Biomedical subjects

M A Korsten

Publications and source records attributed to M A Korsten.

At least 55 records · Page 3Linked to original sources

PubMed1989

Alcohol-induced pancreatic injury (Part I). Unexplained features and ductular theories of pathogenesis.

The pathogenesis of alcoholic pancreatitis continues to be a puzzle. Classical theories of pathogenesis tend to overlook the dual nature of the disease, i.e., symptomatic acute attacks and chronic progressive parenchymal destruction. Furthermore, it is unknown why only a small minority of alcoholics develop clinical pancreatic injury. In addition, there is a lack of basic data concerning the natural history of the condition after cessation of alcohol consumption. The most widely accepted theory of pathogenesis postulates the deposition of protein plugs in peripheral pancreatic ducts as the initial lesion. However, it has not been established that these plugs are the cause rather than a result of pancreatic injury. The so-called "Big Duct" theories of pathogenesis (biliary-pancreatic reflux, duodeno-pancreatic reflux, and obstruction-hypersecretion) are confounded by a lack of agreement concerning the effect of alcohol on the sphincter of Oddi. Nutritional factors and heredity may be responsible for the selectivity of alcohol in this condition; in this regard, a number of dietary and HLA studies have been performed, but these have generally been inadequately controlled. Subcellular pancreatic injury (fat droplets, autophagic vacuoles, and mitochondrial lesions) has been observed in alcoholics without pancreatitis and in animals fed alcohol. In addition, ethanol feeding in animals has been shown to affect pancreatic cholesterol, phospholipid, and fatty acid metabolism as well as pancreatic content of digestive enzymes. Research is hampered by the lack of a suitable animal model of the disease.

Alcohol Drinking↗

PubMed1988

Chronic ethanol administration depresses fatty acid synthesis in rat adipose tissue.

Administration of ethanol as part of a nutritionally adequate liquid diet to female Wistar rats was found to depress markedly incorporation of labelled glucose into adipose-tissue acylglycerol fatty acids. Similar results with labelled pyruvate and acetate suggested inhibition of the fatty-acid-synthesis pathway at, or distal to, the acetyl-CoA carboxylase step. Activities of acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in ethanol-fed animals. The activity of another lipogenic enzyme, phosphatidate phosphohydrolase, was not affected by chronic ethanol feeding. These findings suggest that chronic ethanol administration has marked effects on adipose-tissue lipogenesis.

Acetates↗

PubMed1988

Alterations in synaptic membrane molecular order associated with alcoholization and protein deficiency in rats.

The effects of chronic alcoholization and protein deficiency on synaptic membrane characteristics were studied in rats fed the following four liquid diets for 4 weeks: a protein-deficient diet containing alcohol, a protein-deficient diet containing no alcohol, a non-protein-deficient diet containing alcohol and a non-protein-deficient diet containing no alcohol. A fluorescent probe, diphenylhexatriene (DPH), was used to estimate the fluidity of synaptic membranes and their sensitivity to the fluidizing effect of ethanol added in vitro, in concentrations ranging from 50 mM to 800 mM. Prior to in vitro addition of ethanol, the difference between the fluidity of synaptic membranes of alcoholized and non-alcoholized animals was significant for the two groups of protein-deficient animals but not for the two groups of non-protein-deficient animals. After in vitro addition of ethanol, the differences between the fluidity of synaptic membranes of the alcoholized and non-alcoholized animals were larger and more frequently significant for the protein-deficient animals than for the non-protein-deficient animals. In view of previous observations that rats fed a protein-deficient diet experience more severe withdrawal symptoms following alcoholization than rats fed a nutritionally adequate diet, the results of the present experiment lend additional support to the hypothesis that tolerance and dependence may be mediated by alterations in biomembrane characteristics.

Alcoholism↗

PubMed1988

Combined effects of protein deficiency and chronic ethanol consumption on rat pancreas.

This study was performed in order to delineate the combined effects of protein deficiency and chronic ethanol ingestion on the rat pancreas. Rats fed ethanol in combination with protein-deficient diets developed marked steatosis, whereas alcohol ingestion with nutritionally adequate diets and protein deficiency alone each were associated with a more moderate degree of pancreatic lipid accumulation. On biochemical analysis, it was found that protein deficiency decreased pancreatic phospholipid content. Furthermore, both protein deficiency and chronic ethanol consumption increased pancreatic cholesteryl ester content, and their effects were additive. Functional changes were studied using isolated pancreative acini. Protein deficiency depressed the tissue content of lipase and the ability of pancreatic acini to secrete lipase. Chronic ethanol feeding increased lipase levels in the acini and also their secretory capacity. Thus, to the extent that enzyme accumulation in the pancreas plays a role in the pathogenesis of alcoholic pancreatitis, these results may explain the higher incidence of pancreatitis in well-nourished alcoholics that has been documented in dietary surveys.

Alcoholism↗

PubMed1987

Use of the triolein breath test in alcoholics with liver damage.

The triolein breath test (TBT) is a simple, noninvasive technique for the evaluation of steatorrhea. However, because it depends on intermediary hepatic processes, and because both liver damage and pancreatic dysfunction often co-exist in the alcoholic, the overall usefulness of the test in patients with liver injury was reassessed. We found that even in the absence of steatorrhea, a majority of patients with advanced liver injury (alcoholic hepatitis, cirrhosis, or both) had abnormal TBT results that failed to correct with pancreatic extract. In contrast, patients with less severe lesions (steatosis) had results that were not significantly different from those in normal controls. Inasmuch as the abnormal TBT results in patients with advanced alcohol-induced lesions did not correct with pancreatic extract, the test may not accurately differentiate pancreatic from nonpancreatic steatorrhea in some alcoholics.

Breath Tests↗

PubMed1986

Decrease in lipogenesis and glucose oxidation of rat adipose tissue after chronic ethanol feeding.

This investigation was performed to determine whether chronic ethanol feeding affects adipose tissue lipogenesis and glucose metabolism. Female Wistar rats were pair-fed nutritionally adequate liquid diets containing ethanol as 36% of energy or an isocaloric amount of carbohydrate for 3 weeks. Chronic ethanol feeding resulted in a depression of adipose tissue lipogenesis as assessed by labeled glucose incorporation into glyceride glycerol and glyceride fatty acids. Glucose oxidation was also impaired after chronic ethanol feeding. Such changes may contribute to the postprandial hypertriacyglyceridemia observed in alcoholics.

Adipose Tissue↗

PubMed1986

Protein deficiency alters rat pancreatic lipid composition.

Pancreatic lipid composition was found to be altered in rats fed a protein-deficient diet for 4 wk. Increases in triglycerides and cholesteryl ester content were found in association with a decrease in phospholipids. Alterations in these lipids may adversely affect membrane function and predispose to pancreatic injury.

Animals↗

PubMed1986

New technique for the isolation of functional rat pancreatic mitochondria and its application to models of pancreatic injury.

The role of mitochondria in the initiation or promotion of pancreatic pathologic conditions has not been clearly delineated. In this context, it has recently been suggested that abnormal mitochondrial function may account for the fat accumulation observed in pancreatic acinar cells in alcoholism. To study these issues, we developed a method for the isolation of functional mitochondria from the rat pancreas. The resultant mitochondrial pellet possessed oligomycin-insensitive Mg2+-adenosine triphosphatase (ATPase) activity, and coupled respiration could be demonstrated in the presence of EDTA only after Mg2+ had been excluded from the incubation medium. Albumin was also a requirement for the demonstration of coupled respiration in vitro. When this new technique was applied to a rat model of alcohol-induced pancreatic steatosis, no mitochondrial dysfunction was demonstrated, suggesting that some other mechanism is responsible for fat accumulation in pancreatic acinar cells after long-term ethanol consumption. In contrast, DL-ethionine administration to rats produced partial or total uncoupling of mitochondrial respiration in the absence of morphologic evidence of mitochondrial injury.

Adenosine Diphosphate↗

PubMed1986

Esophageal acid-clearance and motility after endoscopic sclerotherapy of esophageal varices.

To investigate the possible mechanisms which may lead to esophageal strictures after endoscopic variceal sclerotherapy, we performed esophageal motility and acid-clearance studies before and after 24 sclerotherapy sessions in 10 patients. Comparing studies before and after sclerotherapy, we found: a 93% mean increase in the number of swallows required to clear a standard amount of administered acid 24 h after sclerotherapy. Acid clearance returned to baseline within 1 wk of sclerotherapy; minimal changes in esophageal motility, none of which was significant except for swallow-induced simultaneous contractions in the distal esophagus which were a prominent feature in manometric recordings within 24 h of sclerotherapy; no increase in acid reflux from the stomach. We conclude that acid clearance from the distal esophagus is markedly delayed for at least 24 h by sclerotherapy but that this defect in acid clearance is transient, lasting no more than 1 wk. The importance of this observation remains to be demonstrated, but it is consistent with the concept that acid-induced injury contributes to the formation of post-sclerotherapy strictures.

Deglutition↗

PubMed1986

Esophageal function in chronic alcoholics.

We determined whether there are abnormalities in esophageal motility or acid clearance in chronic alcoholics since alterations in these parameters have been implicated in the pathogenesis of esophagitis after chronic ingestion of ethanol. In addition to esophageal manometry, we also performed acid-clearance studies and examined salivary output, acid-neutralizing capacity, and bicarbonate concentration. We found an increased lower esophageal sphincter pressure which reverted to normal after withdrawal from ethanol. Except for a significantly larger number of tertiary contractions, no other abnormality of esophageal motility was found. Salivary flow, acid-neutralizing capacity, and bicarbonate concentration were not significantly different from that in control subjects. However, in contrast to findings in controls, there was no correlation between salivary bicarbonate concentration and acid-neutralizing capacity in the alcoholics. Our results indicate that chronic ethanol ingestion alters some aspects of esophageal function and salivary composition but that these alterations are unlikely to explain the increased risk of esophagitis in alcoholics.

Adult↗

PubMed1985

Balloon cytology in screening of asymptomatic alcoholics for esophageal cancer, Part I.

We assessed the feasibility of using balloon cytology to screen an asymptomatic group of alcoholics at increased risk for esophageal cancer. The results indicate that this group can be studied with minimal morbidity and that useful material can be obtained in 85% of subjects. Keratinization was present in 68% of specimens and fungus was noted in 9%. Individuals with moderate to large amounts of keratinization consumed significantly more alcohol than those without cytologic evidence of keratin. We speculate that keratinization and fungus may represent markers of enhanced malignant potential in this population.

Adult↗

PubMed1985

Esophageal motility and symptoms after endoscopic injection sclerotherapy.

Endoscopic injection sclerotherapy is known to cause a variety of motility abnormalities, but the correlation between these changes and symptomatology has not been clearly defined. To assess the effects of endoscopic sclerosis of varices on esophageal function and symptoms, we prospectively studied esophageal motility in 25 patients undergoing sclerotherapy (group I). Thirteen patients underwent studies before and after sclerosis, and 12 patients were studied after completion of therapy. Acid clearance was studied in five patients (group I). Twenty-four of the 25 patients (group I) completed a course of sclerosis without the development of persistent dysphagia. We found that endoscopic sclerotherapy did not significantly alter the velocity of peristalsis or lower esophageal sphincter pressure, amplitude of contraction, or the duration of contraction. Acid clearance was diminished in three of five patients. Four patients who developed an esophageal stricture following sclerotherapy were studied manometrically (group II). Three of these four patients had a manometric pattern characterized by repetitive, nonperistaltic contractions, and all four patients experienced dysphagia which was relieved by bougienage. We conclude that esophageal motility is generally well preserved following endoscopic injection sclerotherapy and does not result in a long-lasting disturbance of swallowing. Dysphagia and disordered esophageal motility do occur after sclerotherapy when a sufficient fibrotic response has resulted in an esophageal stricture.

Esophageal Stenosis↗

PubMed1985

Pancreatic choriocarcinoma presenting as inflammatory pseudocyst.

A primary pancreatic choriocarcinoma was discovered at surgery in a patient with a clinical diagnosis of pancreatic inflammatory pseudocyst. To our knowledge, this is the first example of an extragonadal choriocarcinoma reported as a primary at this site. We consider this neoplasm to be another example of a visceral choriocarcinoma arising from a primary carcinoma through a process of metaplasia. This case illustrates the inherent difficulties in the preoperative evaluation of cystic lesions of the pancreas, and the importance of recognizing endocrinologic manifestations of malignant disease.

Adult↗

PubMed1985

The relationship of bacteremia to the length of injection needle in endoscopic variceal sclerotherapy.

The authors evaluated whether depth of needle insertion as determined by needle length is an important factor in sclerotherapy-associated bacteremia. In 18 consecutive sclerotherapy sessions in which sodium morrhuate was used, blood cultures were positive in 11% when using an injector with only 3 to 4 mm of needle protruding beyond the sheath, compared with the 39% incidence of bacteremia previously observed when an injector was used which permitted 6 to 8 mm of needle to protrude (0.01 less than p less than 0.05). Twenty-five additional sclerotherapy sessions in which the shorter needle was used were performed with a different sclerosant, 1% sodium tetradecyl sulfate; only 8% of blood cultures were positive. No correlation was found between fever and bacteremia. The authors conclude that the exposed needle length of the injector must be specified in any report of endoscopic variceal sclerotherapy with the flexible endoscope since this length is critical in the incidence of associated bacteremia and possibly other complications.

Endoscopes↗

PubMed1984

The isolation and properties of mitochondria from rat pancreas.

A technique for the isolation of functional rat pancreatic mitochondria is described. The resultant mitochondrial preparations contained oligomycin-insensitive Mg2+-ATPase activity and coupled respiration could only be demonstrated in the absence of Mg2+ and in the presence of EDTA.

Adenosine Triphosphatases↗

PubMed1983

Effects of chronic ethanol feeding and acetaldehyde metabolism on calcium transport by rat liver mitochondria.

The prolonged feeding of ethanol to rats alters in vitro mitochondrial transport of calcium. Hepatic mitochondria isolated from rats fed ethanol for 7 weeks exhibited decreased retention of calcium in the presence of 4mM-Pi. This defect was associated with enhanced efflux of calcium when mitochondria were incubated with EGTA. Acetaldehyde at low, "physiological" concentrations (100 microM) enhanced calcium retention by mitochondria but this response was blunted after chronic ethanol administration. The in vitro actions of acetaldehyde appear to be mediated, in part, by its metabolism in mitochondria since pretreatment of rats with cyanamide (an aldehyde dehydrogenase inhibitor) prevents this effect.

Acetaldehyde↗

PubMed1983

Bacteremia after endoscopic injection sclerosis.

Endoscopic injection sclerosis is a therapeutic alternative in the management of esophageal varices. Complications of sclerotherapy have been minor, including fever, bacteremia, and abnormal chest x-ray. We performed a prospective study to evaluate the frequency of postsclerosis bacteremia. Bacteremia was detected in 14 procedures (50%). There were no cases of bacteremia in a group of control patients with esophageal varices undergoing upper gastrointestinal endoscopy without sclerosis (p less than 0.05). Bacteremia was transient and unrelated to the presence of fever or other clinical complications. The organism most commonly cultured from blood, alpha-hemolytic streptococcus, probably represents a contaminant from the oropharynx, introduced into the bloodstream during sclerosis. We conclude that injection sclerotherapy of esophageal varices is associated with a higher incidence of bacteremia than routine upper endoscopy and that selected patients may require antibiotic prophylaxis when undergoing this procedure.

Esophageal and Gastric Varices↗

PubMed1983

[Clinical spectrum of amebic colitis].

We present six cases to illustrate the protean clinical and sigmoidoscopic features of the amebic colitis. Three cases presented with a clinical picture resembling ulcerative colitis. In one fatal case, diverticular disease, ischemic colitis and toxic megacolon of uncertain origin were considered before arriving at the proper diagnosis. Two cases were believed to have pseudomembranous colitis on sigmoidoscopic examination. Given the multiple expressions of this entity, amebic colitis should be considered a diagnostic possibility in any protracted inflammatory condition of the colon. From the cases summarized here, it is evident that the clinical and endoscopic features of amebic colitis are variable and may often mimic other illnesses.

Adult↗