Robotic assisted living donor nephrectomy - the first in the Czech Republic.

INTRODUCTION: A kidney transplant is the best method for treating terminal kidney failure. Long-term results of kidney transplants from living donors are significantly better than transplants from dead donors. Living kidney donors are healthy people who undergo a major operation in order to improve the health of another person. Therefore, major emphasis is on safety, low level of invasiveness and a desirable cosmetic effect of the donor nephrectomy. Since 2012, the Department of Urology at the University Hospital in Olomouc has performed 12 kidney harvestings from living donors. The kidney harvesting was conducted using various techniques. CASE REPORT: The first robotic assisted kidney harvesting in the Czech Republic was performed in June 2022. The donor was a 57-year-old man who donated his kidney to his 32-year-old daughter. The left kidney was evaluated as suitable for kidney harvesting. The operation took 174 min. The kidney's warm ischemia was 145 s. Based on the Clavien Dindo classification, no 2nd degree or high post-operative complications were recorded. The donor's pre-operative glomerular filtration was 1.63 mL/s. Six months post-operation, it went down to 1.19 mL/s. This represents a 27% decrease. The kidney recipient did not require early dialysis. Six months post-operation, the recipient's glomerular filtration was 2.03 mL/s. CONCLUSION: In the hands of experienced professionals and transplantation centres, robotic assisted donor nephrectomy is a feasible and safe option for this operation. It not only provides all the advantages of a laparoscopic operation but it also adds other technical improvements and minimizes intraoperative stress on the surgeon. Currently, the global trend is moving towards increasing the ratio of robotic assisted donor nephrectomies.

Brachial artery aneurysm as a late complication of arteriovenous fistula.

INTRODUCTION: Brachial artery aneurysm (BAA) is a rare late complication of arteriovenous fistula (AVF). It brings the risk of peripheral embolism and hand ischemia and is defined by brachial artery diameter above 10 mm or by regional dilatation by >50%. BAA is described in the literature in closed radiocephalic arteriovenous fistulas after kidney transplantation. The aim of the study was to analyze the prevalence of BAA and of their more dangerous forms. METHOD: A observational one center study performed on patients after kidney transplantation with AVF or arteriovenous graft (AVG). We invited all patients followed up for kidney transplantation in our center. Arterial diameter greater than 10 mm was considered as a brachial artery aneurysm to simplify the detection and evaluation of aneurysms. RESULTS: About 162 patients with AVF after kidney transplantation were examined between 4/2018 and 4/2020. Brachial artery aneurysm was detected in 34 patients (21%) with AVF or AVG, of them 7 had confirmed wall thrombi. AVF flow volume of more than 1500 ml/min increased the risk of BAA development by 4.54x. Eight aneurysms were treated surgically. After this surgery, the primary patency was 87.5% in 12 months. CONCLUSION: Brachial artery aneurysm was relatively frequent in our study compare to the literature. Aneurysm or dilatation of the brachial artery is more frequent in functional AVFs. Surgical correction is necessary in cases of complicated aneurysms to prevent distal embolization.

Creation of arteriovenous fistula for hemodialysis in the older population.

OBJECTIVE: To evaluate the results of arteriovenous fistula (AVF) created for haemodialysis in patients older than 65 years of age. SUBJECTS AND METHODS: A retrospective analysis of patients with AVF or arteriovenous graft (AVG) creation, who were older than 65 years of age and were operated on at the II. Surgical Clinic at the University Hospital in Olomouc from 2014 - 2018 was performed. RESULTS: 212 patients were evaluated and a total of 239 AVF/AVG were created. 194 AVFs (81.18%) and 45 AVGs (18.82%) were created. Primary failure was seen in 19 arteriovenous fistulas (9.8%) and 2 arteriovenous grafts (4.44%). The primary patency of AVF was 69.9%, 62.8% after 12 and 24 months, respectively, and in the case of AVG it was 54.7% and 32.3% after 12 and 24 months, respectively. Primarily assisted patency of AVF was 77.6% and 66.3% after 12 and 24 months, respectively, and in case of AVG it was 69.1% and 39.7% after 12 and 24 months, respectively. Secondary patency of AVF was 77.6% and 66.3% after 12 and 24 months, respectively, and for AVG it was 69.1% and 39.7% after 12 and 24 months, respectively. CONCLUSION: The type of vascular access should be selected based on a thorough, protocol-based examination. In most seniors, AVF is the method of choice. The AVG is a suitable choice for patients with an exhausted venous bed, in acute need of haemodialysis, in the elderly and in females. A "customized" approach should be matter of fact for older generations.

Arteriovenous Grafts' Types of Indications and Their Infection Rate.

BACKGROUND: Arteriovenous graft infection is a well-known and frequent complication. The objective of this study was to compare infection rates of primary and secondary indicated arteriovenous grafts (AVGs). SUBJECTS AND METHODS: Retrospectively, we evaluated the indications for AVGs created at our institution which became infected. One hundred forty AVGs were evaluated. Of these AVGs, 33 (23.6%) were primary and 107 (76.4%) secondary indicated. RESULTS: Infection of a primary AVG was detected in 5 patients (15.2 %). Infection of a secondary AVG was detected in 30 patients (28.0%). Primary and secondary patency were significantly lower in patients with infected AVG (P = 0.006; P = 0.0001). The effect of diabetes mellitus and age on development of infection was not confirmed. CONCLUSIONS: Indications for AVG creation clearly influence the future risk of infection. If the indication to use the AVG is to correct a complicated arteriovenous fistula, the risk of infection is 2 times higher.

The effect of graphene oxide on signalling of xenobiotic receptors involved in biotransformation.

Graphene oxide (GO) is an engineered nanomaterial which was demonstrated to have outstanding capacity for adsorption of organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), the ligands and activators of the aryl hydrocarbon receptor (AhR). Due to the partially overlapping ligand capacity of AhR and pregnane X receptor (PXR), we tested the impact of GO particles on their signalling. While reporter gene assay revealed potentiating effect of GO on ligand-activated AhR-dependent luciferase activity, there was no effect for PXR. However, inducible target genes for AhR (CYP1A1) or PXR (ABCB1) were decreased at mRNA as well as protein levels by the presence of GO in HepG2 (for AhR), LS180 (for PXR) or primary human hepatocytes (both receptors). Moreover, the presence of GO diminished PXR and AhR protein levels in primary cultures of human hepatocytes. This was partially reversed by proteasome inhibitor MG132 for AhR but not for PXR. In conclusion, GO decreases ligand-stimulated activities of AhR and PXR in human cells.

18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT effectively contribute to early diagnosis of infection of arteriovenous graft for hemodialysis.

OBJECTIVE: An arteriovenous graft (AVG) is indicated in hemodialysis patients with failed arteriovenous access. Early treatment of AVG infection is important because an advanced prosthetic infection leads to the removal of the prosthesis. The aim of this study was to evaluate the benefits of 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT in early detection of AVG infections. SUBJECTS AND METHODS: Fifty-one AVGs were evaluated. 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT studies were performed at intervals of 10, 20-30, and 40-50 weeks after AVG insertion. Agreement between the imaging methods and reference parameters (i.e. clinical presentation, C-reactive protein and microbiological findings on the hemodialysis cannula extracted after hemodialysis from AVG) was evaluated. RESULTS: The study results showed that focal accumulation of the radiopharmaceuticals can be considered a sign of AVG infection. At 10 weeks after AVG implantation, the focal 18F-FDG findings showed the best agreement with the reference parameters (agreement coefficients AC1 - clinical status: 0.693, CRP: 0.605, cannula microbiology: 0.518, respectively). At 20 to 30 weeks after AVG implantation, the diagnostic value of focal 99mTc-HMPAO-WBC accumulation increased (AC1 coefficients: 0.658, 0.658, 0.408) and was similar to that of focal 18F-FDG uptake (AC1s: 0.656, 0.570, 0.409). Between 40 and 50 weeks since AVG implantation, the diagnostic significance of focal 99mTc-HMPAO-WBC accumulation (AC1 coefficients: 0.771, 0.811, 0.611) slightly exceeded the diagnostic value of focal 18F-FDG accumulation (AC1 coefficients: 0.524, 0.456, 0.569). CONCLUSION: 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT can both serve as important tools contributing to early diagnosis of AVG infection.

Surgical revision vs. stent-graft to treat venous anastomosis stenosis following surgical thrombectomy of hemodialysis grafts.

BACKGROUND: There is no unanimous strategy for treating stenosis of the venous anastomosis (VA) of an occluded arteriovenous graft (AVG) following surgical thrombectomy. In this study, we compared classical surgical treatment and endovascular treatment procedures with the use of stent- graft in a single center study. The aim was to evaluate whether, the VA stenosis of thrombosed AVG treated endovascularly by stent-graft implantation, have as good results as surgical VA treatment, so that it may be considered the method of choice. METHODS: The study included patients who underwent surgical AVG thrombectomy with subsequent angiographically confirmed VA stenosis between 1/2009 and 12/2014. Surgical angioplasty was then performed in 15 patients and 17 patients underwent primary stent-graft implantation. RESULTS: In the surgically treated patients, the postintervention primary patency, primary assisted patency and secondary patency after 12 months were 50.7%, 56.3%, 62.4%, respectively. In the group of patients with occluded AVG who underwent stent-graft implantation, the postintervention primary patency, primary assisted patency and secondary patency after 12 months were 32.8%, 44.1% a 55.6%, respectively. No statistically significant difference in primary patency (P=0.391), primary assisted patency (P=0.605), and secondary patency (P=0.702) was observed between the groups. CONCLUSIONS: Stent-graft implantation into stenotic VA of an occluded AVG showed to be effective and maintained good long-term patency. It is the preferred method due to its minimal invasiveness. The superiority of this method must be confirmed on a larger set of patients.

Itraconazole cis-diastereoisomers activate aryl hydrocarbon receptor AhR and pregnane X receptor PXR and induce CYP1A1 in human cell lines and human hepatocytes.

Triazole antimycotic itraconazole contains in its structure three chiral centres; therefore, it forms eight stereoisomers. Commercial preparations of itraconazole are a mixture of four cis-diastereoisomers. There is much evidence that efficacy, adverse effects, and toxicity of chiral drugs may be stereospecific. Therefore, we have prepared 4 pure cis-diastereoisomers of itraconazole and investigated their effects on transcriptional activities of xenoreceptors aryl hydrocarbon receptor AhR and pregnane X receptor PXR. Gene reporter assays showed that itraconazole dose-dependently activated both AhR and PXR, and the activation of AhR but not of PXR was enantiospecific. Itraconazole diastereoisomers transformed AhR and PXR into their DNA-binding forms, as demonstrated by electromobility shift assays. Cytochrome P450 CYP1A1 mRNA and protein were induced by itraconazole diastereoisomers in human hepatoma cells HepG2, human skin cells HaCaT, and in primary human hepatocytes. The expression of CYP3A4 in human intestinal LS180 cells was not influenced by itraconazole, but we observed downregulation of CYP3A4 in human hepatocytes. Collectively, we show that itraconazole is a dual activator of AhR and PXR, with differential effects on the target genes for xenoreceptors. The enantiospecific pattern was observed only in gene reporter assays for AhR. The data presented here might be of toxicological and clinical importance.

Hydroxystilbenes and methoxystilbenes activate human aryl hydrocarbon receptor and induce CYP1A genes in human hepatoma cells and human hepatocytes.

Natural polyphenol resveratrol (trihydroxystilbene) is a partial agonist of human aryl hydrocarbon receptor AhR, thereby, displaying a plethora of biological effects. Biological activities of metoxylated and hydroxylated stilbenes were studied in the past. The aim of the current study was to describe the effects of 13 different hydroxy- and methoxystilbenes, including their cis/trans isomers on the transcriptional activity of AhR and the expression of CYP1A genes in hepatic cancer cells HepG2 and in primary human hepatocytes. Techniques of gene reporter assays, qRT-PCR, Simple Western blotting by Sally Sue™ and electrophoretic mobility shift assay EMSA were employed. All compounds activated AhR, but their efficacies, potencies and dose-response profiles differed substantially. The strongest activators of AhR and inducers of CYP1A1 in HepG2 cells were DMU-212 ((E)-3,4,5,4´-tetramethoxystilbene), trans-piceatannol, cis-piceatannol, trans-trismethoxyresveratrol and trans-pinostilbene. While DMU-212 and trans-trismethoxyresveratrol also induced CYP1A1 and CYP1A2 in primary human hepatocytes, the effects of trans-piceatannol, cis-piceatannol and trans-pinostilbene weaned off. On the other hand, trans-4-methoxystilbene was strong CYP1A inducer in hepatocytes but not in HepG2 cells. Differences between effects of stilbenes in HepG2 cells and human hepatocytes are probably due to the extensive phase I and phase II xenobiotic metabolism in human hepatocytes. The data obtained may be of toxicological relevance.

New hybrid procedures in treating occluded arteriovenous hemodialysis grafts.

BACKROUND: The use of arteriovenous graft is indicated in patients if the subcutaneous venous bed is exhausted or unsuitable for arteriovenous fistula creation. The leading cause of failure of a prosthetic arteriovenous hemodialysis-access graft is venous anastomotic stenosis causing thrombosis of the graft. A number of surgical techniques and endovascular tools have been used to treat this stenosis and thrombosis. None have yet proven to be ideal. This study was designed to evaluate the results of hybrid treatment of arteriovenous graft thrombosis associated with venous anastomotic stenosis. METHODS: Over the period 2013-2014, we treated 16 AVG occlusions. Immediately after the diagnosis of occlusion was made, the patients underwent thrombectomy using a Fogarty catheter. After thrombectomy, a diagnostic fistulogram was performed and if VAG stenosis was confirmed, it was treated with balloon angioplasty and stent graft introduction. Lesions were dilated to reduce the stenosis in the treated area to less than 25%. RESULTS: Primary patency after 12 months was 32.8%. Primary assisted patency was 44.7%, secondary patency was 47.6%. Restenosis of the stent graft was seen in two patients. Recurring AVG occlusion was observed in four patients. The average number of interventions to maintain AVG patency was 1.18 per patient/1 year of dialysis. CONCLUSION: Treatment of AVG thrombosis due to VAG stenosis by hybrid procedure proved to be effective and improved secondary patency.

The effects of drugs with immunosuppressive or immunomodulatory activities on xenobiotics-metabolizing enzymes expression in primary human hepatocytes.

In this paper we investigated the effects of several drugs used in transplant medicine, i.e. cyclosporine A, tacrolimus, rapamycin, everolimus, mycophenolate mofetil, fluvastatin and rosuvastatin, on the expression of major drug-metabolizing enzymes in human hepatocytes. Moreover, we tested the ability of these drugs to affect transcriptional activity of glucocorticoid (GR) and aryl hydrocarbon receptor (AhR). We found that most of tested compounds did not induce expression of CYP1A1/1A2/3A4/2A6/2B6/2C9 mRNAs in human hepatocytes. Slight induction was observed for CYP2A6/2C9 mRNAs and CYP2A6 protein in the rapamycin-treated hepatocytes. Decrease of CYP2A6 and CYP2B6 proteins was observed in rosuvastatin-treated cells. Mycophenolate mofetil antagonized the effects of dexamethasone on GR but it potentiated the action of dioxin on AhR. Induction of CYP1A1 mRNA in HepG2 cells by dioxin was modestly antagonized by mycophenolate mofetil, while the induction by benzo[a]pyren or S-omeprazole was significantly potentiated by this drug. In general, tested compounds can be considered safe in the terms of possible drug-drug interaction caused by induction of drug-metabolizing cytochromes P450. Nevertheless, mycophenolate mofetil is of possible concern and its combination with drugs, environmental pollutants or food constituents, which activate AhR, may represent a significant toxicological risk.

Interaction of rocuronium with human liver cytochromes P450.

Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver microsomal CYP3A4 down to 42% (at rocuronium concentration 189 µM) was found. This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6ß-hydroxytestosterone) and diazepam (temazepam formation). CYP2C9 and CYP2C19 activities were inhibited down to 75-80% (at the same rocuronium concentration). Activities of other microsomal CYPs have not been inhibited by rocuronium. To prove the possibility of rocuronium interaction with other drugs (diazepam), the effect of rocuronium on formation of main diazepam metabolites, temazepam (by CYP3A4) and desmethyldiazepam, (also known as nordiazepam; formed by CYP2C19) in primary culture of human hepatocytes has been examined. Rocuronium has caused inhibition of both reactions by 20 and 15%, respectively. The results open a possibility that interactions of rocuronium with drugs metabolized by CYP3A4 (and possibly also CYP2C19) may be observed.

Arteriovenous graft for hemodialysis, graft venous anastomosis closure - current state of knowledge. Minireview.

UNLABELLED: Backround. The use of artificial vascular grafts (arteriovenous graft, AVG) is indicated in patients in hemodialysis programs if the subcutaneous venous bed is exhausted or unsuitable for arteriovenous fistula (AVF) creation. The native fistula should be the hemodialysis access of first choice: AVF has better results in terms of function and potential complications. However, the use of AVG is necessary in some patients. In these patients, extensive clinical examination, color duplex sonography and angiography should be performed prior to indication. The technique of graft implantation requires respect for geometric relations for the graft anastomoses to minimize the formation of intimal hyperplasia mainly on the venous anastomosis. The main complications of AVG are stenosis on the venous anastomosis (VAG), causing closure of graft and graft infection. The cumulative function of AVG is 59-90% in the first year and 50-82% in the second year. Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. The purpose of this review is to summarise current knowledge of the diagnostics and treatment of graft thrombosis and discuss the issue in combination with relevant publications via Pubmed database. CONCLUSION: The most frequent cause of failure of AVG for hemodialysis is stenosis and closure by VAG. AVG closure can be addressed surgically, endovascularly (amenable to thrombectomy by radiological or surgical means) and by hybrid performance.

Current treatment methods for long occlusions of the femoropopliteal segment in patients with intermittent claudication: Minireview.

UNLABELLED: Backround. Intermittent claudication is a classic symptom of peripheral arterial disease. It is mainly treated conservatively but if this fails, a form of revascularization is indicated. The revascularization in chronic occlusion of femoropopliteal region is currently performed by two basic methods: the standard method of surgical bypass and the newer miniinvasive alternative represented by the endovascular method. The treatment of patients with solely claudication and long occlusion of femoropopliteal region remains controversial. The aim of this minireview was to determine whether surgical bypass is still the best method of choice in a time of endovascular techniques. METHODS: A MEDLINE search for original and review articles using key terms, intermittent claudication and long femoropopliteal oclusion. RESULTS AND CONCLUSION: No ideal treatment for long occlusions of the femoropopliteal segment has been established to date. It is clear that the role of endovascular techniques in the treatment of SFA occlusions is increasing. It remains that, lower risk patients with claudication should be examined to assess the quality of veins suitable for revascularization and bypass should be selected as the first method of choice.

Dual effects of ketoconazole cis-enantiomers on CYP3A4 in human hepatocytes and HepG2 Cells.

Antifungal drug ketoconazole causes severe drug-drug interactions by influencing gene expression and catalytic activity of major drug-metabolizing enzyme cytochrome P450 CYP3A4. Ketoconazole is administered in the form of racemic mixture of two cis-enantiomers, i.e. (+)-ketoconazole and (-)-ketoconazole. Many enantiopure drugs were introduced to human pharmacotherapy in last two decades. In the current paper, we have examined the effects of ketoconazole cis-enantiomers on the expression of CYP3A4 in human hepatocytes and HepG2 cells and on catalytic activity of CYP3A4 in human liver microsomes. We show that both ketoconazole enantiomers induce CYP3A4 mRNA and protein in human hepatocytes and HepG2 cells. Gene reporter assays revealed partial agonist activity of ketoconazole enantiomers towards pregnane X receptor PXR. Catalytic activity of CYP3A4/5 towards two prototypic substrates of CYP3A enzymes, testosterone and midazolam, was determined in presence of both (+)-ketoconazole and (-)-ketoconazole in human liver microsomes. Overall, both ketoconazole cis-enantiomers induced CYP3A4 in human cells and inhibited CYP3A4 in human liver microsomes. While interaction of ketoconazole with PXR and induction of CYP3A4 did not display enantiospecific pattern, inhibition of CYP3A4 catalytic activity by ketoconazole differed for ketoconazole cis-enantiomers ((+)-ketoconazole IC50 1.69 µM, Ki 0.92 µM for testosterone, IC50 1.46 µM, Ki 2.52 µM for midazolam; (-)-ketoconazole IC50 0.90 µM, Ki 0.17 µM for testosterone, IC50 1.04 µM, Ki 1.51 µM for midazolam).

Effects of anthocyanidins and anthocyanins on the expression and catalytic activities of CYP2A6, CYP2B6, CYP2C9, and CYP3A4 in primary human hepatocytes and human liver microsomes.

Anthocyanidins and anthocyanins are pharmacologically active constituents of various berry fruits, such as blueberry and cranberry. These compounds are also contained in massively used nutritional supplements based on extracts or dry matter from berry fruits. The current study evaluated the effects of anthocyanidins and anthocyanins on the expression and catalytic activity of major drug-metabolizing enzymes CYP2C9, CYP2A6, CYP2B6, and CYP3A4 in primary cultures of human hepatocytes and human liver microsomes. Expression of mRNA was quantified by qRT-PCR. Expression of proteins was evaluated by Western blotting and immunochemiluminescence. The catalytic activity of CYP enzymes was measured by HPLC using specific enzyme substrates. Tested anthocyanidins (6) and anthocyanins (21) did not induce the expression of mRNA and protein of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 genes in human hepatocytes. Catalytic activities of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 enzymes were inhibited by all anthocyanidins to different extents (e.g., delphinidin inhibits CYP3A4 by >90% at 100 µM with IC50 = 32 µM). Of 21 anthocyanins tested, only cyanidin-3-O-rhamnoside (CYP3A4 by >75% at 100 µM with IC50 = 44 µM) and two glycosides of delphinidin significantly inhibited examined cytochromes P450. It may be concluded that in the ranges of common ingestion of either food or dietary supplement an induction or significant inhibition of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 activity is most probably not expected.

Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression in primary human hepatocytes and human cancer cells.

Food constituents may cause a phenomenon of food-drug interactions. In the current study, we examined the effects of artificial sweeteners (aspartame, acesulfame, cyclamate, saccharin) on the aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)-dependent expression of CYP1A1 in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cell lines. Sweeteners were tested in concentrations up to those occurring in non-alcoholic beverages. Basal and ligand-inducible AhR- and GR-dependent reporter gene activation in stably transfected HepG2 and HeLa cells, respectively, were not affected by either of the sweeteners tested after 24h of incubation. The expression of CYP1A1 mRNA and protein in primary cultures of human hepatocytes and in LS174T and HepG2 cells was not induced by any of the tested sweeteners. Overall, aspartame, acesulfame, saccharin and cyclamate had no effects on CYP1A1 expression and transcriptional activities of AhR and GR. These data imply the safety of artificial sweeteners in terms of interference with AhR, GR and CYP1A1.

Effects of oral anorexiant sibutramine on the expression of cytochromes P450s in human hepatocytes and cancer cell lines.

Sibutramine is a serotonin-norepinephrine reuptake inhibitor that was used for weight-loss management in obese patients. Even though it was officially withdrawn from the market in 2010, it is still present in some tainted weight-loss pills (as reported by US Food and Drug Administration). Thus, it is still reasonable to study the effects of this compound. The aim of this work was to investigate the potential of sibutramine to induce CYP1A1/CY3A4 in human cancer cell lines and CYP1A1/2, CYP2A6, CYP2B6, and CYP3A4 in human hepatocytes, a competent model of metabolically active cells. The levels of mRNA and protein of CYP1A1/1A2/3A4/2A6/2B6 were compared with the typical inducers, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and rifampicin (RIF) for CYP1A1/2 and for other CYPs, respectively. The mRNA and protein levels of all genes in either cancer cell lines or human hepatocytes were induced when treated with typical inducers but not with sibutramine.

Infected prosthetic dialysis arteriovenous grafts: a single dialysis center study.

BACKGROUND: The prosthetic arteriovenous grafts (AVG) being used increasingly to create hemodialysis access are prone to infections that pose potentially life-threatening infectious and bleeding complications, as well as loss of dialysis access. In this study, we identified the bacteriologic agents of infected AVGs by site swab, blood culture, and prosthesis cultures, and to evaluate the role of microbiological findings in the management of the infection. METHODS: We focused on 51 patients with 53 AVGs operated on in our clinic from January 2006 to December 2009. An infected AVG was identified by clinical, ultrasound, and microbiological findings. Sensitivity to antibiotics was determined for all bacterial strains. Isolates were identified by pulsed-field gel electrophoresis (PFGE) of bacterial DNA. In a few cases, positron emission tomography-computed tomography (PET-CT) examination was performed. RESULTS: Strains of Staphylococcus spp., especially S. aureus, were the most frequent cause of infected AVG. All S. aureus strains were sensitive to methicillin. With the exception of a single case, isolates obtained simultaneously from the skin site and the vascular prosthesis were identical genetically. CONCLUSIONS: Our results suggest that bacterial infectious agents detected in site swab, blood, or graft culture confirm a suspicion of AVG infection. A PET-CT examination can provide confirmation. The combination of microbiologic and radionuclide findings can improve the management of the AVG infection, but surgery remains essential.