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Biomedical subjects

W C Maddrey

Publications and source records attributed to W C Maddrey.

At least 73 records · Page 4Linked to original sources
PubMed1988

Submassive hepatic necrosis associated with the use of progabide: a GABA receptor agonist.

Progabide, a recently introduced gamma-aminobutyric acid mimetic, is currently undergoing clinical evaluation for a variety of convulsive disorders. We describe a patient in whom severe hepatic failure developed after four weeks of Progabide therapy. The patient's course was marked by encephalopathy, jaundice, hypoglycemia, markedly elevated serum aminotransferase levels, and prolongation of the prothrombin time. Liver biopsy showed extensive hepatocellular necrosis. The patient recovered slowly after discontinuation of the drug. The finding of eosinophilia and increased serum IgE suggests an immunologically mediated mechanism for the Progabide-induced hepatic injury. Alternatively, the lipophilic moiety of Progabide may interact with hepatocyte cell membrane lipids leading to toxic injury. We conclude that Progabide may occasionally cause severe hepatic injury.

Adult↗
PubMed1988

Major complications of acute and chronic liver disease.

Many advances have been made in the understanding, diagnosis, and management of severe complications of liver disease. The pathogenesis of hepatic encephalopathy remains a challenge. Several toxins including ammonia, mercaptans, short-chain fatty acids, benzodiazepine-like substances, GABA-like substances, and impaired glutamatergic neurotransmission are at the top of the list of candidates. Use of the benzodiazepine antagonists is an experimental but promising new therapy in patients with hepatic encephalopathy. In patients with cirrhosis, spontaneous bacterial peritonitis (SBP) remains a common and highly lethal complication. The diagnosis of SBP is based on the polymorphonuclear cell count in the ascites and confirmed by culture of ascitic fluid. Early diagnosis and aggressive treatment has reduced mortality of SBP from greater than 90 per cent to 30 to 50 per cent. The appearance of cerebral edema in severe acute hepatocellular failure is associated with high mortality and conventional neurologic signs may be unreliable indicators of brain swelling. Current management of cerebral edema in fulminant hepatocellular failure may include early placement of an extradural sensor for continuous monitoring of intracranial pressure, so that short-term measures can be instituted making later liver transplantation safer. Coagulopathy remains a serious problem in patients with liver disease. Exchange plasmapheresis is a promising short-term adjuvant therapy. However, liver transplantation should be considered the definitive treatment for fulminant hepatocellular failure. The gastroenterologist often encounters multiorgan failure in patients with severe liver disease. Liver transplantation is now an important therapeutic consideration in almost every patient with severe, irreversible liver disease. Efforts should be targeted to early diagnosis of irreversible disease and coordination of patient care with a liver transplant center.

Acute Disease↗
PubMed1987

Surgery in the patient with liver disease.

This article deals with the effects of anesthesia and surgery on the healthy and diseased liver and the preoperative assessment of patients with liver disease. Emphasis is placed on estimating surgical risk. Guidelines for optimal preoperative preparation are discussed.

Humans↗
PubMed1987

Hepatic effects of acetaminophen. Enhanced toxicity in alcoholics.

Alcoholic patients run an increased risk of developing hepatotoxicity from doses of acetaminophen within or only moderately above the recommended usual therapeutic doses. In this review I examine the scientific evidence and clinical observations that indicate such a heightened susceptibility of the alcoholic to acetaminophen-induced injury.

Acetaminophen↗
PubMed1987

The periportal collar: a CT sign of liver transplant rejection.

A low-attenuation region around the peripheral portal tracts (periportal collar) was noted on 13 of 43 computed tomographic studies obtained in 17 patients who had undergone 20 orthotopic liver transplantations. This region was then correlated with acute liver transplant rejection. The periportal collar as a sign of rejection has a sensitivity of 1.0, a specificity of 0.86, a negative predictive value of 1.0, and a positive predictive value of 0.62. This sign corresponds histopathologically with the lymphocytic portal infiltration that occurs during acute liver transplant rejection. Though viral hepatitis and nonspecific portal triad edema can also result in a periportal collar, acute liver rejection is strongly suggested when this sign is seen after liver transplantation. Early diagnosis and confirmation of rejection permit faster and more appropriate clinical intervention.

Adolescent↗
PubMed1986

Pigment gallstone composition in patients with hemolysis or infection/stasis.

The effect of hemolysis and infection/stasis on pigment gallstones was assessed by comparing the composition of stones from (1) U.S. patients without hemolysis or cirrhosis, (2) U.S. patients with sickle cell disease, and (3) Japanese patients with biliary infections. Gallstone composition was quantitated by infrared spectroscopy and chemical analyses. Gallstones from patients with sickle cell anemia contained more pigment, carbonate, calcium, and measured components than stones from U.S. patients without hemolysis (P less than 0.05). However, the similar types of calcium salts in black stones from patients with and without sickle cell anemia suggested that intermittent hemolysis may be a potential mechanism in the formation of black stones found in the general population. In Japanese patients with brown pigment stones, there was an absence of calcium carbonate, low levels of calcium phosphate, and the presence of calcium salts of fatty acids (P less than 0.05). Thus, the accompanying stasis and/or infection in this latter group was associated with the formation of a distinctive stone type and was not involved in the formation of the black stones. The similarly small proportion of cholesterol in each of these groups suggested that it was present due to coprecipitation rather than to cholesterol supersaturation.

Anemia, Sickle Cell↗
PubMed1985

Branched chain amino acid therapy in liver disease.

Patients with hepatic cirrhosis often are malnourished and wasted. If portal-systemic encephalopathy (PSE) develops, restriction of dietary protein in an attempt to treat encephalopathy may further promote negative nitrogen balance. There is considerable interest in providing nutritional supplements to patients with cirrhosis and PSE which would lead to improvement in nitrogen balance while improving or at least not worsening PSE. Amino acid supplements designed to correct the abnormal amino acid pattern characteristically found in patients with cirrhosis and PSE are under investigation as potential therapeutic agents. The levels of the branched chain amino acids (BCAAs) are decreased in almost all patients with cirrhosis and PSE. The exact mechanism for the reductions in BCAA concentrations is unknown. Furthermore, aromatic amino acids (AAA) and methionine (MET) concentrations are usually increased in these patients. It has been suggested that BCAAs and neutral amino acids compete for transport across the blood-brain barrier and that a decrease in BCAA concentrations promotes entrance of neutral amino acids into the brain. Aromatic amino acids, MET, and their derivatives may have a role in the production of PSE. These observations have increased interest in the potential therapeutic benefit of administering BCAAs to patients with cirrhosis and PSE in order to decrease the entrance of putative toxins into the brain. Treatment trials using BCAAs alone or in solutions containing other amino acids in patients with cirrhosis and PSE have given conflicting results. In one trial, there appeared to be less PSE induced by a BCAA-enriched solution when compared to equinitrogenous dietary protein. However, other controlled studies have not demonstrated any advantage to the addition of BCAAs as compared to placebo with regards to reducing mortality or improving cerebral function in patients with acute cirrhosis and PSE. Some of the differences in study outcomes may relate to the patient population evaluated; the type, amount, and duration of treatment; and whether other therapy was administered. BCAA supplements may also be useful in minimizing or reversing the catabolic state characteristic of patients with cirrhosis. A reduction of increased urinary 3-methylhistidine excretion by infusions of BCAAs in cirrhotic patients suggests an anticatabolic effect. These potential anticatabolic effects of BCAAs are most interesting and deserve further study.

Administration, Oral↗
PubMed1984

Cholestatic hepatitis from erythromycin ethylsuccinate. Report of two cases.

Cholestatic hepatitis developed in two patients while they were receiving erythromycin ethylsuccinate. Both patients had received the drug without apparent problem within two months of the episode of drug-related cholestatic injury. In both, there was complete resolution of the hepatic injury upon withdrawal of the drug. Erythromycin ethylsuccinate should be added to the list of drugs causing cholestatic hepatitis.

Chemical and Drug Induced Liver Injury↗
PubMed1984

Sclerosing cholangitis. Anatomical distribution of obstructive lesions.

The cholangiograms of 36 patients with sclerosing cholangitis were reviewed. The mean age of the patient group was 43 years, and the mean disease duration was 4.5 years. Seventeen of the patients had associated inflammatory bowel disease. The mean serum bilirubin was 6.8 mg/dl, the mean SGOT was 105 IU/L, the mean SGPT was 108 IU/L, and the mean serum alkaline phosphatase was 534 IU/L. The cholangiograms demonstrated involvement of the extrahepatic bile ducts in 33 patients, involvement of the hepatic duct bifurcation in 33 patients, and involvement of the intrahepatic bile ducts in 35 patients. The cholangiograms were graded as to the areas of the most severe obstructive involvement. In 24 patients the area of most severe involvement was the hepatic duct bifurcation. In eight additional patients the hepatic duct bifurcation, along with the extrahepatic ducts and/or the intrahepatic ducts, were felt to be the areas most severely affected. This predilection for severe obstructive disease at the hepatic duct bifurcation in sclerosing cholangitis held for both patients with and without inflammatory bowel disease. Thus, most patients with sclerosing cholangitis have cholangiographic evidence of diffuse extrahepatic and intrahepatic biliary tract disease, with the hepatic duct bifurcation being the area generally most severely affected.

Adult↗
PubMed1983

The Budd-Chiari syndrome. Treatment by mesenteric-systemic venous shunts.

Twelve patients with the Budd-Chiari syndrome have been managed surgically. Ten of the patients were female, two were male, with a mean age of 40 years. Three of the patients had polycythemia vera, two had pre-existing cirrhosis, one had ingested estrogens, one had an occult tumor, and in four there were no associated factors. Ten patients presented with ascites and two with bleeding esophageal varices. The diagnosis was confirmed in all 12 patients by liver biopsy and hepatic vein catheterization. Inferior vena cavography revealed the abdominal vena cava to be thrombosed in six patients. The superior mesenteric vein was used to decompress the congested liver in all 12 patients. In five patients, a mesocaval shunt (MCS) was performed and in seven patients, a mesoatrial shunt (MAS) was carried out. There were four hospital deaths (two MCS, two MAS). One late death (MAS) occurred from liver failure following shunt thrombosis. Two additional patients (one MCS, one MAS) re-developed ascites immediately following surgery and angiography revealed a thrombosed shunt. Ascites has been controlled with a LeVeen shunt in these two patients, but liver biopsies showed progression to cirrhosis. The remaining five patients (three MAS, two MCS) did well, and angiography revealed patent shunts. Two of these patients, however, re-developed ascites at 4 and 10 months following MAS and required a second MAS. Follow-up ranges from 6 to 68 months. In three of the patients (two MCS, one MAS) with patent shunts, liver biopsy shows a remarkable return toward normal liver architecture and histology.

Adolescent↗
PubMed1983

Sclerosing cholangitis: biliary reconstruction with Silastic transhepatic stents.

Because of multiple areas of stricturing and small fibrotic ducts, sclerosing cholangitis has generally not been amenable to direct reconstructive procedures. In reviewing the cholangiograms of 29 patients with sclerosing cholangitis, it became apparent that despite diffuse disease, the hepatic duct bifurcation was often (22 patients) the most severely narrowed area. Because of this finding it was decided to manage patients who have sclerosing cholangitis, persistent jaundice, and hepatic duct bifurcation narrowing with a direct surgical approach. In 11 patients the extrahepatic biliary tree including the bifurcation was resected and the right and left hepatic ducts were dilated. Bilateral 6 mm silicone rubber (Silastic) transhepatic biliary stents were inserted and bilateral hepaticojejunostomy was performed. Eight patients were men, three were women, and the mean age was 41.9 years. At the time of surgery the mean serum bilirubin concentration was 15.3 mg/dl (range 1 to 50 mg/dl). The disease had been present clinically for a mean duration of 3.6 years. There was one hospital death. Nine of the ten remaining patients have responded with a decrease in serum bilirubin concentration to a mean of 2.9 mg/dl. These nine patients have returned to normal activity. The tenth patient has done poorly and awaits liver transplantation. Follow-up ranges from 4 to 36 months (mean 18 months). The stents have been left in position permanently.

Adult↗
PubMed1982

Bone disease in primary biliary cirrhosis: histologic features and response to 25-hydroxyvitamin D.

Fifteen female patients with primary biliary cirrhosis were evaluated for vitamin D status and evidence of metabolic bone disease. Full-thickness iliac crest bone biopsy specimens with histomorphometric analysis after double tetracycline labeling were performed before and after 1 yr of treatment with oral 25-hydroxyvitamin D (100 micrograms/day). Initially, serum 25-hydroxyvitamin D levels were low (less than 15 ng/ml) in 11 of the 15 patients and were increased to normal (greater than 25 ng/ml) in all patients within 3 mo. Serum parathyroid hormone levels were low normal or not detectable in all patients and did not change with therapy. No patient had a fracture during the treatment. No evidence of osteomalacia was found initially or in follow-up study in any patient. Follow-up histomorphometric analysis at the end of the 1-yr treatment showed that bone volume decreased during the study interval despite therapy (p less than 0.001). Photon beam densitometry confirmed the loss in trabecular density of the radius over the study interval (p less than 0.03). The mean fractional osteoid surface was not increased initially and did not change with therapy. The mean linear bone appositional rate as measured by double tetracycline labeling was not decreased initially and did not change with therapy. It was concluded that in moderate to severe primary ciliary cirrhosis, initial 25-hydroxyvitamin D levels are low and are rapidly corrected by oral 25-hydroxyvitamin D. These patients have significant osteoporosis which progresses despite 25-hydroxyvitamin D.

25-Hydroxyvitamin D 2↗
PubMed1982

Cutaneous immunoglobulin deposition in primary biliary cirrhosis.

We studied the skin of six patients with primary biliary cirrhosis (PBC) to determine if there is cutaneous deposition of complement and immunoglobulins in PBC. We also investigated serum samples from these patients for the presence of circulating antibodies against nuclear and cytoplasmic antigens. Three of five patients demonstrated immunoglobulins (IgM or IgG) or complement (C3) deposition at the dermoepidermal junction (DEJ) in clinically normal, light-protected skin. Two of six patients had 2- to 5-mm papular-pustular skin lesions as a manifestation of PBC. Serological studies in these patients disclosed low antinuclear antibody titers in three patients and anti-single-stranded DNA antibody titers in the two patients with skin lesions. These histological, immunofluorescent, and serological findings offer further evidence of the occurrence of circulating immune complexes in at least some patients with PBC.

Adult↗