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G Hempelmann

Publications and source records attributed to G Hempelmann.

At least 19 recordsLinked to original sources

Minimal immunoreactive plasma beta-endorphin and decrease of cortisol at standard analgesia or different acupuncture techniques.

BACKGROUND AND OBJECTIVE: Acupuncture has been claimed to be associated with activation of the endogenous antinociceptive system. The analgesic effects of acupuncture have been ascribed to beta-endorphin interacting with opioid receptors. However, firstly, the release of beta-endorphin into the blood has been proven to be induced by stress, i.e. under dysphoric conditions, and, secondly, if released under stress, beta-endorphin has been shown not to be analgesic. Our aim was to test whether beta-endorphin immunoreactive material is released into the cardiovascular compartment during acupuncture comparing the most frequently used types of acupuncture with standard pain treatment under apparently low stress conditions. METHODS: This prospective study included 15 male patients suffering from chronic low back pain. beta-Endorphin immunoreactive material and cortisol were measured in the plasma of patients who underwent, in random order, therapy according to a standard pain treatment, traditional Chinese acupuncture, sham acupuncture, electro acupuncture and electro acupuncture at non-acupuncture points before, at and after the treatment. Statistical analysis was performed using two-way ANOVA with repeated measures. RESULTS: A decrease in plasma cortisol concentration measured over the five treatment protocols was highly significant (P < 0.001). The beta-endorphin immunoreactive material concentrations in plasma were minimal at all times and in all treatment conditions. The influence of treatments by various acupuncture procedures on cortisol and beta-endorphin immunoreactive material plasma concentrations over the three time points was not significantly different. CONCLUSIONS: beta-endorphin immunoreactive material in blood is not released by any type of acupuncture as tested under low stress conditions.

Acupuncture Analgesia↗

Pathways involved in alanyl-glutamine-induced changes in neutrophil amino- and alpha-keto acid homeostasis or immunocompetence.

We examined the effects of DON [glutamine-analogue and inhibitor of glutamine-requiring enzymes], alanyl-glutamine (regarding its role in neutrophil immunonutrition) and alanyl-glutamine combined with L-NAME, SNAP, DON, beta-alanine and DFMO on neutrophil amino and alpha-keto acid concentrations or important neutrophil immune functions in order to establish whether an inhibitor of *NO-synthase [L-NAME], an *NO donor [SNAP], an analogue of taurine and a taurine transport antagonist [beta-alanine], an inhibitor of ornithine-decarboxylase [DFMO] as well as DON could influence any of the alanyl-glutamine-induced effects. In summary, irrespective of which pharmacological, metabolism-inhibiting or receptor-mediated mechanisms were involved, our results showed that impairment of granulocytic glutamine uptake, modulation of intracellular glutamine metabolisation and/or de novo synthesis as well as a blockade of important glutamine-dependent metabolic processes may led to significant modifications of physiological and immunological functions of the affected cells.

Adult↗

Nitric oxide and polyamine pathway-dependent modulation of neutrophil free amino- and alpha-keto acid profiles or host defense capability.

We have examined the effects of N(omega)-nitro-L-arginine-methylester-hydrochloride [L-NAME; inhibitor of nitric oxide synthase], S-nitroso-N-acetyl-penicillamine [SNAP; nitric oxide donor], alpha-difluoro-methyl-ornithine [DFMO; inhibitor of ornithine decarboxylase] arginine or ornithine as well as the combination of arginine or ornithine with L-NAME, SNAP or DFMO on intracellular free amino- and alpha-keto acid profiles and the immune function markers superoxide anion and hydrogen peroxide generation as well as released myeloperoxidase activity in neutrophils (PMN). Although the underlying mechanisms still remain unclear, we believe from our results that nitric oxide as well as polyamine-dependent pathways are involved in the signal transmission of free radical molecule, beneficial nutritional therapy or maleficient pharmacological stress-induced alterations in PMN nutrient composition. Relevant changes in intragranulocyte free amino- and alpha-keto acid homeostasis and metabolism, especially, may be one of the determinants in PMN nutrition that positively or negatively influences and modulate neutrophil host defence capability and immunocompetence.

Adult↗

[Escalating management of progressive neuropathic cancer pain].

The management of tumor-related pain, particularly that which is neuropathic in origin, is both difficult and challenging. According to WHO guidelines, opioids are the first-line analgesics in case of severe tumor-related pain syndromes. Some patients receiving continuous opioid therapy rapidly require increase of the opioid dose. In this case it can be necessary to extend the analgesic regime and to either apply interventional procedures or change the opioid or the route of administration. The case presented is remarkable regarding the severity and persistent nature of the patient's pain despite a variety of commonly employed treatments.

Analgesics, Opioid↗

Relationship of taurine and other amino acids in plasma and in neutrophils of septic trauma patients.

Recently, an interdependency of plasma taurine and other amino acids as well as metabolic and clinical variables implicating therapeutic options was reported. This result may be an indication that plasma taurine levels are directly related to intracellular levels. Therefore, the aim of this study was to analyse the possible relationship between taurine levels in plasma and in neutrophils, the relationship to other amino acids, and variables quantifying metabolic impairment and severity of sepsis in multiple trauma patients developing sepsis. After multiple trauma taurine decreased significantly in plasma in thirty-two patients as well as within the neutrophil and does not recover in sepsis. Lower individual levels in the neutrophil did not follow lower individual levels in plasma and no correlation of taurine in plasma and in the neutrophils could be observed. In sepsis, only plasma showed an interdependency of taurine, aspartate, and glutamate. No association between taurine plasma or intracellular levels and SOFA score as indicator for severity of sepsis or metabolic variables was observed. After multiple trauma and in sepsis, taurine uptake in cells (which is regulated in different ways), and intracellular taurine (which serves e.g. as an osmolyte) can be influenced. Therefore a prediction of the neutrophil taurine pool seems not fully possible from taurine plasma levels. Intracellular taurine has some unique properties explaining the missing interdependency despite some similarities in osmoregulation and metabolic interactions to other amino acids. The association of taurine, aspartate, and glutamate in plasma cannot be simply transferred to the neutrophils intracellular level. The clinical meaning of the plasma correlation remains unclear. A dependency of plasma and neutrophil taurine to severity of sepsis and to metabolic variables seems not possible because of the multifactorial pathophysiology of sepsis.

Adult↗

Alterations in neutrophil (PMN) free intracellular alpha-keto acid profiles and immune functions induced by L-alanyl-L-glutamine, arginine or taurine.

The objective of this study was to determine the dose as well as duration of exposure-dependent effects of L-alanyl-L-glutamine, arginine or taurine on polymorphonuclear neutrophil (PMN) free alpha-keto acid profiles and, in a parallel study, on PMN immune functions. Exogenous L-alanyl-L-glutamine significantly increased PMN alpha-ketoglutarate, pyruvate PMN superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase (MPO) activity. Arginine also led to significant increases in alpha-ketoglutarate, pyruvate, MPO release and H2O2 generation. Formation of O2- on the other hand was decreased by arginine. Incubation with taurine resulted in lower intracellular pyruvate and alpha-ketobutyrate levels, decreased O2- and H2O2 formation and a concomitant significantly increased MPO activity. We therefore believe that considerable changes in PMN free-alpha-keto-acid profiles, induced for example by L-alanyl-L-glutamine, arginine or taurine, may be one of the determinants in cell nutrition that considerably modulates the immunological competence of PMN.

Adult↗

Serum creatinine and perioperative outcome--a matched-pairs approach using computerised anaesthesia records.

BACKGROUND AND OBJECTIVE: A study was designed to utilise the resources of our computerised anaesthesia record keeping system to assess the attributable effects of increased preoperative creatinine (> 1.3 mg dL(-1)) on outcome in patients undergoing non-cardiac surgery. METHODS: This retrospective study was based on data sets of 58 458 patients recorded with a computerised anaesthesia record keeping system over a period of 4 yr at a tertiary care university hospital. Cases were defined as patients with a preoperative creatinine > 1.3 mg dL(-1); controls (creatinine < or = 1.3 mg dL(-1)) were selected and automatically matched according to several parameters (ASA physical status, high risk and urgency of surgery, age and gender) in a stepwise fashion. Main outcome measures were hospital mortality and the incidence of intraoperative cardiovascular events. RESULTS: Three-thousand-and-twenty-eight patients (5.2%) had preoperative creatinine values > 1.3 mg dL(-1). Matching was successful for 54.5% of the cases, leading to 1649 cases (mean creatinine 3.3 +/- 2.2 mg dL(-1)) and 1649 controls (1.0 +/- 0.2 mg dL(-1)). The crude mortality rates for the cases and matched controls were 2.2% (n = 36) and 0.9% (n = 15), respectively (P = 0.003). Intraoperative cardiovascular events were found in 30.1% of the patients (n = 496) and in 28.3% of the matched controls (n = 466; P = 0.25, power = 0.46). Using logistic regression analyses a significant association between preoperative increased creatinine and hospital mortality was found (odds ratio 2.62; 95% confidence interval [1.39; 4.931). CONCLUSIONS: An increased preoperative serum creatinine in patients undergoing non-cardiac surgery is associated with an increased perioperative risk, but not with a higher incidence of intraoperative cardiovascular events.

Adult↗

[Activation of granulocytes and antiproteases in open heart surgery].

OBJECTIVE: Cardiovascular surgical procedures with extracorporeal circulation (ECC) lead to neutrophil activation followed by the release of proteases such as neutrophil elastase (NE) and oxidants. The mis-balance between proteases and their physiological inhibitors may contribute to morbidity in the postoperative period. In this study, the effects of cardiac surgery on neutrophil mediators were evaluated. Release of neutrophil elastase and plasma levels of the natural NE antagonists alpha (1)-proteinase inhibitor (API) and secretory leukocyte proteinase inhibitor (SLPI) were measured. The oxidative burst and the phagocytic activity were also evaluated. Tissue destruction was quantified by measuring the serum concentration of fibronectin. METHODS: Blood samples were obtained from 30 patients undergoing elective coronary artery bypass grafting (n = 30). NE and SLPI concentrations were measured by ELISA, API and fibronectin plasma levels were determined by nephelometry. Neutrophil phagocytic activity and oxidative burst were evaluated by flow cytometry. RESULTS: Neutrophil elastase plasma concentrations rose during ECC (245 +/- 107 microg/ml versus 44 +/- 14 microg/ml after induction, p < 0.001), whereas SLPI and API were decreased after onset of ECC. 24 h after ECC SLPI (54 +/- 17 ng/ml versus 41 +/- 10 ng/ml, p < 0.05) and API (3 +/- 0.5 g/l versus 1.6 +/- 0.3 g/l, p < 0.05) increased significantly compared to baseline values. A minor increase in phagocytic activity was observed after the onset of ECC. There were no significant changes in the oxidative burst. CONCLUSION: Cardiac surgery with ECC leads to neutrophil activation and elastase release. The imbalance between NE and the NE inhibitors API and SLPI may increase the risk for tissue damage due to granulocyte activation after cardiac surgery.

Aged↗

[Influence of continuous positive airway pressure (CPAP) on blood flow velocity in the venous vascular system of the liver -- duplex sonographic investigations].

OBJECTIVE: In the last years, noninvasive techniques of artificial ventilation like continuous positive airway pressure (CPAP) have become more and more important. However, the effects of such procedures on the circulation of the hepatosplanchnic area are, except for the indocyanine green plasma clearance, not yet representative by means of noninvasive investigation methods. METHODS: We studied maximum blood flow velocity in defined areas of hepatic and portal veins by duplex ultrasonography in 20 healthy volunteers (12 male, 8 female; age: 24,7 +/- 4,7 years [mean +/- SD]) before, during and after application of CPAP (10 cm H(2)O). As many measurements as possible were taken in both vascular systems. After division into five minute intervals arithmetical mean values were calculated for each interval. The experiment was divided into a control interval ("before CPAP"), three "CPAP" intervals and finally two "after CPAP" intervals. Heart rate and blood pressure were taken at the beginning of these intervals. RESULTS: Compared with the control interval, maximum blood flow velocity in the area of the hepatic vein decreased significantly by 13,2 %, 16,8 % and 15,7 % (p < or = 0,001 in each case) during each of the three "CPAP" periods. In the portal venous area blood flow velocity decreased by 4,3 %, 8,8 % and 7,0 %, respectively, with a significant decrease only in the second "CPAP" interval (p < or = 0,005). After CPAP, changes returned to baseline within a few minutes. Heart rate and blood pressure showed no significant differences during the whole experiment. CONCLUSION: Parameters taken in both venous vascular areas of the liver show clear correspondence with the results of former studies, which have been determined by means of more invasive investigation methods. Maximum blood flow velocity seems to be useful for monitoring liver blood flow and its individual time course during CPAP, noninvasively and semiquantitatively. Further trials under conditions of controlled mechanical ventilation should be performed to optimize ventilation strategies for the critically ill.

Adult↗

Impact on postoperative pain of long-lasting pre-emptive epidural analgesia before total hip replacement: a prospective, randomised, double-blind study.

Clinical studies on pre-emptive analgesia have produced inconsistent results. We conducted a clinical study investigating the effect of long-lasting pre-emptive epidural analgesia on consumption of analgesics and acute pain. Forty-two patients scheduled for elective hip replacement for osteo-arthritis were randomly assigned to receive, on the day before operation, either 5 ml.h(-1) ropivacaine 0.2% (study group, n = 21) or 5 ml.h(-1) saline (control group, n = 21). Postoperative analgesia was achieved in both groups by patient-controlled epidural analgesia (PCEA) with ropivacaine 0.2%. The main outcome measure was consumption of local anaesthetics. Additional parameters included visual analogue pain scale (VAS) scores, consumption of rescue analgesics, requests for PCEA boluses, and side-effects. The pre-operative parameters and pain scores were similar in the two groups. Epidural blocks provided sufficient operative analgesia in all patients. Pre-emptive analgesia was continued for 11-20 h and led to significantly decreased pain scores before surgery. The consumption of local anaesthetics was decreased postoperatively in the study group (194 mg vs. 284 mg in the postoperative period). Furthermore, bolus requests occurred more frequently in the control group. VAS scores did not differ significantly between groups. Long-lasting "pre-emptive" epidural analgesia decreases postoperative pain with improved pain control.

Adult↗

Benzodiazepine receptor-dependent modulation of neutrophil (PMN) free amino- and alpha-keto acid profiles or immune functions.

We have examined the effects of midazolam, Ro 5-4864 (agonist for "peripheral" [p] benzodiazepine receptors [BR]), PK 11195 (antagonist for pBR), flumazenil (antagonist for "central" BR), naloxone (antagonist for opiate receptors) and the combination of midazolam and Ro 5-4864, PK 11195, flumazenil or naloxone on intracellular amino- and alpha-keto acids and the immune function markers superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)) and released myeloperoxidase (MPO) activity in neutrophils (PMN). Only midazolam and Ro 5-4864 led to significant changes in the dynamic PMN free amino- and alpha-keto acid pools. Concerning PMN immune function markers, midazolam and Ro 5-4864 significantly decreased O(2)(-) and H(2)O(2) formation and released MPO. When midazolam and Ro 5-4864 were applied together they appeared to act additively. Pre-incubation with PK 11195 partially neutralized the midazolam effects whereas flumazenil or naloxone showed no effects. We therefore believe that pBR are involved in the signal transmission of anesthetic-induced cellular metabolic changes in PMN.

Adult↗

Autoimmune etiology of complex regional pain syndrome (M. Sudeck).

Sera of 12 patients with complex regional pain syndrome (CRPS) were tested for the occurrence of autoantibodies against nervous system structures. Immunohistochemistry revealed autoantibodies against autonomic nervous system structures in 5 of 12 (41.6%) of the patients. Western blot analysis showed neuronal reactivity in 11 of 12 (91.6%) patients. The authors hypothesize that CRPS can result from an autoimmune process against the sympathetic nervous system.

Adult↗

Effects of ornithine on neutrophil (PMN) free amino acid and alpha-keto acid profiles and immune functions in vitro.

The objective of this study was to determine the effects of ornithine on polymorphonuclear leucocyte (PMN) free amino- and alpha-keto acid profiles, superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase activity (MPO). Exogenous ornithine significantly increased PMN asparagine, glutamine, aspartate, glutamate, arginine, citrulline, alanine, alpha-ketoglutarate and pyruvate as intracellular ornithine increased. Concerning PMN immune function markers ornithine increased H2O2-generation and MPO activity while O2- -formation was decreased. We believe therefore that ornithine is important for affecting PMN "susceptible free amino- and alpha-keto acid pool" although the mechanisms are not yet clear. This may be one of the determinants in PMN nutrition considerably influencing and modulating PMN host defense capability.

Adult↗

Hypoxic increase in nitric oxide generation of rat sensory neurons requires activation of mitochondrial complex II and voltage-gated calcium channels.

Recently, we have demonstrated that sensory neurons of rat lumbar dorsal root ganglia (DRG) respond to hypoxia with an activation of endothelial nitric oxide (NO) synthase (eNOS) resulting in enhanced NO production associated with mitochondria which contributes to resistance against hypoxia. Extracellular calcium is essential to this effect. In the present study on rat DRG slices, we set out to determine what types of calcium channels operate under hypoxia, and which upstream events contribute to their activation, thereby focusing upon mitochondrial complex II. Both the metallic ions Cd2+ and Ni2+, known to inhibit voltage-gated calcium channels and T-type channels, respectively, and verapamil and nifedipine, typical blocker of L-type calcium channels completely prevented the hypoxic neuronal NO generation. Inhibition of complex II by thenoyltrifluoroacetone at the ubiquinon binding site or by 3-nitropropionic acid at the substrate binding site largely diminished hypoxic-induced NO production while having an opposite effect under normoxia. An additional blockade of voltage-gated calcium channels entirely abolished the hypoxic response. The complex II inhibitor malonate inhibited both normoxic and hypoxic NO generation. These data show that complex II activity is required for increased hypoxic NO production. Since succinate dehydrogenase activity of complex II decreased at hypoxia, as measured by histochemistry and densitometry, we propose a hypoxia-induced functional switch of complex II from succinate dehydrogenase to fumarate reductase, which subsequently leads to activation of voltage-gated calcium channels resulting in increased NO production by eNOS.

Animals↗

[Morphine inhibits complement receptor expression, phagocytosis and oxidative burst by a nitric oxide dependent mechanism].

OBJECTIVE: Monocytes play a crucial role in the immune response by recognition, ingestion, and intracellular killing of microorganisms. We investigated whether morphine and fentanyl influence CD 11b and CD35 surface receptor expression, phagocytic activity and superoxide anion generation of monocytes in a whole blood flow cytometric assay. METHODS: Whole blood of 13 healthy volunteers was incubated with different morphine and fentanyl concentrations. Expression of surface receptors CD 11b and CD35 was determined by fluorochrome-labelled antibodies. Phagocytic activity was assessed by ingestion of fluorescent bacteria. Conversion of dihydrorhodamin served for oxidative burst measurements. RESULTS: Morphine inhibited monocyte function in a concentration and time dependent manner. Morphine-induced changes were abolished by preincubation with the NO synthase inhibitor N-nitro-l-arginine as well as naloxone. Fentanyl failed to inhibit receptor expression, phagocytosis and reactive oxygen production by monocytes in clinically relevant as well as supraclinical concentrations. CONCLUSION: Our results suggest that these monocyte functions are inhibited by a morphine-stimulated NO release mediated by a mu opiate receptor subtype expressed on the surface of monocytes. In contrast, fentanyl did not share morphine's inhibitory effects on monocyte activity.

Adult↗

[To our Readers].

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Anesthesiology↗