Biomedical subjects

W J Millikan

Publications and source records attributed to W J Millikan.

At least 19 recordsLinked to original sources

PubMed1994

Pediatric liver transplantation in Georgia: a paradigm for the health care crisis in the United States?

The United States health care system, felt by many to be the most technologically advanced program in the world, has many critics. Two indisputable facts that drive such criticism are 1) inequitable access and 2) rising costs out of proportion to other countries. Although Georgia is a poor state and ranks nationally near the bottom in most measures of child and adolescent care, we decided to start a pediatric liver transplant program at Egleston Children's Hospital at Emory, Atlanta. Over the past 2 1/2 years, 18 transplants have been performed in 14 patients; 10 children are presently surviving. Looking carefully at the expenses of the first 10 patients, the average cost of orthotopic liver transplantation for the eight survivors was $206,375. The hospital costs for providing care to these 10 children were over $2 million. In a state that ranks 49th out of 50 states in infant mortality and with nearly one-third of its pre-school children not immunized against preventable diseases, is this a fair and equitable distribution of our resources?

Child↗

PubMed1992

Prevalence of invasive cytomegalovirus disease with administration of muromonab CD-3 in patients undergoing orthotopic liver transplantation.

OBJECTIVE: To assess the association of cytomegalovirus (CMV) disease with the administration of muromonab CD-3 (OKT-3) in patients undergoing liver transplant; specifically, to assess the risk of OKT-3 use as an agent for rejection prophylaxis and as an agent for therapy of rejection. DESIGN: Retrospective review of medical records. STUDY POPULATION: 83 liver transplant recipients (43 men, 40 women) with a mean age of 41.5 years (range 16-62). DATA EXTRACTION: The medical record for each liver transplant recipient was reviewed and analyzed for the following variables: (1) preoperative recipient CMV serology, (2) donor CMV serology, (3) incidence of invasive CMV disease, (4) administration of OKT-3, (5) postoperative administration time of OKT-3, and (6) the relationship between the administration of OKT-3 and the prevalence of invasive CMV disease. RESULTS: OKT-3 was administered to 34 of 83 (40.9 percent) liver remainder received OKT-3 as rejection rescue. All patients received OKT-3 5 mg iv for 14 days. Seventeen of the 34 patients receiving OKT-3 (50 percent) developed invasive CMV disease; 58.8 percent of the patients (20/34) receiving OKT-3 were given the agent within the first 14 postoperative days. Sixteen of these 20 patients (80 percent) developed invasive CMV disease. One of 14 patients (7.1 percent) who received OKT-3 after the first 14 postoperative days developed invasive CMV disease. Of those patients 94 percent (16/17) received OKT-3 in the first 14 postoperative days. This prevalence differed significantly from those receiving OKT-3 after the 14th postoperative day and those who did not receive OKT-3 at any time during their hospital course. CONCLUSIONS: The patients who received early administration of OKT-3 in our study had a greater risk of invasive CMV disease than did those who received OKT-3 later in the hospital course.

Adolescent↗

PubMed1991

Selective splenocaval shunt. Report of 26 cases and review of the literature.

Splenocaval shunting was performed in 26 patients for the treatment of variceal bleeding. The indications for this alternative selective shunt were congenital anomalies of the left renal vein, inadequate outflow from the left renal vein on preoperative venography, or an anatomic relationship of the splenic vein favoring direct splenocaval rather than splenorenal anastomosis. Technical considerations in which splenocaval shunts differ from distal splenorenal shunting relate to exposure of the vena cava. Operative mortality was 7.7% (2/26). Immediate shunt patency was documented in 23 of 24 patients studied, and all 14 shunts studied at 13 to 57 months were patent. Portal perfusion was maintained in 95% (20/21) of the patients when studied at 7 to 10 days after shunting and in 57% (8/14) at late follow-up. This experience with distal splenocaval shunting has reaffirmed its place as an alternative technique to selective distal splenorenal shunts, particularly when the left renal vein is abnormal.

Adolescent↗

PubMed1991

Serotonin immunoreactivity in pancreatic endocrine neoplasms (carcinoid tumors).

Primary serotonin secreting pancreatic endocrine neoplasms (carcinoid tumors) are extremely rare and may be associated with manifestations of the carcinoid syndrome. Two cases of primary carcinoid tumor of the pancreas with liver metastases showed clinical and biochemical features of the carcinoid syndrome. Both cases demonstrated strong positive immunoreactivity for serotonin within the tumor cells. In an attempt to determine the relationship between pancreatic carcinoid tumors and other pancreatic endocrine neoplasms, immunostains for serotonin were performed on 11 additional islet cell tumors and on non-neoplastic pancreatic tissues. These cases showed serotonin immunoreactivity within islet cell tumors (36%). In addition, focal staining for serotonin was present in non-neoplastic ducts and ductules (88%), acini (22%), and islets of Langerhans (33%). Based on these observations, specific criteria are suggested for the diagnosis of primary pancreatic carcinoid tumor.

Adult↗

PubMed1991

Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation.

Muromonab CD-3 (OKT-3) is a monoclonal antibody that is highly effective in the treatment of acute rejection in solid organ transplants. Due to its monoclonal nature, each molecule is identical because it is derived from a single antibody-producing clone. OKT-3 is administered only by intravenous injection and has a harmonic half-life of approximately 18 hours. It binds specifically to the CD-3 complex, which is involved in antigen recognition and cell stimulation, on the surface of T lymphocytes. Immediately after administration CD-3-positive T lymphocytes are abruptly removed from the circulation. The route of metabolism for OKT-3 is not clear; it may be removed by opsonization by the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production. The agent has been effective in reversing corticosteroid-resistant acute rejection in renal, liver, and cardiac transplant recipients. Its use in pancreatic and bone marrow recipients is inconclusive. OKT-3 has a considerable number of initial side effects, and some life-threatening reactions may occur. This drug should not be administered to any patient who is greater than 3% usual body weight because of the potential for the development of severe pulmonary edema. OKT-3 may also be associated with a high rate of infection, especially of the viral type. The usual dose is 5 mg administered as an intravenous bolus over 2-4 minutes daily for 10-14 days. Approximately 85% of patients treated with OKT-3 develop reactive human antimurine antibodies that, over time, may lead to tachyphylaxis and neutralization of the murine antibody OKT-3. OKT-3 is potent immunosuppressive agent and is an important prototype of future monoclonal antibodies.

Animals↗

PubMed1991

The surgical pathologist's role in liver transplantation.

Liver transplantation has become an option in treating a wide variety of diseases. The surgical pathologist, as a member of the transplantation team, is increasingly involved in the evaluation of allograft dysfunction. Interpretation of the liver allograft biopsy specimen requires integration of clinical history, biochemical data, and histologic patterns of a wide variety of lesions, including harvesting injury, vascular thrombosis, rejection, infection, and recurrent disease. This article reviews the varied histologic appearances of the more common forms of liver allograft injury, the contexts in which they arise, and their distinction from one another.

Acute Disease↗

PubMed1990

Endoscopic variceal sclerosis compared with distal splenorenal shunt to prevent recurrent variceal bleeding in cirrhosis. A prospective, randomized trial.

STUDY OBJECTIVE: To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis. DESIGN: A prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months. SETTING: A private, tertiary-referral university hospital. PATIENTS: Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval. TREATMENTS: Endoscopic variceal sclerosis or distal splenorenal shunt. MEASUREMENTS AND MAIN RESULTS: Survival was significantly (P = 0.02) improved in patients randomly assigned to receive sclerotherapy: 13 of these 37 (35%) patients failed sclerotherapy and required surgical rescue. A survival advantage (P = 0.01) was seen in patients with alcoholic cirrhosis who had this combined therapy; however, in patients with nonalcoholic cirrhosis, survival for those receiving sclerotherapy and surgical rescue was not significantly (P = 0.36) different from that of patients receiving distal splenorenal shunt. Control of variceal bleeding was significantly (P less than 0.001) better in the distal splenorenal shunt group (34 of 35 [97%] compared with 15 of 37 [41%] in the sclerotherapy group). Using death, uncontrolled rebleeding, or shunt thrombosis as the endpoints resulted in no significant difference between treatment groups. Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt (P = 0.01 and P = 0.001, respectively). CONCLUSIONS: Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding. Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy, but shunting provides better control of variceal bleeding.

Endoscopy↗

PubMed1990

Prevalence and prediction of osteopenia in chronic liver disease.

To obtain information on the prevalence and clinical and laboratory correlates of osteopenia in patients with chronic liver disease, we measured bone densities and 30 selected laboratory variables in 133 subjects (70 men, 63 women) with liver disease. Thirty-two had alcoholic liver disease, 18 had primary biliary cirrhosis, 16 had primary sclerosing cholangitis, 48 had other forms of cirrhosis (cryptogenic, posthepatic) and 19 had chronic hepatitis or fibrosis without cirrhosis. Bone densities of the lumbar spine and three sites of the proximal femur (neck, Ward's triangle, greater trochanter) were estimated by dual-photon absorptiometry. Bone densities at all sites were significantly correlated to one another (r = 0.4 to 0.9; 95% confidence intervals = 0.24-0.54 to 0.81-0.90; p less than 0.0001 for all). Compared with an age- and gender-matched reference group, patients with liver disease had highly significant decreases in bone densities (greater than 2 standard deviations below control values; p less than 0.0008 at all sites). Decreases were particularly marked (24% to 42%) at Ward's triangle, the site of the femoral neck particularly prone to fracture. The prevalence of decreased bone densities ranged from 10% to 56%, depending on the site studied and the nature of the liver disease. Among 30 laboratory variables studied, there were significant (p less than 0.05) correlations with bone densities at more than one site for urinary creatinine (r = 0.21, 0.25), urinary calcium (r = -0.18, -0.23), serum total alkaline phosphatase (r = -0.18, -0.27) and the liver-1 isozyme of serum alkaline phosphatase (r = -0.19, -0.26).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗

PubMed1990

A hypercoagulable state follows orthotopic liver transplantation.

Orthotopic liver transplantation may be associated during the postoperative period with hepatic artery thrombosis, a catastrophic occurrence generally necessitating emergency retransplantation. To assess the contribution of the coagulation mechanism to this complication, the levels of procoagulant and anticoagulant proteins were followed in 41 liver transplant patients during the first 10 postoperative days. The mean activities of all procoagulant factors reach normal values on day 1 except for factors V and VII, which achieve normal activity by day 3. Supernormal levels of factor VIII activity and antigen are noted (peak values on day 5 of 334% +/- 113% and 481% +/- 260%, respectively). The anticoagulant proteins show delayed recovery, with deficient antithrombin III levels seen in 81% of patients on day 3 and 57% on day 5. Similarly, proteins C and S are subnormal in 24% and 21%, respectively on day 3, and 20% and 10%, respectively, on day 5. During this period, elevated levels of thrombin/antithrombin complexes are encountered, reflecting in vivo activation of the coagulation mechanism. Activated thrombin is, therefore, being generated at a time when a decrease in the major regulatory anticoagulant proteins exists. These data suggest an imbalance between the hemostatic and thrombotic mechanisms and indicate a sustained prothrombotic state that may contribute to the risk for hepatic artery thrombosis. Using a regimen of low-dose heparin and fresh frozen plasma infusion, no thromboses have been seen in 65 consecutive liver transplants.

Blood Coagulation Disorders↗

PubMed1990

Surgical options, hematologic evaluation, and pathologic changes in Budd-Chiari syndrome.

This article presents a scheme of management for Budd-Chiari syndrome based on experience with 33 patients. Therapy in acute Budd-Chiari syndrome is dictated by the liver biopsy, with hepatocyte necrosis indicating the need for placement of a decompressive shunt. The type of shunt was determined by intrahepatic vena cava obstruction; a higher morbidity rate was associated with the mesoatrial shunt in 11 patients than with a portacaval shunt in 10 patients. Successful shunt placement allowed stabilization of the liver biopsy and maintenance of good hepatocyte function [galactose elimination capacity (preoperative: 349 +/- 40 mg/minute; 20 months: 344 +/- 60 mg/minute)]. Severe fibrosis and reduced galactose elimination capacity (264 +/- 43 mg/minute) indicated advanced disease--chronic Budd-Chiari syndrome--and were indications for liver transplant. Hematologic evaluation documented a myeloproliferative disorder in 8 of the last 13 patients evaluated; perioperative and late anticoagulation and/or chemotherapy reduced recurrent thrombosis. We conclude that the Budd-Chiari syndrome requires different therapies depending on the stage of disease. If no hepatocyte injury is present on biopsy, therapy may not be needed. Acute, reversible injury can be managed by placement of a decompressive shunt. Irreversible damage requires transplantation. Selection of the right therapy requires a complete evaluation.

Budd-Chiari Syndrome↗

PubMed1990

The Emory perspective of the distal splenorenal shunt in 1990.

The distal splenorenal shunt (DSRS) has been extensively studied at Emory University over the past 18 years to define its role in the management of variceal bleeding. DSRS has been applied broadly in many different patient groups and has been evaluated in prospective randomized trials; thus, a considerable amount of data has accrued on the metabolic and hemodynamic consequences of selective variceal decompression. Its current role is defined as primary therapy for variceal bleeding in patients with portal vein thrombosis and good-risk patients with nonalcoholic cirrhosis. As a therapy for patients whose bleeding is not controlled by sclerotherapy, it should be used as the shunt procedure of choice, but patient evaluation must focus on the choice between DSRS and liver transplantation.

Esophageal and Gastric Varices↗

PubMed1990

Surgical rescue for failures of cirrhotic sclerotherapy.

Bleeding from gastroesophageal varices remains the most devastating complication of the portal hypertensive syndrome. Endoscopic sclerotherapy has emerged as the best initial treatment for bleeding varices because surgery is obviated and survival may be improved. However, sclerotherapy will fail and surgical rescue will be required in at least a third of patients. There are two viable surgical rescue procedures: shunt surgery and liver transplantation. This paper summarizes the available data and concludes that there is a role for both procedures.

Esophageal and Gastric Varices↗

PubMed1990

Angioplasty for long-term treatment of patients with Budd-Chiari syndrome.

The goal of radiologic intervention in patients with Budd-Chiari syndrome is to control portal hypertension and prevent further hepatocellular damage until collateral hepatic venous outflow channels can develop. Percutaneous balloon angioplasty was used to treat six patients with this syndrome who were followed up for an average of 43 months (range, 12-92 months). Standard interventional radiologic techniques were used to dilate the hepatic veins (two patients), inferior vena cava (three patients), and proximal anastomosis of a mesoatrial shunt (one patient). Angioplasty was the only invasive treatment in three patients, whereas the remaining three patients had previous portosystemic shunts. Clinical and hemodynamic improvement occurred after each angioplasty. Multiple dilatations were required in all patients (average, 3.2; range, 2-5) because of restenosis at the angioplasty site and ongoing hepatocyte necrosis shown by biopsy. Long-term benefit occurred in five patients despite ultimate caval occlusion in two patients and restenosis in one patient. One patient who was almost free of symptoms for 36 months developed gastrointestinal bleeding caused by portal hypertension. This experience suggests that balloon angioplasty is a safe and effective treatment for patients with Budd-Chiari syndrome. The therapy is not definitive, but serves to moderate the severity of the disease until collateral venous pathways develop. Multiple angioplasties are required for the long-term care of these patients.

Adult↗

PubMed1990

The relative role of sclerotherapy vs. surgical procedures in portal hypertension.

This review is a discussion of the evolution of different modes of therapy to treat variceal bleeding. At the present time, endoscopic sclerosis represents the mainstay of therapy for most patients with chronic cirrhosis. In patients who fail sclerotherapy, selective shunt surgery is indicated in patients with good hepatic reserve, and liver transplantation for those who have chronic liver failure.

Humans↗

PubMed1989

Increased galactose clearance after liver transplantation: a measure of increased blood flow through the denervated liver?

This study measured the liver blood flow-dependent index of galactose clearance in patients after liver transplantation, to test the hypothesis that liver blood flow is increased in the denervated liver. Eight normal subjects and 16 patients 1 to 8 months after liver transplant were studied. All patients were stable with no evidence of severe rejection at the time of study. Galactose clearance was measured at steady state during continuous infusion of 75 mg per min of 5% galactose. The results show a statistically significant (p less than 0.01) higher average galactose clearance in the transplant patients (1,187 +/- 316 ml per min per m2) compared to the control group (709 +/- 121 ml per min per m2). The major limiting factor in galactose clearance at low concentrations is liver blood flow, and we interpret these data as evidence for increased blood flow in the transplanted liver. Possible mechanisms for the increased galactose clearance are (i) loss of normal vasomotor tone in the denervated liver, or (ii) persistence of abnormal systemic hemodynamics after transplantation. Elucidation of these mechanisms awaits further study.

Adult↗

PubMed1989

Change in hepatic function, hemodynamics, and morphology after liver transplant. Physiological effect of therapy.

Orthotopic liver transplantation (OLT) has become standard therapy for patients with acute hepatic necrosis and end-stage liver disease. This study measured change in hepatic function (galactose elimination capacity [GEC]), liver blood flow (low dose galactose clearance: flow), hepatic volume (CT scan; volume) and morphology after OLT. The aim was to measure the physiologic response after OLT and compare this response with that after selective shunt (SS) and sclerotherapy (ES) to determine which patients should receive specific therapy. Between January 1987 and November 1988, 37 patients underwent OLT. Operative mortality was 18%, which was similar to that of SS in Child's C cirrhotics. GEC and volume were less in transplant patients than in cirrhotics treated with SS or ES. GEC, flow, and volume normalized after OLT; GEC was preserved after ES and SS, but volume decreased. Three preoperative patterns were observed that can aid in selection of OLT candidates. Patients with chronic cirrhosis (chronic active hepatitis; cryptogenic) need OLT when GEC is less than or equal to 225 mg/min and volume is less than or equal to 50% normal. Patients with Budd-Chiari Syndrome require OLT if cirrhosis has evolved. Patients with sclerosing cholangitis and primary biliary cirrhosis qualify for transplants when complications of the portal hypertensive syndrome develop. The studies can also direct therapy for ES failures. Selective shunt is indicated in those patients with stable disease whose GEC is greater than or equal to 300 mg/min and liver volume is greater than 75% normal; OLT is indicated for cirrhotics with GEC that is less than 225 mg/min and liver volume that is less than 50% predicted normal.

Adult↗

PubMed1989

Distal splenorenal shunt with splenopancreatic disconnection. A 4-year assessment.

The aims of distal splenorenal shunt with splenopancreatic disconnection (DSRS-SPD) were to improve maintenance of portal flow and prevent siphoning of hepatotrophic factors from the pancreas, as occurs after standard DSRS. The main patient population targeted for improvement were alcoholic cirrhotics, who have poorer survival than nonalcoholic cirrhotics and greater loss of portal flow (60%) after standard DSRS. Seventy-eight patients had DSRS-SPD during the study period 1983 to 1987: thirty-two patients were Child's A, 25 were Child's B, and 21 were Child's C. The 35 patients with alcoholic cirrhosis were a significantly poorer risk group by Child's class and galactose elimination capacity (GEC) than the 39 patients with nonalcoholic cirrhosis. Four patients had portal vein thrombosis. At 4-year follow-up, portal perfusion is maintained in 84% alcoholic and 90% nonalcoholic patients, with hepatic and systemic hemodynamics showing identical patterns for both groups. Hepatic function measured by GEC was maintained in alcoholic patients (290 +/- 68 mg/min to 303 +/- 74 mg/min) and nonalcoholics patients (342 +/- 92 to 320 +/- 118 mg/min). Gastric variceal rebleeding occurred in 10 patients--4 early (less than 2 months) and 6 late (18 to 54 months), leading to operation in 4 and transhepatic embolization in 4 patients: 2 of these patients died from this complication. Survival data show an operative mortality rate of 6.4% and overall mortality rate of 30%, with no significant difference between alcoholic and nonalcoholic cirrhotics. DSRS-SPD has significantly improved maintenance of portal perfusion and survival in patients with alcoholic cirrhosis requiring selective shunt for variceal bleeding when compared to standard DSRS. In this population DSRS-SPD is the operation of choice. In patients with nonalcoholic cirrhosis, the current data have not shown DSRS-SPD to have advantage over standard DSRS.

Angiography↗

PubMed1989

Comparison of whole-blood cyclosporine levels measured by radioimmunoassay and fluorescence polarization in patients post orthotopic liver transplant.

This study compared the analysis of whole blood cyclosporine concentrations measured by fluorescence polarization immunoassay (FPIA) and radioimmunoassay (RIA) polyclonal and monoclonal procedures. Fifteen orthotopic liver transplant patients with a mean age of 39 +/- 11.06 years were included in the study. One hundred thirteen levels were analyzed using FPIA, RIA polyclonal, and RIA monoclonal procedures. There was no difference statistically in comparing FPIA and RIA polyclonal results (p greater than 0.05). There was a statistical difference between FPIA and RIA monoclonal results p = 0.0001). With use of least squares simple linear regression analysis, FPIA results showed good correlation with RIA polyclonal results (R2 = 0.87). Poor correlation was shown between FPIA and RIA monoclonal results (R2 = 0.51). In this study population, FPIA produced results 2.5% higher than the RIA polyclonal procedure.

Adult↗