Stenocereus huastecorum-fruit juice concentrate protects against cisplatin-induced nephrotoxicity by nitric oxide pathway activity and antioxidant and antiapoptotic effects.

Cisplatin (CP) is an antineoplastic agent used to treat solid tumors, that has high nephrotoxicity caused by physiologic, hemodynamic, and biochemical alterations. Some studies have shown that naturally derived bioactive compounds in CP-induced nephrotoxicity reduce the side effects of this antineoplastic drug. Pitaya is an endemic fruit from Mexico with a high bioactive compound content, including betalains and phenolic compounds, with reports of antioxidant and anti-inflammatory properties. In this study, the aim was to establish the effect of a pitaya juice concentrate (PJC) on CP-induced nephrotoxicity in Wistar male rats through the identification of metabolites, determination of its chemical composition and antioxidant activity, and evaluation of the protective effect of a PJC on CP-induced nephrotoxicity in rats. The PJC showed a high content of betanins with antioxidant activity by an oxygen radical absorbance capacity assay (1299.6 ± 2.80 Trolox equivalents/g). PJC was administered daily (400 mg day-1, p. o.) for 3 days before CP administration until the end of the experiment. On day four, rats were administered a single injection of CP (6 mg kg, i.p.-1) and sacrificed 72 h later. We observed that CP provoked renal dysfunction (1.0 ± 0.1 vs. 0.4 ± 0.07 serum creatinine levels), oxidative stress, a decrease in nitrate and nitrite (NO2¯/NO3¯) levels (0.1 ± 0.08 vs. 0.4 ± 0.3) and activation of apoptosis and immune responses in kidney tissue. In addition, CP treatment induced tubular damage threefold. PJC administration prevented renal dysfunction (0.5 ± 0.06 vs. 1.0 ± 0.1), normalized degenerative structural damage prevented the increase in lipoperoxidation levels (0.04 ± 0.01 vs. 0.2 ± 0.1) and reduced the apoptosis index by 2.5 in kidney tissue. However, it did not modify the immune response caused by CP. Furthermore, PJC treatment increased nuclear factor erythroid two related factors two protein levels two times and NO2¯/NO3¯ levels 22 times in kidney tissue, which may play a role in the renoprotective effect. In conclusion, the renoprotective effect of PJC on CP-induced nephrotoxicity was associated with the attenuation of dysfunction, structural damage, apoptosis activation, and oxidative stress and was related to changes in the tumor necrosis factor-alpha and renal nitric oxide (NO) pathways. The changes in the NO pathway may be involved in renal hemodynamics. Pitaya could be used as a functional food and therapeutic coadjuvant during CP treatments due to its high bioactive levels and renoprotective compounds.

Plasma protein adsorption on Fe3O4-PEG nanoparticles activates the complement system and induces an inflammatory response.

BACKGROUND: Understanding of iron oxide nanoparticles (IONP) interaction with the body milieu is crucial to guarantee their efficiency and biocompatibility in nanomedicine. Polymer coating to IONP, with polyethyleneglycol (PEG) and polyvinylpyrrolidone (PVP), is an accepted strategy to prevent toxicity and excessive protein binding. AIM: The aim of this study was to investigate the feature of IONP adsorption of complement proteins, their activation and consequent inflammatory response as a strategy to further elucidate their biocompatibility. METHODS: Three types of IONP with different surface characteristics were used: bare (IONP-bare), coated with PVP (IONP-PVP) and PEG-coated (IONP-PEG). IONPs were incubated with human plasma and adsorbed proteins were identified. BALB/c mice were intravenously exposed to IONP to evaluate complement activation and proinflammatory response. RESULTS: Protein corona fingerprinting showed that PEG surface around IONP promoted a selective adsorption of complement recognition molecules which would be responsible for the complement system activation. Furthermore, IONP-PEG activated in vitro, the complement system and induced a substantial increment of C3a and C4a anaphylatoxins while IONP-bare and IONP-PVP did not. In vivo IONP-PEG induced an increment in complement activation markers (C5a and C5b-9), and proinflammatory cytokines (IL-1ß, IL-6, TNF-α). CONCLUSION: The engineering of nanoparticles must incorporate the association between complement proteins and nanomedicines, which will regulate the immunostimulatory effects through a selective adsorption of plasma proteins and will enable a safer application of IONP in human therapy.

A comparison of the human and mouse protein corona profiles of functionalized SiO2 nanocarriers.

Nanoparticles are a promising cancer therapy for their use as drug carriers given their versatile functionalization with polyethylene glycol and proteins that can be recognized by overexpressed receptors in tumor cells. However, it has been suggested that in biological fluids, proteins cover nanoparticles, which gives the proteins a biological identity that could be responsible for unexpected biological responses: the so-called protein corona. A relevant biological event that is usually ignored in protein-corona formation is the interspecies differences in protein binding, which can be involved in the discrepancies observed in preclinical studies and the nanoparticle safety and efficiency. Hence, the aim of this study was to determine the differences between human and mouse plasma protein corona profiles in an active therapy model using silicon dioxide nanoparticles (SiO2 nanoparticles) functionalized with polyethylene glycol and transferrin. Functionalized SiO2 nanoparticles were made with a primary particle size of 25 nm and a transferrin content of 50 µg mg-1 of nanoparticles and were PEGylated with a cross-linker. The proteomic analysis by nanoliquid chromatography tandem-mass spectrometry (nanoLC-MS/MS) showed interspecies differences. The most abundant proteins found in the human protein corona profile were immunoglobulins, actin cytoplasmic 1, hemoglobin subunit beta, serotransferrin, ficolin-3, complement C3, and apolipoprotein A-1. Meanwhile, the mouse protein corona adsorbed the serine protease inhibitor A3K, serotransferrin, alpha-1-antitrypsin 1-2, hemoglobin subunit beta, and fibrinogen gamma and beta chains. These protein-corona profile differences in the functionalized SiO2 nanoparticles indicate that biological responses observed in in vivo models could not be translated to clinical use and must be considered in the interpretation of preclinical trials in order to design more efficient and safer nanomedicines.

[Femoroacetabular impingement: minimally invasive hip surgery]. / Femoroazetabulares Impingement: Minimalinvasive Hüftchirurgie.

Minimally invasive hip surgery is an innovative surgical technique mainly used in femoroacetabular impingement (FAI). The purpose of the surgical correction in FAI deformity is to eliminate the etiologic factor in the development of the so-called idiopathic hip osteoarthritis. Decisive for the success of joint preservation is the preoperative assessment of the deformity and the possible damage to the cartilage. The optimal intervention in the presence of substantial cartilage damage is joint replacement. The patient's history and the findings of physical examination with detailed radiographs and magnetic resonance imaging based on a sagittal oblique localizer optionally using intra-articular contrast prevent underestimation of the stage of the disease. Knowledge about the options and techniques of minimally invasive hip surgery helps to identify patients appropriate for other interventions like surgical dislocation of the hip and the periacetabular osteotomy.

Dosing strategies for conversion of haemodialysis patients from short-acting erythropoiesis stimulating agents to once-monthly C.E.R.A.: experience from the MIRACEL study.

AIMS: To analyse the impact of dosing decisions for continuous erythropoietin receptor activator (C.E.R.A.), a continuous erythropoietin receptor activator. METHODS: This was a prospective, multicentre, single-arm study in haemodialysis patients receiving epoetin alfa/beta or darbepoetin alfa. After a 2-month screening phase, patients were converted to monthly C.E.R.A. using pre-filled syringes during a 5-month titration phase and a 2-month evaluation phase. RESULTS: Four hundred and twenty-four eligible patients were converted to C.E.R.A. Mean Hb were 11.7 ± 0.7, 11.7 ± 0.8 and 11.5 ± 0.8 g/dl during screening, titration and evaluation, respectively. C.E.R.A. starting dose was 125 µg (n = 311) or 200 µg (n = 106), with corresponding final doses of 129 ± 61 µg and 203 ± 58 µg. The mean number of C.E.R.A. dose decreases and increases were 0.9 ± 1.0 and 1.1 ± 1.0 per patient, respectively. Hb rarely exceeded 12.5 g/dl after a C.E.R.A. dose increase (< 8%) and remained ≥ 11 g/dl after a dose reduction on approximately three-quarters of occasions. Among the 53 occasions where Hb decreased ≥ 2 g/dl between two consecutive visits, the previous dose had been withheld (n = 9), concomitant blood loss, coagulopathy or infection was present (n = 13), or iron parameters were low (n = 17). There were 104 adverse events/month during screening, and 45/month during the titration/evaluation phases. Serious adverse events occurred in 18.0 and 21.0 patients/month during the screening and titration/evaluation phases, respectively. CONCLUSION: Switching haemodialysis patients from shorter-acting ESA to once-monthly C.E.R.A. using pre-filled syringes is straightforward, and Hb levels remain stable. Starting dose recommendations and dose changes correlated well with the clinical setting. Collateral factors such as infection or aggravating concomitant medical conditions should be taken into account.

[Femur first in hip arthroplasty--the concept of combined anteversion]. / Femur first beim Hüftgelenksersatz--Das Konzept der kombinierten Anteversion.

BACKGROUND: The concept of combined anteversion for total hip arthroplasty (THA) proposes a relationship between the cup and stem components that theoretically maximises the postoperative range of motion and minimises the risk for impingement of the joint. Using computer-assisted navigation tools, an anteversion angle of the cup component can be made to be dependent on the antetorsion angle of the stem component (or vice versa). We studied how this functional concept would be different from the traditional cup placement according to the Lewinnek safe zone. PATIENTS AND METHODS: We prospectively reviewed 42 patients (42 hips) who underwent imageless, computer-assisted THA with cementless implants due to osteoarthritis between May and October 2008. Using computer navigation, we determined the cup anteversion with optimised containment and measured femoral stem antetorsion. Our goal was to implant the original implants with a combined anteversion of 37 degrees. RESULTS: Mean cup anteversion was 22.5 degrees, mean combined anteversion was 35.2 degrees. Femoral antetorsion ranged from -13 to 38 degrees (mean: 18 degrees). Mean anteversion of the trial cup with optimised containment was 15.9 degrees and therefore close to the recommendation according to the Lewinnek safe zone. The total postoperative range of motion (flexion, extension, abduction, internal/external rotation) as measured with the navigation system intraoperatively was 209 degrees compared to 94 degrees measured clinically preoperatively. No THA dislocation occurred during the test. CONCLUSION: The combined anteversion concept results in a cup position with more anteversion when compared to the traditional cup placement according to the Lewinnek safe zone. In this context, modern navigation techniques open a new frontier for an optimised component position. Placing the cup and stem in relation to the anteversion for both components allows consideration of the patient-specific biomechanics.

The IGF system in in-vitro human decidualization.

Decidualization of endometrial stromal cells (ESCs) is critical for a successful pregnancy but the molecular mechanisms of the process are poorly understood. In this study, we investigated whether the insulin-like growth factor (IGF) network is involved in this cellular process. Expression kinetics of members of the IGF system was examined at both mRNA and protein levels during in-vitro decidualization of cultured human ESCs. We found a significant up-regulation of IGF-II as well as of IGF-I receptor and the A and B insulin receptor (InsR) isoforms. In addition, levels of the key adaptor proteins insulin receptor substrate 1 (IRS-1) and IRS-2 increased, suggesting a potential involvement of the IGF signalling pathway in the decidualization process. Expression of two IGF binding proteins, IGFBP-1 and IGFBP-4, which can inhibit IGF action, also increased. In order to determine whether IGF signalling was activated during decidualization, the phosphorylation status of the receptors and the adaptor proteins was estimated. Only IRS-2 was slightly phosphorylated in decidualized cells and was further activated by the addition of exogenous IGF-II. These results suggest that the IGF signalling pathway could play a crucial role in the functions of decidualized endometrial cells.

Propuesta para el desarrollo de la salud en el ámbito rural / Rural health care, a proposal

Este artículo resume una propuesta organizacional para la atención de salud rural, realizada a solicitud del Servicio de Salud Llanquihue Chiloé Palena, por los autores entre enero y abril del 2007. Realiza un análisis esencialmente cualitativo de la situación rural en el área del Servicio de Salud y un diagnóstico centrado en una hipótesis unitaria: la salud rural ha extraviado el espíritu que la animó en las décadas precedentes. Del diagnóstico se desprende la identidad territorial y el conocimiento local como pilares indispensables para recuperar ese espíritu. La propuesta se centra en la construcción de equipos territoriales, autónomos y públicos.

This paper is a summary of an organizational proposal for rural health. Between January and April 2007 we prepared a document requested by Llanquihue Chiloé Palena Health Service. We did a research and qualitative diagnosis of rural health situation in Health Service area. Our analysis is based in a unitary hypothesis: rural health has loosed its spirit. From the diagnosis we recognized territorial identity and local knowledge as essentials tools for the spirit recovery. The proposal is then focused in the construction of public, autonomic and territorial health teams.

Long-term follow-up of the hepatitis C HENCORE cohort: response to therapy and occurrence of liver-related complications.

The aims of the study were to verify the long-term effect of time on viral clearance in hepatitis C virus (HCV) patients and to find out factors possibly associated with disease progression. A total of 1641 patients recruited from eight European centres in 1996-1997 were re-analysed 5-7 years after inclusion. The occurrence of decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation was analysed in relation to different host and viral factors. Ninety-three per cent of the HCV patients who had cleared the virus (spontaneously or after antiviral therapy) remained HCV-RNA-negative during follow up and may be considered as 'cured'. Among patients who were sustained responders at inclusion, 2.3% developed liver complications during follow up, and 31% of non-responders did. Advanced age at infection and presence of the human leucocyte antigen (HLA) DRB1*1201-3 allele were possibly associated with a higher rate of progression to decompensated cirrhosis or HCC. Decompensated cirrhosis might be further associated with male gender, non-response to previous therapy, and lack of HLA DRB1*1301 allele, whereas HCC seems to be associated with the presence of the HLA DQ02 allele. Long-term follow up of HCV patients indicates that virological response persists over time and is associated with a very low incidence of liver complications. Advanced age at inclusion, advanced age at infection, viral genotype 1, non-response to previous therapy and possibly some specific HLA alleles are factors independently associated with a faster rate of progression towards liver complications. The large proportion of patients lost to follow up stresses the need for a strengthened and optimized management of HCV patients.

Speech and swallowing following radial forearm flap reconstruction of major soft palate defects.

Velopharyngeal function is often compromised by the resection and reconstruction of oropharyngeal and palatal tumours. While free tissue transfer has improved the outcomes of head and neck reconstruction. In general, palatal reconstruction remains a challenge. Velopharyngeal function was analysed in eight patients following microsurgical reconstruction of defects of between 50 and 100% of the soft palate. The radial forearm fasciocutaneous free flap was used in all cases. The outcome of reconstruction was analysed by patient questionnaire and with standardised tests of speech and swallowing function. Velopharyngeal function post-operatively ranged from poor to near normal. Poor function appeared due to the loss of active elevation and contracture of the reconstructed palate producing failure of velopharyngeal closure during swallowing and speech. The results emphasise the limitations of reconstruction of a dynamic structure such as the soft palate with the static fold of skin and soft tissue produced by a fasciocutaneous flap. The relatively poor results obtained suggest that an anatomical approach to soft palate reconstruction is inadequate and reduction of the calibre of the velopharyngeal aperture is required to compensate for the lack of mobility in the reconstructed palate.

Altered expression of type I insulin-like growth factor receptor in Crohn's disease.

The fibrotic and antiapoptotic effects of insulin-like growth factors (IGF) are mediated by type I IGF receptor (IGF-1R). IGFs could play a role in intestinal stricturing and in the maintenance of inflammation in Crohn's disease (CD). We aimed to describe IGF-1R expression in CD intestinal lesions, to compare it to other intestinal inflammatory diseases and to correlate it with fibrosis and apoptosis. IGF-1R expression and apoptosis (active caspase-3) were studied by immunohistochemistry. Surgical intestinal specimens [17 CD, nine controls, six diverticulitis and four ulcerative colitis (UC)] were used. IGF-1R was expressed transmurally mainly by inflammatory cells (IC) and smooth muscle cells, both in diseased intestine and controls. IGF-1R positive IC were increased in the mucosa and the submucosa of CD (P < 0.007), and in involved areas compared to uninvolved areas (P = 0.03). In UC, the number of IGF-1R positive IC was only increased in the mucosa, and was not different from controls in the submucosa. In diverticulitis, the number of IGF-1R positive IC did not differ from controls. In CD submucosa, IGF-1R expression in IC was inversely correlated with apoptosis in uninvolved areas (P = 0.01). Expression of IGF-1R in submucosal fibroblast-like cells, subserosal adipocytes and hypertrophic nervous plexi was specific for CD. We have shown a transmural altered expression of IGF-1R in CD. This may suggest a role for IGF-1R in the maintenance of chronic inflammation and stricture formation in CD.

[Viral-induced tumours and pre-malignant cutaneous diseases of the perianal region]. / Virusinduzierte Tumoren und Präkanzerosen der Analregion.

HPV-induced tumours and pre-malignant cutaneous diseases of the anal region are rare, without the exception of condylomata acuminata. Often imposing like an eczema (especially M. Bowen, M. Paget) the danger of mis-interpretation and thereby mis-therapy is great, so that they are not seldom diagnosed in the stage of malignant degeneration. A comparatively high rate of recurrence is caused by primarily insufficient (surgical) therapy, but also by secondary transformation of still unchanged dermal areas and by re-infection. Therefore after-care is indicated.

Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers.

The ERBB2 gene is overexpressed in 30% of breast cancers and this has been correlated with poor prognosis. ERBB2 is upregulated in other cancers such as prostate, pancreas, colon and ovary. In breast cancer cells, the mechanisms leading to ERBB2 gene overexpression are increased transcription and gene amplification. In these cancers, AP-2 transcription factors are involved in ERBB2 overexpression, and AP-2 levels are correlated with p185(c-)(erbB-2) levels. In this work, we wanted to know if the same molecular mechanisms are responsible for the ERBB2 upregulation in non-breast cancers. We compared ERBB2 gene copy number, p185(c-)(erbB-2) and mRNA levels with AP-2 levels in several ovary, prostate, colon and pancreas cancer cells. A moderate expression of erbB-2 mRNA and protein were observed in some cells without gene amplification. In contrast to breast cancer cells, AP-2 factors were absent or low in some non-breast cells which did express ERBB2. It is thus likely that AP-2 is not a major player in the increased levels of erbB-2 transcripts in non-breast cancer cells. The transcriptional activity of the ERBB2 promoter in colon and ovary cancer cells was estimated using reporter vectors. The results showed that the promoter regions involved in ERBB2 gene overexpression in breast cancer cells are different from those that lead to the gene upregulation in colon and ovary cancers. In conclusion, our results indicate that different transcriptional and post-transcriptional mechanisms are responsible for the increased levels of erbB-2 transcript and protein in breast and non-breast cancer cells.

[Cancer and Crohn's disease]. / Das Karzinom beim M. Crohn.

We report 12 cases, complicating Crohn's disease by cancer origin. 8 patients who had chronic anorectal fistula, developed mucinous adenocarcinoma, 4 patients colorectal cancer. Features like early onset of disease, duration of disease for more than 10 years, chronic (pan-)colitis with high inflammatory activity and persistence of chronic fistulas and stenosis seem to trigger malignant transformation. Submucosal growth, overlap-syndromes with Crohn's disease and absence of sufficient clinical control of stenosis or fistula lead to advanced tumour stages at time of diagnosis combined with poor prognosis. Within four years after diagnosis 7 of 10 patients died related to metastatic disease or local recurrence. Absence of sufficient possibilities for clinical control indicates radical and early surgical resection of both endoscopically not surveilable stenosis and longstanding anorectal fistulas.

Diurnal and seasonal variation of the equilibrium state between short-lived radon decay products and radon gas in ground-level air.

To study seasonal and diurnal variations and the effect of meteorological parameters, the equilibrium factor F (i.e. the ratio of equilibrium equivalent radon daughter concentration and radon gas concentration) was determined as a result of measurements on a test field at Munich-Neuherberg, Germany, continuously from October 1995 through March 1997. On average, F was found to be 0.62+/-0.09 (95% confidence level). The time series of F showed no distinct seasonal variations. Nevertheless, typical diurnal variations as well as seasonal variations of the diurnal behaviour were observed. Generally, F was found to be increased in the early afternoon, i.e. under conditions of enhanced vertical mixing in the atmosphere. The daily differences between high and low values of F depended on the season. On average, low F values were characteristic for days with precipitation and high wind speed, i.e. under turbulent atmospheric conditions. Therefore, taking daily mean values into account, F was found to be positively correlated with the aerosol concentration, although a relationship between the diurnal behaviour of the aerosol concentration and that of F was not detectable.

The outcome in myasthenia gravis patients--an eight-year follow-up after finishing immunoabsorption therapy.

Eight years ago four patients suffering from myasthenia gravis (MG) type C and E according to Compston with failed drug therapy were treated three times (one patient 11 times) by protein A immunoabsorption (Immunosorba, Excorim, Fresenius Hemocare GmbH, StWendel, Germany). No further immunoabsorption treatments have been carried out. In addition, three patients were given a thymectomy. The present status of the patients was checked six and eight years thereafter. We could see a beneficial effect in all MG patients. The patients are fit for work; all have an improved Besinger index. The patients were used as their own controls. A higher anti-AChR-ab level six years after protein A immunoabsorption than at the beginning was seen in all patients combined with a less serious MG. In addition, their immunomodulation could be induced as seen in lymphocyte and inflammatory protein changes during the first 36 days after beginning immunoabsorption treatment. A larger population has to be investigated to verify these results.

[Hemorrhoids. On the evaluation of different surgical procedures]. / Hämorrhoiden. Zur Wertung der verschiedenen chirurgischen Verfahren.

The spectrum of procedures for haemorrhoidal disease can deal with all developmental stages if done in a differentiated way. The possibilities, limitations, and risks of the different methods are described. The catalogue stretches from relatively simple operations (Milligan-Morgan, stapler haemorrhoidectomy), which every general surgeon should be able to perform, to extensive anoplastic reconstruction, which is limited to specialists. Although the global risks of the more simple operations make them suitable for outpatient procedures, there are--at least in Germany--severe reservations, as there is the danger of inadequately therapy in more advanced cases, overcharging a lot of patients, lack of cooperation and knowledge about the necessities of early postoperative care by the local practitioners, problems in follow-up in patients living far away, and inadequate payment for the therapeutical costs by the health insurance companies.

Radon concentration in soil gas: a comparison of methods.

Various methods to determine 222Rn concentration in soil gas were tested at two sites with different soil types in a depth of about 1 m. They included instantaneous (spot), continuous (real-time) and time-averaging procedures. The first test site had a porous soil with high gravel content. At this site, radon concentrations obtained with the different methods agreed within the error limits of the procedures. The other site exhibited a largely impermeable clay soil and at this site, the measured radon concentrations differed up to a factor of two depending on the method. The applicability of the various procedures in the field is discussed.

Radon concentration in soil gas: a comparison of the variability resulting from different methods, spatial heterogeneity and seasonal fluctuations.

From the end of 1996 through March 1999, the spatial and temporal variability of the soil 222Rn concentration was investigated at a 20 m x 20 m test field with porous soil in 0.5 m and 1.0 m depth at nine positions each and at 1 m x 1 m plots at four positions each. For this, soil gas was collected weekly into evacuated scintillation cells and was analysed subsequently for radon activity. In the 20 m x 20 m field the spatial variability was characterized by coefficients of variation (C.V.) of 26% at 0.5 m, and 13% at 1.0 m depth. Within the 1 m x 1 m plots the C.V. values were 4% and 2%, i.e. within the uncertainty of the method. Time series analysis (TSA) of the soil radon data shows seasonal variations with maximum concentrations in the winter months. Radon concentrations ranged from 6 to 50 kBq m(-3) in 0.5 m depth, and from 8 to 34 kBq m(-3) in 1.0 m depth. Mostly, the concentrations were higher in 0.5 depth than in 1.0 m depth. However, seasonal variation of the 0.5 m to the 1.0 m concentration ratio has been verified by TSA. To test the variability resulting from different methods, additional procedures and instruments were investigated at the 20 m x 20 m field and at a second test field with a different soil type. Soil gas sampling into evacuated scintillation cells was selected as the reference procedure. Soil radon concentrations obtained with the different sampling procedures and detection methods at the 20 m x 20 m field essentially agreed within the limits of uncertainty of the methods tested. At the second test field, i.e. in a largely impermeable soil, deviations up to a factor of two related to the reference procedure were observed.

Three cases of C-ANCA-positive vasculitis treated with immunoadsorption: possible benefit in early treatment.

Wegener's granulomatosis is a vasculitic disease predominantly affecting the upper respiratory tract, lungs, and kidneys. Three patients with Wegener's granulomatosis and rapidly progressive glomerulonephritis were treated with an intensified regimen of immunoadsorption (IA) (Excorim or Therasorb) in addition to cyclophosphamide (CYC) and methylprednisolone (PRE). Patient A had been in remission under oral CYC/PRE. The first exacerbation was treated successfully with 4 IA treatments without changing medication. Patient B experienced 3 flares within 1 year, which were treated with 28 IA (3-7 IAs/course), intravenous CYC after each course, and PRE. A fall of creatinine levels from 120 to 190 micromol/L to 100 micromol/L was noted after IA and before administration of CYC. Patient C presented in uremia. Autoantibodies were eliminated by 11 IA treatments parallel to CYC/PRE therapy. They remained within a normal range for >1 year's follow-up; however, kidney function did not return. In conclusion, the observations in Patients A and B suggest a beneficial therapeutic effect of early IA in WG.