M Toepfer

University Hospital München, München, Bavaria, Germany

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Publications (43)178.62 Total impact

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    ABSTRACT: The CD40-CD40L (CD154) costimulatory pathway plays a critical role in the pathogenesis of kidney allograft rejection. In renal transplant biopsies, CD4+CD40L+ graft-infiltrating cells were detected during chronic rejection in contrast to acute rejection episodes. Using a rapid noninvasive FACS procedure, we were able to demonstrate CD40L upregulation in peripheral blood of patients with chronic renal allograft dysfunction. Whole blood from recipients of renal allografts was stimulated with PMA and ionomycin and measured by flow cytometry. Patients were assigned to three groups based on transplant function. Group 1: 26 patients with excellent renal transplant function; group 2: 28 patients with impaired transplant function; group 3: 14 patients with chronic allograft dysfunction and group 4: 8 healthy controls. The median percentage +/- SEM of CD4+/CD40L+ cells stimulated ex vivo at 10 ng/ml PMA was as follows: group 1: 28.3 +/- 4.1%; group 2: 18.4 +/- 2.4%; group 3: 50.1 +/- 5.0% and group 4: 40.4 +/- 3.4%. Subdivisions of groups 2 and 3 resulted in different CD40L expression patterns. Patients with increased serum creatinine since the initial phase after transplantation (groups 2a and 3a) revealed a higher percentage of CD4+CD40L+ cells than patients showing a gradual increase over time (groups 2b and 3b). Consequently, patients of group 3a exhibited a significantly reduced transplant function compared with those of group 3b. After PMA + ionomycin stimulation, patients with excellent kidney graft function displayed significantly reduced expression of CD40L surface molecules on CD4+ cells early after transplantation. Those with a chronic dysfunction of the renal graft showed significantly more CD4+ cells expressing CD40L compared to the other transplanted groups. These results demonstrate that the percentage of CD4+CD40L+ cells stimulated ex vivo in peripheral blood may be a valuable marker for chronic allograft nephropathy.
    International Archives of Allergy and Immunology 04/2004; 133(3):276-84. DOI:10.1159/000076835 · 2.67 Impact Factor
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    ABSTRACT: The number of inducible adhesion molecules known to be involved in cell-mediated allograft rejection is still increasing. In addition, recent data describe complement activation during acute humoral allograft rejection. The aim of this study was to assess whether specific molecules from either pathway are excreted into urine and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1) and of the complement degradation product C4d were determined by standardized ELISA technique in 75 recipients of renal allografts and 29 healthy controls. Patient samples were assigned to four categories according to clinical criteria: GROUP 1: acute steroid-sensitive rejection (ASSR, n = 14), GROUP 2: acute steroid-resistant rejection (ASRR, n = 12), GROUP 3: chronic allograft dysfunction (CAD, n = 20) and GROUP 4: stable graft function (SGF, n = 29). All patients with rejection episodes (groups 1-3) had significantly higher values of urinary sC4d compared with healthy controls and patients with stable graft function (p < 0.05). The urinary levels of sVCAM-1 were significantly higher in group 2 (ASRR) compared with all other groups (p < 0.001). Uniformly low amounts of s-VCAM-1 and complement-split product C4d were excreted by healthy controls (group 0). In contrast, urinary sICAM-1 concentration in healthy controls was almost as high as in group 2 (ASRR) whereas patients with a stable functioning graft (group 4) excreted significantly less sICAM-1 (p < 0.05). The evaluation of sVCAM-1 and sC4d excretion in urine can provide a valuable tool with regard to the severity and type of allograft rejection. With respect to long-term allograft survival, serial measurements of these markers should have the potential to detect rejection episodes and prompt immediate treatment.
    Nephron Clinical Practice 02/2003; 94(1):c19-26. DOI:10.1159/000070820 · 1.40 Impact Factor
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    ABSTRACT: A 29-year-old man had finger clubbing since the age of 15 years, and for the last 10 years his hands and feet had grown disproportionately. In addition he suffered from marked whole-body sweating, especially of the hands and feet, as well as persistent pain in the limbs and joints. Biochemical and endocrinological tests were normal. Radiology of the hands and lower legs revealed marked periosteal thickening, while the substantia trabeculosa was unremarkable. Secondary causes having been excluded primary hypertrophic osteoarthropathy was diagnosed. While there is no causal treatment, physio- and balneotherapy improved the symptoms. Early and accurate diagnosis of primary hypertrophic osteoarthropathy is essential, if only because of its favourable long-term prognosis.
    DMW - Deutsche Medizinische Wochenschrift 06/2002; 127(19):1013-6. DOI:10.1055/s-2002-28323 · 0.54 Impact Factor
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    ABSTRACT: The study was designed to investigate the safety and feasibility of gadopentetate dimeglumine, a gadolinium-based contrast medium, as an alternative angiographic contrast agent in patients with impaired renal function and high risk for iodinated contrast-induced nephropathy. Gadopentetate dimeglumine was used as the radiographic contrast agent in 32 diagnostic or interventional angiographic procedures in 29 patients (59% diabetics) with severe renal insufficiency (average serum creatinine of 3.6+/-1.4 mg/dl). The average dose of gadopentetate dimeglumine was 0.34+/-0.06 mmol/kg body weight. Gadopentetate dimeglumine was used either alone (n=20) or in conjunction with carbon dioxide (n=12). Thirty-two angiographic procedures (24 diagnostic angiographies and 8 interventional procedures) were performed in 29 patients. For diagnostic purposes, eleven selective renal arteriographies, six angiographies of the iliac arteries and lower extremities, and seven venous angiographies of the upper extremity and central veins were performed. Interventional procedures consisted of two percutaneous transluminal renal angioplasties with stenting, four percutaneous peripheral vascular interventions, and two balloon angioplasties of a dialysis fistula. None of the patients, except one, had evidence of post-procedure contrast material-induced renal failure (increase in serum creatinine >0.5 mg/dl within 72 h) or other complications. This patient had a clinically important increase in serum creatinine level after percutaneous transluminal renal angioplasty and stenting, probably due to cholesterol embolism. Gadopentetate dimeglumine had sufficient radiographic density to allow adequate diagnostic visualization with digital subtraction equipment in all cases. Gadopentetate dimeglumine is an alternative and safe radiographic contrast agent for angiography and interventional procedures in patients with severe pre-existing renal impairment. In this population with high risk for contrast-induced acute renal failure, it is obviously less nephrotoxic than iodinated contrast media.
    Nephrology Dialysis Transplantation 05/2002; 17(5):824-8. · 3.58 Impact Factor
  • A Calatzis · M Toepfer · W Schramm · M Spannagl · H Schiffl ·

    Nephron 11/2001; 89(2):233-6. DOI:10.1159/000046075 · 13.26 Impact Factor
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    S M Lang · A Bergner · M Töpfer · H Schiffl ·
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    ABSTRACT: Residual renal function (RRF) is of paramount importance to dialysis adequacy, morbidity, and mortality, particularly for long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Residual renal function seems to be better preserved in patients on CAPD than in hemodialysis (HD) patients. We analyzed RRF in 45 patients with end-stage renal disease (ESRD), commencing either CAPD or HD, to prospectively define the time course of the decline in RRF, and to evaluate dialysis-technique-related factors such as cardiovascular stability and bioincompatibility. Single-center prospective investigation in parallel design with matched pairs. Fifteen patients starting CAPD and 15 matched pairs of patients commencing HD were matched according to cause of renal failure and RRF. Hemodialysis patients were assigned to two dialyzer membranes differing markedly in their potential to activate complement and cells (bioincompatibility). Fifteen patients were treated exclusively with the cuprophane membrane (bioincompatible) and the other 15 patients received HD with the high-flux polysulfone membrane (biocompatible). Residual renal function was determined at initiation of dialytic therapy and after 6, 12, and 24 months. Dry weight (by chest x ray and diameter of the vena cava) was closely recorded throughout the study, and the number of hypotensive episodes counted. Residual renal function declined in both CAPD and HD patients, although this decline was faster in HD patients (2.8 mL/minute after 6 months and 3.7 mL/min after 12 months) than in CAPD patients (0.6 mL/min and 1.4 mL/min after 6 and 12 months respectively). It declined faster in patients with bioincompatible than with biocompatible HD membranes (3.6 mL/min vs 1.9 mL/min after 6 months). Eleven percent of the HD sessions were complicated by clinically relevant blood pressure reductions, but there were no differences between the two dialyzer membrane groups. None of the CAPD patients had documented hypotensive episodes. None of the study patients suffered severe illness or received nephrotoxic antibiotics or radiocontrast media. The better preservation of RRF in stable CAPD patients corresponded with greater cardiovascular stability compared to HD patients, independently of the membrane used. Furthermore, there was a significantly higher preservation of RRF in HD patients on polysulfone versus cuprophane membranes, indicating an additional effect of biocompatibility, such as less generation of nephrotoxic substances by the membrane. Thus, starting ESRD patients on HD prior to elective CAPD should be avoided for better preservation of RRF.
    Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 01/2001; 21(1):52-7. · 1.53 Impact Factor
  • F Rommel · M Toepfer · J Eberle · H Schiffl · M Spannagl · W Schramm ·

    Thrombosis and Haemostasis 11/2000; 84(4):733-4. · 4.98 Impact Factor
  • E Tuma · A Eigler · M Toepfer · S Endres · H Schiffl ·

    Nephron 11/2000; 86(2):220-1. · 13.26 Impact Factor
  • E. Tuma · A. Eigler · M. Toepfer · S. Endres · H. Schiffl ·

    Nephron 10/2000; 86(2):220-221. DOI:10.1159/000045758 · 13.26 Impact Factor
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    International Journal of Obesity 07/2000; 24 Suppl 2:S151. DOI:10.1038/sj.ijo.0801309 · 5.00 Impact Factor
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    ABSTRACT: Peripheral polyneuropathies associated with monoclonal IgM gammopathy of undetermined significance often have a progressive course and optimal treatment has not been established. We report on a patient diagnosed with polyneuropathy associated with benign IgM gammopathy, who was successfully treated with antibody-based immunoadsorption only. The neurological symptoms of the patient improved continuously over six months of treatment. Controlled trials should be performed to define this indication for antibody-based immunoadsorption therapy.
    Clinical nephrology 06/2000; 53(5):404-7. · 1.13 Impact Factor
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    ABSTRACT: Hypoxic pulmonary vasoconstriction is associated with but may not be sufficient for the development of high-altitude pulmonary oedema (HAPO). Hypoxia is known to induce an inflammatory response in immune cells and endothelial cells. It has been speculated that hypoxia-induced inflammatory cytokines at high altitude may contribute to the development of HAPO by causing capillary leakage in the lung. We were interested if such an inflammatory response, possibly involved in a later development of HAPO, is detectable at high altitude in individuals without HAPO. We examined the plasma levels of interleukin 6 (IL-6), interleukin 1 receptor antagonist (IL-1ra) and C-reactive protein (CRP) in two independent studies: study A, Jungfraujoch, Switzerland, three overnight stays at 3458 m, n=12; study B: Capanna Regina Margherita, Italy, 3 overnight stays at 3647 m and one overnight stay at 4559 m, n=10. In both studies, probands showed symptoms of acute mountain sickness but no signs of HAPO. At the Jungfraujoch, IL-6 increased from 0.1±0.03 pg/ml to 2.0±0.5 pg/ml (day 2, P=0.03), IL-1ra from 101±21 to 284±73 pg/ml (day 2, P=0.01), and CRP from 1.0±0.4 to 5.8±1.5 μg/ml (day 4, P=0.01). At the Capanna Margherita, IL-6 increased from 0.5±0.2 pg/ml to 2.0±0.8 pg/ml (P=0.02), IL-1ra from 118±25 to 213±28 pg/ml (P=0.02), and CRP from 0.4±0.03 to 3.5±1.1 μg/ml (P=0.03). IL-8 was below the detection limit of the ELISA (<25 pg/ml) in both studies. The increase of IL-6 and IL-1ra in response to high altitude was delayed and preceded the increase of CRP. We conclude that: (1) circulating IL-6, IL-1ra and CRP are upregulated in response to hypobaric hypoxic conditions at high altitude, and (2) the moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence and the kinetics of high altitude-induced cytokines found in this study support the hypothesis that inflammation is involved in the development of HAPO.
    Cytokine 04/2000; 12(3):246-52. DOI:10.1006/cyto.1999.0533 · 2.66 Impact Factor
  • T Bosch · A Lennertz · B Schmidt · E Fink · C Keller · M Toepfer · J Dräger · W Samtleben ·
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    ABSTRACT: Recently, the first apheresis technique for direct adsorption of low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] from whole blood (DALI) was developed that does not require a prior plasma separation. That markedly simplifies the extracorporeal circuit. The aim of the present study was to test the acute biocompatibility, efficacy, and selectivity of DALI apheresis. In a prospective clinical study, 6 hypercholesterolemic patients suffering from angiographically proven atherosclerosis were treated 4 times each by DALI. 1.3 patient blood volumes were treated per session at blood flow rates of 60-80 ml/min using 750 or 1,000 ml of polyacrylate/polyacrylamide adsorber gel. The anticoagulation consisted of an initial heparin bolus followed by a citrate infusion. The sessions were clinically essentially uneventful. Mean corrected reductions of lipoproteins amounted to 65% for LDL-cholesterol, 54% for Lp(a), 28% for triglycerides, 1% for HDL-cholesterol, and 8% for fibrinogen. The selectivity of lipoprotein removal was high. Cell counts remained virtually unchanged and no signs of hemolysis or clotting were detected. Cell activation parameters elastase, beta-thromboglobulin, interleukin-1beta, and IL-6 showed no significant increase. Complement activation was negligible. There was significant, but clinically asymptomatic, bradykinin activation in the adsorber with mean maxima of 12,000 pg/ml in the efferent line at 1,000 ml of treated blood volume. In conclusion, DALI proved to be safe, selective, and efficient for the adsorption of LDL-C and Lp(a), which simplifies substantially the extracorporeal therapy in hypercholesterolemic patients.
    Artificial Organs 03/2000; 24(2):81-90. DOI:10.1046/j.1525-1594.2000.06476.x · 2.05 Impact Factor
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    R Fischer · S.M. Lang · U Steiner · M Toepfer · H Hautmann · H Pongratz · R.M. Huber ·
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    ABSTRACT: A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes >2,500 m. Fourteen healthy male subjects participated in a randomized single-blind placebo-controlled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if <70 kg) or a matched placebo tablet taken twice daily. The acute mountain sickness score (AMSS) was assessed three times a day, beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure. In addition, measurements of respiratory frequency, pulse rate, oxygen saturation and arterial blood gas levels were performed. Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study (mean+/-SD 1.2+/-0.9) with placebo versus 3.6+/-0.8 with theophylline; p=0.03). During the high-altitude study, subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude (0.6 versus 2.3, p=0.03). Oxygenation was improved in both parts of the study. In conclusion, oral slow-release theophylline improves acute mountain sickness.
    European Respiratory Journal 02/2000; 15(1):123-7. DOI:10.1034/j.1399-3003.2000.15a22.x · 7.64 Impact Factor
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    ABSTRACT: Sporadic inclusion body myositis (s-IBM) is an acquired inflammatory muscle disease of unknown cause. In general, s-IBM presents with slowly progressive, asymmetric weakness, and atrophy of skeletal muscle. There is a mild transitory or nil responsiveness to standard immunosuppressive treatment. A controlled cross-over study of 22 s-IBM patients over 3 months showed a partial improvement in those treated with high-dose intravenous immunoglobulin therapy (IVIG) versus placebo. The present study included 22 patients aged 32-75 years and with a mean duration of disease of 5.2+/-3.6 years. They were randomized by a double-blind, placebo-controlled, cross-over design to monthly infusions of 2 g/kg bodyweight IVIG or to placebo for 6 months each, followed by the alternative treatment. After 6 and 12 months the response to treatment was evaluated, using a modified Medical Research Council scale, Neuromuscular Symptom Score (NSS), the patient's own assessment of improvement, arm outstretched time, and electromyography. No serious side effects were seen, in particular no viral infection and no major cardiac or neurological complications. Overall there was no progression of the disease in 90% of patients, unlike that which might have been expected in untreated patients. A mild and significant improvement (11%) in clinical symptoms was found using NSS, but not with other test procedures. There was a trend to mild improvement in treated patients when using other tests. Individual responses to treatment was heterogeneous. The validity of this study may be reduced by mismatch of groups with regard to age at onset and variability in disease expression. The findings of this study largely confirm those of a previous IVIG trial. Treatment with IVIG may be mildly effective in s-IBM by preventing disease progression or inducing mild improvement. Long-term studies are needed to evaluate further the benefit of IVIG therapy in s-IBM.
    Journal of Neurology 02/2000; 247(1):22-8. DOI:10.1007/s004150050005 · 3.38 Impact Factor
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    ABSTRACT: Rippling muscle disease is a rare autosomal dominant disorder that may occur sporadically. In this report two patients presenting with rippling muscles followed by myasthenia gravis are described. Our first patient developed rippling muscles about 1 month after infection with Yersinia enterocolitica. Two years later myasthenia gravis appeared. Our second patient had a 2-year history of asthma prior to the onset of rippling muscles which preceded the myasthenic symptoms by 4-8 weeks. Acetylcholine receptor and anti-skeletal muscle antibody titers were positive in both patients. In both patients the rippling phenomena worsened with pyridostigmine treatment but markedly improved after immunosuppression with azathioprine.
    Neuromuscular Disorders 01/2000; 9(8):604-7. DOI:10.1016/S0960-8966(99)00065-6 · 2.64 Impact Factor
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of motor neurons. However, ALS has been recognized to involve several non-motor systems. Subclinical involvement of the autonomic system (i.e. of cardial or sudomotor regulation) has been described in ALS. Gastrointestinal motor dysfunction can occur in amyotrophic lateral sclerosis, even if patients do not complain of gastrointestinal symptoms. New techniques in non-invasive evaluation of gastrointestinal function showed delayed gastric emptying and delayed colonic transit times in patients with ALS.
    Amyotrophic Lateral Sclerosis 01/2000; 1(1):15-9. DOI:10.1080/146608299300079484
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    ABSTRACT: Upon clindamycin treatment a patient with Parkinson's disease showed marked tremor improvement which may be explained by clindamycin's ability to inhibit in-vitro nicotinergic, but not muscarinic signal transmission.
    The Lancet 12/1999; 354(9192):1792-3. DOI:10.1016/S0140-6736(99)02881-0 · 45.22 Impact Factor
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons. However, ALS has been recognized to also involve non-motor systems. Subclinical involvement of the autonomic system in ALS has been described. The recently developed 13C-octanoic acid breath test allows the noninvasive measurement of gastric emptying. With this new technique we investigated 18 patients with ALS and 14 healthy volunteers. None of the patients had diabetes mellitus or other disorders known to cause autonomic dysfunction. The participants received a solid standard test meal labeled with 13C-octanoic acid. Breath samples were taken at 15-min intervals for 5 h and were analyzed for 13CO2 by isotope selective nondispersive infrared spectrometry. Gastric emptying peak time (tpeak) and emptying half time (t½) were determined. All healthy volunteers displayed normal gastric emptying with a mean emptying t½ of 138 ± 34 (range 68–172) min. Gastric emptying was delayed (t½ > 160 min) in 15 of 18 patients with ALS. Emptying t½ in ALS patients was 218 ± 48 (range 126–278) min (p < 0.001). These results are compatible with autonomic involvement in patients with ALS, causing delayed gastric emptying of solids and encouraging the theory that ALS is a multisystem disease rather than a disease of the motor neurons only.
    Digestion 11/1999; 60(6):567-571. DOI:10.1159/000007708 · 2.10 Impact Factor
  • M Toepfer · H Schiffl · T Sitter · D Pongratz · W Müller-Felber ·
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    ABSTRACT: Extracorporeal procedures for the elimination of autoantibodies are an important therapeutic option in various neuroimmunological diseases, especially those with neuromuscular involvement. Recent advances with the development of selective apheresis methods have given extracorporeal therapeutic procedures a new perspective. In this article, we review the therapeutic use of plasma exchange and immunoadsorption therapy in different neuroimmunological diseases.
    Therapeutic Apheresis and Dialysis 09/1999; 3(3):268-70. DOI:10.1111/j.1091-6660.1999.t01-1-.x

Publication Stats

907 Citations
178.62 Total Impact Points


  • 2004
    • University Hospital München
      München, Bavaria, Germany
  • 1997-2002
    • Ludwig-Maximilians-University of Munich
      • • Department of Internal Medicine II
      • • Friedrich-Baur-Institute
      München, Bavaria, Germany
  • 2000
    • Friedrich Loeffler Institute
      Griefswald, Mecklenburg-Vorpommern, Germany
    • Berufsgenossenschaftliche Unfallklinik Murnau
      Murnau, Bavaria, Germany