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Restricted accessEditorialFirst published January, 2007pp. 1-2
Restricted accessResearch articleFirst published January, 2007pp. 3-5
Restricted accessResearch articleFirst published January, 2007pp. 6-15Numerous investigations have reported that viral hepatitis is associated with significant hepatocellular damage, as expressed by raised aminotransferases in serum, in dialysis population. However, scarce information exists on the activity of gamma glutamyltranspeptidase (GGTP) in dialysis patients with infection by hepatotropic viruses.
We measured serum GGTP values in a large cohort (n=757) of patients receiving long-term dialysis; healthy controls were also included. The relationship between GGTP values and a series of demographic, clinical, and biochemical parameters was analyzed.
Serum GGTP levels were tested by spectrophotometry. A subset (n=333) of dialysis patients was tested by molecular technology (branched-chain DNA (bDNA) assay) to evaluate the relationship between serum GGTP and HCV viremia. A subgroup (n=78) of dialysis patients was analyzed by an ultrasound scan of gallbladder and biliary tract to assess the presence of gallstone disease. Multivariate analyses were made using regression models; serum GGTP values were included as a dependent variable. The usefulness of serum GGTP levels in detecting HBsAg and anti-HCV positivity was evaluated using receiver operating characteristics (ROC) curve analysis.
Univariate analysis showed that serum GGTP levels were significantly higher in HBsAg positive and/or anti-HCV positive patients than in HBsAg negative/anti-HCV negative patients on dialysis; 85.1±184.1 versus 25.86±23.9 IU/l (P=0.0001). The frequency of raised GGTP levels was 22.2% (41/184) among dialysis patients with chronic viral hepatitis. Multivariate analysis showed a significant and independent association between serum GGTP values and positive HBsAg (P=0.005) and anti-HCV antibody (P=0.0001) status. Mean GGTP values were significantly higher in study patients than controls, 32.32±60.02 versus 23.5±16.92 IU/L (P=0.01); however, no significant difference with regard to GGTP between study and healthy cohorts persisted after correction for age, gender, race, and viral markers. No relationship between gallstone disease and serum GGTP was found (NS). An independent and significant association (P=0.0291) between raised GGTP levels and detectable HCV RNA in serum was noted among patients tested by biology molecular techniques. ROC technology demonstrated that GGTP was equally useful for detecting HBV (P=0.0004) and HCV (P=0.0005) among dialysis patients.
We found an independent and significant association between serum GGTP values and HBsAg and/or anti-HCV antibody in dialysis population. Twenty-two percent of dialysis patients with chronic viral hepatitis had elevated GGTP. No difference in GGTP between HBsAg- negative/anti-HCV-negative dialysis patients and healthy individuals was found. Routine testing for serum GGTP levels to assess liver disease induced by hepatotropic viruses or other agents in dialysis population is suggested.
Restricted accessResearch articleFirst published January, 2007pp. 16-24Intradialytic morbid events (IMEs, mostly hypotension) are frequent complications during hemodialysis (HD). This study investigated whether automatic feedback control via adjustment of the ultrafiltration rate reduces IME frequency.
In this multi-center cross-over study, 56 hypotension-prone patients were treated both with standard HD (sHD, applying a constant ultrafiltration rate) and HD applying a blood volume controlled ultrafiltration rate (cHD). The relative blood volume (RBV) was continuously monitored. The individual relative blood volume limit (RBVcrit) was determined from the measured RBV during initial sHD. During cHD, the ultrafiltration rate was automatically adjusted to keep the actual RBV above RBVcrit.
In 3,081 HD treatments, slightly fewer IMEs were observed during cHD than during sHD (0.785±0.613 versus 0.695±0.547 per treatment, P=0.144). Less symptomatic events were seen during cHD: -13% for symptomatic hypotension (0.594 versus 0.685 per treatment, P=0.120), and -32% for cramps (0.049 versus 0.072 per treatment, P=0.009). Thirty-one patients with the highest IME rate (IME in at least every second treatment) especially benefited from cHD: 1.185±0.554 versus 0.979±0.543 IME per treatment (P=0.004).
The reduction in blood pressure (BP) and the increase in heart rate were lower during the treatments with cHD than with sHD: systolic BP: -18.8±26.7 versus -22.2±28.9 mmHg (P=0.007), diastolic BP: -7.8±14.8 versus -9.1±15.3 mmHg (P=0.064), heart rate: 1.8±10.4 versus 2.3±11.6 per minute (P=0.014). Neither treatment duration nor ultrafiltration volume was significantly different between cHD and sHD.
For cHD, less intradialytic morbid events were observed than for sHD, and pre- to post-dialytic changes in blood pressure and heart rate were less pronounced.
Restricted accessResearch articleFirst published January, 2007pp. 25-33The dialyzer apparatus has been widely used as an artificial kidney in medical treatment. However, side effects such as amyloidosis have occurred during long-term treatment. Therefore, we focused on developing a hybrid artificial kidney with a filtration and reabsorption apparatus, but it was found that cells spread extensively and it is difficult to maintain a uniform monolayer with a regular cell shape on a collagen-coated substrate. The purpose of this study was to improve cell adhesion, uniform stable monolayer formation and active transport function by immobilization of arginine-glycine-aspartic acid (RGD) on the culture substratum.
Polycarbonate semipermeable membranes were coated with collagen, fibronectin, laminin and synthetic polypeptide, including RGD (Pronectin F). Cell adhesion and digoxin transport were estimated using a renal proximal tubule cell line that overexpressed the P-glycoprotein gene.
Under initial and confluent conditions, immobilized cell density in Pronectin F-coated wells was higher than that under other conditions. Transepithelial electrical resistance and digoxin transport activity on Pronectin F-coated membranes were the highest of all conditions. This might have been caused by uniform cell morphology and high cell density.
Restricted accessResearch articleFirst published January, 2007pp. 34-43Continuous flow pump support has emerged as an alternative therapy in patients with congestive heart failure. For long-term applications, it is important to have a control system that changes the pump function according to the physiological conditions of the patient, thereby preventing risk situations. In the early stages of development, the evaluation of control algorithms for artificial blood pumps can be done in vitro using cardiovascular mock systems.
A systemic cardiovascular mock loop was constructed and an axial flow pump was connected to it. The level of pump assistance was estimated using a pulsatility index (IPAo) obtained from the aortic pressure wave. An IPAo proportional-integral control system was implemented and its responses to peripheral resistance and systemic compliance changes were evaluated.
IPAo is an indicator of the assistance level of a continuous flow pump operated at constant speed.
The IPAo control algorithm responds by increasing the pump speed when peripheral resistance or systemic compliance is reduced. Control system operation around an IPAo fixed value provides a safety point for pump operation by maintaining aortic pressure pulsatility and avoiding ventricular suction. In vitro experimental results show that the IPAo can be taken into consideration in multiobjective control algorithm designs.
Restricted accessResearch articleFirst published January, 2007pp. 44-52The present study was designed to determine the in vivo patency and recellularization pattern of acellularized small-diameter xenogenic arterial grafts. We implanted acellularized porcine carotid arteries in bilateral carotid arteries of goats and microscopically analyzed the recellularization pattern of these grafts with the recipient's cells over time.
Carotid arteries of pigs weighing 30–40 kg were harvested and decellularized with hypertonic saline followed by sodium dodecyl sulfate. Acellularized porcine carotid vascular xenografts (0.4–0.5 cm in diameter) were prepared into 4 cm-long segments and implanted bilaterally in the carotid arteries of 10 black-haired goats. The in vivo patency of the implanted acellularized xenogenic grafts was evaluated at regular intervals by color Doppler ultrasonography. The goats were sacrificed at predetermined intervals (1 week, 1 month, 3 months, 6 months, 12 months after implantation), two animals at each interval. Upon retrieval, visual inspections and histopathologic examinations of the grafts were performed. To identify smooth muscle cells and functioning endothelial cells, immunohistochemical staining for alpha-smooth muscle actin and von Willebrand factor were also performed.
All experimental animals survived the observation period. Nineteen out of 20 implanted grafts showed patency with no thrombi. Microscopic analysis revealed that the grafts were completely covered with the hosts' endothelial cells, beginning from anastomotic sites. The grafts were gradually recellularized with recipients'cells including fibroblasts, myofibroblasts and smooth muscle cells. In conclusion, this study suggested that acellularized xenogenic vascular grafts can be a good alternative for the small-diameter vascular graft.
Restricted accessResearch articleFirst published January, 2007pp. 53-63The diffusion of peritoneal dialysis (PD) at home is somewhat restricted by the difficulty of transport and storage of a large amount of dialytic solutions. This problem is exacerbated in the case of hemodialysis. With the aim of producing pure water to be used in preparing the solution for peritoneal dialysis, or for hemodialysis in general, as one example, we purified the spent dialysate solution from PD. Experiments were carried out with 24 dialysate solutions taken from 8 patients. Pure water was obtained by means of a thermodialysis process in a hollow fiber reactor operating under nonisothermal conditions. Results show that the yield of the nonisothermal process is dependent on the temperature difference applied across the hydrophobic membranes. The production of pure water per square meter of membrane and per hour was equal to 0.55 or 1.2 or 2.0 liters, with a temperature difference of 11°C or 21°C or 28°C, respectively. These results encourage the use of the thermodialysis process in the production of pure water for clinical uses
Restricted accessResearch articleFirst published January, 2007pp. 64-75A 24 mm long bioartificial nerve graft (BNG) was created to bridge extended peripheral nerve defects of the rat sciatic nerve. In our previous studies, an identical graft had demonstrated good results over nerve gaps of up to 15 mm. The BNG device comprised a collagen-I tube filled with ten Schwann-cell-seeded polyglactin filaments and 106 isogenic Schwann cells suspended in Matrigel which were implanted in 27 rats (group I). Schwann-cell-free grafts (27 rats) and nerve autografts (18 rats) served as controls. Functional recovery was followed over a period of six months using walking track analysis. Terminal analyses of graft efficacy included neurophysiology, muscle weight, and histological assessment of the implants and the distal nerve stumps. In 17/27 cases, axonal regeneration into the distal nerve stump could be detected across the BNG, but all animals in group I and II failed to regain motor function of the hindlimb upon completion of the experiment. Axon diameter and axonal density in the graft and distal nerve stump were greater in group I than in group II. Although Schwann cells had a significant positive effect on axonal regeneration, either granuloma formation or the amount of the inserted foreign material may have impaired nerve regeneration by acting as a physical impediment to nerve regeneration or negatively effecting cell function.
Restricted accessResearch articleFirst published January, 2007pp. 75-85Multiple attempts have been made to replace biliary defects with a variety of materials. Recently, successful biliary reconstruction using the Gore-Tex vascular graft has been reported experimentally and clinically We designed a new artificial bile duct consisting of collagen sponge and polypropylene mesh. We presently evaluated the feasibility of using this prosthesis as a scaffold for bile duct tissue regeneration in a canine model. Our prosthesis, a sponge made from porcine dermal collagen, is reinforced with a polypropylene mesh cylinder. We used the prosthesis to reconstruct the middle portion of the common bile duct in seven beagle dogs to evaluate its efficacy. While one dog died of biliary stricture 8 months after operation, six survived without problems to scheduled time points for tissue evaluation at 1 to 12 months. All prostheses had become completely incorporated into the host. A confluent epithelial lining was observed within 3 months. In cholangiograms the prosthesis displayed long-term patency in the six dogs and provided satisfactory bile drainage for up to 12 months. Our graft thus shows promise for repair of biliary defects and should lead to development of a new treatment for biliary reconstruction.
Restricted accessAnnouncementFirst published January, 2007pp. 86-86