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T Menges

Publications and source records attributed to T Menges.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

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↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2003

Low plasma glutamine after multiple trauma: relationship with intracellular glutamine in polymorphonuclear neutrophils during prolonged ICU stay.

BACKGROUND: Aim of the study was to evaluate whether low plasma glutamine (GLN) is related to low intracellular GLN in stress-affected cells such as polymorphonuclear neutrophil (PMN). We hypothesized, that because low plasma GLN is assumed to have an impact on clinical outcome, stress-affected cells may also show low GLN contents. METHODS: Thirty-nine consecutive severely injured trauma patients staying at least 10 days at a surgical intensive care unit (ICU) of a university hospital were separated into two groups: group one (n = 16) with low plasma GLN (< 420 micromol/l in average during ICU stay), and group two (n = 23) with normal plasma GLN. Initial blood samples for GLN analyses were collected within 24 h of admission at ICU. Further blood samples were taken on days 5 and 10 at 08:00 hours. RESULTS: Patients in both groups showed no differences regarding demographic data, surgical interventions or infections. Acute physiology and chronic health evaluation (APACHE) II and the sequential organ failure assessment (SOFA) score and mortality rate were also comparable. During the study period, intracellular PMN GLN contents and concentrations did not differ between both groups. On the first day, intracellular PMN GLN content in the low plasma GLN group peaked at 5.01 +/- 3.06 x 10(-16) mol and in normal plasma GLN group at 4.73 +/- 2.57 x 10(-16) mol above the level of healthy individuals. In both groups, content decreased significantly towards the end of the observation period (group one: 2.79 +/- 1.59 x 10(-16) mol and group two: 2.63 +/- 1.71 x 10(-16) mol). A correspondent course could be observed for cell volumes. In contrast, variation of intracellular GLN concentrations remained within the reference range throughout the observation period: group one 836 +/- 510 micromol/l on day 1 and 582 +/- 331 micromol/l on day 10, and group two 788 +/- 428 micromol/l on day 1 and 548 +/- 356 micromol/l on day 10. No correlation between plasma GLN and intracellular GLN was found in either group. CONCLUSION: No association between low plasma GLN and low intracellular GLN in PMN was found in a cohort of severely injured trauma patients with a minimum stay of 10 days at ICU.

Adult↗
PubMed2003

Enteral nutrition practice in a surgical intensive care unit: what proportion of energy expenditure is delivered enterally?

The object of this study was to document enteral feeding practice in critically ill patients in a surgical intensive care unit. We asked what proportion of measured energy expenditure is delivered enterally. Patient, material, and therapy-related factors should be assessed and related to enteral nutrition. Sixty patients receiving enteral nutrition for a period of at least 10 days were included in the study. Mean daily energy expenditure was 27.8+8.7 kcal/kg. Mean daily enteral delivered calories reached 19.7+/-10.3 kcal/kg (P<0.05). Twenty-one out of 60 (35%) patients were fed isocalorically; 46% of enteral nutrition days failed to reach 80% of energy expenditure. Ten out of 30 patients (33%) fed over a gastric tube were nourished isocalorically in comparison to 8 out of 20 patients (40%) fed over a duodenal tube. Factors associated with hypocaloric enteral feeding in multiple logistic regression were abdominal, pelvic and lumbal spine trauma, gastrointestinal intolerance, problems with the feeding tube, additional surgical interventions, airway management and use of fentanyl. In the course of the study, gastrointestinal complications were the cause for more than 50% of insufficient enteral delivery cases, while therapy and material related reasons contribute to only a minor part.Abdominal, pelvic and lumbal spine traumas are associated with a higher possibility towards developing problems with enteral delivery, as shown by odds-ratios greater than eight. These diagnoses amounted in our investigation to nearly 40% and make a great difference to medical patients. Therefore, recommendations for optimising enteral feeding must take the concerned patient collective into account.

Adult↗
PubMed2003

[Small pox--infection, therapy and anaesthesiological management (part 1)].

Smallpox is an acute contagious and sometimes fatal infectious disease. It is caused by the variola-virus. Smallpox is characterized by a typical disease form with a progressive distinctive skin rash, especially at face, arms and legs. Smallpox has a fatality rate of about 30 % and the therapy of infected patients is only symptomatically. As prevention the WHO initiated worldwide vaccination programs in the year 1967. The last naturally occurring case of smallpox in the world was in Somalia in 1977. Since then the only known cases of smallpox happened from an outbreak in Birmingham, England caused by a laboratory accident in the year of 1979. On May the 8 th 1980 the disease was declared as eliminated from the world by the WHO (WHO-Resolution 33.33). A natural occurrence of the variola-virus seems to be not given. Nevertheless the virus exists for research in two laboratories, the American Centers of Disease Control and Prevention in Atlanta, Georgia and in the Russian Research Center for Virology and Biotechnics in Kolzowo, Sibiria. Threatening infections with smallpox or other microorganisms, used as bioweapons, get a new dimension through global terrorism. The variola-virus represents an optimal candidate for bioweapons. It is easy to replicate, it is highly contagious and the transmission over aerosol or direct contact from man to man is easy to handle. After the disease was eliminated from the world, routine vaccination among general public was stopped. Therefore younger people don't possess any vaccination protection. Older formerly vaccinated people probably have only a non-sufficient protection. Because of the smallpox elimination a lot of physicians have no experience with this disease. An outbreak of this smallpox isn't only controlled by new vaccination. In our times we need adapted prevention-standards, pox-alarm plans and quarantine standards.

Anesthesia↗
PubMed2001

Plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism and prognosis of severely injured patients.

A single base pair insertion/deletion (4G/SG) promoter polymorphism in the plasminogen-activator-inhibitor-1 (PAI-1) gene is thought to play a part in prognosis after severe trauma. We investigated the relation between outcome of severe trauma, PAI-1 concentrations, and PAP-1 genotype in 61 patients who had been severely injured. 11 (58%) of 19 patients with genotype 4G/4G did not survive, whereas only eight (28%) of 29 patients with heterozygous genotype 4G/SG, and two (15%) of 13 patients with genotype 5G/5G died. The PAI-1 4G allele is associated with high concentrations of PAI-1 in plasma and a poor survival rate after severe trauma.

Alleles↗
PubMed2001

Influence of colloid fluids on polymorphonuclear granulocyte function in vivo.

BACKGROUND: Granulocytes have a role in the immediate immune response. In a previous investigation we could demonstrate in vitro a moderate increase of the complement receptors CR1 (CD35) and CR3 (CD11b/CD18) on the surface of polymorphonuclear neutrophils (PMN) after incubation of whole blood with colloids. To elucidate the clinical significance, we investigated if these changes were also present in vivo. METHODS: The study was performed prior to anaesthesia for orthopaedic surgery. A total of 60 ASA-I patients was evaluated. Patients received in a randomised manner 7 mL/kg of the following solutions: human albumin 5% (HA), gelatine 4% (GEL), hydroxyethylstarch solution 6% with MW 200,000 Da, degree of substitution 0.5 (HES), or Ringer's solution. Prior to the infusion, at the end (30 min) and again 30 min later, blood samples were taken. Blood was incubated with fluorescein-conjugated monoclonal antibodies (CD11b, CD16, CD35, CD62L) and analysed with flow cytometry. RESULTS: HA, GEL, HES, and Ringer's solution failed to induce significant differences in the expression of complement receptors CR1 (CD35) and CR3 (CD11b/CD18), Fc gamma receptor IIIb (CD16), and of L-selectin (CD62L) receptor on the surface of PMN. CONCLUSIONS: Application of colloids like HA, GEL, or HES in moderate amounts shows no short-term effect on adhesion or activation molecules on granulocytes. However, in high doses, infused in situations such as multiple trauma and sepsis, the consequences on the function of PMN may be speculative and require further investigations.

Adult↗
PubMed2001

The influence of intravenous anaesthetics on the activity of enzymes released from polymorphonuclear leucocytes in vitro.

BACKGROUND AND OBJECTIVE: Polymorphonuclear leucocytes make a decisive contribution to defence against bacterial infections. In particular, the effects of anaesthetics on non-oxidative bactericidal mechanisms have previously only been superficially examined. Although the influence of anaesthetic agents on oxidative bactericidal activity has been thoroughly examined, our study concentrated on the effect on non-oxidative processes, which appears to have been a neglected field of research. METHODS: The effects of methohexital, etomidate, ketamine, fentanyl and morphine on the activity of lysozyme and beta-glucuronidase released from polymorphonuclear leucocytes have been studied in vitro. The activity of lysozyme was determined by recording the changes in the turbidity of a suspension of micrococcus lysodeicticus caused by the enzymatic action of lysozyme. beta-glucuronidase activity was photometrically measured by the enzymatic cleavage of phenolphthalein glucuronic acid. RESULTS: High concentrations of methohexital inhibited lysozyme activity; however, etomidate and morphine caused an increase of beta-glucuronidase activity in therapeutic plasma concentrations. While there was no effect of etomidate on lysozyme activity, all concentrations tested significantly stimulated beta-glucuronidase activity. This result was unexpected because intravenous anaesthetics have previously shown a tendency to suppress polymorphonuclear leucocyte functions. Whereas the inhibition of lysozyme activity by the high concentration of methohexital was no surprise, the increase of beta-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine was quite unexpected. CONCLUSIONS: At present, the underlying mechanism for the increase of beta-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine is unknown. The fact that there was no influence of these agents on lysozyme activity possibly suggests that the anaesthetic agents have different effects on azurophilic and specific granules. Since in vitro investigations have their limitations, it is too early to draw practical consequences from our study. Moreover, at present it is unclear whether an increase of beta-glucuronidase activity in vivo is an advantage or not. In any case, we think it advisable to perform further investigations on the influence of anaesthetic agents on oxygen-independent bactericidal mechanisms.

Anesthetics, Intravenous↗
PubMed2001

[Transmissible spongiform encephalopathies--anesthesiologic and intensive care management].

The transmissible spongiform encephalopathies (TSE) are known to affect humans and various animals. The bovine spongiform encephalopathy (BSE) and the human Creutzfeldt-Jacob disease (CJD) are among the most notable degenerative disorders caused by prions. Considering the BSE epidemic and the description of a new variant of Creutzfeldt-Jacob disease (nvCJD), which is probably related to bovine spongiform encephalopathy, TSE have recently gained a lot of public attention. Although the causative factors (prions, viruses) are still under discussion, none of the present concepts are explanatory for all aspects of the human CJD. CJD may present as a sporadic, genetic, or infectious illness and there is now considerable concern that bovine prions may have been passed to humans. To exclude transmission of CJD via medical products and instruments, the effectiveness of cleaning, disinfection and sterilization procedures must be firmly established. This manuscript presents an overview to anaesthesiology and intensive care medicine of recommended inactivation procedures and assessed these procedures in the light of the inactivation of prions.

Anesthesia↗
PubMed2001

Regional hemostatic status and blood requirements after total knee arthroplasty with and without tranexamic acid or aprotinin.

UNLABELLED: Antifibrinolytics seem to reduce postoperative blood loss after total knee arthroplasty. Few studies have shown the impact of these drugs on the mechanisms of coagulation. The purpose of this study was to examine coagulation/fibrinolysis variables as well as blood loss after total knee arthroplasty with and without antifibrinolytics in the operated limb on a regional level. Thirty-six patients were randomized into one of three groups to receive aprotinin, tranexamic acid, or no medication. We took blood samples of the femoral vein before deflating the tourniquet and after 5, 10, 30, 60, 120 min and on the first postoperative day. The implantation of a knee prosthesis in artificial ischemia caused a significant activation of coagulation and fibrinolysis in the regional circulation. Tranexamic acid and aprotinin did not cause a significant modulation of fibrinolysis variables or a significant reduction of postoperative bleeding and transfusion requirements. One of the differences in comparison to other studies was the decreased total blood loss. The use of bone cement as well as surgical hemostasis before wound closure may be regarded as reasons for this. Therefore, primarily these methods should be used because there is no increased risk of adverse drug effects. IMPLICATIONS: After total knee arthroplasty total blood loss may be kept in a low range if methods such as cemented knee prosthesis and surgical hemostasis are used. In this case aprotinin and tranexamic acid did not cause a significant modulation of fibrinolysis variables or a significant reduction of postoperative bleeding.

Adult↗
PubMed2001

Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES Study.

OBJECTIVE: This study investigated whether treatment with the anti-tumor necrosis factor-alpha monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/mL. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. SETTING: Eighty-four intensive care units in academic medical centers in Europe and Israel. PATIENTS: A total of 944 septic patients were screened and stratified by the results of a rapid qualitative immunostrip test for serum IL-6 concentrations. Patients with a positive test kit result indicating IL-6 concentrations of >1000 pg/mL were randomized to receive either afelimomab (n = 224) or placebo (n = 222). Patients with a negative IL-6 test (n = 498) were not randomized and were followed up for 28 days. INTERVENTIONS: Treatment consisted of 15-min infusions of 1 mg/kg afelimomab or matching placebo every 8 hrs for 3 days. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS: The study was terminated prematurely after an interim analysis estimated that the primary efficacy end points would not be met. The 28-day mortality rate in the nonrandomized patients (39.6%, 197 of 498) was significantly lower (p <.001) than that found in the randomized patients (55.8%, 249 of 446). The mortality rates in the IL-6 test kit positive patients randomized to afelimomab and placebo were similar, 54.0% (121 of 224) vs. 57.7% (128 of 222), respectively. Treatment with afelimomab was not associated with any particular adverse events. CONCLUSIONS: The IL-6 immunostrip test identified two distinct sepsis populations with significantly different mortality rates. A small (3.7%) absolute reduction in mortality rate was found in the afelimomab-treated patients. The treatment difference did not reach statistical significance.

APACHE↗
PubMed2000

[The effect of different volume expanders on neutrophil granulocyte function in vitro].

INTRODUCTION: The influence of kolloids on the immune system is not well documented. In this study we investigated the effects of gelatine, hydroxyethylstarch (HES), human albumine, and dextrane on neutrophil function and receptor expression by flow cytometry. METHODS: Whole blood of healthy volunteers was incubated for 30 minutes with either gelatine, HES (6% and 10%), dextrane 40 and 60, or human albumin 20%. Phagocytic capacity was determined by uptake of fluorescein-isothiocyanate labeled bacteria, the conversion of dihydrorhodamine 123 into fluorescent rhodamine 123 was used for oxidative burst measurements. Expression of complement receptors CD 11b and CD35 was investigated using fluorescein-isothiocyanate labeled antibodies. RESULTS: Incubation with gelatine significantly increased expression of complement receptors and oxidative burst. Dextranes and HES had no influence on neutrophil function. Human albumin reduced the oxidative burst, whereas CD 35 expression was increased. CONCLUSION: The physiological significance of these changes in a range of 10% has to be clarified in further investigations.

Bacteria↗