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Biomedical subjects

M Simon

Publications and source records attributed to M Simon.

At least 37 records · Page 2Linked to original sources
PubMed2005

Possibly linezolid-induced peripheral and central neurotoxicity: report of four cases.

BACKGROUND: Linezolid is the first member of the new synthetic class of antibacterial agents that prevent the formation of the 70S ribosomal subunit. It represents an attractive choice in the therapeutic arsenal because it is effective against methicillin-resistant strains of Staphylococcus spp. Adverse hematological events have been reported. They are rapidly reversible after discontinuation of treatment and usually occur during treatment courses of more than 2 weeks. The advised duration of linezolid use is 28 days and the consequences of prolonged use are unknown. In addition, this drug has some dopaminergic properties that can induce the serotonin syndrome if a monoamine oxidase inhibitor is used simultaneously. PATIENTS AND METHODS: Since linezolid became available for use in 2002, four cases of probable central and peripheral linezolid-induced neurotoxicity have been recorded in our unit. RESULTS: Two de novo peripheral neuropathies and one worsening of a preexisting toxic neuropathy have been observed. In each case, linezolid therapy was used during a prolonged duration of 8, 23, and 24 weeks, respectively. First neurological signs appeared in one case during the 2nd week of treatment and beyond the 1st month in the other cases. To date, all cases of peripheral neuropathy resulted in persistent neurological damage after discontinuation of linezolid. Assessments did not reveal any other explanation for these neurological impairments. Another case concerned a patient who developed transient encephalopathy attributed to linezolid during a coadministration with hydroxyzine. CONCLUSION: Linezolid may induce persistent peripheral neuropathy after prolonged use and may cause a transient central neurotoxicity in combination with an anticholinergic agent, such as an antihistamine. Close neurological monitoring should be recommended in prolonged linezolid therapy and coadministration of a serotonin reuptake inhibitor or antihistamine should be avoided to limit neurological adverse events.

Acetamides↗
PubMed2005

Metabolism of [3H]pentosan polysulfate sodium (PPS) in healthy human volunteers.

Pentosan polysulfate sodium (PPS) is the active ingredient in ELMIRON, a drug approved for the relief of bladder pain associated with interstitial cystitis. The study objective was to characterize the pharmacokinetic and metabolic profiles of PPS following oral dosing of [3H]PPS. As specific assays for PPS do not exist, metabolic profiling was accomplished through multiple fraction collections and radiochromatographic techniques. Two groups of eight healthy female subjects sequentially received a single oral dose of 200 microCi [3H]PPS supplemented with 300 mg unlabelled PPS or 300 microCi [3H]PPS supplemented with 450 mg unlabelled PPS. Most of the administered dose (84%) was excreted in faeces as intact PPS, and a smaller percentage (6%) was excreted in urine. In summary, orally administered PPS was very poorly absorbed, with the majority of the drug being excreted in faeces as intact PPS and in urine as low molecular weight and desulfated PPS.

Chromatography↗
PubMed2005

The influence of the Univent endotracheal tube on internal jugular vein cannulation.

This prospective clinical investigation assessed the effect of placement of a Univent tube on the anatomy of the internal jugular veins and the success of cannulation of the left internal jugular vein. After obtaining informed consent, 48 adult patients were enrolled. Of these, 42 patients were eligible and were divided into two groups: Univent tube (group U, n=21) and wire enforced endotracheal tube (group C, n=21). The Univent tube group were having a left thoracotomy. Using horizontal ultrasound scans just above the thyroid gland, the internal jugular vein was visualized and measured before and after Univent placement. The number of needle passes necessary to cannulate the left internal jugular vein in the two groups was also compared. Univent tubes were associated with lateral displacement of the right carotid artery and internal jugular vein on the convex side of the Univent tube, with compression of the right internal jugular vein by the artery, resulting in a kidney-shaped cross-section of the vein. On the left (concave side of the tube), the neck was indented, the sheath of the left carotid artery was displaced medially, and the left internal jugular vein distorted to an ellipse. There was a significant increase in the lateral diameter and a decrease in the cross-sectional area of the left internal jugular vein (t-test, P < 0.05). The first attempt at cannulation of the left internal jugular vein failed significantly more often in the Univent group (13/21 vs 5/21 in group C, Chi-square 6.22, P=0.025). Cannulation of the internal jugular vein before placement of the Univent tube, or placement with ultrasound guidance is suggested.

Carotid Arteries↗
PubMed2005

[Stress echography and pacemakers].

The non-invasive investigation of myocardial ischaemia in pacemaker patients is a common problem. Stress echocardiography seems interesting for this indication, but very few data are available for patients fitted with a pacemaker. We wanted to know whether it would be useful to propose a conventional stress echography, under dobutamine/atropine, for these patients. One hundred stress echographies were performed at our centre between 1998 and 2004 in 113 consecutive ventricular paced patients at rest. We determined the degree of contraction asynchrony related to ventricular pacing and its impact on the interpretation of the test. In this series, the test proved contributory in 87% of cases, with disturbance of the target heart rate in 71% of cases, and contraction asynchrony hindering interpretation in only 11% of cases. Under the effect of the dobutamine/atropine combination, we observed passage into spontaneous rhythm in 54% of cases, with complete disappearance of septal asynchrony, thus facilitating interpretation of the test. It would therefore appear that conventional stress echography is the method of choice for the non-invasive investigation of myocardial ischaemia in patients fitted with a pacemaker, being well tolerated and contributory most of the time.

Aged↗
PubMed2004

[Cross-validation of simple questioning methods to determine patient satisfaction with anaesthesia care].

INTRODUCTION: Evaluation of patient satisfaction with the perioperative care is an integral part of modern quality management. For this purpose simple questioning techniques are often used in clinical practise or reports of clinical trials. However, little research has been performed to investigate whether these tools and methods are useful and provide valid information. METHODS: Two-hundred patients undergoing elective surgical procedures were interviewed. Five different simple techniques or questions that have been used in the international and in the German literature throughout the last years were applied in random sequence together with the validated German translation of the QoR-9 questionnaire to measure quality of recovery. All analyses were performed descriptively. RESULTS: All investigated techniques could be answered without help by another person in 95 % up to 100 %. All simple dichotomous questions regarding satisfaction were insufficient to discriminate satisfied from less satisfied patients. A rating using grades known from the German school system (1 - 6) and a visual analogue scale (VAS; 0 - 100 mm) obtained ratings lower than the maximum possible values in 10 % and 11 % of the patients respectively. Furthermore, the flexibility that was provided by these tools was not utilized by the patients. The results of the QoR-9 questionnaire as a marker of postoperative recovery showed only a moderate correlation with ratings of patient satisfaction. CONCLUSION: Until now, there is no method or questioning technique in the German language that can be recommended for a quality assurance program. Thus, further research is needed to develop tools that provide valid information with adequate resolution to allow discrimination of patient satisfaction with perioperative care.

Adult↗
PubMed2004

N-Acetylglucosamine- an osmotic slute for peritoneal dialysis without inducing hyperinsulinemia.

METHODS: N-Acetylglucosamine (NAG) was compared to glucose as an osmotic solute during peritoneal dialysis in rats. The effect of the tested solutes on blood glucose and insulin levels during dialysis was evaluated. RESULTS: During 6-hour exchange with NAG (220 mmol/l) solution, the dialysate volume was higher than in rats dialyzed with fluid containing glucose (220 mmol/l; GLU: 34.5 +/- 1.7 vs. 32.8 +/- 1.1 ml, respectively; p < 0.05). The peritoneal permeability to protein (D/S x 1,000) was lower in the NAG group (9.7 +/- 2.5 vs. 16.3 +/- 5.6 in GLU; p < 0.02). Dialysis with GLU-based solution resulted in hyperglycemia up to 180 +/- 39 mg/dl; in the NAG group the increase in the blood glucose level was moderate (up to 91 +/- 9 mg/dl; p < 0.001). Dialysis with GLU fluid caused an increase in blood insulin level by 53.2 +/- 62.4 pmol/l, whereas the insulin blood concentration in NAG-treated animals was increased by 5.0 +/- 5.4 pmol/l (p < 0.001). CONCLUSIONS: NAG is more effective than GLU osmotic solute during peritoneal dialysis and it reduces peritoneal permeability to protein. Dialysis with NAG results in lower hyperglycemia and hyperinsulinemia, both effects are favorable in diabetic peritoneal dialysis patients.

Acetylglucosamine↗
PubMed2004

[Platelet function tests for monitoring of acetylsalicylic acid: clinical significance in antiplatelet treatment].

Several studies have demonstrated with the use platelet function tests (PFT) that subgroups of patients under acetylsalicylic acid (ASA) fail to produce the anticipated antiplatelet effect. This phenomenon as well as the clinical failure of ASA to protect patients from thromboembolic complications has been termed ASA resistance (AR) or ASA nonresponsiveness. Several subtypes of AR can be distinguished by PFT. The following PFT were used to characterize AR: optical aggregometry, platelet aggregation in whole blood, platelet function analyzer (PFA-100), platelet reactivity test or platelet aggregate ratio, flow cytometry and thromboxane B(2) generation. All PFT have in common that their widespread clinical use is substantially limited due to complex preanalytic factors, reduced specificity and poor reproducibility. PFT are not interchangeable for monitoring antiplatelet treatment. Three prospective clinical trials revealed a possible relationship between AR and subsequent cardiovascular events. There is a need for a simple and reliable assay for predicting the clinical efficacy of antiplatelet therapy. Recent data demonstrate that none of the currently available assays including the PFA-100 system are capable to accomplish these objectives.

Aspirin↗
PubMed2004

mRNA expression profiles for corticotrophin-releasing hormone, urocortin, CRH-binding protein and CRH receptors in human term gestational tissues determined by real-time quantitative RT-PCR.

Increasing maternal plasma levels of corticotrophin-releasing hormone (CRH) during the last weeks of pregnancy suggest that this stress hormone plays an important role in the control of human parturition. Little is known about the quantitative contribution of gestational tissues (other than placenta) to intrauterine formation of CRH, urocortin and CRH-binding protein (CRH-BP), or about the distribution of CRH receptors within the uterus. We have investigated the mRNA expression of CRH, urocortin, CRH-BP and CRH receptors 1 and 2 (CRH-R1 and -R2) in gestational tissues by real-time RT-PCR. Placenta, myometrium and choriodecidua were collected after uncomplicated pregnancies at term, before the onset of labour. Distribution of CRH-R1 and CRH-R2 protein was also investigated by immunostaining with receptor subtype-specific antibodies. The placenta was identified as the main site of CRH and CRH-BP mRNA expression, displaying mRNA levels >1000 and >20 times higher than those found in the myometrium and choriodecidua respectively (P<0.05 in each case). mRNA expression of urocortin was low in all tissues investigated. Myometrium and choriodecidua expressed relevant amounts of both receptor subtypes, whereas the CRH receptor population in placenta consisted mainly of CRH-R2. The high expression of CRH in placenta and the substantial expression of CRH receptors in choriodecidua and myometrium suggested that CRH derived from placenta exerts direct or indirect actions on these tissues. Neither CRH produced by myometrium or choriodecidua nor urocortin from other intrauterine sources seem to play a major role in the control of labour.

Adult↗
PubMed2004

Bedside assessment of cerebral perfusion reductions in patients with acute ischaemic stroke by near-infrared spectroscopy and indocyanine green.

OBJECTIVE: To detect perfusion reductions in patients with acute cerebral infarcts using near-infrared spectroscopy (NIRS) with indocyanine green (ICG) as tracer. METHODS: Kinetics of an intravenous bolus of ICG were monitored by NIRS in 13 patients with acute infarction in the territory of the middle cerebral artery (mean (SD) age, 62.2 (13.0) years) and 12 controls (64.2 (9.1) years) at 2.8 (2.8) days after onset. NIRS optodes were placed bitemporally, with an interoptode distance of 4-5 cm. Absolute concentration changes in ICG were calculated. The following were assessed: time to peak, maximum ICG concentration, time interval between 0% and 100% maximum ICG concentration (interval), rise time (time between 10% and 90% ICG maximum), slope (maximum Delta ICG/interval), and blood flow index (BFI = maximum Delta ICG/rise time) of each hemisphere. Intraindividual differences were calculated between the two hemispheres. RESULTS: Patients with ischaemic stroke had increased time to peak (p<0.01), interval (p<0.01), and rise time (p<0.01), while maximum ICG concentration (p<0.03), slope (p<0.01), and BFI (p<0.01) were diminished at the site of infarction compared with the unaffected hemisphere. In stroke patients, intraindividual differences in time to peak (p<0.001), interval (p<0.001), rise time (p = 0.001), maximum ICG concentration (p<0.02), slope (p<0.001), and BFI (p<0.001) were greater than in the controls, with excellent sensitivity and specificity for Delta time to peak (100% and 100%, respectively) and Delta time interval (100% and 91.7%). CONCLUSIONS: Measurement of interhemispheric differences in ICG kinetics by NIRS detects perfusion reductions in patients with acute middle cerebral artery infarction. This non-invasive bedside test is rapid, repeatable, without major side effects, and avoids transportation of critically ill patients.

Adult↗
PubMed2003

Consumption of dissolved amino acids and carbohydrates by limnetic bacterioplankton according to molecular weight fractions and proportions bound to humic matter.

We investigated the bacterial decomposition of dissolved amino acids (DAA) and carbohydrates (DCHO) bound to humic substances and in the nonhumic fraction, and of low (< 3 KDA) AND HIGH (> 3 kDa) molecular weight (MW). Experiments were conducted in mesotrophic Lake Constance, Germany, in October and November 1997 and June 1998 during periods of low phytoplankton biomass. Dilution cultures, inoculated with bacterioplankton of the < 1 mm size fraction from 3 m, were run over 5 to 8 days to determine bacterial consumption of the various fractions of DAA and DCHO. In all experiments consumption rates of DCHO were higher than that of DAA. On average, 70% of the DAA and DCHO consumed were associated with the humic fraction, which, however, also consisted of a substantial recalcitrant component. In contrast, there was no preferential consumption of DAA and DCHO in either of the two MW fractions. Overall, we found a highly significant positive correlation between the consumption of the various fractions of DAA and DCHO and their initial concentrations. The consumed DAA, i.e, their labile pool, was dominated by serine and glutamate and that of DCHO by arabinose. In contrast, the residual DAA, i.e., the recalcitrant pool, comprised highest proportions of glycine + threonine and that of DCHO of mannose + xylose. These results indicate that the bacterial consumption of DAA and DCHO was mainly a function of their concentrations, irrespective of the molecular weight and whether they are bound to humic substances or not and despite the fact that they consist of a more labile and a more refractory pool.

Amino Acids↗
PubMed2003

Essential Bacillus subtilis genes.

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximately 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden-Meyerhof-Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Bacillus subtilis↗
PubMed2003

Expression pattern and biochemical characteristics of a major epidermal retinol dehydrogenase.

The biological functions of vitamin A in the epidermis are mediated by all-trans retinoic acid, which is biosynthesized from retinol in two oxidative reactions. The first step involves enzymatic conversion of retinol to retinaldehyde. The physiological significance and relative contributions of the various retinol dehydrogenases to the oxidation of retinol in epidermal cells remain unclear. We report the characterization of a retinol dehydrogenase/reductase of the SDR superfamily, hRoDH-E2, which is abundantly expressed in the epidermis, epidermal appendages and in cultured epidermal keratinocytes. Both in live keratinocytes and in isolated keratinocyte microsomes, where the enzyme normally localizes, hRoDH-E2 functions as a bona fide retinol dehydrogenase. In the prevailing oxidative reaction it recognizes both free- and CRBP-bound retinol, and shows preference toward NADP as a co-substrate. In comparison, hRoDH-E2 retinol dehydrogenase activity in the simple epithelial HEK 293 cells is much lower and in CHO cells is non-existent. hRoDH-E2 transcripts are distributed throughout the epidermal layers but are more abundant in the basal cells. In contrast, the protein is detected predominantly in the basal and the most differentiated living layers. Its synthesis is negatively regulated by retinoic acid. The biochemical properties and the differential expression of hRoDH-E2 in the strata where retinoic acid signaling is critical for epidermal homeostasis support a conclusion that hRoDH-E2 bears the characteristics of the major microsomal retinol dehydrogenase activity in the epidermal keratinocytes in physiological circumstances.

Alcohol Oxidoreductases↗
PubMed2003

Pretreatment with sufentanil reduces myoclonus after etomidate.

BACKGROUND: Myoclonic movements are a common problem during the induction of general anesthesia with etomidate. We investigated the influence of pretreatment with the opioid sufentanil on the incidence of etomidate-induced myoclonus. METHODS: Forty female patients (ASA physical status I-III) were randomly assigned to receive double-blinded either 0.3 micro g kg-1 of sufentanil or placebo 150 s before the induction of sleep with 0.3 mg kg-1 of etomidate. The patients were observed for any myoclonic movement. Grade of dizziness, breathing frequency, non-invasive blood pressure and heart rate were measured during the study period. RESULTS: None of the 20 patients receiving sufentanil had myoclonic movements after the administration of etomidate, whereas 16 patients in the placebo group (80%) experienced such movements (P<0.01). No cases of apnoea before induction of sleep were seen in the sufentanil group. CONCLUSION: Sufentanil 0.3 micro g kg-1 is an effective and safe drug to reduce myoclonus after etomidate without causing any harmful side-effect.

Adult↗
PubMed2003

Comparison of transcutaneous and endtidal CO2-monitoring for rigid bronchoscopy during high-frequency jet ventilation.

OBJECTIVE: To compare endtidal and transcutaneous respiratory monitoring of high-frequency jet ventilation (HFJV) in rigid bronchoscopy. Both techniques provide a noninvasive measurement of pCO2. METHODS: High-frequency jet ventilation was applied via a rigid bronchoscope. Driving pressure (DP) was initially adapted to ensure normal ventilation. It was then changed twice by +/- 30% from the initial value. Endtidal and transcutaneous data were compared with arterial blood gas monitoring (ABG). RESULTS: Results were analyzed separately for the time just after changing the driving pressure (10 min) and the remaining time until the next change of the driving pressure (4 min). The first part was called the dynamic phase, and the second part the steady-state phase. Correlation coefficient between endtidal capnography and ABG was 0.96 for the steady state and 0.94 for the dynamic phase, respectively. Bland-Altman analysis revealed a bias of -0.21 kPa with limits of agreement (LOA) 1.63 kPa for the steady state and -0.25 kPa, 2.08 kPa for the dynamic phase, respectively. Correlation coefficient between transcutaneous monitoring and ABG for the steady state phase was 0.83, and was 0.72 for the dynamic phase. Bland-Altman analysis resulted in a bias of -0.89 kPa with LOA - 3.84 kPa during steady state and 0.92 kPa, 4.06 kPa for the dynamic phase, respectively. CONCLUSION: Endtidal capnography offers accurate respiratory monitoring of HFJV. Transcutaneous monitoring showed a good correlation to ABG only during steady-state conditions. For the dynamic phase the accuracy was significantly lower. Thus, we cannot recommend transcutaneous respiratory monitoring for the specific indication of rigid bronchoscopy using HFJV.

Adult↗
PubMed2003

Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study.

The owl monkey (Aotus trivirgatus) has served as the standard non-human primate model of herpes simplex virus-1 (HSV-1) infection because it is highly susceptible to HSV-1 encephalitis. Owl monkeys, however, are expensive, difficult to obtain, and difficult to maintain in captivity, thus greatly hampering the efficiency of preclinical gene therapy trials for brain tumors using HSV-1-based vectors. We have therefore compared the susceptibility of the common marmoset (Callithrix jacchus) with the owl monkey in a model of intracerebral inoculation of wildtype HSV-1 F-strain at increasing titers. The common marmosets consistently succumbed earlier to viral encephalitis than the owl monkeys. The histological evaluation of the common marmoset revealed extensive HSV-1 infection with a concomitant yet less marked inflammatory response compared to the owl monkeys. PCR for HSV-1 demonstrated a similar extra-CNS shedding route in both experimental models. Our findings show that the common marmoset is at least as susceptible to intracerebral HSV-infection as the owl monkey and that it can therefore serve as a valid and reliable experimental model for the important preclinical safety tests of HSV-based therapeutic viral vector constructs in the brain.

Animals↗
PubMed2003

Immune biology of macaque lymphocyte populations during mycobacterial infection.

Immune responses of lymphocyte populations during early phases of mycobacterial infection and reinfection have not been well characterized in humans. A non-human primate model of Mycobacterium bovis bacille Calmette-Guerin (BCG) infection was employed to characterize optimally the immune responses of mycobacteria-specific T cells. Primary BCG infection induced biphasic immune responses, characterized by initial lymphocytopenia and subsequent expansion of CD4+, CD8+ and gammadelta T cell populations in the blood, lymph nodes and the pulmonary compartment. The potency of detectable T cell immune responses appears to be influenced by the timing and route of infection as well as challenge doses of BCG organisms. Systemic BCG infection introduced by intravenous challenge induced a dose-dependent expansion of circulating CD4+, CD8+ and gammadelta T cells whereas, in the pulmonary compartment, the systemic infection resulted in a predominant increase in numbers of gammadelta T cells. In contrast, pulmonary exposure to BCG through the bronchial route induced detectable expansions of CD4+, CD8+ and gammadelta T cell populations in only the lung but not in the blood. A rapid recall expansion of these T cell populations was seen in the macaques reinfected intravenously and bronchially with BCG. The expanded alphabeta and gammadelta T cell populations exhibited their antigen specificity for mycobacterial peptides and non-peptide phospholigands, respectively. Finally, the major expansion of T cells was associated with a resolution of active BCG infection and reinfection. The patterns and kinetics of CD4+, CD8+ and gammadelta T cell immune responses during BCG infection might contribute to characterizing immune protection against tuberculosis and testing new tuberculosis vaccines in primates.

Animals↗