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Biomedical subjects

C L Mendenhall

Publications and source records attributed to C L Mendenhall.

At least 73 records · Page 4Linked to original sources
PubMed1986

A new therapy for portal systemic encephalopathy.

This report describes a new therapeutic approach to the treatment of adults with portal systemic encephalopathy using sodium benzoate and sodium phenylacetate, two compounds that increase conjugated nitrogen excretion in the urine and that have been shown to be an effective treatment for children with congenital hyperammonemia. The study was a double-blind cross-over study in which each patient was his own control. All patients either improved their mental status (six of eight) or maintained a mental status comparable to that achieved with conventional therapy [lactulose or neomycin (two of eight)]. All decreased their blood ammonias on these medications and seven of eight improved their portal systemic encephalopathy index. It is suggested that these medications may be useful in the treatment of portal systemic encephalopathy.

Aged↗
PubMed1985

Effect of chronic ethanol consumption on the pancreas of the hamster.

The purpose of this study was to determine the effect of chronic ethanol consumption on pancreatic morphology and biochemistry in the hamster, with special attention to lipid changes. A control group of Syrian golden hamsters fed a synthetic liquid diet was compared to an ethanol group pair-fed the same diet with ethanol substituted for 35% of the carbohydrate calories. The animals were sacrificed at 7 weeks and 3, 6, 9, and 12 months. After 12 months of ethanol consumption, a significant decrease in pancreatic triglycerides and a significant increase in pancreatic RNA was seen. These changes were associated with a rise in pancreatic weight and protein content in the ethanol group, reversing a six-month decline in these values. This rise in RNA and protein in the ethanol-treated group corresponded with the appearance of large abnormal zymogen granules. Other ultrastructural features such as lipid droplets, mitochondria, and endoplasmic reticulum were not altered by ethanol. Ethanol did increase the water content of the pancreas. Although ethanol had no effect on the fasting levels of insulin or pancreatic polypeptide, the fasting serum gastrin immunoreactivity was significantly lower in the ethanol animals. This study shows that chronic ethanol consumption produces a metabolic change in the hamster by 12 months which is suggestive of increased protein synthesis with a decrease in pancreatic triglycerides and no lipid droplet formation.

Age Factors↗
PubMed1984

Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone.

A cooperative study was conducted to determine the efficacy of 30 days of treatment with either a glucocorticosteroid (prednisolone) or an anabolic steroid (oxandrolone) in moderate or severe alcoholic hepatitis. One hundred thirty-two patients with moderate disease and 131 with severe disease were randomly assigned to one of three treatments: prednisolone, oxandrolone, or placebo. During the 30 days, mortality in the groups receiving steroid therapy was not significantly different from mortality in the placebo group. Thirteen per cent of the moderately ill patients and 29 per cent of the severely ill patients died. Although neither steroid improved short-term survival, oxandrolone therapy was associated with a beneficial effect on long-term survival. This was especially true in patients with moderate disease: among those who survived for one or two months after the start of treatment the conditional six-month death rate was 3.5 per cent after oxandrolone and 19 to 20 per cent after placebo (P = 0.02). No consistent long-term effect was associated with prednisolone therapy.

Clinical Trials as Topic↗
PubMed1984

Protein-calorie malnutrition associated with alcoholic hepatitis. Veterans Administration Cooperative Study Group on Alcoholic Hepatitis.

Three hundred sixty-three alcoholic patients with alcoholic hepatitis were studied in six Veterans Administration medical centers. By history, alcohol consumption was 227.9 g per day, with a mean duration of 23.8 years. Cirrhosis accompanied the alcoholic hepatitis in 58.7 percent of the patients who underwent biopsy or autopsy. Complete nutritional assessment was performed in 284 patients, and observed nutritional changes were classified into those associated with marasmus or those characterizing kwashiorkor. A smaller comparison group of 21 alcoholic patients matched for age and alcohol consumption but without clinically evident liver disease was also studied in an identical manner. None of the patients with liver disease was completely free from malnutrition, whereas 62 percent of the alcoholic patients without liver disease showed abnormalities. In patients with alcoholic hepatitis, some findings associated with marasmus were seen in 86 percent, and some features of kwashiorkor were observed in 100 percent. When present together, the complete picture of kwashiorkor and marasmus correlated closely with the clinical severity of the liver disease (p less than 0.005). The nearly constant association of either complete or partial kwashiorkor or marasmus suggests that the separation of these two entities is artificial in alcoholic patients with liver disease. Although, experimentally, malnutrition may not be essential for the development of alcoholic hepatitis, clinically, it appears to precede the development of the liver injury, which suggests an interaction. Recognition is important so that appropriate nutritional therapy can be provided.

Adult↗
PubMed1984

Altered proline uptake by mouse liver cells after chronic exposure to ethanol and its metabolites.

A cloned mouse liver cell model (NCTC 1469) treated with either ethanol or one of its metabolites, acetaldehyde or acetate, was used to study proline uptake. Beginning with the stationary phase of cell growth, 14C-proline uptake was markedly accelerated by both ethanol and acetaldehyde (p less than 0.001). When ethanol treatment was combined with 4-methyl pyrazole so as to block ethanol oxidation, the ethanol-induced increase in proline uptake was significantly decreased to levels similar to that seen in controls. Acetaldehyde-induced stimulation of proline uptake was not significantly changed by the addition of 4-methyl pyrazole. While uptake of proline was markedly increased by ethanol and acetaldehyde, proline pool sizes were not significantly changed. An increase in uptake without an increase in pool size suggests an increased utilisation. These studies establish an increase in proline uptake associated with chronic alcoholism and indicate that acetaldehyde is the primary metabolite of ethanol responsible for this increase.

Acetaldehyde↗
PubMed1983

The effects of chronic alcoholism on development of ischemic cerebral infarcts following unilateral carotid artery ligation in gerbils.

To test if chronic alcoholism potentiates mortality and accentuates cerebral infarcts associated with ischemia, 32 male and 33 female Mongolian gerbils were chronically fed ethanol in their diet for 6 weeks. Cerebral ischemia was then induced by ligation and sectioning of the right common carotid artery. Postoperatively, there was a mean difference in survival in the control versus the alcoholic gerbils. Whereas 76% of controls survived the operation, only 55% of alcoholic gerbils survived. Also, the alcoholic gerbils died earlier, usually in the initial 3 postoperation days. The incidence of cerebral infarcts was identical (52%) in both control and alcohol-treated gerbils. There was, however, a difference in the extent (size) of the infarcts and tolerance to them. The alcoholic gerbils tended to develop either large infarcts which were usually lethal, or smaller infarcts but with decreased tolerance. The cerebral infarcts in the controls tended to be smaller with better survival. These findings suggest that chronic alcohol consumption contributes significantly to the risk of mortality associated with ischemic brain infarction reported in human alcoholics, and indicate that the alcoholic gerbil is a good experimental model to study the pathophysiology of this phenomenon.

Alcoholism↗
PubMed1983

The absorption of intramuscular chlordiazepoxide (Librium) in patients with severe alcoholic liver disease.

Intramuscular chlordiazepoxide (CDX) is commonly administered to alcoholic liver disease (ALD) patients requiring prompt management of alcohol agitation, anxiety, and delirium tremors. Sedative action is associated with plasma levels of approximately 2.0 mcg/ml, however, intramuscular CDX has been shown to produce peak concentrations consistently below 2.0 mcg/ml in normal subjects. The present study was designed to define the absorption characteristics of intramuscular 25 mg CDX in males with ALD. Five normal males had mean CDX absorption half-lives of 3.0 h and peaked at 0.8 mcg/ml in 7.2 h, while 11 males with ALD had mean absorption half-lives of 9.0 h, and peaked at 0.7 mcg/ml in 19.1 h when they received the drug dissolved in normal saline. Four other males with ALD who received CDX dissolved in the manufacturer's diluent had significantly slower mean absorption half-lives of 16.1 h which peaked at 0.3 mcg/ml in 35.2 h. Significant linear correlations were found with age (r = 0.60, p less than 0.01), body weight (r = 0.55, p less than 0.01), and serum albumin (r = 0.60, p less than 0.01). Because of the extremely slow intramuscular absorption of CDX dissolved in normal saline or the manufacturer's diluent in males with ALD, we do not recommend this route of administration in this population.

Absorption↗
PubMed1982

Alteration of in vitro human lymphocyte function by ethanol, acetaldehyde and acetate.

Infection is a major cause of morbidity and mortality in chronic alcoholics and may be attributable to altered lymphocyte function. To evaluate this possibility, the effects of physiologic concentrations of ethanol (ETH) and its metabolites, acetaldehyde (ACH) and acetate (ACT), were studied using in vitro mononuclear cell cultures prepared from normal human donors. ETH depressed DNA synthesis induced by both phytohemagglutinin-M(PHA) and Concanavalin A (Con A). ACH significantly impaired Con A and PHA stimulated lymphocyte DNA synthesis. Con A and PHA induced blastogenesis was also significantly reduced by the in vitro addition of ACT. Spontaneous lymphocyte transformation in these three-day cultures was not affected by ethanol but was decreased by the addition of high dose acetate and acetaldehyde. Lymphocyte response to candida and trichophyton antigens was significantly depressed by ETH and its metabolites. Monocyte depletion by adherence had no effect on these results. Treatment of lymphocytes with ETH, ACH or ACT did not change T cell binding of sheep erythrocytes or B cell expression of surface immunoglobulin or receptor sites for complement. It is concluded that both ethanol and its metabolites in physiologic concentrations significantly inhibited lymphocyte function without altering surface markers.

Acetaldehyde↗
PubMed1981

Clinical pharmacokinetics of chlordiazepoxide in patients with alcoholic hepatitis.

The clearance of chlordiazepoxide from the systemic circulation was studied in 20 subjects which included 15 patients with alcoholic hepatitis and 5 normal volunteers. The half-life for the appearance of the drug in the systemic circulation was found to increase exponentially with age (r = 0.73, P less than 0.0005) and was independent of the presence of alcoholic hepatitis. The metabolic clearance of chlordiazepoxide was significantly lower in the patients than in the normal subjects (7.6 compared to 13.8 ml/kg-h, P less than 0.005). Linear regression analysis revealed a significant correlation between clearance and albumin (r = 0.77, P less than 0.00005). However, the predictive value of this relationship was shown to be minimal. Multiple regression analysis produced only a slight improvement in the correlation when both albumin and lactate dehydrogenase were used as variables (r = 0.83, P less than 0.00005). In six of the patients, a second clearance study was conducted three weeks following their initial one. All repeat subjects showed improvement both clinically and as reflected by their laboratory tests for liver injury, but there was not a significant change in their clearance of chlordiazepoxide. Multiple regression analysis of the clearance data on the initial and repeat subjects showed a significant correlation between clearance and the variables age, albumin and lactate dehydrogenase (r = 0.91, P less than 0.0025). This relationship suggests that over a short period of time (where age can be considered constant) changes in albumin and lactate dehydrogenase could be potentially useful in predicting clearance changes in a single individual.

Adult↗
PubMed1980

Peliosis hepatis. Its relationship to chronic alcoholism, aflatoxin B1, and carcinogenesis in male Holtzman rats.

Peliosis hepatis, a condition characterized by blood-filled cystic spaces within the hepatic parenchyma, was observed in 5 of 26 male Holtzman rats after chronic treatment with ethanol (mean consumption 5 g/kg/day) and aflatoxin B1 (2 mg intraperitoneally in divided doses). Matched controls and aflatoxin-treated and ethanol-treated animals failed to exhibit these changes. Most of the peliotic lesions developed in the first two months of treatment. All were associated with death of the animal. No hepatocellular carinomas developed in any of the animals, even after one year of observation.

Aflatoxins↗
PubMed1980

Serum alpha-fetoprotein: changes associated with acute and chronic ethanol ingestion in the resting and regenerating rat liver.

The effect of acute and chronic ethanol consumption on serum alpha-fetoprotein was studied in adult male rats with resting and regenerating livers. Unlike many hepatotoxins, ethanol consumed over both the long and short term suppressed serum alpha-fetoprotein concentrations (p less than 0.05). This suppression was not due to increased degradation, since the half-life of alpha-fetoprotein was not significantly altered by chronic ethanol treatment. However, liver cytosolic alpha-fetoprotein was markedly increased after ethanol consumption, suggesting the presence of impaired secretion or mobilization from the liver cells. During liver regeneration following partial hepatectomy, alpha-fetoprotein increased in both the control (390 ng-hr/ml) and ethanol-treated animals (288 ng-hr/ml). At no time did the ethanol animal values equal the control levels. The change in serum alpha-fetoprotein showed an inverse exponential correlation with the amount of liver removed at hepatectomy and a positive correlation with the amount of nuclear DNA present at sacrifice. However, in the ethanol-treated animals it required the removal of 1.9 times as much liver to stimulate the same degree of liver regeneration as in the controls (p less than 0.001). A significant inverse correlation was observed between 3H-thymidine uptake and the areas under the alpha-fetoprotein time curves in the controls (p less than 0.001). In the ethanol groups the correlation was not statistically significant (p less than 0.2). It is concluded that although changes in serum alpha-fetoprotein may be associated with liver injury and regeneration, they are not a direct result of the regenerative process. The direct correlation with available nuclear DNA indicates the need for existing cells to hypertrophy and produce the alpha-fetoprotein. The depression associated with acute and chronic ethanol ingestion appears to reflect a direct effect of ethanol on protein synthesis and/or release.

Alcoholic Intoxication↗
PubMed1977

Inhibition of hepatocarcinogenesis by adrenocorticotropin in aflatoxin B1-treated rats.

We examined whether hormones would modify the carcinogenic action of aflatoxin B1 (AFB1). Four groups of inbred Fischer rats received AFB1, 125 mug per animal, weekly per os. In three of the groups, certain hormones were administered simultaneously: One group received 1 U growth hormone (GH) sc weekly, another was given 4 U adrenocorticotropin (ACTH) weekly, and a third received 0.5 U insulin weekly sc. AFB1, ACTH, and insulin were given for 20 weeks; GH was given for only 10 weeks. The control group did not receive hormone adjuvant. In each group, 4 animals were killed at 7, 14, 21, 28, and 35 weeks; the remaining rats were killed at 77 weeks. Their livers were carefully examined and samples prepared for light and electron microscopy. Animals receiving AFB1 and ACTH failed to exhibit hepatocellular carcinoma. On the other hand, malignant lymphoma appeared at 56 weeks in 3 of the 6 surviving males on this regime. AFB1, alone or when given with insulin or GH, caused hepatocellular carcinoma in all animals; in these, lymphoma was not observed. Lymphoma comprised two cell types, each with similar neclear characteristics but differing in their nucleocytoplasmic ratios and in the amount and distribution of cytoplasmic organelles. Alterations leading to hepatocellular carcinoma were examined at various stages of development. "Basophilic hyperplasia" reflected an increase in free ribosomes. "Hyperplastic nodules" were composed of hepatocyte aggregates with characteristics similar to those encountered in the earlier stage. Both the "neoplastic nodules" and hepatocellular carcinomas were formed by cells containing large, "smooth fingerprints" and free ribosomal aggregates. These features supported the concept that AFB1 impairs ribosomal binding to endoplasmic reticulum membranes. The failure of ACTH-treated animals to develop hepatocellular carcinoma was ascribed to the effect of adrenal cortical stimulation upon membrane-polysome binding.

Adrenocorticotropic Hormone↗
PubMed1977

"Nonalcoholic" chronic hepatitis in the alcoholic.

Ten alcoholic patients with biopsy proved chronic active or chronic persistent hepatitis were observed. In each patient, the responsible etiological agent appeared to be ethanol. Laboratory abnormalities could be distinguished statistically from those in a group of 121 patients with alcoholic hepatitis by their higher SGPT (262 +/- 139 versus 62 +/- 7 U per ml, P is less than 0.01), lower ratio of SGOT:SGPT (1.96 +/- 0.34 versus 4.71 +/- 0.40, P is less than 0.01), and lower white blood cell count 5,833 +/- 763 versus 10,370 +/- 742, P is less than 0.01). However, the overlap between the groups was sufficiently large that without histological confirmation the correct diagnosis was in doubt for any given patient.

Adult↗
PubMed1975

A simple, rapid method for measurement of acetate in tissue and serum.

A simple and rapid method is described for determining the free acetate concentration in liver and serum. After extraction, the acetate is converted to its benzyl ester by thermal degradation of its benzyldimethylphenylammonium salt in the vaporizer of a gas chromatography. Good quantitation is achieved in the range of 0.033-2.5 mumoles of acetate per gram of liver or per milliliter of serum.

Acetates↗