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Biomedical subjects

R Krom

Publications and source records attributed to R Krom.

9 recordsLinked to original sources
PubMed1999

CD40L (CD154) expression in human liver allografts during chronic ductopenic rejection.

The CD40-CD40L (CD154) interaction plays a pivotal role in the effector mechanisms of allograft rejection. Blockade of the CD40/CD40L costimulatory pathway prevents the development of chronic allograft rejection in several animal transplant models. The relevance of in situ CD40 and CD40L expression in human liver allografts was assessed by immunohistochemistry during ductopenic chronic rejection (CR). In CR allograft specimens (n = 8), marked CD40L expression was detected on Kupffer cells (KCs) and sinusoidal macrophages with a unique centrilobular distribution (P <.001). The CD40L+ KCs and macrophages were shown to be CD68+ after immunohistochemical analysis of serial sections with anti-CD68 monoclonal antibody. Moderate staining of vascular and sinusoidal endothelial cells and mononuclear infiltrates was observed in some CR cases. These findings were in contrast to the absence of CD40L expression in controls (n = 11) consisting of stable liver allograft and normal liver tissue specimens. Only occasional CD40 expression in some cases of CR and controls was observed. In CR, CD40L (CD154) expression is manifested on KCs and macrophages. The present novel data show another important cellular source of CD40L expression and suggest a potential role of KCs/macrophages and CD40/CD40L costimulatory interactions in the pathogenesis of chronic rejection ductopenic liver allograft.

CD40 Antigens↗
PubMed1998

TT-virus infection in North American blood donors, patients with fulminant hepatic failure, and cryptogenic cirrhosis.

A novel DNA virus, TT-virus (TTV), has been reported in patients with non-A-G posttransfusion hepatitis in Japan. We sought to determine whether TTV infection occurs in North American blood donors and to further determine the prevalence of TTV infection in several groups of patients with liver disease, including patients with cryptogenic cirrhosis and idiopathic fulminant hepatic failure. TTV infection was sought by detection of TTV DNA in serum by polymerase chain reaction (PCR) using primers generated from a conserved region of the TTV genome. Blood donors, patients with cryptogenic cirrhosis, idiopathic fulminant hepatic failure, and patients with other forms of advanced liver disease with and without a history of parenteral exposures were studied. TTV infection was present in 1% (1 of 100) of blood donors, 15% (5 of 33) of patients with cryptogenic cirrhosis, 27% (3 of 11) of patients with idiopathic fulminant hepatic failure, 18% (2 of 11) of patients with a history of exposure to blood products, and 4% (1 of 25) of patients without parenteral risk factors. For all patients tested, a history of prior exposure to blood products was associated with an increased risk of TTV infection (relative risk, 4.5; 90% confidence intervals, 0.6-43.9). We conclude that TTV infection is present among North American blood donors and is common in patients with liver disease, including cryptogenic cirrhosis and fulminant hepatic failure. Further studies are required to determine the role of TTV in the pathogenicity of acute and/or chronic liver disease.

Adult↗
PubMed1995

Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation.

Transplant immunosuppression using either cyclosporine (CsA) or FK506 leads to renal vasoconstriction. To examine the role of endothelin (ET) in this process, we measured plasma and urinary ET before and at intervals for two years after liver transplantation. Urinary prostacyclin (as 6-keto-PG-F1 alpha), thromboxane, glomerular filtration rate and renal plasma flow were also measured. Forty-four patients were treated with CsA-based regimens and 31 patients with FK506-based regimens. Prednisone doses after one year were lower with FK506 (5.5 +/- 0.5 vs. 10.5 +/- 0.5 mg/day) by study design. Circulating plasma ET remained above normal, but not different from pre-transplant levels. Urinary ET was elevated before transplant (24.6 +/- 3.4 ng/day vs. normal 16 +/- 1.5 ng/day, P < 0.05) and rose further after transplantation (48.5 +/- 13 ng/day, P < 0.05), remaining elevated for two years. 6-keto-PG-F1 alpha fell from 2567 +/- 338 ng/day to subnormal levels and remained suppressed (1158 +/- 128 ng/day, P < 0.01). Over the same period GFR fell (84 +/- 3 ml/min to 60 +/- 3 ml/min, P < 0.01) and renal vascular resistance index rose (11,119 +/- 561 to 23,279 +/- 1692 d.s.cm-5.m-2, P < 0.01). Similar changes were observed both with CsA and FK506-based immunosuppression. No changes in ET were attributable to dihydropyridine calcium channel blockers. These results demonstrate that urinary ET changes independently from plasma ET after transplantation. Elevated ET and suppression of endothelium-derived prostacyclin persist with intense renal vasoconstriction for at least two years after transplant.

Cyclosporine↗
PubMed1994

Resolution of posttransplant hypertension after liver transplantation despite impaired glomerular filtration.

Hypertension developing after transplantation is characterized by widespread vasoconstriction including the kidney. Late resolution (mean, 29 +/- 4 months) of posttransplant hypertension has been observed in 15 (Group I) of 278 subjects monitored after liver transplantation. These studies were undertaken to define the systemic and renal changes associated with resolution, as compared with a group matched for age, sex, and time after transplant who remained hypertensive (Group II; N = 15) or a group who never developed hypertension (Group III; N = 23). Blood pressure during resolution paralleled changes in the systemic resistance index, which fell from 3,052 +/- 548 to 1,872 +/- 205 dyne/s.cm5/m2 (P < 0.01). GFR and RBF remained low, despite the resolution of hypertension, and renal vascular resistance did not change. Circulating endothelin levels remained above normal in all transplant recipients (Group I, 11.9 +/- 3.0 versus normal subjects, 7.0 +/- 1.1 pg/mL; P < 0.05), and urinary prostacyclin excretion was suppressed (880 +/- 120 versus 2,247 +/- 187 ng/day; P < 0.01). No hormonal differences were apparent between transplant groups. These results demonstrate the capacity for systemic vasodilation to occur after transplantation, independent of vascular tone in the kidney. They further suggest that renal vasoconstriction and impaired GFR alone are not sufficient to explain de novo hypertension after transplantation.

Adult↗
PubMed1992

Antibody response to cytomegalovirus (CMV) polypeptides in liver transplant recipients with CMV hepatitis.

Immunoblotting (IB) was used to detect the presence of serum antibody against each individual CMV structural polypeptide and the major nonstructural antigen during CMV hepatitis in 12 orthotopic liver transplant recipients to evaluate the diagnostic utility of this technique. The basic phosphoprotein p150 primarily, and to a much lesser extent p65 (lower matrix protein) and p52 (nonstructural DNA-binding protein) were the most recognized antigens by both IgG and IgM class antibodies. Collectively, IgM antibodies were detected to p150 in 9 of 12 (75%) patients and were detected before (2 cases), at the same time (1 case), or after (6 cases) detection of virus in cell cultures. IB was equal to indirect immunofluorescence (IIF) and enzyme immune assay (EIA) for the detection of IgG and superior to EIA for IgM class antibodies to CMV in OLT patients. Our results indicate that the p150 phosphoroprotein is an essential component of serologic assays, especially for the detection of IgM antibodies to CMV.

Antibodies, Bacterial↗
PubMed1988

Selective bowel decontamination to decrease gram-negative aerobic bacterial and Candida colonization and prevent infection after orthotopic liver transplantation.

Gram-negative bacterial and fungal infections are a major cause of morbidity and mortality following liver transplantation. We therefore used selective bowel decontamination (SBD) to eliminate the endogenous source of gram-negative aerobic bacteria and Candida pathogens in an attempt to reduce the high incidence of infection related to these organisms. Thirty consecutive patients undergoing liver transplantation were treated with SBD starting 3 days prior to donor search and continuing for 21 days postliver transplantation. Selective bowel decontamination consisted of administering nonabsorbable antibiotics (Polymixin E, gentamicin, Nystatin) and a low bacterial diet. Surveillance cultures of the throat and rectum were obtained to monitor efficacy of selective bowel decontamination. In addition, in the posttransplant period, tracheal, wound, blood, and bile cultures were obtained to screen for gram-negative bacterial and Candida colonization and infection. Our baseline surveillance culture revealed that 29/30 (97%) of recipients were colonized with gram-negative aerobic bacteria and 16/30 (53%) with Candida. Three days after selective bowel decontamination was started, 26/30 (87%) were free of gram-negative bacteria, and 100% were free of Candida colonization of the gastrointestinal tract. There was a similar reduction in the oropharyngeal gram-negative aerobic bacteria and Candida colonization. In the first 30 days following liver transplantation, gram-negative infections were not diagnosed in any of our patients. Following discontinuation of SBD, recolonization of the gastrointestinal tract with gram-negative aerobic bacteria and Candida occurred within 5 days in 26/28 (90%) and 11/28 (35%), respectively. Our study suggests that prophylactive administration of nonabsorbable antibiotics will markedly reduce gram-negative aerobic bacterial and Candida colonization and appears to reduce the high incidence of infection related to these organisms in the early posttransplant period.

Adolescent↗