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Biomedical subjects

R A Krom

Publications and source records attributed to R A Krom.

At least 55 records · Page 3Linked to original sources
PubMed1996

Use of fatty donor liver is associated with diminished early patient and graft survival.

It is well known that implantation of donor livers with severe fatty infiltration (>60%) is frequently associated with early hepatic dysfunction and an increased incidence of primary nonfunction after liver transplantation. The outcome of donor livers with less fatty infiltration has not been well defined. We, therefore, studied the outcome of 59 liver transplantations in which donor livers with up to 30% fat were used. Patient outcome was compared to a time-matched control group of 57 patients. The two groups were similar in terms of age, gender, preservation time, primary diagnosis, and UNOS status. We compared both groups with regard to 4-month and 2-year patient and graft survival. We also assessed the incidence of ischemic type biliary strictures and hepatic artery thrombosis, and evaluated the causes of graft loss in both groups. We found that use of donor livers with up to 30% fatty infiltration was associated with a significant decrease in 4-month graft survival (76% vs. 89%, P<0.05) and in 2-year patient survival (77% vs. 91%, P<0.05). Primary nonfunction and primary dysfunction formed the main cause of graft loss and mortality. Multivariate analysis showed that fatty infiltration is an independent predictive factor for outcome after transplantation. We conclude that liver allografts with up to 30% fat lead to diminished outcome after liver transplantation. However, this diminished outcome should be viewed with respect to the increasing mortality on the national waiting list.

Adult↗
PubMed1996

Risk factors of invasive Candida and non-Candida fungal infections after liver transplantation.

Fungal infections are associated with a high mortality rate after liver transplantation. To describe risk factors for fungal infections, 405 consecutive liver transplant recipients were analyzed. Forty-five patients (11%) developed invasive fungal infection. Median posttransplantation time to the first episode was 60 days. Pathogens were Candida species (spp) (n=24, 53%), Cryptococcus neoformans (n=10, 22%), Aspergillus spp (n=6, 13%), Rhizopus spp (n=l), and others (n=4). Presentations of infection included disseminated (n=9), intra-abdominal (n=9), esophageal (n=9), lung (n=8), blood (n=6), and central nervous system infections (n=3), and sinusitis with esophagitis (n=1). Eighteen patients (40%) with invasive fungal infection died, and 13 (72%) of these deaths were attributable to fungi. Mortality in the nonfungal infection group was 12%. Univariate analysis identified separate risk factors for Candida (intra-abdominal bleeding), Aspergillus (fulminant hepatitis), and cryptococcal (symptomatic cytomegalovirus infection) infections. In both univariate and multivariate analyses, a high intratransplant transfusion requirement and posttransplant bacterial infection were identified as significant risk factors for all types of fungal infection. The risk factor analysis reported here suggests that different pathogenic processes lead to Candida and non-Candida infection in liver transplant recipients. Their identification should prompt specific prophylactic measures to reduce morbidity and mortality in this population.

Analysis of Variance↗
PubMed1996

Relevance and risk factors of enterococcal bacteremia following liver transplantation.

To analyze the clinical characteristics of and identify specific risk factors for enterococcal bacteremia following liver transplantation, we performed a study in 405 consecutive liver transplantation recipients prophylaxed with a selective bowel decontamination regimen. Seventy enterococcal bacteremias in 52 patients were identified. Enterococcus faecalis (50) outnumbered Enterococcus faecium isolates (18), and 49% of enterococcal bacteremias were polymicrobial. Biliary tree complications were present in 34% of enterococcal bacteremias. Of the 15 deaths (29%) among the patients with enterococcal bacteremia, 4 were directly associated with enterococcal bacteremia. In a multivariate analysis, Roux-en-Y choledochojejunostomy (P=0.005), a cytomegalovirus-seropositive donor (P=0.013), prolonged transplantation time (P=0.02), and biliary stricturing (P=0.016) were identified as significant risk factors. Other risk factors identified in a univariate analysis included primary sclerosing cholangitis (P=0.009) and symptomatic cytomegalovirus infection (P=0.008). Enterococcal bacteremia is a frequent infectious complication in liver transplantation recipients receiving selective bowel decontamination. Its association with cytomegalovirus and biliary tree abnormalities suggest specific areas for prophylactic intervention.

Anastomosis, Roux-en-Y↗
PubMed1996

Neuromuscular complications associated with liver transplantation.

We studied neuromuscular complications in a cohort of 520 patients with liver transplantation. Perioperative mononeuropathy developed in 9 patients. The peroneal nerve, radial nerve, and cutaneous branch of the femoral nerve were affected in 2 patients each. Two patients had herpes zoster-associated radiculopathy, and 1 patient had Horner's syndrome. Recovery was good in most patients. In 7 patients, severe quadriplegia complicated the perioperative course. In 5 patients, electrophysiologic studies suggested acute necrotic myopathy, and muscle biopsy specimens showed evidence of rhabdomyolysis in 1 patient. Outcome in survivors was good, all recovering completely. We conclude that neuromuscular complications in liver transplantation are uncommon (less than 1%) and do not significantly contribute to morbidity. Mononeuropathies may have iatrogenic perioperative causes, and rhabdomyolysis may be an important cause of generalized muscle weakness after liver transplantation.

Adult↗
PubMed1996

Liver allograft rejection in rats depleted of CD8+ cells.

The mechanism(s) of rejection or tolerance induction is a competitive, complex process that presumably involves interactions between multiple subpopulations of T lymphocytes. We investigated the roles of CD8+ cytolytic and CD4+ helper T cells in rat strains that tolerate liver allografts and that differ at both the major histocompatibility complex (MHC) (RT1) and minor histocompatibility genes. Orthotopic liver transplantation (OLT) with arterial reconstruction was performed with Brown Norway (BN) (RT1n) donors and Lewis (RT1(1)) recipients, some of which were untreated, others treated with anti-CD8 antibody, and still others treated with anti-CD4 antibody. Liver graft rejection was monitored for 28 days on the basis of two criteria: (1) serum levels of AST enzyme at 3-day intervals and (2) liver biopsies at weekly intervals and at the time of sacrifice at the end of the study period. In the untreated control group, an elevation of AST was found to peak at day 6 after grafting, and it remained elevated until day 28 (AST 542 +/- 72 U/l). Histologically, signs of severe rejection were first observed on day 9; these changed to moderate rejection about day 21 and to mild rejection by day 28, when the animals were sacrificed. Recipients pre-treated with anti-CD8 demonstrated a significant elevation of AST within 6 days that, unlike in the control recipients, continued to rise sharply through the observation period (AST 1127 +/- 181 U/l, P = 0.009 vs control group). Liver biopsies showed mild rejection at day 9 and moderate rejection at days 21 through 28. Recipients pretreated with anti-CD4 showed a time course of enzyme elevation and severity of rejection that was not significantly different from that observed in the control group. However, anti-CD4 treatment resulted in only 75% depletion of CD4+ cells in peripheral blood as compared to complete elimination of CD8+ cells following anti-CD8 treatment. Functional studies of spleen and liver-infiltrating lymphocytes obtained after 28 days showed low proliferative response in mixed lymphocyte culture with both BN and PVG stimulator spleen and lymph node cells. These results suggest that in this donor/recipient combination, removal of CD8+ cells increases the severity of rejection as demonstrated by a progressive rise in AST and histology. Moreover, OLT in this combination results in a profound, nonspecific inhibition of proliferative T-cell responses to MHC alloantigens.

Animals↗
PubMed1996

Granulocyte accumulation in the transplanted liver does not correlate with clinical and histologic evidence of dysfunction.

RATIONALE AND OBJECTIVES: To evaluate the role of granulocytes in reperfusion injury after liver transplantation. The authors injected radiolabeled granulocytes to determine if human liver graft outcome could be correlated with granulocyte accumulation. MATERIALS AND METHODS: Pure granulocyte suspension was prepared from eight patients 12 to 24 hours after orthotopic liver transplantation. The granulocytes were labeled with indium-111 (111In) oxine and reinjected. Total body radionuclide images were performed. Liver uptake of granulocytes was compared with biochemical and histologic evidence of liver injury. RESULTS: No correlation was found between liver uptake of granulocytes, as measured by geometric mean counts, and the biochemical or histologic measures of liver injury. Liver uptake of 111In was 9.6% for the patient who had liver dysfunction and 10.4% mean of the study group. This technique did not detect early signs of liver dysfunction. CONCLUSIONS: This investigation supports the premise that granulocytes do not play a major role in reperfusion injury of the newly transplanted liver graft.

Biopsy↗
PubMed1996

Liver transplantation for primary sclerosing cholangitis: impact of risk factors on outcome.

The results of liver transplantation in patients with PSC are excellent and the quality of life is markedly improved. Indeed, liver transplantation is the therapy of choice for patients with end-stage PSC. However, in an age of cost containment, it appears that there are several advantages to offering transplant to patients with PSC a little bit earlier rather than later in the course of their disease. It appears that we can further improve survival, decrease morbidity, decrease blood usage, and avoid the risk of developing a cholangiocarcinoma, which occurs sporadically but not infrequently in the PSC patient. In addition, avoidance of right upper quadrant surgery, such as biliary or shunt surgery, appears to offer several advantages by decreasing resource utilization and possibly decreasing mortality. Although the UNOS selection guidelines recommend transplantation of the sickest patient, there appears to be accumulating evidence that transplantation in patients earlier in the course of their end-stage liver disease may improve survival, decrease morbidity, and also importantly, decrease the cost associated with this expensive procedure. Ideally, we would recommend consideration for liver transplantation all PSC patients who have (1) a Mayo risk score of > 4.8 in whom malignancy is ruled out, (2) cirrhosis and complications of portal hypertension such as variceal bleeding, refractory ascites, or portosystemic encephalopathy, or (3) disabling symptoms such as fatigue, pruritus, or recurrent bacterial cholangitis. We believe that biliary surgery to treat dominant strictures should be avoided and that such strictures should be approached either endoscopically or radiographically, which should include brushings, biopsies, and histology to reasonably exclude the diagnosis of cholangiocarcinoma. Finally, we continue to search for risk factors and for early markers of cholangiocarcinoma so these patients can be identified early and this devastating complication can be avoided by early transplantation.

Cholangitis, Sclerosing↗
PubMed1995

Organ-specific patterns of donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism in lung, kidney, and liver transplant recipients.

Although their relative importance and interaction are unclear, donor antigen(Ag)*-specific hyporeactivity and allogeneic microchimerism have been associated with improved long-term graft outcome and a lower incidence of chronic rejection in solid organ transplant recipients. We have postulated that a critical level of donor antigen, for a critical time period, is necessary to develop and maintain donor antigen-specific hyporeactivity; both the level and the time may differ by organ transplanted. In our current study, we tested donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism in liver and kidney recipients and compared these values with our previous findings in lung recipients. We tested 25 liver recipients at 12 to 29 months posttransplant: 10 (40%) had developed donor antigen-specific hyporeactivity; 5 (20%), peripheral blood allogeneic microchimerism. For all but 1 of the chimeric and hyporeactive recipients, the level of donor cells was very low (< 1:20,000). Five hyporeactive recipients and all 15 donor antigen-responsive recipients did not have detectable levels of peripheral blood microchimerism. No chronic rejection has developed in any of these recipients to date--however, a lower incidence of acute rejection was observed for those recipients with donor antigen-specific hyporeactivity (30% versus 60% without) or with peripheral blood allogeneic microchimerism (20% versus 55% without) (P = ns). These results differ from our previous findings in 19 lung recipients: at 12 to 18 months posttransplant, 35% of them had developed donor antigen-specific hyporeactivity; 47%, peripheral blood allogeneic microchimerism. All donor antigen-specific hyporeactivity recipients as well as some donor antigen-responsive recipients had peripheral blood allogeneic microchimerism. We expanded our current study to include 26 recipients and a quantitative estimate of the level of allogeneic microchimerism. We observed that the hyporesponsive recipients tended to have higher levels of donor cells in their peripheral blood (> 1:6,000) than did the responsive recipients. We previously reported that 22% of kidney recipients had developed donor antigen-specific hyporeactivity at 12 to 18 months posttransplant. In our current study of 33 kidney recipients, we observed peripheral blood allogeneic microchimerism in 7 (21%) at 12 to 18 months posttransplant. The level of donor cells was very low (approximately 1:75,000), with no correlation between donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism at the time point tested. These studies emphasize the organ-specific nature of the development of donor antigen-specific hyporeactivity and the persistence of peripheral blood allogeneic microchimerism. Donor antigen-specific hyporeactivity correlates with very low levels of donor cells in liver recipients, while a higher critical level of donor cells is important in lung recipients. Additional sequential early posttransplant studies are necessary to further define the possible interrelationship between donor antigen and the development and maintenance of donor antigen-specific hyporeactivity.

Antigen Presentation↗
PubMed1995

Hepatic allograft rejection is associated with increased levels of soluble intercellular adhesion molecule-1.

Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule from the immunoglobulin super family that is recognized to be an important factor in the multistep process of cell transendothelial migration and lymphocyte adhesion during antigen recognition and effector cytolysis, mechanisms known to be involved in the pathogenesis of hepatic allograft rejection. A soluble form of ICAM-1 (sICAM-1) can be shed into the circulation. In this study, we examined the levels of sICAM-1 in hepatic allograft recipients as possible markers of cellular rejection and the presence of cytomegalovirus (CMV) hepatitis. We studied three groups of patients, including eight patients with histologically documented cellular rejection, five patients with histologically documented CMV hepatitis, and a liver transplantation control population. Serum samples were obtained at the following times: baseline (1 to 3 days after transplantation), at time of diagnosis of cellular rejection, and at time of diagnosis of CMV hepatitis and 1 week after treatment of rejection episodes. The levels of sICAM-1 were measured using an established commercial enzyme immunoassay with a sensitivity of 0.3 ng/mL. We found that serum levels of sICAM-1 were significantly increased in liver transplant recipients who were experiencing hepatic allograft rejection but were unchanged in patients with CMV hepatitis or the time-matched liver transplant controls. Serum levels of sICAM-1 decreased significantly after successful treatment of the rejection episode with bolus corticosteroid therapy. We conclude that serum levels of sICAM-1 may be useful in monitoring the occurrence of rejection and the response to antirejection therapy in liver transplant recipients.

Biomarkers↗
PubMed1995

Loss of nocturnal blood pressure fall after liver transplantation during immunosuppressive therapy.

Hypertension, which develops after organ transplantation during immunosuppression with cyclosporine (CSA), is often associated with a loss of nocturnal decrease in blood pressure. Few data correlate circadian blood pressure patterns before transplant with those observed at fixed time points after transplant, or address the role of alternate immunosuppressive agents such as FK506. FK506 is unrelated structurally to CSA and less often leads to hypertension early after transplant. The present study compared nocturnal blood pressure patterns in patients with end-stage liver disease (ESLD) before transplant to those of transplant recipients receiving either FK506 (0.15 mg/kg/day) plus prednisone or CSA (2 to 3 mg/kg/day) plus prednisone and azathioprine after orthotopic liver transplantation. Overnight ambulatory blood pressure profiles were studied in 13 pretransplant ESLD patients and in 34 patients (FK506: n = 13; CSA: n = 21) treated with different steroid doses (24 +/- 11 mg/day FK506; 34 +/- 3 mg/day CSA), according to protocol, 4 weeks (range, 2 to 7 weeks) after liver transplant. Mean blood pressure and heart rate values from awake and nocturnal 5-h time blocks were compared to 13 normotensive control subjects. Patients with ESLD were normotensive and maintained a normal nocturnal blood pressure fall (125 +/- 3/74 +/- 2 mm Hg awake; 109 +/- 3/60 +/- 2 mm Hg nocturnal). Awake ambulatory blood pressures were higher in CSA patients than in FK506 patients (148 +/- 3/95 +/- 2 v 128 +/- 3/78 +/- 2 mm Hg, respectively; P < .01), despite reduced glomerular filtration rates in both transplant groups. Both immunosuppressive regimens led to a loss of nocturnal blood pressure fall, as compared to ESLD patients or normotensive controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1995

A prospective comparison of molecular diagnostic techniques for the early detection of cytomegalovirus in liver transplant recipients.

Forty-one consecutive liver transplant recipients were studied by polymerase chain reaction (PCR) of serum and peripheral blood mononuclear cells, reverse transcription (RT)-PCR of peripheral blood mononuclear cells, and viral blood culture for symptomatic cytomegalovirus (CMV) infection. The techniques were also used to predict the occurrence of CMV infection. For diagnosis of symptomatic CMV infection, the sensitivity and specificity of the different techniques were as follows: PCR of serum, 100% and 45%; RT-PCR, 25% and 97%; PCR of peripheral blood mononuclear cells, 83% and 35%; and blood culture, 83% and 86%, respectively. PCR of serum was positive in 83% of subjects with symptomatic infection before onset compared with 17% positive by blood culture. While viral blood culture was the best technique for the diagnosis of symptomatic CMV infection, PCR of serum was best at predicting the development of symptomatic CMV infection.

Cytomegalovirus↗
PubMed1995

OKT3 treatment for allograft rejection is a risk factor for cytomegalovirus disease in liver transplantation.

The role of OKT3 monoclonal antibody administration was studied as a risk factor for symptomatic cytomegalovirus (CMV) infection in 229 consecutive liver transplant recipients not receiving specific CMV prophylaxis. Twenty-six patients (11.4%) received OKT3 and 17 of them developed CMV infection, 11 (4.8%) being symptomatic. OKT3 use was a significant risk factor for symptomatic CMV infection by both univariate (relative risk [RR], 2.9; 95% confidence interval [CI], 1.5-5.8; P = .002) and multivariate time-dependent (RR, 3.4; 95% CI, 1.7-7.1; P = .001) analyses. A subgroup analysis revealed that OKT3 use was a significant risk factor for symptomatic CMV infection in CMV-seropositive but not seronegative recipients. OKT3 therapy for steroid-resistant rejection is a risk factor for symptomatic CMV infection in liver transplant recipients who are seropositive for CMV before transplantation. This group should be targeted for antiviral prophylaxis when OKT3 antirejection therapy is used.

Cytomegalovirus Infections↗
PubMed1995

Neurotoxicity in liver transplant recipients with cyclosporine immunosuppression.

We studied the clinical features, blood levels of cyclosporine, and neuroimaging findings in 46 patients with cyclosporine neurotoxicity after liver transplantation. The clinical presentation of cyclosporine neurotoxicity was characterized by tremulousness and restlessness in all patients and was associated with acute confusional state and psychosis in 20 patients, seizures in eight, speech apraxia or action myoclonus speech in three, and cortical blindness in two. In 35 patients, cyclosporine neurotoxicity occurred during IV treatment. Neuroimaging studies showed only minor white matter abnormalities in two patients despite dramatic clinical presentations, including speech difficulties, seizures, and cortical blindness. In only 19 of 31 patients (61%) did trough levels of cyclosporine suggest neurotoxicity. Neurologic findings were reversible in all patients after cyclosporine was withheld and then given in lower dosage. In three patients, substituting FK 506 did not result in neurotoxicity.

Adolescent↗
PubMed1995

Renal sodium handling with cyclosporin A and FK506 after orthotopic liver transplantation.

Hypertension is common after orthotopic liver transplantation and may be due, in part, to cyclosporin A-induced renal dysfunction and/or enhanced proximal tubular sodium reabsorption. To determine whether enhanced proximal tubular sodium reabsorption is central to the development of posttransplant hypertension, measurements of renal hemodynamics and fractional clearances of lithium and sodium were compared 1 month after orthotopic liver transplantation in previously normotensive patients receiving either cyclosporin A (N = 24) or FK506 (N = 18), an immunosuppressive agent that is structurally unlike cyclosporin A and that has a lower reported incidence of hypertension. Median prednisone doses were 20 and 13 mg/day in the cyclosporin A and FK506 groups, respectively (P < 0.05). At 1 month, mean arterial blood pressure was higher in the cyclosporin A versus the FK506 group: 108 +/- 2 versus 95 +/- 3 mm Hg (P < 0.05). GFR, RBF, and renal vascular resistance were not different between the two groups: 59 +/- 4 and 53 +/- 5 mL/min per 1.73 m2, 439 +/- 28 and 440 +/- 41 mL/min per 1.73 m2, and 22,429 +/- 1,822 and 22,977 +/- 3,506 dyne s/cm5 per 1.73 m2, respectively. Fractional lithium excretion was similar in the cyclosporin A and FK506 groups: 19.9 +/- 2.2 and 19.4 +/- 2.0% (P = not significant) although both values were lower than those of normal controls (25.5 +/- 1.1%) (P < 0.05). Fractional sodium excretion was 2.7 +/- 0.3 and 2.3 +/- 0.4% in the cyclosporin A and FK506 groups, respectively (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗