Comparing cytomegalovirus prophylaxis in renal transplantation: single center experience.

BACKGROUND: Cytomegalovirus (CMV) presents a serious threat to CMV-seronegative recipients (R-), who have received an organ from a seropositive donor (D+). OBJECTIVES: We compared the effectiveness of three different prophylactic protocols in CMV D+/R- patients and reviewed data on patients who received no prophylaxis. PATIENTS AND METHODS: We reviewed 1137 kidney transplantations from 1995 to 2004. Of these, 147 recipients were CMV negative (D+/R-); 125 patients received CMV prophylaxis. Group I received CMV hyperimmune gammaglobulin only, group II received CMV hyperimmune gammaglobulin plus oral ganciclovir, and group III received prophylaxis with oral ganciclovir only. RESULTS: In group I, CMV infection was observed in 31 of 53 patients (59%), and CMV disease was diagnosed in 9 (17%) during the prophylaxis. In the first year post transplant, a total of 41 of 53 patients (77.5%) had primary CMV infection. In group II, CMV infection occurred in 7 of 30 patients (23%), and CMV disease was diagnosed in only 2 (7%) during prophylaxis. In the first year post transplant, a total of 9 of 30 patients (30%) had primary CMV infection. In group III, 9 of 42 patients (21%) developed CMV infection during prophylaxis, and CMV disease was not observed. In the first year post transplant, a total of 13 of 42 patients (30%) had primary CMV infection. In contrast, all 22 CMV D+/R- patients without prophylaxis developed CMV infection (100%); CMV disease was diagnosed in 10 (45%), and 1 patient died. CONCLUSIONS: Prophylaxis with hyperimmune gammaglobulin and/or oral ganciclovir significantly reduces CMV infection and disease. Prophylaxis with ganciclovir was significantly more effective than hyperimmune gammaglobulin monoprophylaxis, and more cost effective than combined prophylaxis.

Mutation scanning of the p53 tumor suppressor gene in renal and liver transplant patients in Hungary.

INTRODUCTION: The increased incidence of malignancies among transplanted patients is well known. Abnormal function of the p53 tumor suppressor gene has been reported in more than half of all tumors. The aim of our study was to detect point mutations of p53 gene in transplanted patients because the presence of mutations may be a predictive factor for tumor development. An earlier diagnosis can help to develop new strategies for immunosuppressive therapies. METHODS: Three point mutations were chosen based on the literature: exon5-codon175, exon7-codon248, exon8-codon273. Genomic DNA from the plasma of 60 liver, 362 renal transplants, and 45 nontransplanted patients with different tumors and 20 suspected healthy patients were analyzed with a real-time PCR method using the Roche LightCycler. The mutations were evaluated by melting curve analysis. RESULTS: We elaborated a special protocol for scanning the above mentioned p53 point mutations, which were proved by sequencing as well. Among 487 patients, 486 showed a wild-type genotype. The only patient carrying a mutation at codon 273 (heterozygous) was a liver transplant patient, who developed pancreas carcinoma and had already died. CONCLUSION: Our data suggest that mutations of the targeted codons in leukocyte DNA seem to be rare, but a mutation could be lethal. The evaluated three point mutations of p53 gene were not predictive for tumor development.

[Qualitative and quantitative detection of hepatitis C virus RNA by PCR technique. Monitoring of viral copies after liver transplantation]. / Hepatitis C-vírus (HCV)-RNS kvalitatív és kvantitatív kimutatása PCR technikával. A HCV-RNS-kópiaszám monitorozása májtranszplantációt követóen.

The authors demonstrate the HCV nucleic acid amplification method is not wide-spread in Hungary yet. The HCV-RNA is usually detectable 2-4 weeks after infection independently the immunostate of the patients. The authors help to select the adequate measurement(s) in logical order when HCV infection is suspected. The benefit of the PCR method is emphasized. Monitoring of the HCV-RNA titer of the liver transplanted patients promotes to establish the fluctuation of HCV-RNA copies and the effectivity of therapy following transplantation. The detection of HCV-RNA by PCR method is a proof of an acute or chronic infection and rules out past infection. The quantitative PCR measurement is useful for determination of indication and control of efficacy of antiviral therapy.

[Viral screening of organ donors and human cytomegalovirus seroprevalence in the Hungarian population]. / Szervdonorok virológiai szúrése és a hazai lakosság átfertózöttsége human cytomegalovirussal.

The authors investigated 998 organ-donors for Human cytomegalovirus seroprevalence. The donors were divided into three age-groups. In organ-donors the seroprevalence was found to be 84%. A study was also conducted on a fourth group consisting of 200 residents from an old-age home. The youngest donor was 2 years of age, the eldest old-age home resident was of 92 years. The examined persons represent the hungarian population. It was found that as the result of the investigation of all 1198 subjects, the Human cytomegalovirus overall seroprevalence in Hungary is 86%. The age specific prevalence increases starting from 73% in the first group (2 to 20 years old) to 99% in the fourth group (71 to 92 years old). This has indicated that most of the population acquired the primary infection in the childhood or during early adulthood. According to these results the authors resumed that in Hungary the Human cytomegalovirus seroprevalence is high. This would cause problems when a seronegative organ-recipient needs an organ transplantation. Between males and females a significant difference of Human cytomegalovirus seroprevalence was found: 89% of females were seropositive in contrast to 81% of males (p < 0.05). The organ-donors were also examined for the presence of HBsAg, anti-HCV and anti-HIV. 1.8% of donors were HbsAg positive, 0.9% were anti-HCV positive and 1 person was anti-HIV positive, but these results weren't verificated.

Prediction of early renal graft function by the measurement of donor urinary glutathione S-transferases.

BACKGROUND: We have investigated the possibility of urinary alpha- and pi class glutathione S-transferases (GST-a; GST-pi) serving as a valuable parameter to predict early graft function after transplantation. METHOD: Urinary GST concentrations of 61 donors (DON) and recipients (REC) were analyzed at preoperative, intraoperative, and postoperative periods. We grouped recipients according to the early postoperative graft recovery days. RESULTS: The donor graft function, represented by the donor urinary GST concentration (GST-pi:17,1+/-12 microg/l mmol creatinine (crea); GST-a:14,3+/-10 microg/mmol crea), sustained a loss in comparison to the healthy controls (GST-a; pi< or =1 microg/mmol crea). According to statistical analysis, the donor GST-pi level showed a strong correlation with graft recovery days-pi (r = 0.84; P<0.001). The early graft function cannot be predicted by means of cold ischemia time (22.8+/-3.4 hr), nor handling time (42.4+/-11.1 min), nor even the intraoperative enzyme concentrations. The GST-pi cut off level (12.55 microg/mmol crea) might predict the possible posttransplant graft dysfunction. The discriminative analysis showed that using only DON GST-pi alone could discriminate well between the groups among all grafts in 68%. CONCLUSION: Prognosis is poorer if the donor GST-pi concentration is above 12.55 microg/mmol crea. On the basis of the determination of GST-pi concentration in the donor urine, we can predict graft viability before the surgical procedure with a reliability of 68%.

[Diagnostic value of glutathione-S-transferase]. / Glutation-s-transzferázok diagnosztikus jelentösége.

The authors evaluated the diagnostic value of the glutathione-S-transferase (GST) enzyme in the medical practice. The GST is widely distributed in human tissues, the majority of the enzyme protein is present in the cytoplasm. GST plays a pivotal protective role against the environmental damages. It can be made a conclusion from the quantity, the localization of the enzyme expression and enzyme forms to the degree of chemical insult suffered by the organism. The increase of alpha GST izoenzyme can reflect the degree of the hepatocellular and renal proximal tubular epithelium damage. The overexpression of pi-class GST represents the injury of bile epithelium and renal distal tubules. Overexpression of GST is associated with tumor appearances and with resistance to cytostatic agents. It was possible to took the enzyme izoenzymes apart, to identify them--hereby to explore their origin--and to detect their quantity with the development of the separation techniques, the immunological and genetical methods. Since the enzyme expression is in direct proportion to the magnitude organs and tissues damage or/and the presence of specific izoenzymes suspects tumor formation, for this reason the monitoring of the GST expression could give a help for the physicians in creating the diagnosis.

[Follow-up on alpha-glutathione-S-transferase serum level following liver transplantation]. / Alfa-glutation-S-transzferáz szérumszint követése májtranszplantáció után.

The authors followed up six patients after allograft liver transplantation which have been held in the Transplantation and Surgical Clinic. They routinely examined the serum samples of the patients in the post-transplantation period and made a comparison between the serum concentration of alpha-glutathione-S-transferase (alpha-SGT) and conventional liver function enzymes, like aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in association with acute liver allograft rejection. In two cases the authors found that the alpha-glutathione-S-transferase indicated the allograft liver acute rejection-proved by biopsy-2 days earlier than the transminases. In 1 case the alpha-glutathione-S-transferase serum level decrease followed the early post-transplant high level, showed the normalisation of the liver function, but on the 3, day the new elevation was detected, indicating the early acute rejection, the transminases serum levels in all early post-transplant period were elevated. The results of the follow-up-corresponding with the foreign researches-proved that the alpha-glutathione-S-transferase is a reliable marker of the allograft liver acute rejection, in some cases indicates the rejection diagnosis earlier than the conventional liver function enzymes like transaminases.

Evaluation of urinary enzymes in renal allograft damages by histology examination.

Acute allograft rejection (ARE) is one of the most current problem in kidney transplantation. Urinary enzymes (glutathione-S-transferase /GST/. dipeptidil-dipeptidase /DPP/) are frequently used as prognostic factors of ARE. The authors compared the results of light microscopic study (by Banff scheme), and the GST, and DPP secretion in acute rejection. The correlation between the laboratory, and histology findings wasn't significant. our results suggest that both GST, and DPP are very sensitive, but less specific indicators in ARE, since their activity increases in many other damages as well.

Diagnostic value of urinary enzyme determination in renal transplantation.

The measurement of enzyme activity in urine provides a sensitive assessment for renal tubular cell damage. The present study was undertaken to evaluate the clinical value of the determination of tubular brush-border-associated enzymes, alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), leucine aminopeptidase (LAP), and dipeptidyl peptidase IV (DPP), of patients with normal graft function (NOR, n = 20), with acute tubular necrosis (ATN, n = 11), with an acute rejection episode (ARE, n = 17) after transplantation, and of healthy persons (n = 20). The second urine of the morning was collected daily during the patients' stay in hospital. The enzyme activities were measured at 25 degrees C and were expressed as U/mmol creatinine. The enzymuria in NOR is higher than in healthy controls, but is still in the normal range. By 5 days after transplantation the initial increased excretion declines as the graft function improves. Elevated enzymuria (DPP 0.69 +/- 0.56, AP 3.06 +/- 3.24, GGT 4.16 +/- 4.13, and LAP 1.39 +/- 1.27) was observed during the rejection episodes. Two days before clinical diagnosis of rejection, the release of DPP-IV and GGT increases to double, and the AP and LAP increases to 3 times the value on the fourth day before rejection. Successful treatment of rejection coincided with a quick return by the third day of the rejection period to the previous enzyme distribution. In ATN no decrease of enzymuria occurs and the excretion is much higher than in ARE. Our method with the every day monitoring of kidney graft function offers the possibility for the early diagnosis of acute rejection.

[Infectious complications of 227 open fractures of the leg]. / 557 nyílt lábszártörés fertözéses szövödményei

Out of 557 open fractures of the leg we have analysed 472 cases in respect of recovery. We tried to discrive the relationship between the infection and the severity of the lesion and the methods of treatment resp. We have analysed also the further course of the infect.on. In our material considerable risk of the infections in the case of open leg fractures was found, since the incidence of all infections corresponded--in accordance with the data of the literature--to 16,7% of the appreciable cases. Significant relationship between the occurrence of infections and the severity of the lesion was found. In the material analysed according to the ACD code the incidence of infections is in the severely injured patients three times as much as in the case of slight or moderately severe groups. The occurrence of posttraumatic osteitis corresponds to 9,11%--this latter is similarly in relation with the severity of the lesion. The infection leads to the protraction of the osseous union,--however, no convincing data were found in the authors' material in respect of the relationship between the infection and the methods of treatment. The course and the proportion of healing of the infected cases correspond to the mean values reported in the literature. On the basis of their great material it is stated by the authors that only in the case of lesions with identical or at the least similar severity comparison of the results of recovery or of the complications is possible and suitable.