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Biomedical subjects

R A Krom

Publications and source records attributed to R A Krom.

At least 109 records · Page 6Linked to original sources
PubMed1992

Hepatic allograft cyclosporine concentration is independent of the route of cyclosporine administration and correlates with the occurrence of early cellular rejection.

This study compares the hepatic-tissue cyclosporine concentrations in liver biopsy specimens from patients with and without cellular rejection after orthotopic liver transplantation. Nine patients without cellular rejection were studied, including five patients receiving intravenous cyclosporine who had biopsies on posttransplant day 7 and four patients receiving oral cyclosporine who had biopsies on day 21. In these patients no significant differences were seen in blood cyclosporine concentrations (mean +/- S.D.) (310 +/- 162 vs. 273 +/- 310 ng/ml) and hepatic-tissue cyclosporine concentrations (3,451 +/- 1,262 vs. 3,545 +/- 456 ng/gm). These nine patients without cellular rejection were then compared with eight patients with cellular rejection who were receiving intravenous cyclosporine, including seven patients who had biopsies on post-transplant day 7 and one patient who had a biopsy on day 14. In patients with and without cellular rejection blood cyclosporine concentrations were 330 +/- 64 vs. 294 +/- 146 ng/ml, and hepatic-tissue cyclosporine concentrations were 1,879 +/- 998 vs. 3,493 +/- 936 ng/gm, p less than 0.01. We conclude that hepatic-tissue cyclosporine concentrations are independent of the route of cyclosporine administration and that low hepatic-tissue cyclosporine concentrations correlate with early cellular rejection after orthotopic liver transplantation.

Administration, Oral↗
PubMed1992

Ischemic-type biliary complications after orthotopic liver transplantation.

Nonanastomotic biliary strictures that involve only the biliary tree of the graft occur after orthotopic liver transplantation in patients with hepatic artery thrombosis, chronic ductopenic rejection and ABO blood group incompatibility. This complication may also occur in the absence of these known risk factors. The major focus of our study was to evaluate the risk factors for nonanastomotic biliary stricturing of unknown cause after orthotopic liver transplantation. Results demonstrate that the development of biliary strictures is strongly associated with the duration of cold ischemic storage of allografts in both Euro-Collins solution and University of Wisconsin solution. Results also demonstrate that strictures are not associated with the type of biliary reconstruction, the primary liver disease, cytomegalovirus infection, allograft rejection or the presence of a positive lymphocytotoxic crossmatch. More recently, we have markedly reduced the occurrence of nonanastomotic biliary stricturing by decreasing the ischemia time of our allografts. Thus nonanastomotic biliary strictures appear to be the result of the ischemia/reperfusion-induced tissue injury associated with the harvest and implantation of allografts.

Adenosine↗
PubMed1992

Lack of association between cytomegalovirus infection, HLA matching and the vanishing bile duct syndrome after liver transplantation.

In this study we evaluated the association between cytomegalovirus infection alone or in relation to human leukocyte antigen matching and the development of vanishing bile duct syndrome, a form of chronic hepatic allograft rejection. A total of 81 consecutive liver transplant recipients were studied. Cytomegalovirus infection developed in 46 recipients (57%), and vanishing bile duct syndrome occurred in 9 recipients (11%). Cytomegalovirus infection developed in only five of the nine patients with vanishing bile duct syndrome. Univariate analysis of pretransplant recipient/donor cytomegalovirus serological tests and human leukocyte antigen typing showed they were not significant risk factors for the development of vanishing bile duct syndrome. Time-dependent analysis of cytomegalovirus infection after transplantation as a risk factor for vanishing bile duct syndrome, in a multivariate analysis with human leukocyte antigen match, showed no statistical significance. In our study, no association was found between cytomegalovirus infection alone or in relation to class I or II human leukocyte antigen match and the subsequent development of vanishing bile duct syndrome.

Acyclovir↗
PubMed1992

Renal hemodynamics, urinary eicosanoids, and endothelin after liver transplantation.

Patients with hepatic cirrhosis develop widespread abnormalities in kidney function and vasoactive hormones. These change rapidly after liver transplantation during immunosuppression with cyclosporine. The role of changing eicosanoid excretion and endothelin levels in regulating renal function after transplantation in humans remains uncertain. We studied 32 patients with regard to renal hemodynamics, glomerular filtration, urinary prostacyclin (6-keto-PG-F1-alpha), thromboxane (TBX2), and endothelin before and during the first four weeks after orthotopic liver transplantation. Arterial pressure rose from 106 +/- 2/61 +/- 2 to 146 +/- 4/81 +/- 2 mmHg, (P less than .001), while renal blood flow fell (686 +/- 38 to 453 +/- 24 ml/min/1.73 m2, P less than .05), as did GFR. Pretransplant excretion of 6-keto and TBX2 was above that of normal subjects and fell progressively after transplant, as did plasma renin activity and aldosterone. The 6-keto levels fell below normal after two weeks. The ratio of TBX2/6-keto remained elevated compared with normal subjects throughout the month after transplant (1.54 +/- 0.38 vs. 0.54 +/- 0.07, P less than .01). Endothelin levels rose during the first week (7.4 +/- 1.4 vs. 12.4 +/- 2.7 pg/ml, P less than .05), but fell back to baseline thereafter. These results indicate that high levels of urinary eicosanoids in patients with liver disease fall rapidly after liver transplantation during CsA immunosuppression. Unlike results in many experimental models, these data suggest that renal vasoconstriction in humans may be associated primarily with suppression in renal prostacyclin excretion rather than stimulation of thromboxane.

Adult↗
PubMed1992

A prospective study of pulmonary function and gas exchange following liver transplantation.

Pulmonary function and gas exchange were prospectively studied in 95 patients before and 9 to 15 months following liver transplantation. Pretransplant, the most common PF abnormality was impaired efficiency of gas exchange as measured by Dss. As a group, the mean Dss was 78.0 +/- 16.6 percent predicted and was found to be less than 80 percent predicted in 50 patients. As a group, patients with the most severe liver diseases clinically (Child's C classification) had the lowest mean Dss pretransplant. Posttransplant, three findings were of clinical importance: PaCO2 significantly improved posttransplantation, suggesting a resolution of pretransplant respiratory alkalosis. Expiratory airflow obstruction, measured by a change in the FEV1/FVC, was extremely uncommon posttransplant. Mean Dss improved significantly in patients with Child's C severity of liver disease. The most frequent deteriorations in Dss statistically were associated with posttransplant thoracotomy, ARDS, nonspecific pneumonitis, significant pleural effusions and hepatic retransplantation.

Female↗
PubMed1992

Selection and timing of liver transplantation in primary biliary cirrhosis and primary sclerosing cholangitis.

In summary, we answer the three questions we have previously posed: (a) Can liver transplantation prolong survival? Evolving data from several centers indicate that liver transplantation indeed prolongs survival in patients with PBC and PSC as compared with estimated survival using disease-specific risk scores based on the natural history of PBC and PSC. (b) Can we optimize timing of liver transplantation? Although many factors enter into the timing of liver transplantation, including when the patient is actually referred for liver transplantation and the individual desires of the patient to pursue liver transplantation, evidence is growing that having patients with chronic liver diseases like PBC and PSC undergo transplantation a little earlier in the course of the disease rather than waiting until the patients have experienced life-threatening complications or are on life-support measures can indeed improve early postliver transplant survival. In patients with PBC and PSC, the survival risk score, which reflects disease severity, can serve as an objective measurement to assess and evaluate the effect of liver disease severity on transplant outcome. Indeed, a number of studies have strongly suggested that optimal timing of liver transplantation may indeed be important to improve outcome, decrease morbidity and decrease cost. (c) Does the present allocation system in the United States allow for optimal use of our scarce donor organ resource?(ABSTRACT TRUNCATED AT 250 WORDS)

Cholangitis, Sclerosing↗
PubMed1992

Role of endoscopic retrograde cholangiopancreatography after orthotopic liver transplantation.

We reviewed the records of 20 liver transplant patients who underwent 28 procedures [endoscopic retrograde cholangiopancreatography (ERCP)] to rule out biliary obstruction, treat bile leaks, dilate and/or stent strictures, or remove stones and debris. Three patients (two with abnormal T-tube cholangiograms and one with hyperbilirubinemia) underwent ERCP to rule out obstruction. Therapeutic ERCP (sphincterotomy with balloon dilatation or stone extraction) was successful in 16 of 17 patients, including seven of nine in whom there was resolution of bile leaks without the use of stents or surgery. Mild pancreatitis occurring in one patient was the only complication experienced that was related to ERCP. We conclude that ERCP is a safe and important modality in the medical management of biliary tract complications after orthotopic liver transplantation.

Adult↗
PubMed1991

Successful orthotopic liver transplantation in a patient with refractory biliary candidiasis.

The authors present a nonimmunocompromised patient who developed refractory fungal (Candida albicans) cholangitis and who subsequently underwent successful orthotopic liver transplantation for progressive destruction of intrahepatic and extrahepatic bile ducts. Liver biopsy specimens showed periductal abscesses, and cholangiograms showed rapidly progressive destruction of intrahepatic and extrahepatic bile ducts. Standard immunosuppressive therapy and perioperative amphotericin B were administered. At 6 months, the patient was clinically well with no evidence of recurrent biliary candidiasis. The authors suggest that orthotopic liver transplantation may be a reasonable therapeutic option for patients with refractory biliary candidiasis.

Candidiasis↗
PubMed1991

Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure.

Hepatic allograft rejection is presently classified into acute and chronic rejection based on histological features, timing and reversibility. However, because features of both types of rejection can occur at any time, and in many combinations, the terms "acute" and "chronic" seem inappropriate in some instances. Thus the term "cellular rejection" better defines the histological features of portal hepatitis, nonsuppurative destructive cholangitis and endotheliitis, which are independent of time and response to therapy. Similarly, because progressive bile duct destruction leading to a decrease in the number of interlobular and septal bile ducts is the major histological feature of "chronic rejection," the term "ductopenic rejection," defined as the loss of bile ducts in 50% or more of portal tracts independent of time and reversibility, seems more appropriate. The pathogenesis of cell-mediated rejection has not been completely explained; however, direct immunocytic attack on small bile ducts and small arteries appear to be the major feature. The process may lead to bile duct loss ("ductopenia"). The pathogenetic role of foam-cell arteritis resulting in ischemic bile duct injury and the role of humoral mechanisms in causing ductopenic rejection awaits further clarification. In the past, irreversible ductopenic rejection occurred in approximately 10% of all patients who underwent their first liver transplantation; this figure, however, appears to be decreasing. The clinical features of irreversible rejection include persistent and progressive cholestasis; rising serum levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase; and a decrease in hepatic synthetic function. Ductopenic rejection can occur early (2 to 5 wk after liver transplantation) but most often develops between 6 wk and 6 mo after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Evidence that combined procurement of pancreas and liver grafts does not affect transplant outcome.

We compared outcome after pancreas and liver transplantation when both organs were retrieved from the same donor to outcome when only one or the other organ was retrieved. A total of 166 cadaver pancreata were transplanted at our institution between November 1984 and August 1989; 64 were obtained from donors in whom the liver was also donated (LD), and 102 were retrieved from non-liver donors (non-LD). Of the 64 LD pancreata, 53 were the entire organ with a segment of duodenum and 11 were segmental. Both the superior mesenteric artery (SMA) and celiac axis (CA) were retained with the pancreas in 13, while in 40 pancreata the CA was retrieved with the liver and the blood supply to the pancreas was reconstructed [end-to-side anastomosis of splenic artery (SA) to SMA in 11 and a Y-graft of donor iliac bifurcation to SA and SMA in 29]; a graft of common iliac vein was used to extend the portal vein in 10. The technical failure rate was 8/64 (12%) in LD pancreata, and 13/102 (13%) in non-LD pancreata (P greater than 0.1). The overall pancreas allograft survival rate at 1 year was 76% for pancreata obtained from LD (n = 64) and 64% for technically successful transplanted pancreata obtained from non-LD (n = 102, P greater than 0.1). One-year actuarial patient survival was 95% in the LD group and 90% in the non-LD group (P greater than 0.1). Among the 64 livers from pancreas donors (PD), 20 were transplanted at our hospital, 42 were transported to other institutions, and 2 were not transplanted. Follow-up information regarding 47 primary orthotopic adult, whole liver PD recipients (18 at our hospital, 29 at other institutions) was available for analysis and was compared with information concerning 62 adult recipients of primary orthotopic whole livers from non-PD transplanted during the same period at our institution. The total PNF rate among 47 PD liver allografts was 2/47 (4%), compared with 1/62 (1%) for the livers from non-PD (P greater than 0.1). The technical failure rate for the PD group was 1/47 (2%) versus 5/62 (8%) in the non-PD group (P greater than 0.1). The overall liver allograft survival rate at 1 year was 75% for livers obtained from PD (n = 47) and 81% for livers obtained from non-PD (n = 62, P greater than 0.1). One-year actuarial patient survival was 88% in the PD group and 81% in the non-PD group (P greater than 0.1). We concluded that simultaneous procurement of liver and pancreas grafts had no significant detrimental effect on the rate of technical failure, or on allograft or patient survival after either pancreas or liver transplantation.

Adult↗
PubMed1991

Elevation of plasma endothelin associated with systemic hypertension in humans following orthotopic liver transplantation.

Endothelin (ET) is a 21-amino-acid peptide of endothelial origin, is a potent systemic and renal vasoconstrictor associated with sodium retention and modulation of the renin-angiotensin-aldosterone system. The present study was designed to determine if plasma ET is elevated in humans with cirrhosis (n = 12), a state characterized by sodium retention and increased plasma renin activity (PRA) and plasma aldosterone (PA), and to determine the effect of orthotopic liver transplantation (OLT) upon plasma ET, PRA, and PA at 1, 3, and 7 days after transplantation. Plasma ET before OLT was 1.62 +/- 0.23 pg/ml, which was not different as compared with normal controls. Plasma ET significantly increased to 4.18 +/- 0.66, 3.87 +/- 0.58, and 4.07 +/- 0.61 pg/ml, respectively following OLT. PRA remained elevated throughout the postoperative course, in contrast to PA that decreased following OLT. Mean arterial pressure increased significantly from 82 +/- 4 pre-OLT to 98 +/- 4 and 103 +/- 2 mmHG on days 3 and 7 respectively.

Aldosterone↗
PubMed1991

Persistent bile leak after liver transplantation: biloma drainage and endoscopic retrograde cholangiopancreatographic sphincterotomy.

Persistent bile leaks after liver transplantation were successfully treated in three patients with percutaneous or surgical drainage of bilomas and endoscopic retrograde ampullary sphincterotomy. In all three patients, biliary anastomoses were achieved by means of choledochocholedochostomies, with a T-tube stent in the anastomosis. The bile leaks led to subhepatic bilomas that had persistently high catheter outputs (greater than 200 mL per 24 hours) for longer than 1 month. Biloma drainage decreased shortly after sphincterotomy.

Ampulla of Vater↗
PubMed1991

Epstein-Barr virus and persistent graft dysfunction after liver transplantation.

Epstein-Barr virus infection has been associated with a broad spectrum of clinical manifestations, depending on the immune status of the host. In this report, we describe two liver transplant patients who received hepatic allografts from donors serologically positive for Epstein-Barr virus and who experienced primary infection with Epstein-Barr virus associated with prolonged liver graft dysfunction. In both patients, Epstein-Barr serologies converted within 3 mo of liver transplantation, and hepatic histological study revealed mononuclear infiltration of the sinusoids evolving to pronounced immunoblastic features suggestive of evolving lymphoma. In both cases, in situ hybridization studies confirmed the presence of Epstein-Barr virus genome in the liver. Furthermore, polymerase chain reaction analysis suggested that high levels of Epstein-Barr virus DNA were present in biopsy specimens obtained during the episode of acute hepatitis that followed Epstein-Barr virus seroconversion. The degree of Epstein-Barr virus DNA estimated by polymerase chain reaction appeared to increase in parallel with the progression of parenchymal lymphocytic infiltrates. In one patient, a biopsy sample from a cervical node also revealed high levels of Epstein-Barr virus DNA estimated using the polymerase chain reaction technique. Furthermore, in these patients, Epstein-Barr virus DNA levels appeared to decrease dramatically after discontinuing azathioprine administration and beginning treatment with acyclovir. These two cases illustrate the dynamics of Epstein-Barr virus immune regulation and confirm chronic hepatic allograft dysfunction related to Epstein-Barr viral infection.

Adult↗
PubMed1991

The metabolic bone disease of primary sclerosing cholangitis.

The incidence and severity of osteopenic bone disease in primary sclerosing cholangitis is poorly defined. Clinical, biochemical and radiographic assessment and bone mineral density measurements of the lumbar spine were carried out in two groups of patients. Group 1 consisted of 30 patients with advanced primary sclerosing cholangitis; group 2 consisted of 18 patients with newly diagnosed primary sclerosing cholangitis. Only one patient had bone pain. All patients were normocalcemic; two had elevated serum parathormone levels. Fourteen patients (47%) from group 1 but no patients from group 2 had low serum 25-hydroxyvitamin D levels. Mean bone mineral density was significantly reduced in group 1 patients (0.97 +/- 0.04 gm/cm2) compared with age-matched and sex-matched controls (1.25 +/- 0.01 gm/cm2, p less than 0.0001), and in 15 patients (50%) bone mineral density was below the fracture threshold (0.98 gm/cm2). The bone mineral density in group 2 was not significantly different from controls, and no patient was below the fracture threshold. In neither group did bone mineral density correlate with serum bilirubin, 25-hydroxyvitamin D, fecal fat excretion, previous drug therapy or the presence of chronic ulcerative colitis. Histomorphometrical examination of bone from four group 1 patients showed increased bone resorption, reduced bone formation, moderate-to-severe osteopenia and no osteomalacia. In conclusion, severe osteopenic bone disease is common in advanced primary sclerosing cholangitis and, like that seen in other cholestatis diseases, is consistent with osteoporosis.

Adult↗
PubMed1991

Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis.

Atraumatic fractures caused by osteoporosis may be a serious complication of primary biliary cirrhosis. Mean (+/- S.D.) bone mineral density in the lumbar spine in 210 ambulatory women with primary biliary cirrhosis was 1.02 +/- 0.19 gm/cm2, 7% lower than that in 139 age-matched normal women (after adjustment for age and body weight) (p less than 0.001). Bone mineral density in the lumbar spine was inversely related to a risk score index of liver disease severity (r = -0.29, p less than 0.001). The mean rate of bone loss in 105 of these 210 women was 2%/yr +/- 4%/yr, twice as great as in the 139 normal women (p less than 0.02). In 20 women with primary biliary cirrhosis followed up after orthotopic liver transplantation, bone mineral density in the lumbar spine decreased at 3 mo (p less than 0.01), and this decrease may have resulted in atraumatic fractures in 13 of them. Bone mineral density in the lumbar spine then increased (p less than 0.01) so that by 12 mo the median bone mineral density in the lumbar spine was similar to that before transplantation and by 24 mo it was 5% above it. Therefore we conclude that the progressive bone loss observed in primary biliary cirrhosis (which is further accentuated immediately after transplantation) may be halted, and the bone mass may be restored toward normal within 2 to 3 yr after orthotopic liver transplantation.

Absorptiometry, Photon↗