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W T van Dorp

Publications and source records attributed to W T van Dorp.

31 records · Page 2Linked to original sources

Ganciclovir effectively treats cytomegalovirus disease after solid-organ transplantation, even during rejection treatment.

Ganciclovir (DHPG) was used to treat eight patients with severe cytomegalovirus (CMV) disease after renal transplantation. Four had generalized disease, one had severe recurrent gastrointestinal bleeding and three had interstitial pneumonia. All patients responded to treatment, symptoms disappearing within 7 days (range: 3-22 days). Leukocytopenia and confusion were the main side-effects, both occurring in three patients. Encouraged by the effectiveness and the mild side-effects of ganciclovir we enlarged the indication for treatment. Five patients with CMV disease and concomitant rejection were treated with ganciclovir together with antirejection therapy. Four patients received methylprednisolone, one patient anti thymocyte globulin. CMV-related symptoms disappeared in all five patients. The only side-effect observed was a mild leukocytopenia in one patient. Renal function was preserved in three of the five patients. The virological response to the drug was also evaluated. Twelve patients had positive cultures in blood and/or urine before ganciclovir was started. In three patients the cultures became negative during follow-up. In eight patients cultures remained positive after ganciclovir treatment although in seven of these CMV had initially been absent from blood and/or urine. We conclude that ganciclovir treatment is clinically effective in severe CMV disease and that treatment with ganciclovir makes antirejection therapy during CMV disease possible.

Adult↗

The polymerase chain reaction, a sensitive and rapid technique for detecting cytomegalovirus infection after renal transplantation.

Fifty-nine renal transplant recipients were followed during the first 3 months after transplantation. Once weekly, cultures of urine and buffy coat for CMV were taken. Furthermore, peripheral blood leukocytes were examined by an immunocytochemical assay for immediate early antigens of CMV (IEA assay) and by a polymeric chain reaction for CMV DNA. Forty-four patients had a CMV infection; 23 of them were symptomatic. PCR was positive in 22 of the 23 patients with symptomatic CMV disease. For cultures of urine, buffy coat, and the IEA assay these figures were 23, 20, and 21, respectively. The PCR was the first test to become positive in 10 patients. For the cultures of urine and buffy coat and the IEA assay these figures were 0, 2, and 2, respectively. In the other 9 patients, 2 or more tests became positive at the same time. In the patient group with a CMV infection but without symptoms the PCR also had a good correlation with the other diagnostic techniques. These results together with its short processing time of 6 hr make the PCR a sensitive and rapid technique for monitoring CMV infections after renal transplantation.

Antigens, Viral↗

The effects of a maintenance immunosuppressive protocol after renal transplantation on infectious complications, comparing cyclosporine/prednisone, cyclosporine/azathioprine/prednisone, and conversion.

Infectious complications of either high-dose (16 mg/kg/day) or low-dose (9 mg/kg/day) cyclosporine in combination with azathioprine (Aza) (1 mg/kg/day) were studied in 128 renal transplant patients who also received low-dose prednisone (P). Three months after transplantation all patients were again randomly assigned to either continuation with CsA/P or conversion to Aza/P. During the first 3 months the number of infections was significantly lower in the CsA/P treatment than in the CsA/Aza/P group. In both groups the number of infections doubled after rejection treatment. The frequence of symptomatic CMV disease did not differ between the 2 groups. Three months after transplantation, the patient group assigned to Aza/P had a small but not significant increase of minor infections when compared with the patients who continued with CsA/P. The number of major infections did not differ between these two groups.

Adult↗

Interleukin 2 mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells.

Previous reports have suggested the production of complement components C4, C2, and factor B by renal tissue. However, the cells involved in production of complement have not been identified. In this study metabolic labeling experiments demonstrated that human proximal tubular epithelial cells (PTEC) synthesize a 180-kD precursor of C3 that is secreted after proteolytic cleavage into a disulphide linked two-chain molecule as found in plasma. C3 present in culture supernatants of PTEC was functionally active, however, during the culture period there was a partial inactivation of the C3 molecule as assessed by hemolytic titration. Recombinant IL-2 enhances the rate of C3 synthesis in a dose-dependent manner reaching maximal stimulation at doses of 200-400 U/ml IL-2. Northern blot analysis demonstrated a 5.2-kb C3 mRNA species present in PTEC that was increased within 24 h of IL-2 treatment. IL-2-induced enhancement of C3 production by PTEC could be neutralized with specific antibodies to IL-2. This study demonstrates that C3 synthesis in PTEC is upregulated by IL-2, the major cytokine produced by activated T cells.

Animals↗

Symptomatic cytomegalovirus (CMV) infections identified by image cytometry and other parameters for CMV infection.

Thirty-eight renal transplant recipients were followed during the first 3 months after transplantation. Once weekly, cultures of urine and buffy coat for cytomegalovirus (CMV) were taken and an immunocytochemical assay for immediate early antigens of CMV (IEA assay) was performed. Thirty patients had evidence of a CMV infection and 11 had a symptomatic CMV infection. All symptomatic patients had one or more positive urine cultures or a positive IEA assay. However, 15 patients with positive urine cultures and 12 patients with a positive IEA assay lacked any signs of symptomatic CMV disease. Moreover, 6 out of 15 patients with positive buffy coat cultures for CMV did not have symptomatic CMV disease. Using a computerized system to quantify IEA-positive granulocytes, we show that the absolute number of positive cells per million correlates very well with the occurrence of symptomatic CMV disease.

Antibodies, Viral↗

Direct induction of MHC class I, but not class II, expression on endothelial cells by cytomegalovirus infection.

MHC expression on endothelial cells after cytomegalovirus infection was investigated using double antibody radioimmunoassays and immunofluorescence flow cytometry. After CMV infection there was an increase in class I and beta 2 microglobulin expression. This increase corresponds to the percentage of cells that are infected with CMV. There was no evidence that the increased class I expression was due to soluble factors produced by the infected cells. Although CMV only affects approximately 10% of the endothelial cells, class I and beta 2 microglobulin expression on the cell population exceeds that induced by an optimal dose of alpha-interferon. Class II expression is not increased after CMV infection. However, when gamma-interferon was added to the medium after CMV infection a normal increase in class II expression was found, suggesting that CMV infection does not inhibit the gamma-interferon-induced expression of these molecules.

Cells, Cultured↗

Infections in renal transplant patients treated with cyclosporine or azathioprine.

The incidence and severity of infectious complications were retrospectively investigated in 80 renal transplant patients who had been selected randomly to receive either cyclosporine (CsA) or azathioprine (Aza) in combination with low doses of corticosteroids. In the first 3 months, the incidence of infections was twice as high in the Aza-treated patients (p less than 0.05) which was due to an increase of predominantly minor infections. This increased incidence of infections was related to the increased number of anti-rejection treatments in the Aza-treated group. The types of infections were not different between the 2 treatment groups nor did the incidence of CMV infections differ. In the CsA-treated group, patients were randomly assigned at 3 months after transplantation to either continuation of CsA therapy or conversion to Aza. After conversion a small but not significant increase in predominantly minor infections was observed, which may be attributable to increased doses of corticosteroids given during the conversion. We conclude that in the first 3 months following transplantation, CsA therapy is associated with significantly less infections than Aza therapy; following conversion of CsA to Aza at 3 months only a small increase in the infection incidence is found.

Azathioprine↗

Renal failure due to granulomatous interstitial nephritis after pulmonary sarcoidosis.

Two patients, who had had pulmonary sarcoidosis, developed renal failure due to sarcoid granulomatous interstitial nephritis after their original pulmonary symptoms had subsided. Treatment with prednisone resulted in almost complete recovery of renal function. Lysozyme and angiotensin-converting enzyme levels and gallium scintigraphy can be of diagnostic value.

Adult↗

Meningococcal pericarditis in the absence of meningitis.

A 16 year-old female presented with cardiac tamponade due to purulent meningococcal pericarditis without concomitant meningitis or meningococcaemia. She recovered after aspiration of the pericardial effusion and administration of a high dose of benzylpenicillin via a continuous infusion.

Adolescent↗