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.     

Detection of cytomegalovirus from blood leukocytes separated by sepracell-MN and Ficoll-Paque/Macrodex methods.

Two density gradient separation techniques for separation of blood leukocytes were compared for the laboratory diagnosis of cytomegalovirus (CMV) viremia. Of 510 blood specimens processed by both methods, 76 (14.9%) yielded CMV. Of the 76 positive specimens, 66 (87%) and 65 (86%) were processed by the Ficoll-Paque/Macrodex (F-P/M; Macrodex is dextran 70 in normal saline; Pharmacia, Pisataway, N.J.) and Sepracell-MN methods, respectively. Of the 76 CMV-positive blood specimens, 72 (95%) were detected in shell vial cell cultures, whereas only 42 (55%) were detected in conventional tube cell cultures. The time for recognition of specific cytopathic effects due to CMV in tube cell cultures (8.0 versus 7.1 days), the number of fluorescent foci in each positive shell vial culture (19.3 versus 20.1), and the costs of the reagents ($3.50 versus $2.80) were similar and independent of the leukocyte separation method (F-P/M versus Sepracell-MN). Recovery of CMV from heparinized blood (F-P/M method) was similar to that from EDTA-anticoagulated blood (Sepracell-MN method). The Sepracell-MN method is a rapid and sensitive method for detection of CMV from blood specimens and is recommended as a replacement for the more tedious and time-consuming F-P/M procedure.     

The economic impact of cytomegalovirus infection after liver transplantation

BACKGROUND: We studied the economic impact of cytomegalovirus (CMV) disease and its effective reduction with antiviral prophylaxis in liver transplant recipients. METHOD: Analysis of institutional charge data accumulated during a prospective, randomized, controlled trial comparing oral acyclovir 800 mg four times daily for 120 days (ACV) and intravenous ganciclovir 5 mg/kg every 12 h for 14 days followed by ACV for 106 days (GCV) was performed. RESULTS: Liver transplant recipients who developed CMV disease had significantly higher charges (median: $148,300) than those who developed asymptomatic CMV infection ($119,600) or experienced no CMV infection ($114,100) (P<0.01). A multiple linear regression analysis indicated that CMV disease is associated with a 49% increase in charges, independent of other factors influencing increased hospitalization charges. In CMV-seronegative patients who received a CMV-seropositive donor organ, GCV prophylaxis was associated with a significant reduction in charges, as compared to ACV prophylaxis ($113,900 vs. $153,300, respectively; P=0.02). CONCLUSIONS: CMV disease is an independent risk factor for increased resource utilization associated with liver transplantation. The use of an effective prophylactic antiviral regimen provides savings in health care resources, particularly in patients at high risk for developing CMV disease.     

Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients

The impact of cytomegalovirus (CMV) infection post-transplantation is in part influenced by the degree of immunosuppression. While mycophenolate mofetil (MMF) does not increase the overall incidence of CMV infection, we have questioned whether or not it increases its severity. Using a case control study design in which 29 renal transplant patients developed CMV disease [17 (59%) of which received azathioprine (AZA) and 12 (41%) received MMF], increases in the frequency of organ involvement with CMV (58 vs. 18%; p = 0.03) and in the number of organs involved with CMV were noted in the MMF versus the AZA group (2.0 vs. 1.0; p = 0.015). These results indicate that the increased immunosuppressive activity of MMF impacts the morbidity of CMV infection, thus warranting the use of effective anti-CMV preventive regimens while patients are treated with MMF.     

Diagnostic value of tissue polypeptide-specific antigen (TPS) in neuroblastoma and Wilms' tumour.

Although tissue polypeptide-specific antigen (TPS) has been described as a potentially useful serum marker of tumour activity in adult epithelial tumours, few data are available for childhood malignancies. Neuroblastomas and Wilms'' tumours are the commonest types of solid malignancies found in the retroperitoneum of children. At this time, a widely used marker for Wilms'' tumour is not available. Using an enzyme-linked immunosorbent assay (ELISA) kit, serum TPS levels in 23 children with neuroblastomas, nine with Wilms'' tumours and 22 with benign tumours were evaluated to test the usefulness of the marker in identifying malignancies. Compared with healthy children (n = 110), the preoperative least-square means (LSM) of serum TPS were considerably elevated in both neuroblastoma (LSM = 209 U l(-1)) and Wilms'' tumour (LSM = 235 U l(-1)), whereas values in benign tumours were only slightly elevated. Although the Wilms'' tumours were associated with higher preoperative serum TPS levels, there was no statistically significant difference compared with neuroblastomas. Receiver operating characteristic analysis (ROC curves) showed a high sensitivity and specificity for both malignancies. Successful treatment resulted in decrease in TPS serum values. Serum TPS measurements in children presenting with abdominal masses can help in diagnosing the two commonest extracranial solid malignancies of childhood. Furthermore, TPS could acquire a pivotal role in monitoring therapy.     

CT and MR imaging of generalized cystic lymphangiomatosis in pediatric patients

OBJECTIVE: The aim of this study was to describe the spectrum of abnormalities seen in generalized cystic lymphangiomatosis as shown by CT and MR imaging and to correlate these findings to gross pathology. CONCLUSION: MR imaging and CT may substantially broaden visualization of the spectrum of abnormalities seen in generalized cystic lymphangiomatosis by revealing the complete extent of disease and, thus, may contribute to clinical management of the disease by preventing initial misdiagnosis.     

Immunodeficiencies Associated with Abnormal Newborn Screening for T Cell and B Cell Lymphopenia

Newborn screening for SCID has revealed the association of low T cells with a number of unexpected syndromes associated with low T cells, some of which were not appreciated to have this feature. This review will discuss diagnostic approaches and the features of some of the syndromes likely to be encountered following newborn screening for immune deficiencies.     

Absence of cytomegalovirus-resistance mutations after valganciclovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients

We investigated the emergence of cytomegalovirus (CMV) ganciclovir-resistance mutations in 301 high-risk solid-organ transplant (SOT) recipients after oral prophylaxis, for 100 days, with either valganciclovir or ganciclovir. For patients treated with ganciclovir, the incidence of CMV UL97 mutations was 1.9% (2/103) at the end of prophylaxis and 6.1% (2/33) for patients with suspected CMV disease up to 1 year after transplantation. No resistance mutations were detected in samples from valganciclovir-treated patients. Dual polymerase (UL54) and UL97 resistance mutations were not seen. Valganciclovir was associated with negligible risk of resistance and thus constitutes a useful alternative to ganciclovir prophylaxis for CMV in high-risk SOT recipients.     

Differences in circadian blood pressure variability during gestation between healthy and complicated pregnancies

BACKGROUND: Changes in circadian variation of blood pressure (BP) could be used either to predict preeclampsia or to assess its severity. We examined and compared characteristics of circadian variability in BP in women with both healthy and complicated pregnancies who were systematically monitored throughout gestation. METHODS: We analyzed 2430 BP series sampled by ambulatory monitoring for 48 h once every 4 weeks from the first obstetric visit until delivery in 235 women with uncomplicated pregnancies, 128 with gestational hypertension, and 40 with preeclampsia. The circadian pattern of BP variation for each group and trimester of gestation was established by population multiple-components analysis. RESULTS: The differences in 24-h mean and amplitude between healthy and complicated pregnancies were highly significant in all trimesters (P < 0.001). Results further indicated similar circadian characteristics between gestational hypertension and preeclampsia in the first trimester of pregnancy. The difference between these two groups in 24-h mean was statistically significant for systolic (P =.002) and diastolic BP (P =.038) in the second trimester and, to a larger extent, in the third trimester (P < 0.001). CONCLUSIONS: The differences in BP between healthy and complicated pregnancies that can be observed as early as in the first trimester of pregnancy are found when both systolic and diastolic BP for women with a later diagnosis of gestational hypertension or preeclampsia are well within the accepted range of normotension. These differences offer new end points that may lead to an early identification of hypertensive complications in pregnancy as well as to the establishment of prophylactic intervention.