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Biomedical subjects

D R LaBrecque

Publications and source records attributed to D R LaBrecque.

At least 37 records · Page 2Linked to original sources

Serial bilirubin determinations as a prognostic marker in clinical infections.

Patients with documented serious infection and total bilirubin values of greater than 2 mg/dl were surveyed for serial changes in bilirubin and other laboratory and clinical features. Of 19 patients studied, 12 (Group A) had persisting or increasing hyperbilirubinemia, and 7 (Group B) had decline in bilirubin after infection onset. None demonstrated marked changes in other liver tests. Only one patient had infection directly involving the hepatobiliary system. There were no significant differences between the two groups with respect to underlying illnesses, active hepatobiliary diseases, pathogens, bacteremia, or administration of cholestatic drugs. All Group A patients died because of uncontrolled infections, whereas all Group B patients survived with resolution of infection (p less than .001). Ten of 15 patients with available preinfection liver tests demonstrated serial bilirubin increases without marked changes in other liver tests prior to clinical recognition of infection. These findings demonstrate that hyperbilirubinemia disproportionate to increases in other tests may manifest before recognition of infection and that persistent or progressive hyperbilirubinemia is indicative of ongoing active infection.

Adult↗

Successful treatment of hepatic venocclusive disease in a bone marrow transplant patient with side-to-side portacaval shunt.

Hepatic venocclusive disease developed in a 14-yr-old white girl after allogenic bone marrow transplantation from an HLA-identical sibling donor. Clinical diagnosis of venocclusive disease was based on the development of ascites, hepatomegaly, and jaundice 3 wk after transplantation. Current treatment of hepatic venocclusive disease is ineffective. The pathophysiology of the hepatic lesion suggests that construction of a side-to-side portacaval shunt should be beneficial in relieving the ascites and preventing further hepatic damage. Because the ascites was refractory to medical therapy and she was clinically deteriorating, a side-to-side portacaval shunt was performed. Histologic examination of a liver biopsy specimen obtained at surgery documented the presence of venocclusive disease. Postoperatively, the patient diuresed and returned to her baseline weight. One year after surgery the patient was doing well, her weight was stable, and she was being maintained on salt restriction alone. While the resolution of ascites and improvement of hepatic function in our patient after side-to-side portacaval shunt does not guarantee that such an approach will be uniformly successful, it should serve to encourage others to consider such therapy for this frequently devastating complication of chemoradiation therapy.

Adolescent↗

Hepatic veno-occlusive disease associated with renal transplantation and azathioprine therapy.

Four patients with renal transplants developed hepatic veno-occlusive disease after immunosuppressive therapy with azathioprine. Severe progressive portal hypertension developed in all patients, with the clinical presentation varying from a mild viral-like syndrome to rapidly fulminant liver failure and death. The disease was associated with cytomegalovirus infection but not with the dose of azathioprine, the type or duration of transplant, or the type of underlying kidney disease. In view of the high mortality rate associated with veno-occlusive disease (a combined 55% in our four patients and in five reported in the literature) and wide spectrum of clinical presentation in patients with renal transplants, a high index of suspicion is required and aggressive intervention indicated.

Adult↗

Corset liver.

We describe four patients with a benign hepatic malformation most consistent with the rarely described anomaly known as corset liver. Three of these patients were extensively evaluated to rule out a malignancy because of an abdominal mass. These patients illustrate several features which may help in making the diagnosis and avoiding unnecessary surgery.

Age Factors↗

Cholesterol metabolism in regenerating liver of the rat.

The regenerating rat liver was used as a model to investigate the necessity for new cholesterol synthesis prior to the onset of cell division. Plasma cholesterol levels in partially hepatectomized rats were significantly decreased 24 and 48 h after surgery compared with levels in sham-operated animals. Hepatic cholesteryl ester content was also significantly increased in livers from partially hepatectomized animals, but the hepatic content of unesterified cholesterol was not affected. Hepatic triglyceride content was significantly increased within 6 h after surgery in the regenerating liver. The triglyceride levels reached a peak at 24 h, and by 72 h they had decreased back to levels that were no different from control. In the regenerating liver, microsomal 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was increased 12 h after surgery. The activity of this enzyme remained significantly elevated throughout the 72-h period after surgery. In contrast, 12 h after partial hepatectomy the rate of hepatic cholesterol synthesis was significantly lower than that observed in livers from sham-operated rats. An increase in the rate of cholesterol synthesis was not observed until 48 h after partial hepatectomy, some 32 h after the start of DNA synthesis. Microsomal acyl-CoA:cholesterol acyltransferase activity was unchanged except for a 28% decrease at 72 h after partial hepatectomy. The data suggest that new cholesterol synthesis is not a requirement prior to the initiation of DNA synthesis in the regenerating rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyl Coenzyme A↗

Severe hepatic damage after acetaminophen use in psittacosis.

A 63-year-old man with acute psittacosis had severe hepatic damage after ingesting about 10 g of acetaminophen over a 48 hour period. Transaminase levels showed striking elevation, with a serum glutamic-oxaloacetic transaminase level of over 15,000 IU/liter, and decreased rapidly, consistent with a toxic insult. No other etiologic agents were identified by history or serologic testing to explain this degree of damage. Liver histologic findings at autopsy showed severe central necrosis. Although psittacosis may infrequently cause a similar pattern of hepatic injury, disease of this severity has not been previously reported. It is postulated that acetaminophen may have accentuated hepatic disease produced by Chlamydia psittaci in this patient.

Acetaminophen↗

Hepatic stimulator substance: physicochemical characteristics and specificity.

This laboratory has reported previously that a cytoplasmic extract of weanling or regenerating adult rat liver (but not normal rat liver) will produce a 2.5-fold increase in the incorporation of tritiated thymidine ([3H]dThd) into liver DNA of a 34%-hepatectomized test animal. (J. Physiol. London 248: 273-284, 1975). The present study showed that hepatic stimulator substance (HSS) will stimulate DNA synthesis in normal adult rats and CF1 mice as well. The increased incorporation of [3H]dThd into DNA produced in the normal, nonhepatectomized adult rat was comparable with that induced by a 34% hepatectomy. Autoradiographic studies revealed that the [3H]dThd was incorporated into nuclear DNA and that the stimulation occurred almost exclusively in parenchymal cells. HSS was shown to be heat stable (100 degrees C for 15 min) and was precipitated but not inactivated by alcohol. Ultrafiltration and dialysis studies suggested a molecular weight slightly greater than 10,000. HSS proved to be organ specific, stimulating the liver but not the kidney, bone marrow, or spleen. HSS was found to contain no insulin, glucagon, epidermal growth factor, or peptides of the nonsuppressible insulinlike/multiplication-stimulating activity (somatomedin) group.

Animals↗

In vitro stimulation of cell growth by hepatic stimulator substance.

An extract of normal weanling or adult regenerating rat liver called hepatic stimulator substance (HSS) stimulates incorporation of tritiated thymidine ([3H]dThd) into liver DNA. In vivo, it is organ specific, species nonspecific, displays diurnal rhythm, and has a molecular weight of approximately 10,000-20,000. It has now been further characterized in vitro. HSS retained organ specificity, stimulating normal adult hepatocytes in primary culture, the HTC, PLC, and MH1C1 hepatoma cell lines, and the PRC rat liver cell line. It did not stimulate human or mouse lymphocytes, 3T3 mouse fibroblasts, Y1BS1 mouse adrenal cells, Chinese hamster ovary cells, rat hypernephroma cells, C6 rat glial cells, or L1210 mouse leukemic cells. More detailed studies of the response of HTC cells to HSS revealed a dose-dependent increase in [3H]dThd incorporation (up to 30-fold) with a response to as little as 140-ng purified extract/ml culture medium. Autoradiography confirmed that the thymidine was taken up by nuclear DNA. This represented a true stimulation of growth as shown by an almost twofold increase in cell number after 6 days of exposure to low doses of HSS.

Animals↗

Lymphoreticular malignancy presenting as fulminant hepatic disease.

Four cases of fulminant hepatic disease caused by lymphoreticular infiltration are described. All 4 patients died within a few weeks and clinical diagnoses included viral hepatitis, alcoholic hepatitis, and drug hepatitis. A diagnosis of malignancy was made prior to autopsy in only 1 of the 4 patients. Autopsies revealed typical malignant histiocytosis in 3 patients and the fourth had a primitive lymphoreticular malignancy with malignant histiocytosis the favored diagnosis. The extent of the liver infiltrate as judged histologically was mild compared with the severe clinical illness. Randomly scattered foci of necrosis associated with the malignant infiltrate were seen in the 2 patients who had marked elevations of serum glutamic oxaloacetic transaminase.

Adult↗

Ocular findings in arteriohepatic dysplasia (Alagille's syndrome).

The ocular findings in a father and two offspring with arteriohepatic dysplasia are reported in this paper. All three people had bilateral posterior embryotoxon, Axenfeld's anomaly and a pigmentary retinopathy. Other ocular findings were exotropia, an ectopic pupil, band keratopathy, choroidal folds, anomalous optic discs and infantile myopia. Persons with arteriohepatic dysplasia typically present with prolonged neonatal jaundice. Cognizance of the associated eye findings helps distinguish this syndrome from other types of familial intrahepatic cholestasis.

Adult↗

Sulindac (Clinoril) hepatitis.

A patient with Sulindac-induced hepatitis is presented. Sulindac was confirmed as the cause of the patient's liver disease when hepatic dysfunction abruptly recurred after an inadvertent reexposure to Sulindac and quickly resolved when the drug was withdrawn. The prompt reappearance of fever, chills, pruritus, rash, tender hepatomegaly, and abnormal liver tests after only two doses of Sulindac suggested a hypersensitivity reaction.

Adult↗

The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature.

The charts of 238 patients with systemic lupus erythematosus (SLE) were reviewed. Although not routinely screened for biochemical evidence of liver disease, 124 of 206 patients tested had at least one abnormal result, and 43 met strict criteria for the existence of liver disease. In most patients, a specific viral or drug etiology could not be implicated. The spectrum of liver disease in 33 patients from whom liver tissue was available included cirrhosis, chronic active hepatitis, granulomatous hepatitis, chronic persistent hepatitis and steatosis. Three of four cirrhotic patients demonstrated a peculiar form of cholestasis which resembled a "canalicular cast" of bile. Of the nine patients who had serial liver biopsies, four showed progression of their disease. Three patients died of liver failure. Liver involvement in SLE is more common than previously recognized. Severe and even fatal liver disease can occur.

Adolescent↗

The evolving nature of "infantile obstructive cholangiopathy".

We report four patients with neonatal conjugated hyperbilirubinemia in whom the nature of the disease varied from that predicted by the initial diagnostic work-up. In two the initial liver biopsy showed paucity of the intrahepatic bile ducts; one cleared her conjugated hyperbilirubinemia and appeared normal at 3 years, but the other proved to have extrahepatic biliary atresia. The initial liver biopsy in two additional patients showed bile duct proliferation; both patients had a paucity of intrahepatic bile ducts later in the course of their disease. These cases illustrate the necessity of carefully following patients with neonatal conjugated hyperbilirubinemia to be certain that their courses continue to conform to the original diagnoses.

Bile Ducts↗

Pyloric stenosis and direct hyperbilirubinemia with alpha-1-antitrypsin deficiency.

The occurrence of unconjugated hyperbilirubinemia in infants with pyloric stenosis is common. We report an infant who presented with projectile vomiting secondary to pyloric stenosis. In addition, he had conjugated hyperbilirubinemia which proved to be due to alpha-1-antitrypsin deficiency of PiZZ phenotype. This is the first case report of such an association. Infants with pyloric stenosis and conjugated hyperbilirubinemia should be investigated for underlying infectious, metabolic causes or anatomical defects of the biliary tree.

Humans↗

Hemosiderosis without cirrhosis: an unusual case of portal hypertension.

A renal transplant recipient presented with bleeding esophageal varices. Needle biopsy, later confirmed by operative wedge biopsy, showed slight periportal fibrosis but no cirrhosis or hepatitis. No etiology for his liver disease could be determined and he could not be differentiated from other reported patients with idiopathic noncirrhotic portal hypertension (IPH). His liver biopsy did show massive hepatic iron deposition. He had received about 115 units of blood while on hemodialysis and had taken oral iron supplementation for 8 years. IPH has been associated with toxin exposure, especially arsenic and vinyl chloride. This case suggests that excessive iron deposition may also lead to IPH and the indiscriminate use of iron supplementation in hemodialysis or renal transplant patients should be avoided.

Adult↗

Diurnal rhythm: effects on hepatic regeneration and hepatic regenerative stimulator substance.

The effect of a controlled lighting schedule on the activity of a weanling rat liver extract that stimulates DNA synthesis in regenerating adult rat liver, and on the response of the test animals to the extract, has been investigated. Both activity of the extract and endogenous DNA synthesis in the weanling animals follow the same distinct diurnal rhythm. Reversal of the lighting schedule reverses the rhythm of endogenous DNA synthesis but activity of the extract no longer correlates with the peak of DNA synthesis. Diurnal rhythm also has a striking effect on DNA synthesis in the regenerating test animal, but the extract increases DNA synthesis to the same relative degree, regardless of the time of day the hepatectomy is performed.

Animals↗