrett's esophageal mucosa, characterized by incomplete intestinal metaplasia of the esophageal mucosa, is associated with the development of adenocarcinoma. Although the intestinal disaccharidase sucrase-isomaltase (SI) has been shown in incomplete intestinal metaplasia of the stomach, it is commonly believed that Barrett's mucosa does not express SI based on the lack of enzymatic activity. This study was undertaken to determine whether the SI gene is expressed in Barrett's epithelium and its associated adenocarcinoma at the level of messenger RNA (mRNA) and protein. METHODS: Reverse transcription polymerase chain reaction was used to determine the presence of SI mRNA in Barrett's esophagus and esophageal adenocarcinomas. Cellular localization of SI protein was determined by immunohistochemistry. RESULTS: SI mRNA was identified in 76% of Barrett's epithelium and 82% of esophageal adenocarcinomas. The transcriptional initiation site for SI in these tissues was identical to that of the small intestine. Immunohistochemical localization showed that SI was directed to the apical membrane in Barrett's epithelium in contrast to a more diffuse cytoplasmic pattern in esophageal adenocarcinomas. CONCLUSIONS: Columnar cells of specialized Barrett's epithelium express SI and are, therefore, phenotypically similar to those in incomplete intestinal metaplasia of the stomach with respect to intestinal gene expression.

Adenocarcinoma↗
PubMed1992

Biochemical and histopathological correlation in liver transplant: the first 180 days.

It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A familial form of incomplete septal cirrhosis.

The clinical features and hepatic histology of a disorder resembling idiopathic portal hypertension and nodular regenerative hyperplasia but most consistent with incomplete septal cirrhosis, occurring in four family members, are described. This represents the first description of the familial occurrence of this entity. Features common to incomplete septal cirrhosis and the noncirrhotic nodular conditions of the liver that may present with complications of portal hypertension are discussed.

Adult↗
PubMed1992

Familial visceral neuropathy with neuronal intranuclear inclusions: diagnosis by rectal biopsy.

A family with a visceral neuropathy manifested as chronic idiopathic intestinal pseudo-obstruction is reported. Diagnoses were made histologically by simple rectal biopsy. Discrete eosinophilic intranuclear inclusions, diagnostic of a disease known as neuronal intranuclear inclusion disease, were found in the submucosal ganglion cells. Abnormalities of the autonomic nervous system were identified by pupillary examination and electroretinography. In this family, three of four siblings were affected by the disease, which is apparently transmitted from the paternal side. This pedigree was unique for several reasons: (a) diagnosis in multiple members of two generations indicates that this familial visceral neuropathy was expressed in an autosomal dominant manner, (b) central autonomic nervous system abnormalities were detected by eye examination, and (c) the definitive pathological diagnosis was established antemortem by rectal biopsy in all cases.

Adult↗
PubMed1992

Recurrence of hepatitis B and delta hepatitis after orthotopic liver transplantation.

The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in he native liver increased the risk of HBV induced tissue damaged in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function.

Adolescent↗
PubMed1992

Appendiceal involvement in ulcerative colitis.

Little information has been published regarding appendiceal changes in ulcerative colitis of any extent. An early study has shown the appendix to be involved in over 50% of all cases of ulcerative colitis for which a proctocolectomy was performed, but the extent of the colitis was not always defined. While some investigators have found appendiceal involvement only in continuity with adjacent involved cecum, others believed it may occur as a skip lesion. In this study, the colons and nonobliterated appendices of 87 patients who underwent total proctocolectomy for ulcerative pancolitis were examined to determine the frequency of appendiceal involvement and to determine the frequency with which such involvement truly occurs as a skip lesion. All 87 cases had ulcerative pancolitis, and 66 (62%) had colitic changes in the appendix. In the remaining 21 cases, there was no appendiceal inflammation. In all cases in which the appendix was involved, the cecum was also involved. Cecal activity or lack of activity correlated with appendiceal activity in 52 of the 87 cases (60%). Of the 35 cases in which there was some discrepancy in disease activity between the appendix and cecum, nine had more active disease in the appendix, and 26 had greater activity in the cecum, but in none of the cases where the cecum was normal or near normal was the appendix more severely involved. These data suggest that appendiceal involvement in resected ulcerative pancolitis always occurs in continuity with adjacent involved cecum, although there may be differences in disease activity between the two sites.

Adolescent↗
PubMed1991

Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial.

Chronic hepatitis B is a severe and frequently progressive disease. We assessed the safety and efficacy of thymosin fraction 5 and thymosin-alpha 1 in a prospective, placebo-controlled trial in 12 patients with chronic hepatitis B. All patients had histological and biochemical evidence of active liver disease for at least 6 mo before treatment and were positive for serum hepatitis B virus DNA and HBsAg. Seven patients received thymosin fraction 5 or thymosin-alpha 1 and five patients received placebo twice weekly for 6 mo. By the conclusion of the study (1 yr), serum aminotransferase levels had improved significantly in thymosin-treated patients, but not in the placebo group. Six (86%) of the thymosin treated patients and one (20%) patient given placebo cleared hepatitis B virus DNA from serum (p less than 0.04, Fisher's exact test). After treatment, replicative forms of hepatitis B virus DNA were present in the liver specimens of four of five placebo-treated patients but in only one of seven thymosin-treated patients (p less than 0.04, Fisher's exact test). Response to thymosin therapy was associated with significant improvements in peripheral blood lymphocyte and CD3 and CD4 counts and in in vitro production of interferon-gamma over initial values. No significant side effects were observed in patients given thymosin or in placebo-treated patients. Clinical, biochemical and serological improvement in patients responding to thymosin were sustained during 26 +/- 3 mo of follow-up. The results of this pilot trial suggest that thymosin therapy promotes disease remission and cessation of hepatitis B virus replication in patients with chronic viral infection.

Adolescent↗
PubMed1990

Phenotypic variation in colorectal adenoma/cancer expression in two families. Hereditary flat adenoma syndrome.

Clinical, pathologic, and genetic studies on two colorectal cancer-prone families have disclosed right-sided colonic flat adenomas and colorectal cancer. Adenomatous polyp counts exceeded those found in hereditary nonpolyposis colorectal cancer (HNPCC) but were fewer than in familial adenomatous polyposis (FAP). Colon cancer occurred at a later age than in HNPCC or FAP and showed right-sided predominance. The older age of patients with colonic cancer, the right-sided predominance of colon cancer, and the paucity of rectal adenomas make FAP unlikely. Vertical transmission of polyps and colon cancer fit the pattern of autosomal dominant inheritance. A characteristic feature of this phenotype is the predominance of flat adenomas. Molecular genetic studies, with careful description of phenotype, should help clarify classification.

Adenocarcinoma↗
PubMed1990

Colorectal adenomas in the Lynch syndromes. Results of a colonoscopy screening program.

Forty-four asymptomatic putative Lynch syndrome patients participated in a colonoscopy screening program. There were 18 men and 26 women; mean age was 44 yr. Thirty percent of Lynch syndrome patients had at least one adenoma; 20% had multiple adenomas. In 18% of the patients, adenomas were discovered proximal to the splenic flexure. In a reference group of 88 age- and sex-matched patients, 11% had adenomas, 4% had multiple adenomas, and 1% had right-sided adenomas. Twenty-one Lynch syndrome patients had follow-up colonoscopies. Of 7 patients with adenomas on initial examinations, 6 had adenomas at follow-up. Of 14 patients with negative initial examination results, 3 had adenomas at follow-up. The prevalence of adenomas in the Lynch syndromes is greater than in an unselected reference group. The adenomas are more proximally located, corresponding to the site of cancer distribution in the Lynch syndromes. A high rate of synchronous and metachronous lesions is found. Our findings support the hypothesis that adenomatous changes are the premalignant lesion in the Lynch syndromes. We also found evidence of heterogeneity among Lynch syndrome families in adenoma incidence.

Adenoma↗