[Informed consent in complementary and alternative medicine].
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Complementary Therapies↗
Biomedical subjects
G Dobos
Publications and source records attributed to G Dobos.
[Mind-body medicine as a part of German integrative medicine].
Mind-body medicine (MBM) as a holistic approach to health and healing has been shaped by research into stress physiology and stress psychology, by psychoneuro(endocrino)immunology and by Antonovsky's salutogenetic paradigm. MBM seeks to acknowledge physical, psychological as well as social and spiritual aspects of human beings. MBM constitutes one of the traditions, which the emerging field of integrative medicine in Germany draws upon, others being mainstream medicine, traditional European naturopathy and non-European methods like traditional Chinese medicine. The article outlines historical aspects of MBM, gives a brief review of research evidence, and introduces clinical MBM institutes in Germany. Especially the Clinic and Chair of Complementary and Integrative Medicine, Alfried Krupp von Bohlen und Halbach Foundation at the University Duisburg-Essen has been integrating MBM into the concept of integrative medicine. Considering that a growing number of health issues arises due to maladaptive lifestyles, MBM is being identified as a development that supports a shift from increasingly expensive treatments to more cost-effective preventive approaches.
Delivery of Health Care, Integrated↗
Different modes of manual acupuncture stimulation differentially modulate cerebral blood flow velocity, arterial blood pressure and heart rate in human subjects.
The psychophysiological effect of different modes of manual acupuncture stimulation was investigated in 12 healthy, right handed, male subjects (mean age 29). The cerebral blood flow velocity (CBFV) in both middle cerebral arteries, arterial blood pressure (BP), heart rate (HR) and the perceived intensity of the stimulation were monitored while an acupuncture needle in the right dorsal thenar muscle (point Hegu, Li 4) was repetitively rotated with either high frequency (4-8 Hz) and low amplitude (hf-la) or low frequency (1-2 Hz) and high amplitude (lf-ha). Response patterns induced by hf-la and 1f-ha [corrected] stimulation differed significantly (P < 0.05) as tested by Student's t-test: (1), 1f-ha [corrected] stimulation was perceived as more intense and induced a more marked right hemispheric CBFV increase; (2), while hf-la stimulation lead to a slight decrease of BP and HR, lf-ha stimulation induced an initial pressor response (increase of BP, decrease of HR) and a more marked long term decrease of BP. Data indicate that the mode of manual acupuncture stimulation has a differential effect on the perceived stimulation intensity, the cerebral activation and the cardiovascular reflex response.
Acupuncture↗
[Short-term therapeutic fasting in the treatment of chronic pain and fatigue syndromes--well-being and side effects with and without mineral supplements].
BACKGROUND: Fasting followed by vegetarian diet has shown to be an effective treatment for rheumatoid arthritis, moreover fasting is frequently used as an adjunctive treatment in chronic pain and stress/exhaustion syndromes. Data on well-being and the frequency of side effects during fasting are mostly retrospective. Mineral supplements are frequently used in order to compensate for fasting-induced tissue acidosis and to reduce side effects. There are only limited data that support this practice. OBJECTIVE: To study the effects of oral mineral supplements on common side effects and well-being during short-term fasting. PATIENTS AND METHODS: 209 consecutive inpatients with chronic pain/exhaustion syndromes were recruited. In a controlled non-randomised study design all patients underwent fasting (250 kcal; 3 l fluid intake/day) over 7 days, in study phase 1 without (n = 103) and in study phase 2 with (n = 106) concomitant prescription of standardised oral mineral supplements (3 x 2 to 3 x 3 Bullrich's Vital). Weight, blood pressure and urinary pH were recorded daily. Well-being and mood as well as common side effects (i.e. fatigue, hunger, heart burn, headache) were assessed with standardised self-reports. RESULTS: Baseline characteristics of the 209 patients (mean age 54.7 +/- 10.5 years; 83.3% female) were balanced. Both groups showed a fasting-induced decrease of blood pressure, a slight decrease in mood and well-being on days 3 and 4 with consecutive increase and moderate hunger, i.e. in the evening. Side effects and general tolerability of fasting as well as well-being and mood were not different between the groups. There were no serious side effects in both groups. CONCLUSIONS: Short-term fasting in inpatients with pain and stress syndromes is safe and well tolerated, concomitant mineral supplements have no additive benefit.
Chronic Disease↗
[Comment on the contribution by G. Keyser, "Are there reliable dietary recommendations for patients with rheumatoid arthritis?"].
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Arthritis, Rheumatoid↗
Acute stress and ventricular arrhythmias.
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Acute Disease↗
Effect of leeches therapy (Hirudo medicinalis) in painful osteoarthritis of the knee: a pilot study.
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Aged↗
The CC chemokine receptor 3 CCR3 is functionally expressed on eosinophils but not on neutrophils.
The chemokine subclasses differ in their biological activity to stimulate different kinds of effector cells via distinct chemokine receptors. Controversial results about the expression of the CC chemokine receptor CCR3 on the surface of human neutrophils have been described. To find out whether eosinophil contamination might be responsible for these diverse observations, CCR3 expression on highly purified neutrophils and eosinophils was investigated. We enriched neutrophils from a heterogeneous granulocyte population with immunomagnetic beads coated with various anti-CD52 monoclonal antibodies. This procedure was suitable to enrich neutrophils with a purity of up to 99.85%. Reverse transcriptase-PCR revealed that CCR3 mRNA was not expressed by CD52-negative selected neutrophils. In contrast to these cells, CCR3 mRNA could be detected in a heterogeneous granulocyte population and CD16-negative selected eosinophils. In addition, spectrofluorometric measurement of intracellular calcium concentration ([Ca2+]i) demonstrated that CD52-negative selected neutrophils did not show a transient [Ca2+]i increase following stimulation with the CCR3 ligand eotaxin, whereas the heterogeneous granulocyte population as well as eosinophils did respond. Therefore, previous studies demonstrating the expression of CCR3 on human neutrophils have to be re-evaluated because CCR3 mRNA detection on human neutrophils due to contamination by mRNA from eosinophils could not be excluded.
Adult↗
[Hyperthermia-induced priming effect in neutrophil granulocytes].
BACKGROUND AND OBJECTIVE: Whole-body infrared-A irradiation (WBIAI) according to Ardenne is a newly developed version of hyperthermia. In clinical use benefits for patients with chronic infections have been reported. In order to find out more about the immunological background of the method we studied the question whether hyperthermia leads to priming effects in human polymorphonuclear leukocytes (PMN). MATERIAL AND METHODS: We therefore investigated the production of reactive oxygen radical species (ROS) measured by lucigenin-dependent chemiluminescence after stimulation with N-formylpeptide (FMLP, 10(-6) and 10(-7) M), C5a complement (10(-7) and 10(-8) M) or phorbolester (PMA, 10(-7) and 10(-8) M) in isolated PMN of 8 volunteers undergoding a 60-min hyperthermia treatment with the WBIAI. Blood was drawn 0/60/240/510 min after the start of hyperthermia treatment. In addition, we measured blood pressure, pulse, and temperature. RESULTS: In 5 cases a significant increase in ROS (p < 0.05) could be measured beginning 240 min after start of hyperthermia and further increasing until the 510-min time point. These results suggest a priming effect in PMN lasting far beyond the actual treatment period. The increase of ROS production following stimulation with FMLP, C5a or PMA was 60.4 +/- 21.6, 86.0 +/- 23.3, and 63.3 +/- 15.9% (SEM), respectively. Moreover, in all probands the maximal ROS production in PMN was observed 510 min after the beginning of WBIAI treatment. In 3 cases no difference in ROS could be observed. There was no difference in temperature, blood pressure, and pulse between responders and nonresponders. CONCLUSIONS: Our results show a hyperthermia-dependent priming effect of ROS production in PMN, suggesting an increase in immune reaction within the observation period of 510 min. Further investigations are necessary in order to specify responders and nonresponders and to characterize the results in specific diseases and the constitutions of the patients.
Complement C5a↗
[Changes of short-time heart rate variability during hyperthermia treatment with infrared A whole body irradiation].
BACKGROUND: Measures of heart rate variability (HRV) are widely recognized as being an important indicator method for autonomical function and cardiovascular neural regulation. The low-frequency component in spectral analysis is increased during conditions of raised sympathetic activation, the high-frequency component is closely correlated with vagal activity. Whole-body infrared-A irradiation (WBIAI) according to von Ardenne is a newly developed version of hyperthermia. In clinical use peripheral vasodilatation with significant increases in heart rate and hypotension were noted as acute effects of WBIAI. In order to evaluate the effect of WBIAI on autonomic function, we measured HRV during serial hyperthermias. PATIENTS AND METHODS: Power spectral density analysis of HRV during the first and the last of 4 serial WBIAI treatments with 30-60 min endurance was performed in 10 patients with chronic pain disorders. Tympanal body temperature was recorded continuously and was supposed to increase by 1 degrees C during treatment. Electrocardiographic monitoring was performed using a Marquette HoIter ECG. RR data were manually edited and standard frequency domain measures of the first and the last 5 min of treatment computed. The subjective efficacy of the treatment was rated by prestandardized interviews. RESULTS: Body temperature increased by 0.9 degrees C during the first treatment and 1.2 degrees C during the last treatment. In all patients the rise in body temperature due to treatment was accompanied by a significant increase in heart rate and a decrease of arterial blood pressure. During hyperthermia a slight decrease of absolute low-frequency and total power as well as a sharp decrease of high-frequency power and a significant increase of the low/high-frequency ratio could be noted. The rise in low/high-frequency ratio during WBIAI was less distinct at the last treatment compared to the initial treatment. Hyperthermia was regarded as a safe, well-tolerable and effective treatment. CONCLUSION: The results suggest that the cardiovascular response during WBIAI is accompanied by significant changes in autonomic cardiac regulation: A significant decrease of low-frequency power corresponding to depressed vagal activity results in an increase of Iow/high-frequency ratio. During serial hyperthermias the acute response is diminished suggesting an adaption of the autonomic response to hyperthermia. Further studies are necessary to investigate the long-standing autonomic effects of the treatment and include analysis of influencing factors such as the level of physical activity and constitutional individual conditions.
Body Temperature↗
[Trends in alternative medicine use in the USA].
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Adult↗
Reduction of granulocyte activation during hemodialysis with regional citrate anticoagulation: dissociation of complement activation and neutropenia from neutrophil degranulation.
Neutropenia and degranulation of neutrophils during hemodialysis with cellulosic membranes have been linked to complement activation, whereas in the synthetic polymethyl methacrylate (PMMA) membrane, degranulation occurs without notable complement activation. The mechanisms of neutrophil degranulation under these conditions have not yet been elucidated. Ionized calcium is an important prerequisite of granulocyte activation during in vitro blood contact with both types of artificial surfaces. This study compared the effect of normal ionized calcium during heparin anticoagulation with the effect of extracorporeal calcium depletion during regional citrate anticoagulation on activation of blood components. Because ionized calcium is reduced only in the extra-corporeal circuit, citrate anticoagulation in addition helps to differentiate between extracorporeal and systemic activation phenomena. Twelve chronic hemodialysis patients were dialyzed with polymethyl methacrylate (PMMA, 16 treatments) or cuprophane (CUP, 16 treatments) membranes either during regional citrate anticoagulation or while anticoagulated with heparin. During hemodialysis with CUP, anticoagulation with citrate significantly reduced neutropenia, C3a levels, and lactoferrin release. Elastase concentrations, however, were not reduced by citrate, probably because elastase release occurred not locally in the cuprophane dialyzer, but mostly in the systemic circulation of the patient. PMMA did not elevate C3a levels, and neutropenia was only mild. Both parameters were not influenced by citrate anti-coagulation. However, PMMA profoundly induced elastase and lactoferrin release during heparin anti-coagulation. Depletion of ionized calcium markedly reduced PMMA-mediated neutrophil degranulation in the extracorporeal circuit. The results indicate that ionized calcium is a requirement for neutrophil degranulation during hemodialysis. In PMMA membranes, neutrophil degranulation occurs independent of high complement levels, occurs at least partially inside the dialyzer, and requires the presence of ionized calcium in the extracorporeal circuit. In cuprophane membranes, degranulation was uncoupled from neutropenia and did not correlate with the degree of complement activation. Even in cuprophane dialysis, degranulation of secondary granules was markedly dependent on ionized calcium levels in the extracorporeal circuit.
Anticoagulants↗
A novel ELISA for the assessment of classical pathway of complement activation in vivo by measurement of C4-C3 complexes.
Measurements of complement split products by enzyme-linked immunosorbent assays (ELISA) are well established for the assessment of in vivo complement activation. We have combined two monoclonal antibodies (mAb) with specificities for C3b/iC3b/C3dg (mAb I3/15) and C4/C4b/C4d (mAb M4d2), respectively, in a sandwich ELISA to quantitate C4-C3 complexes as an indicator of complement activation. Serum incubated with heat aggregated IgG (HAG) was used as a standard and the C4-C3 levels expressed as microgram equivalent HAG/ml (microgram HAG-equ/ml). Normal values of C4-C3 complexes in plasma (EDTA) of healthy probands (n = 11) were 6.3 micrograms HAG-equ/ml +/- 1.5 (mean +/- 1 standard deviation (SD), with a range from 3.6 to 9.1). In patients with systemic lupus erythematosus (SLE, n = 23) C4-C3 values were clearly elevated (48.8 micrograms HAG-equ/ml +/- 52.9, range 7.5-184.7) as compared to samples from patients with idiopathic hypertension (IDH, n = 10) (6.5 micrograms HAG-equ/ml +/- 1.7, range 4.1-9.4). For SLE patients C4-C3 levels significantly correlated with values for C3b/iC3b/C3d (r = 0.69, p < 0.001) and C3 containing immune complexes (r = 0.68, p < 0.001), but not with the C4d fragment (r = 0.26). C4-C3 levels of 96% of the studied SLE patients were increased more than 2 SD above the normal mean as compared to 74% of C4d and activated C3 values, respectively. Serum treated with zymosan as an activator of the alternative pathway of complement did not exhibit higher C4-C3 values. These results demonstrate that the quantitation of in vivo generated C4-C3 complexes by ELISA provide a novel, sensitive parameter for classical pathway of complement activation.
Antibodies, Monoclonal↗
C3a activates reactive oxygen radical species production and intracellular calcium transients in human eosinophils.
Whereas C5a is a well-established potent activator of eosinophils, the functional role of C3a in the activation of eosinophils is, so far, poorly understood. Here, the activation of human eosinophils stimulated with C3a was analyzed and compared to C5a activation. Flow-cytometrical measurements revealed that stimulation of eosinophils by C3a resulted in a transient elevation of the intracellular calcium concentration ([Ca2+]i) in a dose-dependent manner. In addition, the production of reactive oxygen radical species (ROS) of eosinophils after C3a and C5a stimulation was measured by lucigenin-dependent chemiluminescence and quantified by superoxide dismutase-inhibitable reduction of ferricytochrome C. Half maximal and maximal ROS production in response to C3a was observed at 50 ng/ml and 1000 ng/ml, respectively, whereas C3a-desArg was inactive. To ensure that C3a stimulation was not caused by contamination with C5a, monoclonal antibodies were used to demonstrate the specificity of C3a. The effect of C3a was completely abolished in the presence of monovalent antigen-binding fragments of a functionally blocking anti-C3a monoclonal antibody. In addition, blockade of the C5a receptor by the monoclonal anti-C5a receptor antibody S5/1 totally inhibited the C5a-evoked ROS production, whereas the C3a response in the presence of S5/1 was unaffected. Finally, desensitization experiments revealed a homologous desensitization of C3a after restimulation with C3a. In contrast, no cross-desensitization was observed upon stimulation with C5a. Furthermore, the C3a- and C5a-induced production of ROS of eosinophils was totally inhibited by pertussis toxin, indicating the involvement of guanine nucleotide-binding proteins (Gi-proteins). In summary, these results demonstrate that C3a is a potent activator for eosinophils initiating transient [Ca2+]i changes and production of reactive oxygen species. C3a therefore may play a part in the pathophysiology of diseases with eosinophil and complement activation.
Calcium↗
[Ca2+]i-transients and actin polymerization in human neutrophils under stimulation with GRO alpha and complement fragment C5a.
The neutrophil chemotaxins, complement fragment C5a (C5a) and GRO alpha, induced the mobilization of Ca2+ from intracellular stores and the polymerization of actin in human neutrophils as assayed by flow cytometric measurements. [Ca2+]i-transients developed as an "all-or-none" response. Individual neutrophils required different threshold concentrations of added ligand to induce [Ca2+]i-transients which were then always maximal. In contrast, chemotaxin-induced formation of actin filaments in single neutrophils occurred in a dose-dependent manner. Pertussis toxin blocked chemotaxin-induced actin polymerization and [Ca2+]i-transients indicating that both cell responses shared initial activation steps such as ligand binding and activation of guanine nucleotide-binding proteins (G-proteins).
Actins↗
Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease.
Impaired platelet function and a bleeding tendency are well-recognized complications of chronic renal failure. Because the fibrinogen receptor GPIIb-IIIa plays a central role in platelet aggregation and adhesion to the subendothelium, it was reasoned that a defect in this receptor may underlie the impaired platelet function in uremia. To test this hypothesis, the function of this receptor in the platelets of 11 uremic patients was studied. Aggregation studies were performed with flow cytometric techniques with anti-GPIIb-IIIa conformation-specific monoclonal antibodies (mAb) (anti-LIBS1 and anti-PMI-1). Antifibrinogen and antithrombospondin mAb were used to characterize fibrinogen binding to GPIIb-IIIa and the release of alpha-granules, respectively. Platelets from patients with chronic renal failure showed significantly decreased binding of conformation-dependent anti-LIBS1 mAb after ADP, phorbol myristate acetate, or RGD-peptide stimulation compared with normal controls, suggesting a defect related to the ability of the fibrinogen receptor to undergo a conformational change. Moreover, antifibrinogen and antithrombospondin binding to activated platelets were reduced in uremic patients, implying impairment of both ligand-binding and alpha-granule release. Hemodialysis partially restored GPIIb-IIIa function, which may account for the observed effects of this therapy in restoring platelet aggregation. These findings indicate that platelets of patients with chronic renal failure reveal an aggregation defect at least partially due to an intrinsic GPIIb-IIIa dysfunction and the presence of a putative uremic toxin that inhibits fibrinogen binding to GPIIb-IIIa.
Adenosine Diphosphate↗
Complement fragment C3a stimulates Ca2+ influx in neutrophils via a pertussis-toxin-sensitive G protein.
The signal pathways of neutrophils following stimulation with the complement fragment C3a (C3a) were studied in neutrophils and compared to the pathways activated by complement fragment C5a (C5a). Analysis of polyphosphoinositol lipid turnover showed that C5a, but not C3a, activated phosphatidylinositol-bisphosphate-3-kinase (PtdInsP2 3-kinase) indicating that different signal pathways are activated by the two anaphylatoxins. To examine whether C3a stimulated Ca2+ transients, cytosolic free Ca2+ levels were analyzed in Fluo-3-labelled neutrophils by flow cytometry. C3a stimulated a fast and concentration-dependent increase of cytosolic free Ca2+. Comparison of the C3a response with that of C5a revealed a more pronounced C5a-triggered Ca2+ rise. Addition of EGTA to the extracellular buffer prior to stimulation did not significantly alter the initial Ca2+ rise at low C5a concentrations, but reduced the time course of the Ca2+ transients at high concentrations. In marked contrast, EGTA completely blocked the Ca2+ response stimulated by C3a in neutrophils labeled with either Indo-1/AM or Fluo-3. Preincubation of neutrophils with pertussis toxin inhibited both C3a- and C5a-stimulated Ca2+ transients, indicating the involvement of guanine-nucleotide-binding proteins (G proteins) in these processes. In order to examine whether the C3a receptor is coupled to G proteins, binding of guanosine 5'-O-(3-[35S]thiotriphosphate) ([35S]GTP[S]) to purified neutrophil plasma membranes was studied. Both C3a and C5a stimulated high-affinity binding of [35S]GTP[S] up to 1.5-fold and 3-fold, respectively. These data suggest that the two anaphylatoxins activate pertussis-toxin-sensitive G proteins, which then trigger different signal transduction pathways. C3a specifically stimulated Ca2+ influx from the extracellular medium, whereas C5a additionally activated the PtdInsP2 3-kinase and stimulated Ca2+ mobilization from intracellular stores.
Calcium↗
Sequelae after infection with Trichinella spiralis: a prospective cohort study.
It is still a matter of debate whether or not infection with Trichinella spiralis is followed by long lasting sequelae. A common source epidemic of trichinosis which occurred in Bitburg, FRG, in October 1982 gave us the opportunity of performing a controlled cohort study (171 patients and 51 controls). 145 patients and 44 controls completed the 3 year follow-up. Complaints persisted in 36% of patients aged less than 30 years and in 100% of patients aged greater than 50 years. Complaints in order of frequency were: muscular complaints 84%, ocular complaints 63%, cardiac complaints 48%, cephalgia 43%, neurological complaints 35%, gastrointestinal complaints 18%, m fatigue and weakness 18%, oedema 12% and fever less than 1%. IgG antibodies to T. spiralis were still present in all but 5 patients 3 years after infection. IgM antibodies were either low or absent. In our patients the frequency and pattern of complaints and the correlation to the specific antibody response provide evidence that trichinosis causes long-lasting disease. Yet, from our data we were unable to draw conclusions as to the causative pathophysiological mechanisms.
Adolescent↗