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Biomedical subjects

H Böhrer

Publications and source records attributed to H Böhrer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Molecular cloning of genes differentially regulated by TNF-alpha in bovine aortic endothelial cells, fibroblasts and smooth muscle cells.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic-cytokine binding to and thereby stimulating vascular cells. TNF-alpha mediated intermediate stimulation of vascular cells is believed to play a pivotal role in the development of arteriosclerosis. While extensive information has recently become available on gene induction by TNF-alpha, less is known about gene suppression by TNF-alpha in vascular cells. Endothelial cells are the first cell layer within the vessel wall interacting with circulating, cytokine releasing cells. Therefore, they were selected as target for these study. METHODS: A differential screening approach has been used to isolate cDNAs whose abundance was suppressed by incubating bovine aortic endothelial cells (BAEC) for 6 h with 1 nM TNF-alpha. The gene expression of 6 isolated cDNAs after TNF-alpha was investigated by dot blots and nuclear run-on analysis in BAEC. The investigated genes were partially or completely sequenced. Differential expression after TNF-alpha stimulation of BAEC, bovine fibroblasts and vascular smooth muscle cells (SMC) was studied by Northern blots. RNA transcripts of the clone C7 in aortic aneurysms were examined by in situ hybridization. RESULTS: 49 independent cDNAs were isolated by the differential screening approach and 6 clones were further analyzed. These genes were downregulated in a time and dose dependent manner in BAEC. Sequence analysis revealed that 3 cDNAs encoded previously unidentified genes (C1, C5, C7), while 3 encoded known genes: connective tissue growth factor (CTGF; A1), fibronectin (A8) and the mitochondrial genome (B1). A1 and B1 were suppressed in BAEC, fibroblasts and SMC, whereas A8, C1, C5 and C7 were not uniformly downregulated in the investigated cells. C7 RNA transcripts were exclusively induced in the endothelium of an uninflamed aortic aneurysm. The transcripts were undetectable in an inflamed aortic aneurysm and control vessels. CONCLUSIONS: Gene suppression is a prominent feature of the intermediate effect of TNF-alpha on endothelial cells. Differences in the expression of the tested genes in endothelial cells, fibroblasts and vascular smooth muscle cells open possibilities for the study of cellular interactions in the vascular wall in disease situations with high local TNF-alpha concentrations.

Animals↗
PubMed1998

Cardiac output measurement by transpulmonary versus conventional thermodilution technique in intensive care patients after coronary artery bypass grafting.

OBJECTIVE: The aim of the present study was to evaluate the correlation, accuracy, and precision of transpulmonary thermodilution cardiac output (CO) measurement. For this purpose, this technique was compared with the clinical gold standard, the CO measurement by pulmonary artery catheter in patients after coronary artery bypass grafting (CABG). DESIGN: A prospective clinical study. SETTING: A university medical center. PARTICIPANTS: Seventy-five patients in an intensive care unit (ICU) after CABG. INTERVENTIONS: Standard (SCO) and transpulmonary thermodilution CO measurement (TPCO) measurements were simultaneously performed in triplicate by central venous injection of cooled saline solution. All variables were recorded at five different time points of measurement during weaning from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: CO measurements yielded 375 data pairs. SCO ranged from 2.0 to 10.2 L/min, and TPCO from 1.3 to 10.6 L/min. During the entire observation period, TPCO measurements tended to yield relatively high values, whereas SCO measurements resulted in lower values. Correlation between TPCO and SCO measurements was significant (r = 0.73; p < 0.05), accompanied by an accuracy with a bias of 0.456 L/min (7.3%) and a precision of 1.156 L/min (18.5%). CONCLUSION: In most patients, TPCO measurement will not replace the conventional technique by pulmonary artery catheter, but in some patients it offers an attractive, reliable, and safe method to determine CO.

Aged↗
PubMed1998

Blood transfusion facilitating difficult weaning from the ventilator.

We report a case series of five anaemic patients (haemoglobin: 8.7 +/- 0.8 g.dl-1) with chronic obstructive lung disease in whom trials of weaning from the ventilator were unsuccessful. After transfer to our regional weaning centre, blood was transfused to increase the haemoglobin value to 12 g.dl-1 or higher. Subsequently, all patients were weaned successfully. We conclude from our experience that in anaemic patients with chronic obstructive lung disease there should not be a fixed transfusion threshold. In anaemic patients in whom difficulty in weaning from the ventilator is experienced, blood transfusion should be tailored to the individual patient's needs. Transfusion in those with chronic obstructive airways disease may lead to successful weaning.

Adult↗
PubMed1998

Effects of preinduction and intraoperative warming during major laparotomy.

We have investigated the influence of active warming before and during operation on blood loss, transfusion requirements, duration of stay in the post-anaesthesia care unit (PACU) and perioperative costs in 40 patients undergoing major abdominal surgery. Patients were allocated randomly to one of two groups: in the study group (n = 20), patients were actively warmed using forced air for 30 min before induction of general anaesthesia and during anaesthesia. Passive protection against heat loss consisted of circulating water mattresses, blankets and fluid warming devices, and was used both in the active warming group and in the control group (n = 20). At the end of surgery the change in core temperature was significantly less in the group of actively warmed patients (0.5 (SD 0.8) degree C vs 1.5 (0.8) degree C; P < or = 0.01). Blood loss and transfusion requirements were less in the actively warmed patients, who had a shorter duration of stay in the PACU (94 (SD 42) min vs 217 (169) min; P < or = 0.01) and a 24% reduction in total anaesthetic costs.

Adult↗
PubMed1998

Bedside troponin T testing is not useful for early out-of-hospital diagnosis of myocardial infarction.

BACKGROUND: A new commercially available rapid qualitative bedside immunoassay for cardiac troponin T has been developed. The aim of the study was to investigate whether this new rapid bedside cardiac troponin T assay facilitates diagnosing myocardial infarction in a pre-hospital setting. METHODS: We evaluated the sensitivity and specificity of the new rapid bedside troponin T assay for myocardial infarction. In 68 patients with acute, central, crushing chest pain, who were strongly suspected of having myocardial infarction, the emergency doctor performed preclinically a bedside cardiac troponin T test. The results were compared with the diagnosis after admission to hospital, using the criteria of the World Health Organization. RESULTS: The diagnosis of myocardial infarction was confirmed in 16/68 (24%) patients after admission to hospital, but only in 4/16 (25%) patients with myocardial infarction was a positive result observed preclinically with this test. The result was false positive in 1/5 patients (20%). CONCLUSIONS: In contrast to an excellent specificity (0.98), sensitivity (0.25) of the rapid troponin T assay was poor. Thus, we conclude that this test cannot improve the distinction between myocardial infarction and angina pectoris in a pre-hospital setting.

Aged↗
PubMed1998

Relationship between hepatic cytochrome P450 3A content and activity and the disposition of midazolam administered orally.

It was recently shown by others that the clearance of midazolam/kg body weight after iv administration correlates with hepatic cytochrome P450 (CYP or P450) 3A content in liver transplant patients. However, after po administration midazolam undergoes significant first-pass metabolism, with significant intestinal extraction. The relationship between hepatic CYP3A and midazolam disposition after po administration had not previously been investigated. The aim of this study was to compare intraindividually hepatic CYP3A content and activity with the in vivo pharmacokinetics of midazolam (7.5 mg) administered po. For 15 patients scheduled for partial liver resection, the AUC values for the observed time period (AUC0-5hr) and to infinity (AUCinf) and the clearance were determined. In a macroscopically normal area of resected liver tissue, the microsomal CYP3A4 content (nanomoles per nanomole of total P450) was measured by immunoblot analysis and parameters (apparent Vmax, apparent KM, and intrinsic clearance) for the microsomal alpha-hydroxylation of midazolam were determined. Clearance/kg in vivo correlated with the apparent Vmax (r2 = 0.45, p < 0.01) and the CYP3A4 content (r2 = 0.29, p < 0.05). We conclude that interindividual variability in the pharmacokinetics of po administered midazolam is in part determined by interindividual variability in the hepatic microsomal Vmax for the alpha-hydroxylation of midazolam. However, the relationship between the disposition of midazolam administered po and hepatic CYP3A content is weaker than that reported after iv administration, indicating the importance of the contribution of intestinal CYP3A to the in vivo disposition of midazolam administered po.

Adult↗
PubMed1997

Role of NFkappaB in the mortality of sepsis.

Binding activity for nuclear factor kappa B (NFkappaB) consensus probes was studied in nuclear extracts from peripheral blood mononuclear cells of 15 septic patients (10 surviving and 5 not surviving). Nonsurvivors could be distinguished from survivors by an increase in NFkappaB binding activity during the observation period (P < 0.001). The increase in NFkappaB binding activity was comparable to the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer with an expression plasmid coding for IkappaBalpha was used to investigate the role of members of the NFkappaB family in a mouse model of endotoxemia. In this model, increased NFkappaB binding activity was present after injection of LPS. Intravenous somatic gene transfer with IkappaBalpha given before LPS attenuated renal NFkappaB binding activity and increased survival. Endothelial cells and monocytes/macrophages were the major target cells for somatic gene transfer, transfected with an average transfection efficiency of 20-35%. Tissue factor, a gene under regulatory control of NFkappaB, was induced by LPS. Somatic gene transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated NFkappaB-dependent stimulation by LPS. Intravenous somatic gene transfer with IkappaBalpha reduced LPS-induced renal tissue factor expression, activation of the plasmatic coagulation system (decrease of thrombin-antithrombin III complexes) and renal fibrin/fibrinogen deposition. Somatic gene transfer with an expression plasmid with tissue factor cDNA in the antisense direction (in contrast to sense or vector alone) also increased survival. Furthermore, antisense tissue factor decreased renal tissue factor expression and the activation of the plasmatic coagulation system.

Adult↗
PubMed1997

[Pressure versus volume constant ventilation in chronic ventilatory insufficiency].

BACKGROUND: Volume controlled intermittent ventilation (IPPV) via face mask is a treatment of proven efficacy for chronic respiratory failure (CRF). Pressure support ventilation has recently been introduced in the treatment of CRF. In this study we investigated whether pressure constant ventilation (PCV) via face mask could be an adequate long term alternative to IPPV. PATIENTS AND METHODS: We studied 30 (24 male, age: 52.2 +/- 15.9 years) patients with CRF. We measured the following parameters at baseline, after 1, 2 and 6 months, respectively: blood gas analysis, oxygen saturation, vital capacity, forced exspiratory volume, breathing frequency, tidal volume, inspiratory mouth occlusion pressure, maximal inspiratory pressure, subjective symptom scores and ventilator acceptance scores. In all patients, we attempted to treat with IPPV over 1 month, followed by 1 month's trial of PCV. If PCV, compared to IPPV, was adequate, PCV was continued for a follow-up period of 4 months' duration. If patients deteriorated after PCV they were treated the following 4 months with IPPV. RESULTS: In 28 out of 30 patients CRF improved concerning subjective and objective parameters. After IPPV 18 out of 28 patients changed to PCV, with an equal quality of treatment (PCV-responder). Ten patients were PCV-nonresponders since compared to IPPV the subjective scores deteriorated and the PaCO2 increased again. In all patients of either therapy group, subjective and objective parameters remained constant for another 4 months period. At baseline the PCV-nonresponders had significantly higher degree of hypercapnia and oxygen desaturation; no other parameters were found to be of predictive value concerning the efficacy of PCV. CONCLUSIONS: PCV proved to be an alternative to IPPV in the treatment of chronic respiratory insufficiency in approximately 60% of the patients with CRF. However there is a subgroup with more severe CRF at baseline in whom PCV is inadequate.

Adult↗
PubMed1997

[Economic aspects of modern inhalation anesthetics with sevoflurane as an example].

The economic impact of the new German health care laws requires an awareness of cost-effectiveness when using newer drugs. The main goal in patient care, i.e., effective treatment, must be achieved by the rational use of restricted resources at a maximum degree of effectiveness. Economic aspects of the new inhalational anaesthetics such as sevoflurane are discussed in this article. The cost of inhalational anaesthetic agents accounts for up to 5% of all the running expenses of an anaesthesia department. The consumption and cost of an inhalational agent depend on fresh gas flow, vapour setting, and duration of anaesthesia. Comparing the cost for 1 MAC-h of anaesthesia, desflurane is more expensive at current market prices than sevoflurane and isoflurane. However, at low or minimal fresh gas flows, the price for one MAC-h is almost the same for these volatile anaesthetics. Total intravenous anaesthesia using propofol is even more expensive, partly due to wastage, i.e., opened ampoules with a remainder of propofol that has to be discarded after each case. When choosing an anaesthetic agent, the price of 1 ml liquid anaesthetic is an important factor. However, the overall cost-effectiveness analysis must balance the cost of the agent with its pharmacodynamic advantages such as more rapid recovery from anaesthesia. Furthermore, the indirect costs of side effects have to be taken into account. For example, nausea and vomiting lead to a prolonged stay in the recovery room after anaesthesia for outpatient surgery, which in turn incurs additional costs for antiemetic drugs and the extra time for nursing care. Therefore, a lower incidence of nausea and vomiting and a more rapid recovery from anaesthesia leading to earlier discharge from the recovery room may compensate for the higher price. Volatile agents account for up to 1% of the total intraoperative costs. In analysing the costs of 1 h of anaesthesia, other products such as plasma substitutes and blood products account for a much higher proportion than anaesthetic agents, and reductions or increases in costs pertaining to these products have a bigger impact on overall costs than do volatile anaesthetics. We conclude that volatile anaesthetics account for only a minor portion of the anaesthesia department budget and the cost of anaesthesia delivery. The higher market price of the new agents may be compensated for by the economic impact of fewer side effects and a shorter post-anaesthesia stay in the hospital. In analysing data for sevoflurane, this agent may be cost-effective, for example, for outpatient anaesthesia.

Anesthesia Department, Hospital↗
PubMed1997

Effect of the 21-aminosteroid tirilazad mesylate on leukocyte adhesion and macromolecular leakage during endotoxemia.

BACKGROUND: Interstitial accumulation of leukocytes has been related to the development of multiple organ failure after sepsis. Oxygen radicals are involved in the process of leukocyte adherence to the microvascular wall. This study investigates the effects of the oxygen radical scavenger tirilazad mesylate on leukocyte-endothelial interactions, macromolecular leakage, and microhemodynamics in mesenteric venules during endotoxemia. METHODS: Male Wistar rats were randomly allocated to receive tirilazad mesylate (group A, n = 10), its vehicle (group B, n = 10), or saline 0.9% (group C, n = 10) before a 120-minute infusion of endotoxin (2 mg/kg/hr). Furthermore, a control group without receiving endotoxin (group D, n = 10) was investigated. Leukocyte adherence, emigration of leukocytes, and macromolecular leakage were determined in postcapillary venules of the mesentery by using intravital videomicroscopy. RESULTS: During the administration of endotoxin the number of adherent leukocytes per square millimeter of vessel surface progressively increased in group B (baseline, 431 +/- 35 cells/mm2; 120 minutes, 1121 +/- 71 cells/mm2) and group C (baseline, 398 +/- 44 cells/mm2; 120 minutes, 1290 +/- 116 cells/mm2). In group A no increase in leukocyte adherence was observed after 120 minutes (baseline, 415 +/- 81 cells/mm2; 120 minutes, 638 +/- 87 cells/mm2). In control animals the leukocyte adherence remained unchanged (baseline, 347 +/- 41 cells/mm2; 120 minutes, 507 +/- 75 cells/mm2). After 120 minutes, tirilazad mesylate prevented the increase in leukocyte emigration observed in group B and C. Increased macromolecular leakage during endotoxemia (groups B and C) was not influenced by pretreatment with tirilazad. Tirilazad did not affect the decrease in red cell velocity, volumetric blood flow, and venular shear rate observed during endotoxemia. CONCLUSIONS: This study demonstrates inhibitory effects of tirilazad on endotoxin-induced leukocyte adherence and emigration, suggesting a potential therapeutic role for this substance in the prevention of sepsis-induced multiple organ failure.

Animals↗
PubMed1997

Changes in intrathoracic fluid volumes during weaning from mechanical ventilation in patients after coronary artery bypass grafting.

PURPOSE: Although it is known that weaning from mechanical ventilation is associated with alterations in intrathoracic pressure, lung volume, and venous return, changes in intrathoracic fluid volumes during weaning are not reported. Especially in patients with impaired cardiac function, the development of pulmonary edema during weaning has been described. Thus, we investigated changes in intrathoracic fluid volumes in patients after coronary artery bypass grafting after changing the ventilatory pattern from mechanical to spontaneous ventilation. MATERIALS AND METHODS: Intrathoracic blood volume index (ITBVI), pulmonary blood volume index (PBVI), and extravascular lung water (EVLW) were calculated during mechanical ventilation (T1), T-piece breathing (T2), and spontaneous breathing after extubation of the trachea (T3) in 72 consecutive patients after coronary artery bypass grafting using a combined dye-thermal dilution method. RESULTS: Changing from mechanical ventilation to T-piece breathing resulted in an increase in ITBVI from 880 +/- 22 mL/m2 to 970 +/- 22 mL/m2 (P < .01), and in PBVI from 162 +/- 6 mL/m2 to 173 +/- 6 mL/m2 (P < .01). After extubation of the trachea, both parameters decreased again (ITBVI, 879 +/- 20 mL/m2; PBVI, 160 +/- 7 mL/m2). EVLW remained unchanged after transition to T-piece breathing (T1, 5.8 +/- 0.3 mL/kg; T2, 6.0 +/- 0.3 mL/kg), but increased to 6.6 +/- 0.5 mL/kg (P < .01) after extubation of the trachea. However, pathological values of EVLW were not observed. CONCLUSIONS: In patients after coronary artery bypass grafting, changes in intrathoracic intravascular fluid volumes during weaning are restricted to the period of T-piece breathing and reflect an increased venous return. The maintenance of EVLW in the normal range during weaning indicates that cardiac function was matched to this elevated preload.

Blood Volume↗
PubMed1997

Gastric intramucosal pH: a predictor of survival in cardiac surgery patients with low cardiac output?

OBJECTIVE: To assess the value of gastric intramucosal pH measurement in patients with low output after cardiac surgery. DESIGN: Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Fifteen patients with low output after cardiac surgery were included. Those who survived the first postoperative day (n = 14) remained in the study. INTERVENTIONS: Gastric intramucosal pH and arterial lactate concentrations were measured 6, 12, and 24 hours after admission to the intensive care unit. Intravenous infusion of buffer solutions was strictly avoided during the equilibration period and in the half hour before injection of saline into the gastric balloon of the tonometer. MEASUREMENTS AND MAIN RESULTS: Eight patients survived during the 28-day observation period, and six patients died. On admission to the intensive care unit, no difference in cardiac index (1.56 v 1.54 L/min/m2) or pulmonary capillary wedge pressure (17.3 v 17.7 mmHg) was found between survivors and nonsurvivors. During the first 24 hours after surgery, arterial lactate was significantly higher in the nonsurvivor group (61 v 23 mg/dL), but there was no difference between the gastric intramucosal pH of survivors and nonsurvivors (7.41 v 7.42 on admission). CONCLUSIONS: Calculated gastric mucosal pH is not an early predictor of survival in cardiac surgery patients with postoperative low cardiac output syndrome. Further studies are required to assess whether the gradient between arterial and intramucosal partial pressure of carbon dioxide (PCO2) might be a more useful predictive value.

Adult↗
PubMed1997

In-use contamination of propofol. A clinical study.

Reports about post-operative infections associated with the use of propofol prompted us to investigate the in-use contamination of lipid-formulated intravenous (i.v.) anaesthetics used for general anaesthesia or for sedation of intensive care patients in this department. The level and incidence of extrinsic contamination of propofol ('Diprivan') and of another intravenous anaesthetic, etomidate, formulated in lipid solution ('Etomidat-lipuro') was found to be low during two study periods. However, the need to observe strict aseptic precautions in handling these intravenous drugs must be emphasized.

Anesthetics, Intravenous↗
PubMed1997

Predominant involvement of motor fibres in patients with critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) is a recognized cause of muscle weakness and failure of weaning from a ventilator. In order to characterize the features of CIP, we have examined 28 consecutive surgical patients with severe sepsis using bedside electrophysiology. Of the 28 patients (median APACHE II score 31), 20 developed moderate to severe CIP, as shown by the presence of moderate to severe denervation activity on resting EMG. The median nerve compound muscle action potential (CMAP) amplitudes were reduced to 3.24 (SEM 0.48) mV, while sensory nerve action potential (SNAP) amplitudes obtained from the same nerve were normal (13.1 (1.9) microV). In approximately 50% of these patients, the reduction in CMAP exceeded 50% of the lower limit of normal. Similar results were obtained from stimulation of the ulnar nerve. We conclude that CIP is a major complication in patients with severe sepsis and prolonged artificial ventilation. It predominantly involves motor fibres and thus markedly interferes with weaning from the ventilator.

Adolescent↗