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Biomedical subjects

W S Rosenthal

Publications and source records attributed to W S Rosenthal.

At least 19 recordsLinked to original sources
PubMed1997

Pruritus in chronic hepatitis C: association with high serum bile acids, advanced pathology, and bile duct abnormalities.

Pruritus is a common symptom of chronic cholestatic liver diseases but is considered rare in chronic hepatitis. We observed pruritus to be an unusually common complaint in patients with advanced chronic hepatitis C. We reviewed the records of 175 chronic hepatitis C patients to identify patients with severe, diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing liver biopsy for chronic hepatitis C served as controls. Assessment included laboratory biochemical tests and assessment of liver pathology by stage, grade, hepatic activity index, and a bile duct score. Pruritus was present in nine (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and ferritin were similar in pruritics and controls. Pruritics had higher serum bile acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05). Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P < 0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/- 1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4, P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT response and one relapsed. Pruritus followed a relapsing course and only three patients partially responded despite a variety of interventions. In conclusion, pruritus is a common complication of advanced CHC. Its presence is associated with high serum bile acids, advanced pathology and bile duct abnormalities. The clinical course of pruritus is relapsing and response to therapy is inconsistent. These features suggest that pruritus in CHC has a pathogenesis that may vary from that of chronic cholestatic diseases.

Antiviral Agents↗
PubMed1995

Photodynamic therapy for obstructing esophageal cancer: light dosimetry and randomized comparison with Nd:YAG laser therapy.

BACKGROUND & AIMS: Light dosimetry analysis to achieve predictable tumor necrosis has not been performed for photodynamic therapy (PDT) in the gastrointestinal tract. We evaluated dihematoporphyrin ethers for sensitizing esophageal carcinomas to 630 nm light and compared PDT with neodymium:yttrium-aluminum-garnet (Nd:YAG) laser therapy in a randomized trial. METHODS: Of 52 patients with dysphagia, 32 received palliative PDT. Ten patients treated with PDT participated in a preliminary trial using various doses of 630-nm light, and 22 patients treated with PDT participated in a randomized trial using a derived standardized light dose for comparison with 20 patients treated with the Nd:YAG laser. RESULTS: Light dosimetry correlated with depth of tumor necrosis (r = 0.664; P < 0.001). PDT activity was similar for squamous cell and adenocarcinoma. Among randomized patients, both PDT and Nd:YAG therapy relieved dysphagia, but PDT resulted in improved Karnofsky performance status at 1 month (+7 vs. -7; P < 0.001) and longer duration of response (84 vs. 57 days; P = 0.008). Skin photoreactions were unique to PDT. CONCLUSIONS: The extent of PDT tumor ablation correlates with light dosimetry, enabling selection of a standardized light dose. PDT can relieve esophageal obstruction from squamous cell and adenocarcinoma and is an alternative to Nd:YAG thermal necrosis with a longer duration of response. However, PDT requires patient precautions to minimize skin photoreactions.

Adenocarcinoma↗
PubMed1995

The breakthrough phenomenon during alpha-interferon therapy of chronic hepatitis C: incidence, management, and outcome.

OBJECTIVES: Some patients treated with alpha-interferon (alpha-IFN) for chronic hepatitis C (CHC) initially respond with normalization of ALT only to encounter a rise in ALT while still on the drug. This phenomenon is called breakthrough (BT). We reviewed our experience with BT to clarify its incidence, pathogenesis, management, and outcome. METHODS: Charts from 71 consecutive patients with CHC treated with alpha-IFN were reviewed. Forty of these patients were part of a study of 1-yr escalating dose alpha-IFN, initiated at 2 million units (MU) 3 times per week. Endpoints that were evaluated were: reachievement of normal ALT, complete response (CR) (defined as normal ALT at the end of therapy), and sustained CR maintained for 6 months after therapy. RESULTS: Twenty-one (29.5%) patients sustained 28 BT events. Thirteen (46.4%) BT events occurred during the first 6 months of a course of alpha-IFN therapy, and 15 (53.6%) occurred during months 7 through 12. Of patients experiencing BT, six (28.6%) completed their course of therapy with a CR, of which two (9.5%) were sustained. By comparison, of 22 patients who normalized ALT without BT, all completed their course with a CR by definition (p < 0.0001), and nine (40.9%, p < 0.05) had a sustained CR. Of 28 BT events, 13 (46.4%) were followed by reattainment of normal ALT. Of 16 BT events managed with continuation of the same dose of alpha-IFN, normal ALT was reachieved in seven (43.8%). Of 12 BT events managed with an escalation in alpha-IFN dose, six (50%) reachieved normal ALT. A full sequential series of hepatitis C virus RNA PCR from periods of elevated, normal, and again elevated ALT was available for 12 BT events. The pattern was +/+/+ in six, +/-/+ in five, and +/-/- in one. In one additional patient, an apparent BT was attributable to alpha-IFN-induced autoimmune hepatitis. CONCLUSIONS: BT is a common event that may occur at any point during alpha-IFN therapy of CHC. This may limit the benefits of maintenance strategies. After a BT event, normal ALT can be reestablished in about 50% of cases, although the chance of a sustained CR falls to less than 10%. No advantage was demonstrated for escalating the alpha-IFN dose after a BT event. Therefore, we recommend continuation of the same dose as the initial approach. We suspect that BT relates to nonspecific ALT fluctuation in some patients and to emergence of resistant hepatitis C virus strains in others. Other causes of ALT elevation must also be considered in patients with apparent BT.

Adult↗
PubMed1994

Open label study of long-term effectiveness of cisapride in patients with idiopathic gastroparesis.

Cisapride induces acetylcholine release in cells of the myenteric plexus, thus promoting gastrointestinal motility. We studied the effects of cisapride on 11 patients with idiopathic gastroparesis. All had negative gastrointestinal endoscopy, normal glucose, and took no drugs capable of influencing motility. Most (9/11) were prior metoclopramide treatment failures. Patients' symptoms were scored (0-60) for pain, satiety, bloating, nausea, vomiting, and heartburn. All underwent a solid gastric emptying study using a Technetium-99-labeled egg meal and received placebo prior to cisapride. There were 10 females and one male with a mean (+/- SE) age of 37.8 +/- 2.6 years. Disease duration was 7.9 +/- 2.8 years. The dose of cisapride was 30-60 mg/day and the duration of therapy was 12.6 +/- 2.6 months (range 2.5-25 months). The symptom score improved on cisapride from 30.9 +/- 3.6 to 14.4 +/- 2.7 (P < 0.002 signed rank test). Emptying half-time improved from 113 +/- 4 min to 94 +/- 6 min, and 46.9 +/- 2.4% food remaining at 120 min decreased to 35.5 +/- 3.6% (both P < 0.05). Emptying half-time in normals was 68 +/- 5 min with 16.9 +/- 2.9% remaining at 120 min. Nine of 11 patients gained weight, with a mean increase of 6.7 +/- 1.6 lb (range 2-12 lb). We conclude that cisapride significantly reduces gastrointestinal symptoms and promotes weight gain in patients with idiopathic gastroparesis and is associated with improvement in solid gastric emptying. The drug is useful in patients who previously failed metoclopramide.

Adult↗
PubMed1992

Resolution of radiographic abnormalities with ursodeoxycholic acid therapy of primary sclerosing cholangitis.

Ursodeoxycholic acid therapy has shown encouraging results in relieving symptoms and decreasing liver biochemical abnormalities in patients with primary sclerosing cholangitis. However, established biliary strictures are generally considered irreversible. A case of primary sclerosing cholangitis with extensive intrahepatic biliary as well as pancreatic duct strictures that resolved to near normal on ursodeoxycholic acid therapy is reported. The implications of these findings are discussed.

Cholangiography↗
PubMed1991

Upper gastrointestinal bleeding following open heart surgery. Predominant finding of aggressive duodenal ulcer disease.

We reviewed our experience with endoscopically evaluated severe upper gastrointestinal hemorrhage following open heart surgery. Of 4892 patients undergoing open heart surgery, 18 (0.4%) sustained upper gastrointestinal hemorrhage requiring endoscopic evaluation. Endoscopy identified the source of bleeding in all cases. No significant complications of endoscopy were observed. Duodenal ulcers (DUs) were found in 16 (89%) of cases and were felt to be the source of bleeding in 15 (83%). Aggressive features, such as multiplicity, large size, or distal location were associated with 13 (81%) of the DU cases. Complications necessitated endoscopic or surgical therapy in eight (44%) patients with DUs. We conclude that aggressive DU disease accounts for the majority of severe upper gastrointestinal bleeding following open heart surgery.

Aged↗
PubMed1991

Liver diseases unique to pregnancy.

Severe liver diseases occur in less than 0.1% of pregnancies. Accurate diagnosis and appropriate therapy are essential to the health and survival of both the mother and fetus. Because of their low incidence and the fact that most pregnant women are cared for primarily by their obstetricians, gastroenterologists only infrequently encounter these diseases. This review is intended to update the practicing gastroenterologist on the complex spectrum of liver diseases unique to pregnancy.

Female↗
PubMed1989

Role of arachidonic acid metabolites in acid-pepsin injury to rabbit esophagus.

The role of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in experimental esophageal were lumenally perfused for 1 h with acidified saline (pH 2.0) with or without pepsin followed by a second hour with acidified saline. Separate groups of pepsin-perfused animals were pretreated with indomethacin, a cyclooxygenase inhibitor, or BW755C, a lipoxygenase-cyclooxygenase inhibitor. Esophageal injury was graded grossly. H+ and hemoglobin fluxes were determined. Acidified saline caused no significant damage. Pepsin induced moderate injury. Indomethacin decreased pepsin-induced H+ flux by 55% without affecting the other indices. BW755C, by all measurements, dramatically increased pepsin-induced injury. In separate experiments, cyclooxygenase activity was decreased by indomethacin and BW755C by 62% and 49%, respectively. Lipoxygenase activity was decreased 74% by BW755C and was not significantly affected by indomethacin. These results suggest that esophageal cytoprotection is mediated by endogenous lipoxygenase metabolites.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1988

Decreased hepatic selenium content in alcoholic cirrhosis.

Selenium deficiency has been implicated as contributing to hepatic injury in alcoholics. The mechanism by which this occurs is most likely lipoperoxidation secondary to decreased activity of the selenoenzyme glutathione peroxidase. To further assess this relationship, we measured selenium content in autopsy livers in 12 patients with alcoholic cirrhosis compared to 13 patients matched for age and sex dying from other causes, mostly with cardiopulmonary diseases. The mean (+/- SEM) hepatic selenium content in cirrhosis was 0.731 +/- 0.077 microgram/g dry weight versus 1.309 +/- 0.166 microgram/g in controls (P less than 0.005; Student's t test). Clinical and biochemical indices of significant hepatic dysfunction, including encephalopathy, ascites, and elevations of serum bilirubin or prothrombin time, were only present in the cirrhotic group. A significant inverse correlation between hepatic selenium content and the prothrombin time was noted (r = -0.50; P less than 0.02). No significant relationships between hepatic selenium and the abnormalities of bilirubin, albumin, or aspartate aminotransferase were found. We conclude that significantly decreased hepatic selenium stores are present in patients with severe alcoholic cirrhosis compared to controls. The magnitude of that selenium deficit does correlate with some indices of hepatic function, specifically the prothrombin time. These data lend further support to a true selenium deficiency state in alcoholic cirrhosis. It is highly possible that selenium deficiency represents an important link, synergistically joining the nutritional and hepatotoxic backgrounds of alcoholic liver injury and cirrhosis.

Bilirubin↗
PubMed1988

Rabbit esophagus metabolizes arachidonic acid predominantly via a lipoxygenase pathway.

Eicosanoids modulate the response of gastrointestinal mucosa to noxious stimuli. Though these compounds have been extensively investigated in the stomach, their role in the esophagus has received less attention. Thus, the metabolism of 14C-arachidonic acid by homogenates of rabbit esophageal mucosa was investigated. The major metabolites formed and separated by TLC and HPLC had the chromatographic characteristics of (percent conversion follows each metabolite) 6-keto-prostaglandin F1 alpha (3.80 +/- 1.15), prostaglandin F2 alpha (2.05 +/- 0.37), prostaglandin E2 (5.92 +/- 1.65) and 12-hydroxyeicosatetraenoic acid (26.03 +/- 4.58). Indomethacin, a cyclooxygenase inhibitor, caused a significant decrease in prostaglandin formation without affecting 12-hydroxyeicosatetraenoic acid. BW755C, a combined cyclooxygenase-lipoxygenase inhibitor, dramatically decreased formation of all metabolites. It is concluded that esophageal mucosa metabolizes arachidonic acid primarily to a lipoxygenase derived product. This is the most abundantly produced eicosanoid yet described in the gastrointestinal tract. The importance of this compound to esophageal function is unknown but its presence suggests that future studies of eicosanoids in the esophagus should focus on lipoxygenase metabolites.

Animals↗
PubMed1988

Campylobacter pylori and gastroduodenal disease: a prospective endoscopic study and comparison of diagnostic tests.

A series of 72 adult patients undergoing 76 upper gastrointestinal (GI) endoscopies because of GI signs or symptoms were studied for the presence of Campylobacter pylori by culture, histology, and rapid urease determination of gastric antral biopsy specimens. C. pylori was found by culture or histology in all 10 cases of gastric and duodenal ulcer, and in 77% of endoscopies with histologically proven active gastritis. Positive culture for C. pylori was highly correlated pathologically with active gastritis, but not endoscopically, and was rarely seen in the absence of acute inflammation on biopsy. There was no correlation between C. pylori and alcohol ingestion, smoking, age, sex, antibiotics, or nonsteroidal anti-inflammatory drug use. The rapid urease test was positive in 70% of cases with positive cultures and 89% with positive cultures or acridine orange stains. Acridine orange-stained histological samples were positive in 97% of cases with positive cultures. In addition, 31% of endoscopies with negative cultures were also positive by acridine orange stain. Acridine orange stain, culture, and urease reaction of antral mucosal biopsies all are effective methods for demonstration of mucosal C. pylori-like organisms. However, of the three methods used, acridine orange staining is positive in the largest group of patients and is the most sensitive method for detecting colonization of gastric antral mucosa. In general, positive urease and culture identify those patients with larger numbers of organisms on the mucosa. Differences in urease and culture positivity from case to case suggest that factors other than numbers of organisms, such as viability and urease levels, affect the results. All these results support a role for C. pylori as an aggressive factor in peptic ulcer disease and gastritis.

Acridine Orange↗
PubMed1988

The hepatobiliary manifestations of human immunodeficiency virus infection.

Liver abnormalities are common in patients with acquired immune deficiency syndrome. These relate to 1) coincident exposure to hepatotropic viruses, 2) complications, either infectious, neoplastic, or iatrogenic, of the immunosuppressed state, or 3) nonspecific changes associated with chronic debilitating illness. We review the hepatobiliary manifestations of acquired immune deficiency syndrome, and discuss our approach to the clinical evaluation of these problems.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Hepatic amyloidosis presenting as severe intrahepatic cholestasis: a case report and review of the literature.

Although hepatic involvement is common in all forms of amyloidosis, jaundice is infrequent and usually mild. We report a case of a 74-yr-old man with severe intrahepatic cholestasis and hepatic amyloid. The topography of amyloid deposition was unusual, in that deposits were confined predominantly to the portal tract. They appeared as a dense eosinophilic infiltrate that stained with congo red. A review of the English-language literature revealed only 18 prior patients with hepatic amyloid associated with severe intrahepatic cholestasis. The histology of only one of these patients showed a similar distribution of amyloid deposits.

Aged↗
PubMed1988

Selenium status and the polyp-cancer sequence: a colonoscopically controlled study.

Diminished blood selenium levels have been associated with increased risk of gastrointestinal cancers in man, while dietary selenium supplementation reduces the incidence of experimental colon cancer in rats. However, no previously published data are available concerning selenium and the evolution of colon cancer from benign neoplastic colonic polyps through localized and metastatic cancer. To assess any influence of selenium on this polyp to cancer sequence, we measured plasma and erythrocyte selenium levels in colonoscopically and histologically evaluated patients with adenomatous polyps (group I), locally resectable colon cancer (group II), metastatic colon cancer (group III), and selected colonoscopy negative controls (group IV). We found no difference in selenium levels between groups IV versus groups I or II. Likewise, within group I, no difference in selenium was present for different polyp histologies or numbers of polyps. However, selenium levels did drop progressively (p = 0.028, ANOVA) from polyp (group I) to local cancer (group II, p = NS vs group I) to metastatic cancer (group III, p less than 0.05 vs group I or group II). Parallel changes were seen in both plasma and erythrocyte levels, suggesting that these selenium abnormalities are of long duration, reflecting tissue stores, and therefore capable of influencing cancer risk. We conclude that selenium stores may not be an important factor in the de novo formation of benign neoplastic colonic polyps. Although these data suggest that selenium does not affect the polyp-cancer sequence, it is possible that a subset of patients with polyps and the lowest selenium levels are at higher risk for malignant transformation. However, these human data do not support a significant role for selenium in colon carcinogenesis.

Aged↗