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Biomedical subjects

D R LaBrecque

Publications and source records attributed to D R LaBrecque.

52 records · Page 3Linked to original sources

A father and son with cholestasis and peripheral pulmonic stenosis: a distinct form of intrahepatic cholestasis.

We report a father and son with the syndrome of cholestasis and peripheral pulmonic stenosis. These cases demonstrate the clinical and biochemical features noted in previous reports of this entity and allows us to differentiate clearly this syndrome, with its benign course, from other more progressive forms of intrahepatic cholestasis. The vertical transmission supports a genetic etiology for this disease. Although serum bile acid levels are elevated in these patients, the individual bile acids do not display a distinctive pattern and no abnormal bile acids are identified.

Adult↗

Preparation and partial characterization of hepatic regenerative stimulator substance (SS) from rat liver.

1. The elucidation of the biochemical controls of growth processes is basic to understanding both normal and malignant growth. The exquisitely sensitive control demonstrated in the regenerating liver provides an excellent model system for growth studies. 2. Intraperitoneal injection of an extract from weanling rat liver into 34% hepatectomized rats stimulates [3H]thymidine incorporation into recipient hepatic DNA 2.5-fold. This stimulation is seen after a 10 hr lag period. 3. Extracts from weanling rat liver contain the highest level of the hepatic regenerative stimulator substance (SS), whereas extracts from adult liver give no significant stimulation. 4. If adult rats are partially hepatectomized, SS is demonstrated in their livers 12-15 hr after hepatectomy. 5. Partial characterization of SS shows that it is a soluble material not sedimented by centrifugation for 2 hr at 145,000 g. The stimulator activity is stable to heating at 65 degrees C and 100 degrees C for 15 min but is lost when treated with 10% perchloric acid.

Age Factors↗

The risk of hepatitis B transmission from staff to patients in hemodialysis units--an overrated problem?

The staff and patients in hemodialysis units have the greatest hospital risk of acquiring hepatitis B (HB) infection. We followed the patients of two dialysis nurses in two different dialysis units. One nurse dialyzed 19 patients a total of 50 times during the prodrome of acute HB. The second nurse was a known, asymptomatic carrier of HBsAg who was also HBeAg(+) and anti-HBc(+). Over a 2-year period, she dialyzed 30 patients a total of 742 times. Neither group of patients showed evidence of having acquired HB, suggesting that the risk of HB transmission from staff to patient is low even in the high-risk setting of a dialysis unit and a presumably highly infectious HBeAg(+) chronic carrier. In our study, the risk in this latter setting was less than 0.0040 (binomial probability p less than 0.05). The data do not support restricting care of patients by health workers who are chronic carriers of the virus.

Adult↗

Four generations of arteriohepatic dysplasia.

Arteriohepatic dysplasia (AHD) is a multisystem disorder which is characterized by liver, heart, eye, and bony abnormalities. A characteristic facies is also present. The etiology is not clear, and some authors have favored an in utero toxin or infection as the cause. Other reports have shown parent-to-child transmission suggesting an autosomal dominant form of inheritance. This study documents the presence of AHD characteristics in four successive generations of a single kindred. Overall, 15 of 24 members had at least some characteristics of AHD. In addition to the usual findings, renal disease, a small flat face on lateral X-ray, and mild conductive hearing loss were frequently noted in this kindred. Physiological studies on one member revealed a normal bromosulfophthalein Tm and S but a late rise in plasma bromosulfophthalein and indocyanine green. This study strongly supports an autosomal dominant form of transmission for the AHD syndrome. The ease of determining the eye, bone, and heart abnormalities should simplify genetic studies of other patients' families. In addition, because these characteristics are recognizable at birth, documenting their presence in a jaundiced neonate should spare the infant unnecessary and potentially dangerous surgery to rule out extrahepatic obstruction, especially if one or more family members demonstrate the same abnormalities.

Abnormalities, Multiple↗

Detection of hepatitis B virus DNA directly in human serum by a simplified molecular hybridization test: comparison to HBeAg/anti-HBe status in HBsAg carriers.

A simple, direct molecular hybridization test was employed to detect hepatitis B virus (HBV) DNA sequences in human serum. In 61 HBsAg carriers, many with HBV-related diseases (chronic persistent hepatitis, chronic active hepatitis, or posthepatitic cirrhosis), 28/28 (100%) who were HBeAg+ and 16/32 (50%) who were anti-HBe+ had HBV DNA sequences in their serum. Among 22 South African black patients with hepatocellular carcinoma, 7 (32%) had detectable HBV DNA in their serum but at reduced levels when compared to HBsAg carriers without hepatocellular carcinoma, suggesting that viral replication is suppressed or inactive in many hepatocellular carcinoma patients. Hybridization analysis also distinguished carriers with high, moderate, or low amounts of HBV DNA in serum. Ten to 20% of HBsAg+/HBeAg+ carriers showed high serum levels of HBV DNA but, surprisingly, a similar percentage of HBsAg+/anti-HBe+ carriers also showed relatively high serum levels of HBV DNA. Five patients who had undergone immunosuppression therapy and most of whom were on chronic hemodialysis had very high serum levels of HBV DNA, in the range observed during acute HBV infection. By epidemiologic analysis, two of these individuals were implicated in transmission of hepatitis to other hemodialysis patients, paramedical personnel, or intimate family contacts. Serum HBV DNA hybridization analysis identifies carriers with high serum levels of HBV irrespective of HBeAg/anti-HBe status and may define individuals with potentially high risk of transmitting infection to their immediate contacts.

Antibodies, Viral↗

Liver ultrastructure in mitochondrial urea cycle enzyme deficiencies and comparison with Reye's syndrome.

The liver ultrastructural findings in two girls with partial carbamyl phosphate synthetase I (CPS) deficiency and their heterozygote parents and two siblings with ornithine transcarbamylase (OTC) deficiency are described. Liver ultrastructure in the four patients with inherited deficiencies of urea cycle enzymes showed minimal alterations with essentially normal mitochondria when biopsy was performed during periods of good control of their hyperammonemia. Mitochondrial ultrastructure was also essentially normal in the heterozygotes for carbamyl phosphate synthetase I deficiency. These findings are in contrast to the marked alterations in mitochondrial ultrastructure found in the study of two cases of Reye's syndrome in which severe depression of ornithine transcarbamylase and carbamyl phosphate synthetase I activities was noted.

Adolescent↗

Effect of chronic ethanol ingestion on hepatic and intestinal acyl coenzyme a:cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme a reductase in the rat.

Two groups of rats were pair-fed diets in which 36% of the calories were provided by either ethanol or dextrimaltose. After 60 days on these liquid diets, rats fed ethanol were significantly smaller than control rats fed dextrimaltose. Serum cholesterol levels in ethanol-fed animals were 20% higher than control rats. Cholestasis was not observed histologically, and serum alkaline phosphatase and bilirubin levels were the same in both groups. The livers of animals ingesting ethanol accumulated triglycerides and cholesterol. The increase in cholesterol was due to an increase in cholesteryl esters. The cholesterol content of liver microsomes, however, was unchanged by ethanol feeding. A small increase in unesterified cholesterol was observed in intestinal microsomes prepared from animals receiving ethanol. Microsomal fatty acids in liver and intestine were unchanged by the ethanol diet. Chronic ingestion of ethanol in these animals failed to change acyl coenzyme A:cholesterol acyltransferase or 3-hydroxy-3-methylglutaryl-coenzyme A reductase activities in the intestine. In contrast, the activities of acyl coenzyme A:cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl-coenzyme A reductase were significantly increased in the livers of rats receiving ethanol. Thus, the chronic ingestion of ethanol caused a marked accumulation of hepatic cholesteryl esters. This was associated with a significant increase in the activities of enzymes that control the rates of both cholesterol synthesis and cholesterol esterification in the liver. These observed changes in enzyme activities may contribute to the lipid accumulation which occurs in these livers. Chronic ethanol consumption did not alter cholesterol metabolism in the intestine.

Acyl Coenzyme A↗

The risk of hepatitis B transmission from health care workers to patients in a hospital setting--a prospective study.

A prospective study was designed to determine the risk of hepatitis B transmission from health care deliverers to patients in the hospital setting. Six chronic carriers of hepatitis B were identified: 2 surgeons, 1 dialysis nurse, 1 pediatric ICU nurse, 1 pharmacist and 1 orderly. Three of the six were HBeAg-positive. Two of the HBeAG-positive chronic carriers also had circulating hepatitis B virus DNA and accounted for approximately two-thirds of the total patient contacts. Two hundred thirteen patients were exposed 450 times to these six hepatitis B carrier staff without evidence of hepatitis B acquisition over a 6-month follow up. One-hundred nineteen control patients, exposed 789 times to noncarrier health care deliverers, were also negative. Another 33 patients were exposed to three additional individuals who were in the prodrome of acute hepatitis B: an intensive care nurse, a dental hygienist and a medical student. These patients showed no evidence of hepatitis B during 6 months of follow-up, nor did 25 separate control patients. Thus, 246 patients were exposed a total of 483 times to nine health care personnel who had either acute or chronic hepatitis B. No evidence of hepatitis B transmission was found. One-hundred forty-four controls revealed similar results after 814 exposures. Based on the number of exposures to chronic carriers alone, the risk of hepatitis B transmission is estimated to be less than 1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier State↗

Purification and physical-chemical characterization of hepatic stimulator substance.

Hepatic stimulator substance is a liver growth stimulator derived from the hepatocyte cytosol of weanling or regenerating adult rat livers. The present paper reports the almost 9,000-fold purification of hepatic stimulator substance with an approximately 100,000-fold increase in specific growth stimulator activity. Purification steps included heating at 95 degrees C for 15 min, 40% cold ethanol precipitation, passage over Procion Red HE3B, DEAE cellulose and Sephadex G75 columns and gel filtration and reverse-phase fast protein liquid chromatography techniques. As little as 27 ng per ml of the purest material produced a 2-fold stimulation in the standard HTC cell activity assay. Further studies indicate that hepatic stimulator substance is a highly negatively charged protein and that disulfide bonds or a complex tertiary structure are not essential to its activity. Hepatic stimulator substance is stable over a wide range of pH's and temperatures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver stain revealed 1 major band at 12,400 daltons and 1 minor band at 17,500 daltons.

Animals↗

Personality disorder as a contraindication for liver transplantation in alcoholic cirrhosis.

Severe personality disorder has been proposed as a contraindication for liver transplantation. Seventy-three subjects with alcoholic-related liver disease were evaluated for personality disorder and followed for 6 months. The subjects with severe personality disorder had higher rates of divorce, higher rates of comorbid drug abuse or dependence, lower Weschler Adult Inventory Scale IQ estimates, and higher scores on indicators of emotional impairment. Personality disorder was not associated with a higher rate of return to alcohol use during the follow-up period. Three subjects with personality disorder underwent liver transplantation without behavioral or substance abuse complications. This study does not support routine exclusion of subjects based solely on a diagnosis of a severe personality disorder.

Adult↗

Frequency and characteristics of hyperbilirubinemia associated with bacteremia.

One hundred consecutive patients with blood cultures positive for microbial growth were prospectively surveyed for the presence of hepatic abnormalities and clinical evidence of infection. Complete data for 82 patients were available for analysis. Fifty-four percent had elevated bilirubin levels, and 34% had total bilirubin values of greater than or equal to 2.0 mg/dl. The levels of total bilirubin were disproportionately elevated compared with those of aspartate aminotransferase, alkaline phosphatase, and cholesterol. Nine of the 23 patients with elevated bilirubin levels had an increase in serum bilirubin one to nine days before their initial positive blood culture. Disproportionate elevations of direct and total serum bilirubin values compared with values for other liver-function tests appear to be associated with bacteremia in adults more frequently than previously recognized and may have some predictive value in such patients.

Adolescent↗

Ophthalmic features of Alagille syndrome (arteriohepatic dysplasia).

Eight patients with Alagille syndrome (AGS) are reported. In addition to previously reported findings of posterior embryotoxon, pigmentary retinopathy, and choroidal folds, new findings include decreased axial eye lengths, small corneal diameters, and shallow anterior chambers. Optic disc swelling was noted ophthalmoscopically and abnormally increased orbital subarachnoidal fluid was detected through measurements of the arachnoidal diameters with standardized echography.

Adolescent↗

The role of hepatotrophic factors in liver regeneration--a brief review including a preliminary report of the in vitro effects of hepatic regenerative stimulator substance (SS).

Details are presented of a technique for maintaining adult liver parenchymal cells in culture in a nonproliferating state. Hepatic regenerative stimulator substance (SS), prepared from weanling rat liver, will stimulate tritiated thymidine incorporation into liver DNA when injected into another rat or mouse. Preliminary experiments are presented which show that SS stimulates non-proliferating adult hepatocytes to incorporate increased amounts of (3)HT dr into DNA when SS is added to the culture medium. The response is dose dependent and a lag period of about 12 hours exists between addition of SS to the cultures and the stimulation of DNA synthesis. Preliminary screening of several cell lines in culture reveals that only liver related cell lines (hepatomas) respond to SS. A brief review of other hepatotrophic factors is also included.

Animals↗