We have retrospectively analyzed the incidence of cytomegalovirus (CMV) infection in 250 consecutive renal allograft transplants performed in 244 recipients. The mean follow-up was 35.1+/-25.4 months. Immunosuppression was cyclosporine- or tacrolimus-based triple therapy. CMV infection prophylaxis with ganciclovir for 3 months post transplant was prescribed in CMV-seronegative recipients of allografts from seropositive donors (D+R-) and in all recipients treated with OKT3. CMV antigenemia was monitored by the pp65-antigen assay. Thirteen of 57 D+R- recipients (22.8%) developed CMV antigenemia. One recipient had a breakthrough of CMV antigenemia during ganciclovir prophylaxis; 12 D+R- recipients developed CMV antigenemia 147.5+/-173.8 days after transplantation. Four of 13 (30.7%) D+R- recipients had asymptomatic CMV infection, 8 (61.6%) had CMV infection with non-specific symptoms including fever, and 1 (7.7%) developed CMV pneumonia. Six of 13 (46.1%) D+R- patients had been treated with intensified immunosuppressive therapy before CMV infection. In the low-risk CMV groups (D+R+; D-R+; D-R-), 28 recipients (14.5%) developed CMV antigenemia 42.5+/-15.2 days post transplantation. Ten of the 28 (35.7%) recipients had asymptomatic CMV infection, 17 (60.7%) developed CMV infection with non-specific symptoms, and 1 (3.6%) developed CMV pneumonia. Twenty-one of 28 (75.0%) had intensified immunosuppressive therapy before CMV infection. In conclusion, ganciclovir prophylaxis diminished and delayed the onset of CMV infection but did not totally prevent it from occurring in D+R- renal transplant recipients. Clinicians should be vigilant to the possibility of CMV infection in both seronegative and seropositive recipients, especially after anti-rejection therapy.
and conclusions Thirty-nine renal allograft recipients who had received continuous immunosuppression for six to 13 years were examined clinically and virologically for evidence of past or present viral infection. Twenty-five had common warts, usually on the hands. In most the warts had appeared about one year after transplantation; once present, they never disappeared. Six patients had had a zoster rash from two months to four years after transplantation. None had had jaundice, and there was no change in the frequency of colds or non-specific febrile illness. Four patients had no cytomegalovirus complement-fixing antibodies throughout the observation period; in the other 35 the antibody titre had risen appreciably during the first three to four months after transplantation. Antibody titres were high (mean 64) at follow-up, being only slightly lower than the highest titres achieved during the immediate postoperative period. None of the patients had had symptomatic cytomegalovirus infection, and in only two was the virus isolated from the urine at follow-up; the titres were extremely low. No changes occurred in the frequency of herpes simplex eruptions. Although all patients had herpes simplex humoral antibody, none excreted the virus. Although cytomegalovirus antibody titres were high, virus excretion was rare, indicating that chronic cytomegalovirus infection in these patients is immunologically well controlled.
We have screened 110 unrelated Alport syndrome kindreds for mutations in the exon 48 region of the COL4A5 collagen gene. Denaturing gradient gel electrophoresis (DGGE) of the PCR-amplified region of exon 48 revealed sequence variants in DNA from affected males and carriers of three unrelated kindreds. All three kindreds have classical Alport syndrome of the juvenile type. DNA-sequencing analyses demonstrated two different single base changes in the codon for arginine-1563 located in exon 48. In Utah kindred 2103, there was a substitution of C by T resulting in the change of the CGA codon for arginine to the translation stop codon TGA. In Utah kindred 2123 and in the Danish kindred A13, there was a C-->T mutation in the noncoding strand changing the same codon to CAA for glutamine. Both mutations were confirmed by allele-specific hybridization on PCR-amplified DNA from other family members.
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