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Biomedical subjects

M Toepfer

Publications and source records attributed to M Toepfer.

At least 19 recordsLinked to original sources
PubMed2000

High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein.

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 micrograms/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 micrograms/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.

Adult↗
PubMed2000

High-dose immunoglobulin therapy in sporadic inclusion body myositis: a double-blind, placebo-controlled study.

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.

Adult↗
PubMed2000

DALI apheresis in hyperlipidemic patients: biocompatibility, efficacy, and selectivity of direct adsorption of lipoproteins from whole blood.

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.

Acrylic Resins↗
PubMed2000

Theophylline improves acute mountain sickness.

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.

Administration, Oral↗
PubMed2000

Successful management of polyneuropathy associated with IgM gammopathy of undetermined significance with antibody-based immunoadsorption.

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.

Humans↗
PubMed1999

Clindamycin and nicotinic neuromuscular transmission.

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.

Animals↗
PubMed1999

Neuromyotonia, myocloni, sensory neuropathy and cerebellar symptoms in a patient with antibodies to neuronal nucleoproteins (anti-Hu-antibodies).

A middle-aged patient presented with subacute muscular stiffness, myocloni of both extremity and facial muscles, gait ataxia and symmetrical distal painful paraesthesias. Electrophysiologically, neuromyotonia was confirmed. High titer anti-Hu antibodies were detected, but no other paraneoplastic antibodies were found. Small-cell lung cancer was diagnosed. Under chemotherapy tumor remission was achieved and, except for minor sensory deficits, neurological symptoms disappeared. This report shows that paraneoplastic syndromes associated with antibodies to neuronal nucleoproteins (anti-Hu antibodies) may be associated with a syndrome including neuromyotonia, sensory neuropathy, cerebellar symptoms and myocloni.

Antibodies, Neoplasm↗
PubMed1999

Localization of transforming growth factor beta in association with neuromuscular junctions in adult human muscle.

Transforming growth factors-beta 1, 2, and 3 are known for their regulatory function in embryogenesis, fibrogenesis, and tissue repair of different cell types. A trophic function of TGF-beta subclasses for motoneurons has been shown in vitro. TGF-beta 1 is a potent survival factor for cultured embryonic rat motoneurons. In addition, TGF-beta 1 stimulates proliferation of rat Schwann cells. Recently, TGF-beta 2 has been reported to be associated with the subsynaptic nuclei of mature rat neuromuscular junctions. In this study, we investigated the expression of TGF-beta 1, 2, and 3 at neuromuscular junctions in skeletal muscle of 11 adults without neuromuscular disease. On muscle biopsies, neuromuscular junctions were depicted by acetylcholine esterase reaction and acetylcholine receptor antibodies. TGF-beta 1; 2, and 3 were stained immunohistochemically with monoclonal antibodies. Some muscle fibers showed low levels of inhomogeneous immunoreactivity for both TGF-beta 1 and TGF-beta 3. Intense immunoreactivity of TGF-beta 1 and 3 was shown at the postsynaptic area of neuromuscular junctions. TGF-beta 2 was expressed in the same subcellular distribution, but less strongly. In conclusion, the colocalization of TGF-beta with neuromuscular junctions may suggest a significant function in neuromuscular communication.

Acetylcholinesterase↗
PubMed1999

Extracorporeal antibody elimination in neuroimmunological diseases.

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.

Demyelinating Diseases↗
PubMed1998

Tenascin is a useful marker in the diagnosis of inflammatory myopathies.

The expression of tenascin, NCAM, vimentin and HSP-70 was examined in 15 patients with dermatomyositis and 12 patients with polymyositis. All biopsies with dermatomyositis showed a confluent network of tenascin expression in the extracellular space. This network surrounded numerous fibers (39 up to 320). Tenascin expression preceded other histological and immunohistochemical signs of dermatomyositis such as the expression of N-CAM and vimentin and the appearance of perifascicular atrophy and inflammatory response. Tenascin expression was found in 3 biopsies where microtubular inclusions in the arteriolar walls were absent. In contrast, tenascin expression was confined to the surroundings of necrotic fibers also expressing vimentin or N-CAM in polymyositis. In general, tenascin was found in the vicinity of inflammatory cells, only. These findings suggest that tenascin is induced by ischemic stress in dermatomyositis. Widespread tenascin expression in a fascicular distribution is a specific marker, if an inflammatory myopathy has been proven by standard techniques. In some cases, tenascin staining might confirm the clinical diagnosis of dermatomyositis, where other histological findings are inconclusive.

Adolescent↗
PubMed1998

Drug-induced systemic lupus erythematosus after 8 years of treatment with carbamazepine.

This is the report of a late-onset carbamazepine-induced systemic lupus erythematosus in a 34-year-old patient who had been treated with daily carbamazepine for 8 years because of complex partial seizures. When carbamazepine was discontinued, symptoms rapidly improved and antinuclear antibodies disappeared. So far, few cases have been reported of carbamazepine-induced lupus erythematosus within months after the start of treatment. This is the first case report about carbamazepine-induced systemic lupus erythematosus with serological confirmation after years of treatment without side effects.

Adult↗
PubMed1998

DALI-the first human whole-blood low-density lipoprotein and lipoprotein (a) apheresis system in clinical use: procedure and clinical results.

BACKGROUND: The DALI low-density lipoprotein (LDL) apheresis system is the first whole-blood apheresis system in regular clinical use. DALI stands for direct adsorption of lipoproteins, which describes the basic principle of operation of this newly developed LDL apheresis procedure. METHODS: The selective removal of LDLs and lipoprotein (a) [Lp(a)] is performed in human whole blood by adsorption onto polyacrylate-coated polyacrylamide beads in an adsorber. This article describes the results of the first open multicentre clinical trial in 14 patients in whom the safety and the efficacy of the system were tested. All patients were treated on average 17 times on a weekly basis. In total, 238 sessions were carried out during the study without severe side-effects. On average, 7675 mL of the patients' whole blood was processed in about 2 h. Anticoagulation in the extracorporeal system was carried out by first giving a heparin bolus followed by continuous addition of an acid citrate dextrose (ACD-A) infusion during the treatment. RESULTS: The processing of nearly 1.6 times the patient blood volumes resulted in a reduction in the median LDL-cholesterol level by 66-77% (dependent on the system configuration). The Lp(a) concentrations were reduced by 59-73% (dependent on the system configuration). HDL-cholesterol, blood cell count and the other clinical parameters were not significantly affected. CONCLUSION: Based on this short-term evaluation, the DALI apheresis system is a well-tolerated, effective and simple way of reducing LDL and Lp(a) in human whole blood. The system has been introduced to clinical practice. However, to use the DALI apheresis system in clinical routine, further evaluation of long-term effects is required.

Adult↗