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M Heck

Publications and source records attributed to M Heck.

At least 19 recordsLinked to original sources
PubMed2006

Distribution of molecular subtypes within Salmonella enterica serotype Enteritidis phage type 4 and S. Typhimurium definitive phage type 104 in nine European countries, 2000-2004: results of an international multi-centre study.

This study investigates the distribution of pulsed-field gel electrophoresis (PFGE) profiles within Salmonella enterica serotype Enteritidis phage type (PT) 4 and S. Typhimurium definitive phage type (DT) 104, from cases of human infection in nine European countries from 2000 to 2004. Isolates were subtyped using standardized methods and gel images submitted by each participating country to the coordinating centre (Health Protection Agency Centre for Infections, London, UK), where they were entered into a central database, developed within BioNumerics software, and designated using an agreed nomenclature. S. Enteritidis PT4 (n=3637) was differentiated into 38 different profiles. Simpson's index of diversity (D) of profiles ranged from 0.2 to 0.4. Profile SENTXB.0001 represented at least 80% of all profiles in each country. S. Typhimurium DT104 (n=1202) was differentiated into 28 different profile types. Simpson's D was at least 0.6 in all countries except in Austria and Italy. In both these countries over 74% of S. Typhimurium DT104 profiles were STYMXB.0013. Profile STYMXB.0061, was predominant in Denmark, Spain, Finland and England and Wales where it represented between 36% and 45% of profiles. Profile STYMXB.0001 represented nearly half of all profiles in Scotland and 23% in England and Wales. PFGE is proving useful for further discrimination within S. Enteritidis PT4 and S. Typhimurium DT104. Ascertainment of international outbreaks involving common serotypes and phage types may be increased by the timely pooling of PFGE profiles within a central database readily accessible to all participating countries.

Bacteriophage Typing↗
PubMed2005

Herbicide binding and thermal stability of photosystem II isolated from Thermosynechococcus elongatus.

Binding of herbicides to photosystem II inhibits the electron transfer from Q(A) to Q(B) due to competition of herbicides with plastoquinone bound at the Q(B) site. We investigated herbicide binding to monomeric and dimeric photosystem II core complexes (PSIIcc) isolated from Thermosynechococcus elongatus by a combination of different methods (isothermal titration and differential scanning calorimetry, CD spectroscopy and measurements of the oxygen evolution) yielding binding constants, enthalpies and stoichiometries for various herbicides as well as information regarding stabilization/destabilization of the complex. Herbicide binding to detergent-solubilized PSIIcc can be described by a model of single independent binding sites present on this important membrane protein. Interestingly, binding stoichiometries herbicide:PSIIcc are lower than 1:1 and vary depending on the herbicide under study. Strong binding herbicides such as terbutryn stabilize PSIIcc in thermal unfolding experiments and endothermically binding herbicides like ioxynil probably cause large structural changes accompanied with the binding process as shown by differential scanning calorimetry experiments of the unfolding reaction of PSIIcc monomer in the presence of ioxynil. In addition we studied the occupancy of the Q(B) sites with plastoquinone (PQ9) by measuring flash induced fluorescence relaxation yielding a possible explanation for the deviations of herbicide binding from a 1:1 herbicide/binding site model.

Binding Sites↗
PubMed2005

[Unilateral spinal anaesthesia in elderly patient for hip trauma: a pilot study].

INTRODUCTION: Fractured neck of femur is encountered more frequently as life expectancy increases. All anaesthetic techniques aim to avoid deleterious fall in arterial blood pressure. The haemodynamic effects of hypobaric unilateral spinal anaesthesia have been rarely assessed in patients over 80 year's old. This study aims to do that in a prospective manner. PATIENTS AND METHODS: Twenty-five patients were enrolled. Following a preload with HES 240/0.576 % (Hesteril) (5 ml/kg) and the administration of an iliofascial block, patients were placed in the lateral decubitus position, operative side uppermost. 3.5 ml of 0.12% hypobaric bupivacaine was administered intrathecally at a rate of 0.25 ml/second. Patients were kept in position for 15 minutes. Systolic, mean and diastolic arterial pressures, heart rate, SaO2 % and ephedrine consumption were recorded at five minutes intervals as was the rate of onset, height and duration of sensory and motor block and extent of bilateralization. Patient and surgeon satisfaction scores were also recorded. RESULTS: No significant changes in systolic, mean and diastolic pressures, or SaO2 % occurred. Median onset times of sensory and motor block were 8+/-5 and 16+/-7 minutes on the operative side and 30+/-15 and 36+/-15 minutes on the contralateral side in those with bilateralization, respectively. The maximum height of sensory block was T6 for sept patients, T8 for huit patients and T8-T10 for the remainder. Mean duration of sensory and motor block was 134+/-26 and 119+/-24 minutes on the operative side and 100+/-26 and 98+/-25 minutes on the contralateral side, respectively. In 12 patients (48%) bilateralization of their block occurred. Patients and surgeons rated the technique highly. CONCLUSION: Hypobaric unilateral spinal anaesthesia is a simple technique, produces satisfactory operative conditions and induces very little haemodynamic change in the elderly population.

Aged↗
PubMed2005

Conversion from cyclosporine to tacrolimus after renal transplantation improves cardiovascular risk factors.

BACKGROUND: It is vital that after, renal transplantation, immunosuppression is efficacious and causes few complications. It is especially important that hyperlipidaemia, hypertension and toxic influences should be avoided because these conditions can reduce patient and transplant survival. Many studies have demonstrated beneficial effects of tacrolimus in comparison with cyclosporine with regard to these conditions. These results have suggested that a conversion to tacrolimus from cyclosporine is advantageous. Our study investigated whether patients with deteriorating renal functions can profit from this conversion. METHODS: Thirty patients with a renal transplant were studied retrospectively, using data recorded from 3 years before to 3 years after conversion from cyclosporine to tacrolimus. RESULTS: While renal function (glomerular filtration rate [GFR]) deteriorated progressively under cyclosporine, it stabilised and even improved under tacrolimus (creatinine: Delta(Cyc)=+1.4 mg/d; Delta(Tac=)-0.7 mg/dl; GFR: Delta(Cyc)=-35 ml/min; Delta(Tac)=14 ml/min). In addition, uric acid level (7.0 vs. 6.4 mg/dl, p<0.05) and cholesterol level (258 vs. 225 mg/dl, p<0.05) were both significantly lower under tacrolimus. CONCLUSION: Conversion from cyclosporine to tacrolimus is recommended for patients with a kidney transplant, in which there has been a progressive fall in renal function. It leads to stabilisation or even improvement of transplant function and a reduction in cardiovascular risk factors.

Adult↗
PubMed2005

Cyclosporine and tacrolimus: influence on cardiovascular risk factors.

After allogenic transplantations, a dramatic increase in the development of arteriosclerotic plaques can be observed, which might be due to metabolic alterations, changes in the transplant organ, or the immunosuppression regimen. Many studies have demonstrated beneficial effects of tacrolimus compared with cyclosporine with regard to these conditions. These results have suggested that conversion to tacrolimus from cyclosporine is advantageous. Our study investigated whether patients with deteriorating renal function profit from this conversion. Thirty renal transplant patients were studied retrospectively, using data recorded from 3 years before to 3 years after conversion from cyclosporine to tacrolimus. While renal function (GFR) deteriorated progressively under cyclosporine, it stabilized and even improved under tacrolimus (creatinine: DeltaCyc = +1.4 mg/d; DeltaTac = -0.7 mg/dL; GFR: DeltaCyc = -35 mL/min; DeltaTac = 14 mL/min). In addition, uric acid levels (7.0 mg/dL vs 6.4 mg/dL, P < .05) and cholesterol levels (258 mg/dL vs 225 mg/dL, P < .05) were both significantly lower under tacrolimus. Conversion from cyclosporine to tacrolimus is recommended for kidney transplant patients in whom there has been a progressive fall in renal function. It leads to stabilization or even improvement of transplant function and a reduction in cardiovascular risk factors.

Adult↗
PubMed2005

Differential effects of cyclosporine and tacrolimus on mycophenolate pharmacokinetics in patients with impaired kidney function.

In a single-center prospective randomized controlled study, the impact of calcineurin inhibitor (CNI) reduction or withdrawal on the pharmacokinetics of mycophenolic acid (MPA) was studied in a group of renal transplant recipients with impaired renal function. Mycophenolate mofetil (MMF) was added to a baseline regimen of prednisolone and CNI. Afterwards the patients were randomized into "CNI withdrawal" and "CNI continuation" groups. The dosage of CNIs, cyclosporine or tacrolimus, was gradually reduced and withdrawn within 6 weeks from patients in the withdrawal group. The continuation group was maintained on therapy with CNI, MMF, and steroids. These regimens were maintained until the ninth month. In contrast to the withdrawal of tacrolimus, which has no significant effect on MPA pharmacokinetics, cyclosporine withdrawal was associated with a significant increase in the trough levels and areas under the curve of MPA. Serum creatinine and urine albumine levels stabilized on average after CNI withdrawal in this population. The results are consistent with the hypothesis that cyclosporine attenuates the enterohepatic recirculation of MPA. The withdrawal of CNI has a positive effect on renal function in chronic allograft dysfunction.

Adult↗
PubMed2004

Postoperative analgesia after total knee replacement: the effect of an obturator nerve block added to the femoral 3-in-1 nerve block.

Femoral nerve block (FNB) does not consistently produce anesthesia of the obturator nerve. In this single-blind, randomized, controlled study we added a selective obturator nerve block (ONB) to FNB to analyze its influence on postoperative analgesia after total knee replacement (TKR). Before general anesthesia, 90 patients undergoing TKR received FNB (Group 1), FNB and selective ONB (Group 2), or placebo FNB (Group 3). Postoperative analgesia was further provided by morphine IV via patient-controlled analgesia. Analgesic efficacy and side effects were recorded in the first 6 h after surgery. Adductor strength decreased by 18% +/- 9% in Group 1 and by 78% +/- 22% in Group 2 (P < 0.0001). Total morphine consumption was reduced in Group 2 compared with Groups 1 and 3 (P < or = 0.0001). Patients in Group 2 reported lower pain scores than those in Groups 1 and 3 (P = 0.0003). The incidence of nausea was more frequent in Groups 1 and 3 (P = 0.01). We conclude that FNB does not produce complete anesthesia of the obturator nerve. Single-shot FNB does not provide additional benefits on pain at rest over opioids alone in the early postoperative period. The addition of an ONB to FNB improves postoperative analgesia after TKR.

Aged↗
PubMed2001

Topochemical investigation of ancient manuscripts.

Various modern instrumental techniques for surface analysis were applied for the non-destructive physicochemical examination of works of art. As samples, pieces of ancient manuscripts endangered by iron-gall ink corrosion were used. Surface characterisation of the morphology of the cellulose fibres within corroded and non-corroded parts of the manuscript performed by scanning electron microscopy (SEM) showed seriously damaged cellulose fibres in the written parts. The elemental composition of selected parts of the manuscript was determined by energy dispersive X-ray fluorescence analysis (EDX). A more detailed study of the paper surface was then performed by electron probe microanalysis (EPMA). This technique yields the morphological characteristics of the surface as well as element distribution maps over the written area of the investigated manuscript.

Journal Article↗
PubMed2001

[Acceptance of preoxygenation in clinical routine by patients and by anaesthesiologists].

Preoxygenation is a simple technique to expand the time under planned apnea till the patient is endangered by hypoxia. In this study, we analysed how preoxygenation is used by anaesthesiologists in clinical routine and how this method is tolerated by the patients. One hundred and twenty-one anaesthesiologists of 4 hospitals were interviewed anonymously about training level, rank, indication for preoxygenation and techniques of preoxygenation, as well as their estimation of the patients' discomfort during preoxygenation. Data on 100 patients about oxygen-mask-tolerance were acquired by an anonymous questionnaire from a standard quality control inquiry. We received back 76 of the 121 questionnaires of anaesthesiologists (63 %). Fifty-nine percent of the anaesthesiologists (45/76) preoxygenated in clinical routine. With increasing training time and higher ranks, less anaesthesiologists preoxygenated routinely: junior residents: 80 %; senior residents: 68 %; consultants: 60 %; assistant medical directors: 48 %.80 % of the anaesthesiologists (61/76) used imperfect techniques for preoxygenation (e. g. oxygen-flow < 8 l/min). At the time of preoperative evaluation, the patients estimated the discomfort during preoxygenation on a continuous scale (1 to 10) as 2 (median; 1 - 7: 95 % confidence interval). Postoperatively, the patients mentioned no discomfort: 1 (1 - 1). The anaesthesiologists overestimated their patients' discomfort significantly with 5 (3 - 7) (p < 0.001).In conclusion, preoxygenation, a simple safety procedure, is not routinely used by many anaesthesiologists and imperfect methods are often employed. A possible reason for the anaesthesiologists' reluctance to preoxygenate is an overestimation of the patients' discomfort, though the patients tolerate preoxygenation very well.

Anesthesiology↗
PubMed2000

Maximal rate and nucleotide dependence of rhodopsin-catalyzed transducin activation: initial rate analysis based on a double displacement mechanism.

Despite the growing structural information on receptors and G proteins, the information on affinities and kinetics of protein-protein and protein-nucleotide interactions is still not complete. In this study on photoactivated rhodopsin (R*) and the rod G protein, G(t), we have used kinetic light scattering, backed by direct biochemical assays, to follow G protein activation. Our protocol includes the following: (i) to measure initial rates on the background of rapid depletion of the G(t)GDP substrate; (ii) to titrate G(t)GDP, GTP, and GDP; and (iii) to apply a double displacement reaction scheme to describe the results. All data are simultaneously fitted by one and the same set of parameters. We obtain values of K(m) = 2200 G(t)/microm(2) for G(t)GDP and K(m) = 230 microm for GTP; dissociation constants are K(d) = 530 G(t)/microm(2) for R*-G(t)GDP dissociation and K(d) = 270 microm for GDP release from R*G(t)GDP, once formed. Maximal catalytic rates per photoexcited rhodopsin are 600 G(t)/s at 22 degrees C and 1300 G(t)/s at 34 degrees C. The analysis provides a tool to allocate and quantify better the effects of chemical or mutational protein modifications to individual steps in signal transduction.

Animals↗
PubMed2000

Electroencephalogram bispectral index predicts hemodynamic and arousal reactions during induction of anesthesia in patients undergoing cardiac surgery.

OBJECTIVE: To evaluate hemodynamic and clinical responses to induction of anesthesia and intubation at 3 different values of the electroencephalogram bispectral index (BIS). DESIGN: Prospective randomized trial. SETTING: University-affiliated hospital. PARTICIPANTS: Forty-five patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were assigned to 3 groups (n = 15 for each group). Anesthesia was induced with midazolam, sufentanil, and pancuronium. In each group, sufentanil was titrated to a BIS value of 60, 50, or 40 before intubation. Mean arterial blood pressure, heart rate, incidence of coughing, tearing, and need for fluid replacement or injections of norepinephrine were recorded before intubation as well as immediately and 1 and 2 minutes after intubation. MEASUREMENTS AND MAIN RESULTS: Thirteen patients intubated at a BIS value of 60 coughed and 14 experienced tearing after intubation, whereas no patient of the other groups showed signs of arousal. Mean arterial blood pressure remained stable in the BIS 60 and 50 groups, whereas in the BIS 40 group it decreased significantly to lower values before and after intubation. Patients in the BIS 40 group needed significantly more fluid replacement and injections of norepinephrine compared with the other groups. No significant changes in heart rate were detected. CONCLUSIONS: Electroencephalogram BIS predicts hemodynamic and arousal reaction resulting from induction of anesthesia and endotracheal intubation. BIS value should be kept at 50 before intubation to ensure safe hemodynamic conditions during induction of anesthesia in cardiac surgical patients.

Anesthesia, Inhalation↗
PubMed2000

Sufentanil does not prolong the duration of analgesia in a mepivacaine brachial plexus block: a dose response study.

UNLABELLED: To date, results of studies evaluating the efficacy of opioids and local anesthetic combinations in the brachial plexus are inconclusive. We examined whether increasing sufentanil in doses of 5, 10, and 20 microg decreased onset time or increased duration of an axillary brachial plexus block. Ninety-two patients scheduled for carpal tunnel release under axillary brachial plexus block were enrolled in the study. Patients were randomized to receive axillary plexus block with 40 mL 1.5% mepivacaine and saline (Group 1), sufentanil 5 microg (Group 2), 10 microg (Group 3), or 20 microg (Group 4). Onset and duration of sensory and motor block were measured. Opioid-related side effects were recorded. The addition of sufentanil did not improve speed of onset or increase the duration of sensory or motor block. Paradoxically, duration of sensory and motor block was longest in the control group: sensory, 241 min (188-284) and motor, 234 min (128-305), and decreased with increasing doses of sufentanil in Group 4: sensory, 216 min (115-315) and motor, 172 min (115-260) (P < 0.05). Side effects occurred in 55% of patients belonging to Groups 2 and 4, and in 60% of the patients in Group 3. In contrast, only 10% of the patients reported side effects in the control group. We conclude that sufentanil added to mepivacaine does not increase the onset or prolong the duration of an axillary plexus block. Furthermore, the addition of sufentanil was associated with a frequent incidence of side effects. IMPLICATIONS: This study demonstrates that the addition of sufentanil in a dose-dependent manner to 1.5% mepivacaine in the axillary plexus does not improve onset or duration of blockade, and that this admixture is associated with an increased incidence of side effects.

Adult↗
PubMed1999

Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors.

The assembly of signalling molecules into macromolecular complexes (transducisomes) provides specificity, sensitivity and speed in intracellular signalling pathways. Rod photoreceptors in the eye contain an unusual set of glutamic-acid-rich proteins (GARPs) of unknown function. GARPs exist as two soluble forms, GARP1 and GARP2, and as a large cytoplasmic domain (GARP' part) of the beta-subunit of the cyclic GMP-gated channel. Here we identify GARPs as multivalent proteins that interact with the key players of cGMP signalling, phosphodiesterase and guanylate cyclase, and with a retina-specific ATP-binding cassette transporter (ABCR), through four, short, repetitive sequences. In electron micrographs, GARPs are restricted to the rim region and incisures of discs in close proximity to the guanylate cyclase and ABCR, whereas the phosphodiesterase is randomly distributed. GARP2, the most abundant splice form, associates more strongly with light-activated than with inactive phosphodiesterase, and GARP2 potently inhibits phosphodiesterase activity. Thus, the GARPs organize a dynamic protein complex near the disc rim that may control cGMP turnover and possibly other light-dependent processes. Because there are no similar GARPs in cones, we propose that GARPs may prevent unnecessary cGMP turnover during daylight, when rods are held in saturation by the relatively high light levels.

ATP-Binding Cassette Transporters↗
PubMed1999

Molecular determinants of the reversible membrane anchorage of the G-protein transducin.

Transducin is a heterotrimer formed by a fatty acylated alpha-subunit and a farnesylated betagamma-subunit. The role of these two covalent modifications and of adjacent hydrophobic and charged amino acid residues in reversible anchoring at disk model membranes is investigated at different pH values, salt concentrations, and lipid packing densities using the monolayer expansion technique and CD spectroscopy. The heterotrimer only binds if the acetylated alpha-subunit is transformed into its surface-active form by divalent cations. In the presence of salts the alpha(GDP)-subunit, the betagamma-complex, and the heterotrimer bind to POPC monolayers at 30 mN/m, estimated to mimic the lateral packing density of disk membranes, with apparent binding constants of Kapp = (1.1 +/- 0.3) x 10(6) M-1 (reflecting the penetration of the fatty acyl chain together with approximately three adjacent hydrophobic amino acid residues), Kapp = (3.5 +/- 0.5) x 10(6) M-1 (reflecting the penetration of the farnesyl chain), and Kapp = (1.6 +/- 0.3) x 10(6) M-1 (reflecting a major contribution of the alpha(GDP)-subunit with only a minor contribution from the betagamma-complex). The apparent binding constant of the alpha(GTP)-subunit is distinctly smaller than that of the alpha(GDP)-subunit. Binding to negatively charged POPC/POPG (75/25 mole/mole) monolayers is reinforced by 2-3 cationic residues for the betagamma-complex. The alpha-subunit shows no electrostatic attraction and the heterotrimer shows even a slight electrostatic repulsion which becomes the dominating force in the absence of salts.

Animals↗
PubMed1999

Signal transfer from rhodopsin to the G-protein: evidence for a two-site sequential fit mechanism.

Photoactivation of the retinal photoreceptor rhodopsin proceeds through a cascade of intermediates, resulting in protein-protein interactions catalyzing the activation of the G-protein transducin (Gt). Using stabilization and photoregeneration of the receptor's signaling state and Gt activation assays, we provide evidence for a two-site sequential fit mechanism of Gt activation. We show that the C-terminal peptide from the Gt gamma-subunit, Gtgamma(50-71)farnesyl, can replace the holoprotein in stabilizing rhodopsin's active intermediate metarhodopsin II (MII). However, the peptide cannot replace the Gtbeta gamma complex in direct activation assays. Competition by Gtgamma(50-71)farnesyl with Gt for the active receptor suggests a pivotal role for Gtbeta gamma in signal transfer from MII to Gt. MII stabilization and competition is also found for the C-terminal peptide from the Gt alpha-subunit, Gtalpha(340-350), but the capacity of this peptide to interfere in MII-Gt interactions is paradoxically low compared with its activity to stabilize MII. Besides this disparity, the pH profiles of competition with Gt are characteristically different for the two peptides. We propose a two-site sequential fit model for signal transfer from the activated receptor, R*, to the G-protein. In the center of the model is specific recognition of conformationally distinct sites of R* by Gtalpha(340-350) and Gtgamma(50-71)farnesyl. One matching pair of domains on the proteins would, on binding, lead to a conformational change in the G-protein and/or receptor, with subsequent binding of the second pair of domains. This process could be the structural basis for GDP release and the formation of a stable empty site complex that is ready to receive the activating cofactor, GTP.

Animals↗
PubMed1999

Aldosterone, not estradiol, is the physiological agonist for rapid increases in cAMP in vascular smooth muscle cells.

BACKGROUND: Steroid-induced gene regulation in the endocrine tissues and vascular wall is achieved through the interaction of specific receptor proteins and promoters of target genes. In addition to these delayed steroid actions, rapid effects of steroids have been reported in various tissues that were clearly incompatible with the classic theory of genomic steroid action. METHODS AND RESULTS: Because high doses of 17beta-estradiol have been shown to modulate intracellular cAMP levels in vascular smooth muscle cells, steroid-induced stimulation of adenylate cyclase stimulation and phosphorylation of cAMP response element binding protein was investigated in porcine coronary artery vascular smooth muscle cells. Aldosterone induces a approximately 1.5- to 2.5-fold increase in intracellular cAMP levels (EC50 approximately 0.01 to 0.1 nmol/L) within 1 minute, whereas 17beta-estradiol and hydrocortisone act only at supraphysiological concentrations (10 micromol/L). Aldosterone-induced changes in intracellular cAMP are calcium dependent; they are not blocked by inhibitors of mineralocorticoid receptors, transcription, or protein synthesis. In addition, aldosterone induces a time-dependent phosphorylation of cAMP response element binding protein with potential transcriptional importance. CONCLUSIONS: A nongenomic modulation of vascular smooth muscle cells by aldosterone is consistent with the data that aldosterone, not estrogen, is the physiological stimulus for cAMP.

1-Methyl-3-isobutylxanthine↗