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Biomedical subjects

R W Busuttil

Publications and source records attributed to R W Busuttil.

At least 235 records · Page 13Linked to original sources
PubMed1990

The impairment of true glomerular filtration rate in long-term cyclosporine-treated pediatric allograft recipients.

We performed indium-111-DTPA plasma clearance studies in 61 pediatric kidney and liver recipients treated with cyclosporine to compare true glomerular filtration rate with calculated GFR (cGFR). The mean true GFR of 61.9 +/- 36.6 ml/min/1.73 m2 indicated renal impairment. The mean cGFR of 85.2 +/- 22.4 ml/min/1.73 m2 was significantly higher (P less than 0.001), and overestimated GFR by 38%. cGFR alone did not accurately reflect the degree of renal dysfunction. A group of 48 pediatric orthotopic liver transplant recipients was studied in more detail: 73% of these patients had a true GFR less than 70 ml/min/1.73 m2, while 85% had a true GFR below 90 ml/min/1.73 m2, the lower limit for normal GFR in children. The mean true GFR for patients treated more than 24 months with CsA was lower (P = 0.02) than patients treated with CsA for 12 to 24 months. OLT patients with normal true GFR (greater than 90 ml/min/1.73 m2) had significantly lower plasma CsA levels, and 50% of patients with a true GFR less than or equal to 50 ml/min/1.73 m2 had hypertension. There was no effect on true GFR of age, liver function, azathioprine use, or peritransplant treatment with other nephrotoxic drugs. We conclude that true GFR is significantly impaired in long-term CsA-treated allograft pediatric recipients. Calculations of GFR underestimate the degree of renal dysfunction. As patients treated greater than 24 months had the lowest true GFRs, the fall in GFR may be progressive.

Adolescent↗
PubMed1990

Comparison of UW solution and Euro-Collins solutions for cold preservation of human liver grafts.

University of Wisconsin solution, a new organ preservation medium, is reported to extend the period of cold storage. In order to evaluate the efficacy of UW solution in human liver preservation we compared 58 donor liver grafts preserved in Euro-Collins (EC) solution. All livers were harvested in a similar manner. Donor and recipient characteristics in the two groups were comparable. The mean preservation time of the UW solution was 11.5 +/- 4.2 hr (range 3-20 hr), significantly longer than the EC mean preservation time of 4.9 +/- 1.6 hr (2-9.6 hr) (P = 0.0001). Evaluation of mean postoperative liver function tests and coagulation factors on days 1-7 showed no statistical difference between the two groups. There was one primary graft nonfunction in the EC group and none with the UW organs. Hepatic artery thrombosis was similar in each group. The incidence of early retransplantation was similar. Three-month graft survival was 81% in the UW group vs. 73% in the EC group. Patient survival at three months was 87% with the UW organs and 84% with the EC organs. We conclude that cold storage of liver grafts in the UW solution has allowed for significantly longer preservation, permitting transplantation to be performed under semielective conditions and procurement of organs from much further distances. Grafts stored in UW solution perform as well as those stored in Euro-Collins, with no significant difference in liver function abnormalities postoperatively.

Adenosine↗
PubMed1990

The role of tumor necrosis factor in allograft rejection. II. Evidence that antibody therapy against tumor necrosis factor-alpha and lymphotoxin enhances cardiac allograft survival in rats.

In the previous study we demonstrated that circulating levels of TNF-alpha are elevated during liver allograft rejection and may precede clinical manifestations. The current study was designed to investigate the efficacy of antibody therapy against tumor necrosis factor-alpha and lymphotoxin (LT) in a rat heterotropic cardiac transplant model utilizing Buffalo donors and Lewis recipients. Control animals received no immunotherapy and experienced rejection on postoperative day 11 +/- 0.4 (mean +/- SEM). Experimental animals received immunotherapy either intraperitoneal or intravenous from days 1 to 10. The i.p. administered anti-TNF-alpha prolonged graft survival to 16 +/- 2.7 days (P less than 0.05 vs. controls); the i.v. administration prolonged survival to 15 +/- 1.4 days (P less than 0.004). Animals treated with i.p. anti-LT survived 17 +/- 1.7 days (P less than 0.002 vs. controls). Combination immunotherapy of anti-TNF-alpha and anti-LT increased function to 21 +/- 2.2 days (P less than 0.001 vs controls). Conversely, administration of purified TNF-alpha or LT to graft recipients accelerated the time to rejection. Mean survival for both treatments was 7 days (P less than 0.001 vs. controls). Histologic examination of the transplanted cardiac tissue showed a typical pattern for acute rejection; there was no evidence of hemorrhagic or coagulative necrosis. In contrast, administration of purified TNF-alpha or LT to recipients of a syngeneic heart did not stimulate rejection. These data suggest that TNF-alpha and LT may play a role in the pathogenesis of acute allograft rejection. In addition, the mechanism appears to be distinct from that seen in TNF-alpha or LT-mediated cytotoxicity of tumor cells.

Animals↗
PubMed1990

Color Doppler imaging of portosystemic shunts.

This study was designed to investigate the utility of color Doppler sonography in the evaluation of portosystemic shunts. Thirty-one patients with a total of 32 shunts were imaged. The types of shunts examined included portacaval, five; mesocaval, eight; distal splenorenal (Warren), 14; and mesoatrial, five. Sonography was performed without knowledge of the status of the shunt, although the type of shunt was known before beginning the study. The sonographic studies were evaluated to determine their sensitivity and specificity on the basis of a prospective comparison with angiography or MR imaging (22 cases). The possible advantages of color Doppler over duplex Doppler sonography in evaluating portosystemic shunts were also investigated, as was the ability of color Doppler sonography to image specifically the shunt anastomoses. Color Doppler sonography successfully inferred shunt patency (17 cases) or thrombosis (five cases) in all 22 shunts for which correlative imaging was available (sensitivity = 100%, specificity = 100%). In comparing duplex with color Doppler sonography in all 32 shunts, the two techniques were almost equally effective in establishing patency in portacaval, mesocaval, and mesoatrial shunts. Duplex Doppler sonography, however, provided useful diagnostic information in only four of 14 splenorenal shunts. Color Doppler correctly inferred patency or thrombosis in all 14. Among all 32 shunts, the anastomosis was shown clearly by color Doppler in 23, probably in four, and not all in five. Our results suggest that color Doppler sonography is an excellent method for the evaluation of all varieties of surgically created portosystemic shunts. In particular, color Doppler sonography appears to be superior to duplex Doppler sonography in imaging splenorenal communications.

Adolescent↗
PubMed1990

False-negative duplex Doppler studies in children with hepatic artery thrombosis after liver transplantation.

Recent reports describe formation of collateral vessels in children who have hepatic artery thrombosis after liver transplantation. This led us to reevaluate the role of duplex Doppler imaging in this population. Among 135 pediatric liver transplant patients, 20 had arteriography for suspected hepatic artery thrombosis. Duplex and/or color Doppler imaging was performed in 13 of these children. The Doppler examination failed to show hepatic artery signals in five patients. Arteriography showed hepatic artery thrombosis in all five. In three of these, subsequent Doppler examinations showed reappearance of arterial Doppler signals. Arteriography confirmed the interval development of collaterals. Hepatic artery signals were found on the Doppler examinations of the remaining eight patients. Four had normal arteriograms, but the remaining four had hepatic artery thrombosis with collateral formation. Patients with hepatic artery thrombosis and collateral circulation tended to have increased diastolic flow (decreased resistive index). In addition, early scans clearly identified patients with complete thrombosis before collateral formation. On the basis of our preliminary experience, a child with a liver transplant and a clinical history strongly suggestive of hepatic artery compromise should have arteriography despite an apparently normal Doppler examination.

Child↗
PubMed1990

Disease recurrence following liver transplantation.

Recurrence of disease following liver transplantation is emerging as a major area of concern. We retrospectively investigated for evidence of recurrent hepatitis B, hepatitis non-A, non-B (NANB), primary biliary cirrhosis (PBC) and malignancy in 106 transplant patients. Recurrence of hepatitis B was diagnosed in 11 of 14 (79%) patients who survived longer than 2 months posttransplant. The first histologic evidence of recurrence occurred at 4 to 64 weeks posttransplant (mean, 22.2 weeks). In two patients, progression to cirrhosis was documented histologically. Recurrence was diagnosed in three patients transplanted for fulminant hepatic necrosis due to hepatitis B. Administration of hepatitis B vaccine and hepatitis B immunoglobulin was ineffective in preventing recurrence. Recurrence of hepatitis NANB was diagnosed in only two of 23 patients transplanted for hepatitis NANB cirrhosis. Evidence of posttransplant hepatitis was also detected in one of 10 patients transplanted for fulminant hepatitic failure presumably caused by hepatitis NANB. Recurrence of PBC was not diagnosed in any of 15 patients, but the length of follow-up was too limited in most patients to allow definite conclusions to be made. Posttransplant antimitochondrial antibodies titers remained elevated in nine of 11 patients tested. Six of 13 patients transplanted for hepatocellular carcinoma (46%) developed recurrent tumor, and five died. The role of preoperative and postoperative chemotherapy is currently undefined.

Adolescent↗
PubMed1989

Absence of hyperparathyroidism in severe liver disease.

Elevated serum levels of intact parathyroid hormone (PTH) have been reported in severe versus mild biliary cirrhosis. The aim of this study was to determine whether hyperparathyroidism was present in severe liver disease on the basis of the inability of the liver to catabolize the hormone. Because biologic activity resides in the amino terminal, and amino terminal PTH determinations have not been routinely made in liver disease, it is possible that hyperparathyroidism was previously missed in these patients. Accordingly, we obtained fasting blood from 11 patients with severe liver disease and 8 age-matched controls. We measured intact, amino terminal, and mid-region PTH, vitamin D metabolites, bone gamma carboxyglutamic acid protein (BGP), ionized calcium, phosphorus, magnesium, and liver function tests. Serum levels of PTH were normal with all assays and 1,25(OH)2D levels were not elevated. These findings argue against the possibility that hyperparathyroidism plays a role in the pathogenesis of hepatic osteodystrophy.

Adult↗
PubMed1989

Amanita poisoning: treatment and the role of liver transplantation.

Fatal mushroom poisoning has long been recognized as a major health problem in western Europe and more recently in the United States. The majority of deaths are attributable to the genus Amanita. Amanita phalloides (death cap) has been found with increasing frequency across the United States and presents a significant health hazard in this country to those who pick and consume wild mushrooms. This article discusses the pharmacologic basis and clinical manifestations of Amanita intoxication. It outlines the rationale of various treatment modalities and, from these, summarizes a protocol that the authors believe will be useful to the clinician. In addition, two patients are presented who underwent successful orthotopic liver transplantation for fulminant hepatic failure secondary to Amanita poisoning. The role of liver transplantation both acutely and as treatment for chronic active hepatitis secondary to severe intoxication is discussed.

Adult↗
PubMed1989

Effect of a prior portasystemic shunt on subsequent liver transplantation.

Fifteen patients who had a prior portasystemic shunt underwent orthotopic liver transplantation. Shunt types were portacaval in six patients, H-graft mesocaval in six, distal splenorenal in two, and proximal splenorenal in one. Mean blood loss and hospital stay were highest in the portacaval group. Retransplants (two patients) and deaths (two patients) also were limited to this group. In this report, technical considerations, advantages, and disadvantages of the various shunt types are described. Management of patients with late stages of portal hypertension must include estimation of the effects of a portasystemic shunt on subsequent liver transplantation. It is concluded that portacaval shunts should be avoided in patients who may be considered for transplantation. Distal splenorenal shunts are best performed in younger patients with intractable variceal bleeding who are not expected to require transplantation in the near future. A mesocaval H-graft is the shunt of choice in patients who are current liver transplant candidates.

Adult↗
PubMed1989

Use of aminoglycosides during cyclosporine A immunosuppression after liver transplantation in children.

To determine the frequency of renal dysfunction associated with the use of aminoglycosides with cyclosporine A (CyA) in children, the records of 26 consecutive children receiving CyA after liver transplantation were reviewed. Fourteen patients with normal baseline serum creatinine concentrations received an aminoglycoside postoperatively. These children received CyA and an aminoglycoside for 249 days (average, 17.8 days/patient). Forty of the 249 days included treatment with vancomycin or amphotericin B. Twelve children (86%) showed no evidence of renal dysfunction after aminoglycoside therapy. Two children developed renal dysfunction and eventually succumbed. In neither case could aminoglycoside nephrotoxicity be identified as the main cause of renal dysfunction. Multiple other factors, including ischemia and high CyA concentrations, probably contributed to renal deterioration. We conclude that aminoglycosides can be used safely in children receiving CyA following liver transplantation, provided serum CyA concentrations are followed closely and other risk factors for renal dysfunction are minimized.

Acute Kidney Injury↗