[Adenoma of the parathyroid gland in a young woman with chronic kidney disease: primary or tertiary hyperparathyroidism?]

Clinical observation of a young woman with chronic kidney disease IV stage and hyperparathyroidism is presented. Ultrasound and99mTc-sestamibi scintigraphy of the anterior surface of the neck visualized a tumor of the left upper parathyroid gland. In a histological examination of distant education was diagnosed a solid parathyroid adenoma. The difficulty of differential diagnosis between primary and secondary/tertiary hyperparathyroidism in chronic kidney disease is discussed.

[The clinical course and treatment of fungal infections in the early period after kidney transplantation].

The article discusses the critical issues of clinical manifestations and treatment of fungal infections in patients after kidney transplantation. In fungal infection, which is usually detected in the composition of microbial associations, lungs are more often affected. In this case, mortality reaches 60%. Affecting the renal transplant by Candida spp. or Aspergillus spp. can lead to the loss of function of transplanted kidneys. At the current stage, lipid formulations of amphotericin B are drugs of choice for antimycotic therapy in posttransplant period. Nephrotoxic effect of amphotericin B is reversible and does not represent a serious threat to the function of the transplantate. Administration of lipid formulations of amphotericin B is the most justified, since it does not affect the concentration ofimmunosuppressive drugs in the blood serum of patients after transplantation.

[A case of complication of system scleroderma with AL-amyloidosis].

The article describes a case of systemic scleroderma complicated by a severe nephrotic syndrome after seven years in a 46-year-old patient. Rectal mucosal biopsy and right renal biopsy were performed to clarify the origin of the nephrotic syndrome and because amyloidosis was suspected. Massive amyloid deposits were found in biopsy material, colored with Congo red and studied in normal and polarized light. After processing with guanidine and coloring with Congo red, the material was studied in normal and polarized light; amyloid deposits preserved their congophilia and double refraction during two hours of incubation, which is typical of AL-amyloidosis. The patient was directed to a specialized nephrological department for the treatment of AL-amyloidosis.

[Fast detection of DNA of hepatitis B virus by real time PCR].

90 blood plasma samples from patients with suspected chronic viral hepatitis B (CVHB) were analyzed by real-time polymerized chain reaction (PCR). The findings were compared with the results obtained by 2 PCR electrophoresis-based test-systems; the sensitivity limit for the quantification of DNA of hepatitis B virus (HBV) was determined; in the present case, the limit corresponded to 30 replications of HBV DNA to reaction (600 GE/ml). The positive result of real-time PCR was registered in 53.3% of cases. The quantity of HBV DNA replications in blood plasma samples varied from 30 to 3.9 x 10(6) per reaction (600-7.8 x 10(7) GE/ml). Serological profiles were analyzed in 18 patients with the verified diagnosis of CVHB. HBV DNA was detected in blood of 65% of HBsAg(+)-patients. The markers of HBeAg replication were noted in 35.5% of patients; it is noteworthy, that HBeAg(+)-samples were characterized by a higher level of viral loads (> or = 10(6) GE/ml) versus HBeAg(-)-samples (> or = 6 x 10(3) GE/ml). An analysis of blood-plasma samples dynamically obtained from one patient with chronic renal insufficiency and CVHB showed a decreased level of viral load from 1.7 x 10(7) GE/ml to a negative finding of real-time PCR registered after a therapy course by zeffix. Hence, the automated and standardized real-time PCR, when used at a multi-field patient-care facility, ensures a better diagnosis of viral hepatitis B.

[Infectious complications in using mofetil micofenolate in patients with renal allotransplant].

AIM: To study infectious complications in renal transplant recipients receiving mycophenolate mofetil (MMF) for prevention of acute transplant rejection or treatment of chronic allograft nephropathy (CAN). MATERIAL AND METHODS: A group of renal transplant recipients (n=47) receiving 1.0-2.0 g/day MMF with cyclosporine A (CsA) and steroids as maintaining immunosuppression was compared to a group (n=47) taking triple immunosuppressive therapy which included azathioprine (Aza). Separate group of patients (n=9) received MMF for treatment of CAN. In all groups etiology and incidence of infections were evaluated. RESULTS: During 2 years various posttransplant infections developed in 72.3% patients on MMF and 93.6% on Aza. The incidence of viral infections was 53.2% in MMF and 59.6% in Aza group, the incidence of bacterial infection--55.3 and 70.2%, respectively. Among 9 recipients with CAN the infections occurred in five. There were two cases of active tuberculosis in Aza group, one--in MMF group and one in patients with CAN. CONCLUSION: We suggest that MMF in the dose 1-2 g/day does not increase infection rates in renal transplant recipients comparing Aza.

Does mycophenolate mofetil increase the incidence of infections in renal transplant recipients?

The aim of this study was to investigate infectious complications in renal transplant recipients (RTRs) receiving mycophenolate mofetil (MMF) for prevention of acute transplant rejection. A group of RTRs (n = 47) receiving 1.0-2.0 g/day of MMF with cyclosporine A (CsA) and prednisolone to maintain immunosuppression was compared with a group (n = 47) taking triple immunosuppressive therapy including azathioprine. In both groups the etiology and incidence of infections were evaluated. During 2 years post-transplant, various infections developed in 72.3% of patients who received MMF and in 93.6% of those who received azathioprine. The incidence of viral infections was 53.2% in the MMF group and 59.6% in the azathioprine group and the incidence of bacterial infection was 55.3% and 70.2%, respectively There were two cases of active tuberculosis in the azathioprine group and one in the MMF group. MMF 1.0-2.0 g/day does not increase infection rates in RTRs compared with azathioprine.

Sustained high-level expression of full-length human factor VIII and restoration of clotting activity in hemophilic mice using a minimal adenovirus vector.

The successful prophylactic treatment of hemophilia A by frequent infusions of plasma concentrates or recombinant factor VIII (hFVIII) indicates that gene therapy may be a potential alternative for the treatment of the disease. For efficient delivery and long-term expression of the hFVIII gene, a novel minimal adenovirus (mini-Ad) vector, MiniAdFVIII, has been developed. The vector is devoid of all viral genes and carries the full-length hFVIII cDNA under the control of the human 12.5-kb albumin promoter. The MiniAdFVIII vector was propagated with the assistance of an ancillary vector in 293 cells and was purified by CsCl banding. Sustained expression of hFVIII at physiologic levels (100-800 ng/mL) was achieved in mice after a single intravenous injection of MiniAdFVIII. The expressed hFVIII had a structure identical to that of recombinant hFVIII, as determined by Western blot analysis. The functionality of the protein was confirmed by the restoration of blood coagulation capacity in MiniAdFVIII-treated hemophilic mice, as determined by tail clipping observations. Although antivector or antihuman FVIII antibodies at various levels were detected, long-term expression of the transgene was observed in the mice that did not generate antibodies against the transgene product. The vector DNA persisted in the liver tissues of the mice with long-term expression. No significant histopathologic findings or toxicities were observed to be associated with the vector in the MiniAdFVIII-treated C57BL/6 mice. These results support the further development of MiniAdFVIII for clinical trials toward the treatment of hemophilia A.

[Malignant tumors in patients with kidney transplants ]. / Zlokachestvennye opukholi u bol'nykh s peresazhennoi pochkoi..

In this retrospective study we evaluated incidence of malignancies observed among 718 renal transplant recipients with at least 6 months of follow-up. A total of 461 men and 257 women (mean age at transplantation 36.3 +/- 8.3 years) were included. Thirty three out of 718 recipients (4.6%) developed malignant neoplasia: 45.4% of these were Kaposi's sarcomas, 12.1%--cancers of the uterine cervix, 12.1% cancers of the stomach, 12.1%--basal cell carcinomas, 6.06%--posttransplant lymphoproliferative disorder. There was no significant effect of either cyclosporin A doses or OKT3/ATG on the incidence of the tumors. Mean age of transplant recipients with malignancies was statistically higher as compared to those without malignancies (45.5 +/- 8.2 years versus 36.1 +/- 8.4 years, p < 0.00001). The median time from onset of end-stage renal failure (dialysis start) and from the transplantation to the diagnosis of the tumor make up 32 (16-161) and 23 (5-158) months, respectively. One renal transplant patient suffered from multiple myeloma with aggressive course.

Development and application of a minimal-adenoviral vector system for gene therapy of hemophilia A.

To achieve efficient delivery and sustained expression of the human factor VIII cDNA in vivo, a minimal-adenoviral (mini-Ad) vector system was developed. The system is composed of a mini-Ad vector with essential cis-elements (less than 1 kb) of the viral genome, an E1-deleted ancillary Ad with packaging attenuation, and an E1-complementing production cell line. Based on this system, MiniAdFVIII was generated to deliver a 27 kb expression cassette consisting of a full-length human factor VIII cDNA flanked by human albumin promoter and genomic sequences. The MiniAdFVIII vector mediated expression of functional human factor VIII in HepG2 and 293 cells. A single-dose intravenous injection of 10(11) viral particles in hemophilic mice of MiniAdFVIII produced a sustained high-level expression of human factor VIII (at 100-800 ng/ml up to 369 days) which corrected the FVIII-deficient phenotype. Safety studies of MiniAdFVIII showed that there were no significant toxic effects in mice and dogs after single intravessel doses of up to 3 x 10(11) and 6 x 10(12) viral particles, respectively. Studies for developing the MiniAdFVIII vector with a site-specific integration mechanism and progress in the development of a human factor VIII-tolerized mouse model for pre-clinical studies of MiniAdFVIII are reported. Further pre-clinical studies and product development of MiniAdFVIII for clinical trials are also discussed.

[Generalized tuberculosis after kidney transplantation]. / Generalizovannyi tuberkulez posle transplantatsii pochki.

Tuberculosis is one of severe infectious complications in patients on hemodialysis and after kidney transplantation. Incidence of disseminated and generalized forms is high, whereas clinical symptoms are weak and nonspecific. An aggressive generalized form of tuberculosis was observed in a kidney transplant recipient. M. tuberculosis, the antigen and DNA were registered only a few days before death. Disseminated foci in the lungs were seen on CT image only in the agonal period in spite of multiple x-ray investigations. Thus, our experience and experience of other investigators evidence that if recipients of renal transplant have fever of unknown genesis and do not respond to standard antibiotic therapy, tuberculosis should be suspected and a course of specific antituberculosis therapy should be started as early as possible.

[Use of plasmapheresis in intensive therapy of acute steroid-resistant rejection reaction in renal transplants]. / Primenenie plazmafereza v intensivnoi terapii ostroi steroidrezistentnoi reaktsii ottorzheniia renal'nykh transplantatov.

For many years the treatment of steroid-resistant rejection (SSR) remains a common problem od renal transplantation. We used plasmapheresis (PPH) in the treatment of SRR in 29 renal transplant recipients. All patients had progressive deterioration of renal function and compatible biopsy histology. The first group (15 patients) was administered PPH with methylprednisolone (MP). The second group (14 patients) was treated by intravenous MP. There was no significant difference in the time of beginning and severity of rejection. In the PPH group the results were better: a significant increase in SSR reversion was attained (73.3%) in comparison with the control (42.8%), the number of grafts lost during the first year was less (26.7 versus 57.2%). Better results were observed in patients with high levels of serum anti-HLA antibodies. Their transplants functioned well during 12 months after SSR. Hence, PPH can be used in patients with SSR with high levels of anti-HLA antibodies.

Complementation of helper-dependent adenoviral vectors: size effects and titer fluctuations.

The complementation of adenoviral vectors with large deletions in the viral genome was studied. The helper adenovirus used to complement these vectors contains a partial deletion of the packaging signal and the E1 region substituted by the lacZ gene. The effect of vector size on packaging efficiency was analysed in 293 cells using decreasingly shorter vectors expressing GFP from a CMV enhancer-beta-actin promoter. Vectors with longer genomes propagated more efficiently than shorter ones. Vectors containing only the packaging signal and the ITRs of Ad5, having all the viral genes replaced with unrelated sequences packaged as efficiently as vectors of the same size containing adenoviral DNA instead of exogenous DNA. The amounts of helper and vector produced in coinfected 293 cells exhibited the typical cycling fluctuation observed during serial propagation of a virus with defective interfering particles.