Improved outcome for haemodialysis patients treated with high-flux membranes. (49/3384)

Improved survival for haemodialysis patients has been reported for synthetic, high-flux biocompatible membranes. The reported data fail to answer the question whether improved survival is related to an effect of enhanced biocompatibility or to increased clearance of larger molecular species of putative uraemic toxins. A retrospective analysis of 715 patients treated by continuous haemodialysis for up to 5 years was undertaken. Low-flux polysulfone dialysis was used exclusively for 252 patients and 463 patients were exposed for at least 3 months to high-flux polysulfone dialysis. Patients treated with high-flux dialysis had a lower mortality (21 vs 36 per 1000 years) and significantly lower standardized mortality ratio. For non-diabetic patients the 5-year probability of survival was significantly greater for high-flux patients (Kaplan-Meier: 92% vs 69%; P=0.036). High-flux dialysis significantly reduced the adverse effect of age on survival. In a Cox proportional hazard model membrane flux (high vs low) was one of the covariates with strong predictor value for reduction of death risk in non-diabetic patients. Although other variables may explain the better survival of patients exposed to high-flux dialysis the data reported here suggest that higher membrane flux, implying higher clearance of larger molecular species and independent of biocompatibility, is associated with improved survival for haemodialysis patients.  (+info)

On-line haemodiafiltration versus low-flux haemodialysis. A prospective randomized study. (50/3384)

BACKGROUND: Current methods of renal replacement therapy lead only to an insignificant removal of larger, potentially toxic, substances, which are excreted by healthy kidneys. On-line preparation of substituate from dialysate and the use of high-flux membranes allow substantial convective removal of such substances. A modified on-line haemodiafiltration method with the use of a large membrane surface and a high convective part was chosen to test whether the elimination of larger substances, such as low-molecular-mass proteins, has a clinical impact. METHODS: In a prospective, controlled study over 24 months, 44 unselected chronic dialysis patients were randomized to undergo either low-flux haemodialysis (HD; n = 21) or haemodiafiltration (HDF; n = 23). To eliminate confounding factors, low-molecular efficacy was matched (Kt/V 1.8), and the same membrane material (polysulfone), ultrapure dialysate and the same treatment duration (4.5 h) were applied to each group. RESULTS: Morbidity, mortality, blood pressure, dialysis-associated hypotensive episodes, haematocrit and erythropoietin dose did not differ between the groups. The same was true for body weight and, accordingly, bioimpedance values, clinical hydration score, skinfold thickness, plasma albumin, prealbumin and transferrin. beta2-Microglobulin in the plasma did not change in the HD group and varied between 32 and 43 mg/l throughout the 2 years. In HDF, beta2 microglobulin decreased from similar values to 18 mg/l predialysis (P<0.01) in the first 6 months of HDF treatment and then remained constant during the remaining 18 months. CONCLUSION: In the absence of any clinical marker of uraemic toxicity the removal of larger molecules over the time-span of 2 years during HDF had no clinical implication compared with extremely (and for routine practice unrealistically) well-dialysed patients with low-flux HD. In the absence of any side-effects of on-line HDF and supposing that plasma beta2-microglobulin is a marker of morbidity, on-line HDF ensures an excellent dialysis quality which apparently takes time to translate into measurable clinical sequelae.  (+info)

On-line haemodiafiltration. Remarkable removal of beta2-microglobulin. Long-term clinical observations. (51/3384)

BACKGROUND: The accumulation of beta2-microglobulin (beta2-M) in long-term dialysis patients may lead to dialysis amyloidosis. In this respect, the removal with different modes of on-line haemodiafiltration (HDF) of beta2-M was studied. Long-term clinical observations in patients with more than 10 years of dialysis, treated mainly with biocompatible and highly permeable membranes and in the last years with on-line HDF are also reported. METHODS: In the first part of this report, the reduction ratios and clearances of beta2-M, blood urea nitrogen, creatinine and phosphorus (P) of on-line HDF with 40 to 120 ml/min replacement fluid are compared with bicarbonate haemodialysis (HD). In the second part, we investigated 16 patients with more than 10 years of dialysis treatment. The prevalence of dialysis amyloidosis and the mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol and parathyroid hormone are reported, as well as the mean dose of erythropoietin. RESULTS: In the first part with on-line HDF, starting from HDF 60 ml/min a significantly higher beta2-M reduction ratio and clearance vs HD is noted. In HDF100 (i.e. with 241 replacement volume per 4-h treatment) vs HD, a beta2-M reduction ratio of 72.7% vs 49.7% (P= 0.0000) and a beta2-M clearance of 116.8 vs 63.8 ml/min (P=0.0000) was obtained. Comparing HDF120 with HDF100, there is a significantly higher beta2-M clearance with the former (P<0.005), although the beta2-M reduction ratio was not significantly better. In the HDF120 session the amount of beta2-M in the total dialysate was 292 mg per session. If one adds the known 17% adsorption on the polysulfone membrane, a total of 341.6 mg beta2-M per session is removed, which adds up to 1024.8 mg a week. Concerning the small molecules, our results with HDF100 also show a higher creatinine and especially P clearance vs HD. In the second part with 16 patients with more than 10 years of dialysis treatment (mean 14 years 1 month), the mean time on HDF amounted to 39.5% of the total treatment time. In four patients only biocompatible and highly permeable membranes were used, AN69 and mainly polysulfone, and in four other patients these membranes were used for more than 95% of the treatment time. Therefore, it is not surprising that the prevalence of carpal tunnel syndrome was only 12.5% in the patients after 10 years of dialysis. Twenty-five percent of these patients met the criteria for diagnosis of beta2-M bone-amyloidosis, proposed by van Ypersele de Strihou et al., but without a retrospective X-ray analysis. The mean predialysis beta2-M value was 29.6 mg/l. The mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol were within normal limits. For the parathyroid hormone a mean of 287.5 pg/ml was found. Subtotal parathyroidectomy was performed in five patients. The mean dose of 43 U erythropoietin/kg per session is comparable with those reported in the literature. Conclusions. Like Canaud, in our renal unit, treatment with on-line HDF with a highly permeable and biocompatible membrane has proven to be an efficient, well-tolerated and safe technique. Furthermore it leads to a low prevalence of dialysis amyloidosis and a superior P clearance. However, continuous attention must be paid to an on-line sterile and apyrogenic dialysate. Although on-line HDF is undoubtedly a more optimal approach of chronic dialytic treatment, it also carries a higher cost, which is currently evaluated to be nearly US$11 per session.  (+info)

Long-term survival of retinal cell cultures on retinal implant materials. (52/3384)

The aim of the present study was to evaluate cell adhesion and cell survival of mammalian retinal neurons on different materials used for the production of multi-photodiode arrays (MPDAs) intended for implantation in the subretinal space of patients suffering from progressive photoreceptor cell loss. The survival rates of different types of retinal neurons and glia cells were monitored by conventional histochemical techniques and immunocytochemistry up to 4 weeks. Whereas most of the materials tested showed good biocompatibility, cell survival of retinal glia and neurons was markedly reduced on titanium nitride (TiN), especially for culturing periods longer than 2 weeks. The effect was not mediated by diffusible factors released from TiN material. In conclusion, most of the materials tested in this study are suitable for the production of functional MPDAs and no complications are to be expected from long-term implantations of them in the subretinal space.  (+info)

A new model of chronic cardiac ischemia in rabbits. (53/3384)

Chronic cardiac ischemia has mainly been studied in large species such as pigs or dogs. Little research has been performed using small species such as rabbits. In the present study, 1-3 wk after implantation of a novel device (ameroid) on the circumflex coronary artery of New Zealand White rabbits, vessel patency was evaluated by coronary angiography, corrosion cast, and radiolabeled microspheres. Coronary angiograms showed, after 21 days, either total occlusion or severe stenosis in seven of eight arteries, which was confirmed by corrosion casts. The ameroid group had less blood flow in the epicardial (-62%) and endocardial (-54%) layers of the ischemic area compared with sham-operated rabbits (P < 0.05). Blood flow increased in the ischemic area compared with day 0 during acute occlusion, suggesting that progressive coronary occlusion initiated the growth of de novo collateral vessels. Thus we have developed a new model of chronic cardiac ischemia in rabbits with documented progressive coronary stenosis and occlusion that is suitable to test various therapeutic angiogenesis strategies.  (+info)

Inhibition of angiogenesis and vascular tumor growth by interferon-producing cells: A gene therapy approach. (54/3384)

We developed an in vivo gene therapy approach to characterize and optimize the anti-angiogenic activity of class I interferons (IFNs), using packaging cell lines producing an amphotropic LXSN-based retrovirus expressing either IFN-alpha1 (alpha1Am12), IFN-beta (betaAm12) murine cDNAs, or the vector alone (neoAm12). Pretreatment of endothelial-like Eahy926 cells in vitro with conditioned media (CM) from alpha1Am12 or betaAm12 cells for 48 hours significantly inhibited their migration and invasion as compared to neoAm12-CM-treated cells. betaAm12-CM also inhibited the formation of capillary-like structures on Matrigel by EAhy926 cells. In vivo, inclusion of the betaAm12 cells strongly inhibited, and alpha1Am12 partially inhibited, the angiogenic response in the Matrigel sponge model in both immune-competent and athymic nude mice. Electron microscopy showed a reduction of host cell infiltration in alpha1Am12- and betaAm12-containing sponges and reduction of invading tubular clefts of host cells as compared to controls. Finally, inoculation of either alpha1Am12 or betaAm12 cells (10%) along with a highly angiogenic Kaposi's sarcoma cell line (90%) resulted in a powerful reduction of tumor growth in nude mice in vivo, as did infection with the interferon-alpha-producing retroviruses. These data suggest that a gene therapy approach using class I interferons can effectively inhibit tumor angiogenesis and growth of vascular tumors.  (+info)

Biomaterial-induced sarcoma: A novel model to study preneoplastic change. (55/3384)

In the study of carcinogenesis most interest has focused on carcinomas, as they represent the majority of human cancers. The recognition of the adenoma-carcinoma sequence both in humans and in animal experimental models has given the field of basic oncology the opportunity to elucidate individual mechanisms in the multistep development of carcinoma. The relative scarcity of human sarcomas coupled with the lack of adequate animal models has hampered understanding of the molecular genetic steps involved. We present an experimental model in the rat in which a high incidence of malignant mesenchymal tumors arise around a subcutaneously implanted biomaterial. Nine commercially available biomaterials were implanted in a total of 490 rats of the Fischer strain for 2 years. On average, macroscopic tumors were found in 25.8% of implantation sites over a period from 26 to 110 weeks after implantation. The most frequent tumors were malignant fibrous histiocytomas and pleomorphic sarcomas, although fibrosarcomas, leiomyosarcomas, and angiosarcomas readily developed, the latter especially around polyurethane implants. Of particular interest are the results of a detailed histological study of the capsules around the implanted biomaterials without tumors. Here a spectrum of change from focal proliferative lesions through preneoplastic proliferation to incipient sarcoma could be observed. A parallel immunohistochemical study of peri-implant capsules showed that proliferating cell nuclear antigen was of particular help in identifying these atypical proliferative lesions. To our knowledge this is the first description of a sarcoma model in which preneoplastic lesions can be readily identified and also reproducibly induced. This model provides the molecular biologist with defined stages in the development of mesenchymal malignancy, with which the multistage tumorigenesis hypothesis can be tested, analogous to the well-known adenoma-carcinoma sequence.  (+info)

Monolithic microfabricated valves and pumps by multilayer soft lithography. (56/3384)

Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.  (+info)