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Biomedical subjects

P D Greig

Publications and source records attributed to P D Greig.

At least 55 records · Page 3Linked to original sources
PubMed1993

Small encapsulated hepatocellular carcinoma of the liver. Provisional analysis of pathogenetic mechanisms.

BACKGROUND: Small hepatocellular carcinomas frequently were found incidentally during routine pathologic examinations of adult livers removed at liver transplant. METHODS: Sixty-nine carcinomas of all sizes were found in 25 patients; 39 of the tumors were smaller than 1 cm in diameter, and 18 of the carcinomas in five patients were not clinically suspected. These small incidental carcinomas lend themselves to analysis of the morphologic basis of human hepatocellular carcinogenesis. RESULTS: All of these tumors arose in cirrhotic livers. Most of the small carcinomas were multilobulated and subdivided by pre-existing fibrous septa. The surrounding capsule usually was not a true capsule. They were all well differentiated, most formed bile, Mallory bodies, or showed alpha-1-antitrypsin (A1AT) positivity. Transition from cirrhotic nodular parenchyma to areas of hyperplasia or atypical hyperplasia to well-differentiated carcinoma were common. Large cell dysplasia also was common. CONCLUSIONS: These morphologic transitions closely parallel changes seen in experimental chemical carcinogenesis. They also strongly suggest a multicentric origin of the tumors. In addition, in every instance, the lesions were multiple in the liver and involved both lobes. This latter finding has possible implications for recurrence after local surgical excision of small hepatocellular carcinomas.

Adult↗
PubMed1993

Peritoneovenous shunting restores atrial natriuretic factor responsiveness in refractory hepatic ascites.

BACKGROUND: Sodium retention in cirrhosis has been attributed to an imbalance between vasoconstrictive, antinatriuretic forces such as the renin aldosterone angiotensin system and the sympathetic nervous system, and vasodilatory, natriuretic agents such as atrial natriuretic factor (ANF). Patients with diuretic resistant refractory ascites may require peritoneovenous shunting (PVS) to control ascites. METHODS: To study the factors responsible for the improvement in sodium homeostasis post-PVS, we compared the response to ANF infusion before and 1 month after PVS in 6 patients with massive ascites. RESULTS: Before PVS, sodium excretion at baseline and in response to ANF infusion was blunted but became more normal post-PVS. ANF infusion post-PVS induced a significant increase in the glomerular filtration rate and filtration fraction and also in distal delivery of sodium. ANF's distal effect of increasing the fractional excretion of distally delivered sodium was present pre-PVS and was not significantly increased post-PVS. Changes in sodium handling were accompanied by a significant decrease in antinatriuretic forces (baseline aldosterone, 2079 +/- 507 vs. 647 +/- 17 nmol/L; P < 0.04) post-PVS. CONCLUSIONS: The improvement in sodium homeostasis and response to ANF infusion post-PVS appears to be associated with the decrease in antinatriuretic forces with the loss of massive refractory ascites. Thus, PVS restores the balance toward ANF responsiveness.

Adult↗
PubMed1993

Prediction of the outcome of transplantation in man by platelet adherence in donor liver allografts. Evidence of the importance of prepreservation injury.

We examined platelet adhesion in thirty human donor livers to determine if the degree of platelet adhesion could predict outcome of transplantation. Wedge liver biopsies were taken at the start of the donor operation (biopsy 1) and 1 hr after reperfusion in the recipient (biopsy 2). Biopsies were stained with a monoclonal antibody against platelet glycoprotein Ib and graded for platelet adhesion. Hematoxylin and eosin-stained sections were examined for polymorphonuclear leukocyte adhesion and necrosis. Platelet adhesion was much more frequent and extensive than expected in biopsy 1. Nine of 30 biopsies showed moderate or high-grade platelet adhesion. Thus in this study endothelial cell damage was present in about one-third of donors before the donor operation. The injury was not detectable by routine microscopic or clinical examination or biochemical tests. The degree of platelet adhesion in biopsy 1 predicted development of PMN adhesion and necrosis in biopsy 2 and postoperative transaminase concentrations and prothrombin times in recipients. During preservation and implantation some livers converted from low to either moderate or high grades of platelet adhesion. The grade of platelet adhesion in biopsy 2 predicted postoperative outcome as measured by transaminase and PT levels. Patients whose platelet grade converted to a higher level during preservation and implantation did not do as well as patients who remained at a low adhesion grade. These findings strongly suggest that the degree of platelet adhesion is an important determinant in assessing outcome and may provide a means of measuring the status of liver allografts prior to transplantation.

Age Factors↗
PubMed1993

The role of transjugular liver biopsy in fulminant liver failure: relation to other prognostic indicators.

Early and accurate diagnosis and prognosis of patients with fulminant liver failure is of critical importance for optimum management. We investigated the role of transjugular liver biopsy in the management of patients with fulminant liver failure and assessed its value in comparison with the recently proposed King's College criteria. Sixty-one patients with fulminant liver failure, ages 2 to 82 yr, were retrospectively analyzed. The main outcome measures were survival vs. death or progression to orthotopic liver transplantation. Transjugular liver biopsy was successful in 60 of 61 patients, with a mean core tissue length of 2.1 cm. There were eight minor complications, all of which were managed conservatively. Biopsy specimens were evaluated for degree of fibrosis, percentage of hepatocellular necrosis and presence of bile duct proliferation, hepatocellular mitotic figures and binucleate hepatocytes for each of the 54 specimens available for analysis. In 34 of 54 patients (63%), the presumed clinical diagnosis was confirmed by transjugular liver biopsy. In 11 patients the procedure served to clarify clinical uncertainty, whereas in 9 of 54 (16.7%) the diagnosis was altered after transjugular liver biopsy. The percentage of necrosis was the only histological parameter that appeared to have significant discriminatory prognostic value, with only 2 of 19 survivors having greater than 70% necrosis. Twenty-one of these biopsy specimens were reviewed by two pathologists, and their degree of correlation for the various features was assessed. Almost perfect concordance was found between the two pathologists on the percentage of hepatocellular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1992

Effect of intraportal glucose infusion on hepatic glycogen content and degradation, and outcome of liver transplantation.

Recent animal studies suggest that nutritional repletion may improve function of liver allografts, and the authors have found that intraportal glucose infusion in pigs produces rapid and substantial hepatic glycogenation. A controlled prospective randomized study in 32 patients was done to determine glycogen content and degradation in human livers during transplantation, and the effect of intraportal glucose-insulin infusions during the donor operation on these variables and on outcome of transplantation. Peripheral blood glucose concentrations were "clamped" at 14 mmol/L during the glucose-insulin infusion. Liver biopsies were taken at various stages of the procedure. Liver glycogen decreased 2.0 +/- 1.2 g/100 g dry weight liver (mean +/- standard error of the mean) in controls, but increased 6.8 +/- 1.8 g/100 g dry weight in glucose-infused donors. In both groups there was glycogen degradation during periods of cold preservation, anoxic rewarming, and after reperfusion with portal blood. Degradation rates were greater in the glucose-infused group than in controls in all three periods (p less than 0.05). Despite wide variation in postoperative aspartate aminotransferase (AST) levels among recipients in both groups, the difference in peak postoperative AST levels approached significance (p = 0.06). In addition, peak AST levels were closely correlated to anoxic rewarming time in both groups, but the slope of the relationship was much lower (3834 versus 734, p less than 0.01) in the glucose-infused group. Thus at anoxic rewarming times over 90 minutes, glycogenation was protective of liver function. Peak postoperative AST was significantly correlated to glycogen degradation in the cold preservation and rewarming periods in the glucose-infused group only. Intraoperative glucose infusions in humans can reglycogenate the liver, increase glycogen degradation, and improve certain outcome measures in liver transplantation.

Adult↗
PubMed1992

Non-Hodgkin lymphoma in the porta hepatis after orthotopic liver transplantation: sonographic findings.

The sonographic appearances of primary non-Hodgkin lymphoma developing in the porta hepatis in three patients soon after hepatic transplantation were reviewed. The lymphomas appeared as large hypoechoic masses encasing vital portal structures--the hepatic artery and the common bile duct--in all three cases and displacing the portal vein in two. The liver was only locally involved. All patients presented with jaundice soon after transplantation (average interval, 6.3 months). Rapid tumor progression caused hepatic infarction, necessitating retransplantation in two patients. The third patient died shortly after diagnosis. The authors believe this complication will be seen increasingly as liver transplantation becomes more common. Non-Hodgkin lymphoma should be considered when an obstructing mass is found in the porta hepatis, even when the time interval since transplantation is short.

Common Bile Duct↗
PubMed1992

Post-transplant recurrent hepatitis B viral liver disease. Viral-burden, steatoviral, and fibroviral hepatitis B.

Recurrence of hepatitis is a well-documented complication of hepatitis B liver disease, post-transplantation. It is well established also that the earliest hepatocellular change is the appearance of hepatitis B viral (HBV) markers and that the disease is rapidly progressive. In this article on 17 liver transplants in 16 HBV positive patients with long-term follow-ups (100-1234 days), the distinctive pathologic features of this disease are emphasized: the extreme viral load, the steatosis, and/or fibrosis. An attempt to quantitate the magnitude of the viral burden was made and the result was a staggering figure. In one patient, an estimated 10(18) HBV core particles were present in the liver. One of two patterns of progression were noted. In four patients in addition to the massive nuclear hepatitis B core antigen (HBcAg) and cytoplasmic hepatitis B surface antigen (HBsAg) positivity, superimposed hepatitic changes led to diffuse hepatic fibrosis (fibroviral hepatitis B); and in another six patients, extraordinary hepatocellular viral marker positivity and steatosis were the hallmarks (steatoviral hepatitis B). Steatosis is not usually considered a feature of HBV liver pathology. These results suggest that more than one type of posttransfusion recurrent hepatitis B liver disease exists pathologically.

Fatty Liver↗
PubMed1992

Rapid donor liver nutritional enhancement in a large animal model.

Organ donors are typically subject to acute hyponutrition that might affect postpreservation liver function. Livers from nutritionally supplemented rats function better after preservation than livers from fasted rats. We have developed a method to glycogenate the liver of large animals in the temporal context of a human donor liver operation and have studied the fate of glycogen stores during preservation. Starved anesthetized pigs were infused with a hexose solution (glucose, fructose or galactose) by way of the superior mesenteric vein for 3 hr. Regular porcine insulin was infused to maintain a hyperglycemic hyperinsulinemic arterial glucose clamp at 12 to 16 mmol/L. Liver biopsy specimens and blood samples were taken before infusion and hourly. At 3 hr the liver was excised, stored for 24 hr at 1 degrees C in University of Wisconsin solution and biopsied. It was then placed at 20 degrees C for 1 hr to simulate the reimplantation stage of transplantation. Glycogen and nucleotide levels were measured, and results were corrected for starch in the University of Wisconsin solution. A 20% glucose infusion produced rapid hepatic glycogenation without side effects. Greater glycogenation was obtained with 20% fructose but at the cost of lactic acidosis and a fall in pH. A combination of 15% glucose and 5% fructose produced intermediary glycogenation without significant side effects. Galactose (20%) was less efficient than glucose alone. The addition of alanine and glutamine (20 mmol/L) did not significantly improve glycogenation. Metabolism of glycogen at 1 degree C did occur. Glycogen content fell 0.15% +/- 0.05% dry weight liver per hour during cold preservation and 5.49% +/- 2.15% per hour during ischemic rewarming.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1991

Syncytial giant-cell hepatitis. Sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features.

BACKGROUND AND METHODS: We describe a new form of hepatitis, occurring in 10 patients over a period of six years, characterized clinically by manifestations of severe hepatitis, histologically by large syncytial giant hepatocytes, and ultrastructurally by intracytoplasmic structures consistent with paramyxoviral nucleocapsids. RESULTS: The patients ranged in age from 5 months to 41 years. The tentative clinical diagnosis before biopsy was non-A, non-B hepatitis in five patients and autoimmune chronic active hepatitis in the others. Five patients underwent liver transplantation; the others died. The diagnosis of syncytial giant-cell hepatitis was established pathologically. The liver cords were replaced in all 10 patients by syncytial giant cells with up to 30 nuclei. In 8 of the 10 the cytoplasm contained pleomorphic particles of 150 to 250 microns, filamentous strands, and particles of 14 to 17 nm with peripherally disposed spikes resembling paramyxoviral nucleocapsids. Structures resembling degenerated forms were found in the other two patients. One of two chimpanzees injected with a liver homogenate from the index patient had an increase in the titer of paramyxoviral antibodies, probably an anamnestic reaction to previous paramyxoviral infection, suggesting that a paramyxoviral antigen but not viable virus was present in the liver homogenate. CONCLUSIONS: Although further virologic studies will be required for precise classification, we believe that paramyxoviruses should be considered in patients with severe sporadic hepatitis.

Acute Disease↗
PubMed1990

Early experience with reduced-size liver transplants.

Scarcity of small donors results in a high mortality rate for children on liver transplant waiting lists. To alleviate this problem, we have recently started to reduce the size of livers from older donors to use in children. In the last year, a total of 20 liver transplants were performed in 17 patients, including seven reduced-size liver transplants (RSLT) in six children. Mortality on the waiting list has been reduced to negligible amounts compared with a mortality rate of 25% before starting RSLT in patients with acute liver failure or those whose weight was less than 10 kg. Children undergoing RSLT weighed 10.8 +/- 8.5 kg compared with 20.9 +/- 20.3 for all others (NS). Cold ischemia time was significantly longer in the RSLT group (9.5 +/- 3.0 v 6.0 +/- 2.8 hours, P less than .05) as was intraoperative blood loss (9.4 +/- 9.4 v 3.0 +/- 3.5 blood volumes). There was no significant difference in postoperative aspartate aminotransferase and prothrombin time between the two groups. Four children received a RSLT as a primary procedure and three have survived with good liver function. Two patients were retransplanted with RSLT after a failed first transplant and both died of nonhepatic complications. This compares with 11 of 13 survivors in the whole liver transplant group. Causes of death in children who died after RSLT include cytomegalovirus sepsis (2) and myocardial infarction(1).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1990

Selective or total shunts for variceal bleeding.

Shunt surgery remains an important therapeutic option in the management of variceal bleeding, and both total and selective shunts have a role to play. The distal shunt is associated with a lower long-term encephalopathy rate and may yield better survival in the nonalcoholic patient; it is, therefore, the preferred shunt in the elective situation. The total shunt is technically easier to perform and more widely available; it is, therefore, preferred in the emergency situation. Ordinarily, the side-to-side and end-to-side shunts have similar outcomes; however, in patients with hepatic venous outflow obstruction and patients with intractable ascites, the side-to-side shunt should be used.

Esophageal and Gastric Varices↗
PubMed1990

Emergency surgical treatment of variceal hemorrhage.

Emergency surgery should be considered one of the treatment options for the patient with acute variceal bleeding in whom the usual nonsurgical modes of therapy fail, and who is deemed fit to tolerate a major operation. A total shunt (portacaval or mesocaval) is recommended for most of these patients, although a distal splenorenal shunt might be considered for some very good risk, nonalcoholic patients who have only moderate bleeding. Devascularization procedures have a limited role in the emergency situation, but they may be useful in patients who are nonshuntable because of splanchnic venous thrombosis. The Sugiura type of operation is appropriate for the nonalcoholic patient, and esophageal transection is appropriate for the alcoholic patient with cirrhosis. Patients with end-stage nonalcoholic liver disease should also be considered for liver transplantation.

Emergencies↗
PubMed1990

Delta and conjugated bilirubin as complementary markers of early rejection in liver-transplant recipients.

For 51 liver allograft recipients, we evaluated whether serum profiles of delta (Bd) and conjugated bilirubins (Bc) could be used to diagnose rejection during the first 30-50 postoperative days, in comparison with histology as the "gold standard." Daily measurements of aspartate aminotransferase, alkaline phosphatase, total bilirubin, Bd, and Bc were made, the last two by liquid chromatography. In 34 patients without any biochemical or histological evidence of rejection, within seven to 10 postoperative days Bd increased to greater than 40-50% of total bilirubin, while Bc decreased to less than 10%. In patients with severe rejections resulting in death, Bc increased rapidly to greater than 50%, while Bd remained less than 30%. In 24 histologically proven episodes of rejection in 17 patients there was either a rapid decrease in Bd or its persistence at 30%, plus either a steep increase in Bc, or its remaining at greater than 50% total bilirubin. Treatment of rejection resulted in a prompt reversal of these trends. Individually promising as prognostic adjuncts to existing liver-function markers, Bd and Bc also complemented each other, rendering the diagnosis of liver rejection much more incisive.

Adult↗