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Biomedical subjects

C Cho

Publications and source records attributed to C Cho.

At least 73 records · Page 4Linked to original sources

Failure of exogenous prostaglandin to afford complete protection against acetaminophen-induced hepatotoxicity in the rat.

The protective effect of 16, 16-dimethylprostaglandin E2 (dm-PGE2) against acetaminophen-induced hepatotoxicity was determined in the rat. The dm-PGE2 was administered at two dose levels both before and after acetaminophen administration. The hepatotoxicity was evaluated by a rise in serum transaminases 24 h after acetaminophen administration and by histological examination of liver preparations. The urinary acetaminophen and its metabolites were determined by high-pressure liquid chromatography. The results suggest that exogenous dm-PGE2 administration had a modest protection against acetaminophen-induced hepatotoxicity, in contrast to its well established cytoprotective effect against many noxious agents in the gastrointestinal tract. Prostaglandin treatment had little effect on acetaminophen metabolites excretion in the urine, suggesting that it did not affect the cytochrome P-450-dependent mixed-function oxidase drug-metabolizing enzyme system. The livers from dm-PGE2-acetaminophen-treated rats showed less advanced necrosis compared to those from saline-acetaminophen-treated rats. Whereas only 2 of 13 rats died in the prostaglandin-treated group, 4 of 13 rats died in the saline-treated group.

Acetaminophen↗

Subclavian venous stenosis. A complication of subclavian dialysis.

Subclavian hemodialysis catheters are widely employed for temporary hemodialysis access, but there are few reports of serious complications. We report three cases in which the prolonged (greater than 15 days) use of subclavian dialysis catheters ipsilateral to the permanent vascular access was associated with the development of subclavian vein (SCV) stenosis three to six months after the temporary catheter was removed. In one case, the use of the permanent access was severely limited by massive arm edema. We conclude that, in addition to the usual complications of SCV cannulation, long-term use of SCV hemodialysis catheters can be associated with major late obstructive complications that may compromise permanent vascular access. We recommend that, wherever possible, temporary dialysis catheters and other subclavian lines be placed contralateral to the permanent vascular access site in patients undergoing hemodialysis.

Aged↗

Acquired renal cystic disease and renal neoplasms in hemodialysis patients.

Noninvasive imaging studies were performed on 26 patients undergoing chronic hemodialysis. We found cysts in 46% of patients and neoplasms in 7.7%. The cysts were relatively easy to detect. However, the neoplasms were very difficult to detect; this problem has been described before in the literature. The natural history of acquired cystic disease and neoplasms in hemodialysis patients is largely unknown. A review of the problems associated with the imaging and management of these patients is included.

Adenocarcinoma↗

Sarcoidlike granulomas as an early manifestation of Whipple's disease.

Whipple's disease is often accompanied by a long, preintestinal phase of vague symptoms, such as weight loss, fever, and migratory arthralgia, which may delay diagnosis and proper treatment. We report a patient who presented with sarcoidlike granulomas in the lung 1.5 yr before the development of gastrointestinal symptoms. He was treated with prednisone and his lung lesions improved dramatically. However, steroids could not be discontinued until the diagnosis of Whipple's disease was made and he was started on antibiotic treatment. Whipple's disease was diagnosed from a small intestinal biopsy specimen by electron microscopic demonstration of characteristic bacillary bodies. Liver biopsy specimens also demonstrated a few Kupffer cells containing degenerative bacillary bodies. Based on this case and other reported cases of Whipple's disease with sarcoidlike lesions in various organs, we suggest that sarcoidlike tissue reaction can be an early manifestation of Whipple's disease, recognition of which may have practical value in facilitating an early diagnosis and treatment.

Diagnosis, Differential↗

Prevention of acetaminophen hepatotoxicity by propylthiouracil in the glutathione depleted rat.

This study was designed to investigate the protective effect of PTU pretreatment against acetaminophen hepatotoxicity in rats whose hepatic GSH had been depleted by prior diethylmaleate (DEM) administration. A single injection of DEM depleted hepatic GSH showing lowest level after 90 min in both control and PTU pretreated rats. Triple injection schedule kept the hepatic GSH concentrations consistently very low up to 6 hr. Whereas a toxic dose of acetaminophen administration did not effect SGOT and SGPT levels after 30 hr in PTU pretreated rats given either a single or multiple injections of DEM, the same dose of acetaminophen in the control rats raised these transaminases to a very high level. High activity of transaminases was associated with significant histological hepatic damage. Our results suggest that PTU pretreatment affords significant protection against acetaminophen hepatotoxicity even under conditions when hepatic GSH concentrations have been significantly depleted prior to acetaminophen administration.

Acetaminophen↗

Hepatotoxicity and metabolism of acetaminophen in male and female rats.

This present study was designed to assess the role of metabolic and pharmacokinetic factors in the lower susceptibility of female rats compared to male rats to xenobiotics metabolized by the cytochrome P-450-dependent mixed-function oxidase (MFO) system. Adult intact male and female Sprague-Dawley rats were administered labeled acetaminophen (1 g/kg body weight + 5 microCi [3H]acetaminophen) after an overnight fast. They were bled and killed at 0.5, 1, 2, 3, 6, 12, 24, and 36 h after drug administration. The percentage of [3H]acetaminophen radioactivity remaining in blood, liver, GI tract, and excreted in the urine was determined at all time intervals. Plasma prothrombin time and serum transaminases were determined as indices of hepatotoxicity. Hepatic GSH and glycogen were assayed. Total urinary acetaminophen and its metabolites and the molar percent of various metabolites excreted during the first 6 h were determined. Castrated male and ovariectomized female rats and their respective controls were also given acetaminophen (APAP) and were killed 24 h later to determine hepatotoxicity. The extent of hepatic damage in the intact male rats was greater and appeared sooner than in the female rats. Hepatic GSH and glycogen were depleted earlier in female rats. The percent of the administered dose excreted in the urine during the first 6 h was 17.5 for the male rat versus 24.5 for the female rat. While the APAP glucuronide conjugate concentration was significantly higher, the APAP sulfate conjugate concentration was lower in the female than it was in the male rat. Although peak radioactivity in serum was reached by 30 min in both male and female rats, suggesting quick intestinal absorption, it was significantly higher in female rats and was associated with decreased intestinal and hepatic levels and increased urinary excretion when compared to male rats. While castration of male rats decreased susceptibility to hepatotoxicity, ovariectomy of female rats tended to increase susceptibility to hepatotoxicity in comparison to their respective controls. Our data suggest that aside from the reported sex differences in the cytochrome P-450-dependent MFO enzymes, there are significant differences in GSH utilization. There are also significant changes in glucuronidation and sulfation pathways, as well as in the pharmacokinetics of acetaminophen, which tend to protect female rats against acetaminophen hepatotoxicity.

Acetaminophen↗

Effects of propylthiouracil on urinary metabolites of cyclophosphamide in rats.

Our previous studies have shown a protective effect of propylthiouracil (PTU) pretreatment against the toxicity of cyclophosphamide (CP). The present study was undertaken to investigate the mechanism of the PTU protection. CP is metabolized by the cytochrome P-450 drug-metabolizing enzyme system in the liver to alkylating metabolites, to active antineoplastic agents, and to acrolein, the most toxic and least antineoplastic metabolite. Measurements of CP metabolites in blood and urine during a 4-hr i.v. infusion of CP (50 mg/kg body weight/hr) showed urinary acrolein excretion to be 2.5 times higher in control rats as compared to PTU-treated rats. Since it has been reported that urinary acrolein levels are directly related to the frequency and severity of hemorrhagic cystitis, it is concluded from our observations that prevention of hemorrhagic cystitis is probably mediated by the PTU effect on lowering urinary acrolein concentration and excretion. Serum alkylating activity was significantly higher in the PTU-pretreated rats, which may enhance the antineoplastic potential of CP.

Animals↗

Effect of riboflavin status on acetaminophen toxicity in the rat.

The effect of riboflavin status on acetaminophen hepatotoxicity was determined in the rat. Groups of rats were fed one of the following diets: "riboflavin-free" (RFF), low riboflavin (LRF), high riboflavin (HRF), or high riboflavin pair-fed (HRF pair-fed) with RFF group. After riboflavin deficiency was established by determining erythrocyte glutathione reductase activity coefficient, rats in all groups were administered a toxic dose of acetaminophen (1 g/kg body weight) orally. Their controls were given the vehicle alone. All animals were killed 24 h later and hepatotoxicity was assessed by the elevation of serum transaminases and by a necrotic score based on histological examination. The RFF diet induced biochemical riboflavin deficiency, decreased food intake and body weight gain, and was associated with almost complete protection against acetaminophen toxicity. Rats on the LRF diet, with less severe riboflavin deficiency and no significant change in weight gain, showed some necrosis, but it was much less than in the HRF ad libitum-fed rats. The HRF pair-fed rats with no biochemical riboflavin deficiency but with considerable growth retardation also showed very little hepatic necrosis. Our results suggest that riboflavin deficiency protects rats against acetaminophen toxicity but it is confounded by decreased food consumption and body weight.

Acetaminophen↗

Colonic lymphoma producing alpha-chain disease protein.

Alpha-chain disease with involvement of small intestine-resulting in characteristic villus atrophy and malabsorption has not been reported in this country. We studied a 57-yr-old male who presented with a polypoid tumor of the hepatic flexure of the colon. There was no evidence of malabsorption as manifested by a normal fat balance, serum carotene, and D-xylose absorption studies and the small bowel biopsy did not show villus atrophy. The tumor in the colon was surgically removed and diagnosed as a malignant lymphoma of lymphocytic type. Tumor tissue infiltrated in the mesentery could not be excised. Alpha-chain disease protein was demonstrated in serum and urine, and also in tumor tissue by immunoperoxidase techniques. The alpha-chain disease protein was further purified and classified as subclass 1. The patient had a good clinical response to cyclophosphamide and prednisone, but still has intraabdominal lymphoma with gastric involvement, and his serum alpha-chain protein persists. This case report may represent a distinct variant of alpha-chain disease.

Colonic Neoplasms↗

Heat stroke. Report of three fatal cases with emphasis on findings in skeletal muscle.

Three fatal cases of heat stroke were encountered in the central New York area over a two-month period. Although in each instance one or more predisposing factors were identified, exertion clearly played a role in its development in only one case. In addition to laboratory and postmortem findings indicative of dysfunction of many organ systems, there was morphological evidence of widespread damage to skeletal muscle.

Adult↗

Bile duct adenomas as liver nodules.

Bile duct adenomas can be difficult to differentiate at laparotomy from small metastatic tumor nodules in the liver. This can present a problem to the pathologist and surgeon relative to the advisability of attempted curative vs pallative surgery. We report two such cases. Review of our autopsy materials shows the incidence of bile duct adenoma to be higher than usually reported. Even though they all present as grayish-white, firm nodules, usually frozen section will reveal the true nature of the lesion. Occasionally, however, the lesions with active bile duct proliferation can cause problems in diagnosis, even after such examination. Accurate diagnosis by recognition of the entity and its histological characteristics may be very important in the surgical treatment of patients.

Adenocarcinoma↗

Effects of chronic beta-glycerophosphate administration on growth rate and on serum, liver and bile lipid composition in the squirrel monkey--a toxicity study.

Oral administration of beta-glycerophosphate lowers the lithogenic index in patients with cholesterol gallstones and is considered to have potential for dissolving them. A high dose of beta-glycerphosphate was fed to primates (Squirrel monkeys) for a period of 15 months. There were no adverse effects on body weight, hematological or liver function tests. Serum, liver and bile lipids concentrations were not significantly changed, although serum and hepatic bile phospholipids were increased. Organ weights expressed as percent of body weight were not changed except for a slight increase in kidney weight. Histological examination of liver and kidneys did not reveal any pathological findings. Slight renal hypertrophy was attributed to the sodium content of beta-glycerophosphate.

Animals↗