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Biomedical subjects

S Fitzal

Publications and source records attributed to S Fitzal.

At least 19 recordsLinked to original sources

Differential expression of tumor necrosis factor receptor subtypes on leukocytes in systemic inflammatory response syndrome.

OBJECTIVE: To determine the expression of tumor necrosis factor (TNF) receptor in patients with systemic inflammatory response syndrome (SIRS). DESIGN: Prospective study. SETTING: Intensive care unit and central laboratory. PATIENTS: Blood specimens from 18 healthy volunteers (controls) and 16 patients with SIRS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using monoclonal antibodies, fluorescence labeling, and high sensitivity flow cytometry, we measured the expression of membrane TNF receptor subtypes TNF-R55 and TNF-R75 on peripheral blood leukocytes. Receptor expression is expressed as mean fluorescence intensity +/- SD (units: detection channel number). In controls, TNF-R55 was only weakly expressed (monocytes: 2.5+/-1.8; neutrophils: 0.7+/-0.8), whereas expression of TNF-R75 was higher (monocytes: 28.6+/-9.0; neutrophils: 4.8+/-1.0) and was also found on lymphocytes (on CD8+ lymphocytes: 5.7+/-1.8; CD16+: 5.5+/-1.2; CD4+: 9.7+/-3.7). In SIRS, we observed increased expression of TNF-R55 on monocytes (6.9+/-3.4, p<.001) and neutrophils (2.2+/-1.9, p<.01), as well as decreased expression of TNF-R75 on monocytes (17.3+/-13.2; p<.001). The extent of TNF-R55 up-regulation did not correlate with that of TNF-R75 down-regulation. TNF-R55 on monocytes and neutrophils strongly correlated with body temperature but not with survival, whereas monocyte TNF-R75 was considerably lower in nonsurvivors, albeit not significantly (12.3+/-7.1 vs. 23.9+/-16.7; p = .07). CONCLUSIONS: These data indicate that leukocyte TNF-R55 and TNF-R75 react differentially and probably serve different functions in SIRS, which prompts the investigation of receptor subtype-specific therapeutic approaches.

Adult↗

[Ketamine and neuroprotection. Clinical outlook].

As the mechanism of action of ketamine, particularly its non-competitive antagonism at the N-methyl-D-aspartate receptor (NMDA), has become better understood, the use of the drug as a neuroprotective agent has received increasing interest. Although the potential prometabolic effects of ketamine might be counterproductive to neuroprotection, the increase in intracranial pressure it has repeatedly been reported to produce does not appear to be relevant clinically under certain conditions, e.g. in patients with normocapnia and a stable blood pressure. Also, the drug has been shown to be anticonvulsant in clinically applied doses rather than epileptogenic, as was previously assumed. These insights have opened up entirely new perspectives for the use of ketamine as a neuroprotective agent. But as both in vitro and in vivo studies are inconclusive, the benefits of the drug are still controversial. In addition, the potential neurotoxicity attributed to extremely high ketamine doses is poorly understood. Consequently, well controlled animal experiments and studies in humans would be necessary to establish the role of ketamine and its more potent enantiomer S-(+)-ketamine in combination with other neuroprotective measures and to shed light on its true neuroprotective potential and its possible neuroregenerative effects.

Animals↗

Alveolar macrophages of patients with adult respiratory distress syndrome express high levels of heat shock protein 72 mRNA.

Adult respiratory distress syndrome (ARDS), a multifactorial disease with poor prognosis, is characterized by an accumulation of inflammatory cells within the airspaces of the lungs. There is evidence that alveolar macrophages (AM) are involved in the pathogenesis of this pulmonary disease. It has been demonstrated that AM synthesize heat shock proteins (HSPs) after exposure to certain stress factors. Increasing evidence suggests that HSPs could confer protection against oxidative injury, noxious molecules, and bacterial toxins. In stressed cells HSP 72 appears to be essential for survival during and after exposure to cellular injury. The aim of this study was to evaluate the magnitude of HSP 72 expression by human AM of patients with ARDS and correlate that with respiratory burst activity. Bronchoalveolar lavage was performed in six ARDS patients, 10 patients with high risk for developing ARDS, and two patients who underwent bronchoscopy for other reasons. Spontaneous ex vivo expression of HSP 72 in AM could be demonstrated by immunocytochemistry. Total RNA as well as poly(A)-rich mRNA were extracted from recovered AM and analyzed by Northern blot and slot blot using a human HSP 72-specific probe. Signals of slot blot were analyzed by densitometry and expressed as relative levels of HSP 72 mRNA of stressed (42 degrees C) HT 1080 control cells. Significantly (p < .001) higher levels of HSP 72 mRNA were measured in patients with ARDS (96.2 +/- 9.5 relative levels) in comparison to those not developing this syndrome (46.0 +/- 4.2). With regard to respiratory burst activity of AM in patients with ARDS, there was a negative correlation between HSP 72 expression and reactive oxygen species production. The AM of patients with ARDS with high relative levels of HSP 72 expression showed low respiratory burst activity. A predictive value for disease severity of high level of HSP 72 mRNA in AM in patients at risk for ARDS has to be evaluated by future studies. This demonstration of HSP 72 expression ex vivo suggests a protective role of HSP response against endo/exogenously generated stress factors in AM.

Adult↗

The influence of temperature on somatosensory-evoked potentials during cardiopulmonary bypass.

Somatosensory-evoked potentials (SEPs) after median nerve stimulation were recorded in 10 neurologically normal patients during cardiopulmonary bypass and hypothermia. In all patients the changes of the latencies (spinal N13, cortical N20 and N35) and the central conduction time during cooling, and the decrease in latencies during rewarming was described by a gamma function. The analytic discussion of pooled data of all patients led to another SEP-latency-temperature relationship than the observation of each single patient. In 6 of 10 patients there was found a maximum of latency increase before the minimal temperature was reached. The cooling and the rewarming curve had to be considered separately. Latency changes of SEPs during hypothermia are discussed as a very complex phenomenon influenced by many technical and patient factors. This reduces the value of SEPs as an index of central nervous system integrity during open heart surgery and hypothermia.

Adult↗

[Tramadol in postoperative pain therapy. Patient-controlled analgesia versus continuous infusion].

UNLABELLED: Patient-controlled analgesia (PCA) is a well-proven procedure for individual pain relief in the post-operative period. Despite its superior approach regarding pharmacokinetic and pharmacodynamic considerations, PCA equipment is not available to many in the clinical practice. The goal of this study was to compare the efficacy and safety of PCA with continuous infusion (CI), an easily feasible method, using tramadol (T) as a centrally acting opioid with minor side effects on circulation and ventilation. METHODS: The study was conducted on 20 ASA I or II patients aged 20-60 years undergoing gynecological operations under standardized general anesthesia. They were randomly allocated to two groups receiving i.v. T for postoperative pain relief via Lifecare PCA 4200 Infuser. Group 1 (G1, PCA, n = 10): loading dose 3 mg/kg T, demand dose 30 mg T, lock-out time 5 min, concurrent infusion 5 mg/h T; group 2 (G2, CI, n = 10): loading dose 3 mg/kg T, continuous infusion 0.35 mg/kg per h T. If the analgesia was inadequate, additional doses of 50 mg T were available in G2. During a mean trial period of 20 h, the heart rate, blood pressure, respiratory rate and blood gas analysis were documented. The plasma levels of T and beta-endorphins were determined. The quality of analgesia was assessed by using a verbal and a visual analogue scale. RESULTS: The mean applied doses of T were 339 +/- 100 mg and 364 +/- 46 mg (G1 and G2, respectively) after 6 h and 565 +/- 243 mg and 707 +/- 139 mg (G1 and G2, respectively) in total (NS). Interindividual differences were substantial in G1. Five patients in G2 required an additional dose of 50 mg T. Pain scores decreased rapidly in both groups. The pain relief achieved was comparable and excellent after 6 h. The next morning, G2 reported significantly better analgesia in accordance with the higher availability of T as CI during the sleeping period. Mean plasma T levels were 994 +/- 440 ng/ml and 1170 +/- 357 ng/ml (G1 and G2, respectively). No correlation was found between T-levels and pain scores. The plasma levels of beta-endorphins were substantially elevated after the operation. They returned to normal during T-administration in both groups. No correlation was found between plasma levels of beta-endorphins and pain scores or T-consumption. Hemodynamic changes were minor and without clinical significance. PaO2 and paCO2 remained within small deviations from the physiological range. The respiratory rate, which was initially increased, dropped slightly in both groups. A high incidence of nausea and vomiting was observed, starting in the early phase of the loading dose. CONCLUSIONS: T is well suitable for postoperative pain relief after major gynecological surgery using both PCA and CI. PCA ensures adjustment of the medication to the individual demand, whereas CI provides better analgesia after sleeping periods. We recommend antiemetic prophylaxis before treatment with T.

Adult↗

[Nonsurgical removal of iatrogenic intracardiac foreign bodies. A study in a 5-month-old infant].

The development of new techniques and special catheter instruments permit iatrogenically embolized polyethylene catheter fragments to be retrieved nonsurgically. A case is reported in which a fragment of a central venous catheter was removed from the right atrium and ventricle by a DORMIA catheter in a 5-month-old child. The literature concerning nonsurgical retrieval of catheters is reviewed and indications for removal and complications discussed.

Cardiac Catheterization↗

[Comparison of fentanyl and tramadol in pain therapy with an on-demand analgesia computer in the early postoperative phase].

17 patients undergoing cholecystectomy in non-opiate general anaesthesia received tramadol (n = 7) or fentanyl (n = 10) for immediate postoperative pain relief using the on-demand analgesia computer (ODAC). Heart rate, blood pressure, and respiratory rate were monitored at half-hourly intervals during the 6-h trial period. Arterial blood was withdrawn at hourly intervals for blood gas analyses and beta-endorphin plasma level assays. Fentanyl and tramadol serum levels were determined prior to each on-demand bolus injection during the first 2 h of the study. At the end of the trial period, the quality of analgesia was assessed retrospectively using a visual analog scale. Mean opiate consumption was 0.53 +/- 0.1 mg for fentanyl and 412 +/- 11.6 mg for tramadol, resulting in an equipotency ratio of about 1:980 (relating to body wt., consumption/h, and pain score). No correlation was found between body wt.-based opiate requirements and pain score. Heart rate increased slightly but significantly under both opiates. Fentanyl produced a significant drop in mean arterial pressure by a maximum of 16%, while tramadol left mean arterial pressure unchanged. Respiratory rate, which was elevated initially, dropped significantly in both groups. Arterial pO2 and pCO2 were within the normal range throughout the observation period, reflecting the absence of respiratory side effects. Opiate blood levels showed major inter- and intraindividual variations (minimal and maximal levels for fentanyl ranged from 0.44-3.44 ng/ml, for tramadol from 272-1,900 ng/ml) and were thus poor predictors of the quality of analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Uptake and elimination of isoflurane and halothane by children and adults].

The rate of increase of alveolar concentrations (FA/FI) of isoflurane and halothane was studied in children and adults during general anaesthesia and controlled ventilation. After 30 min of body equilibrium, elimination curves of the volatile anaesthetics were determined by measurement of alveolar (FA/FA0; infrared technique) and venous concentrations (gas chromatography). The distribution and elimination half-times (t1/2 alpha, t1/2 beta), clearance (Cl), volume of central and peripheral compartment (V1, Vz) and the volume of distribution at steady state (Vss) were calculated from the intercepts and slopes of a two-compartment model. During the uptake of anaesthetic concentrations of isoflurane and halothane, the FA/FI ratio of each gas was found to rise significantly faster in children than in adults. The reason for the more rapid approach to equilibrium in children seems to be related to physiological differences. Irrespective of age, uptake of isoflurane was more rapid than that of halothane, as it is less soluble. Similarly, isoflurane was eliminated from the lung or blood faster than halothane. Moreover, anaesthetic wash-out in children differed from that in adults. In the paediatric age group t1/2 beta under isoflurane was shorter than in adults, whereas halothane excretion took longer in children. This could be accounted for by the larger volumes of distribution Vz and Vss in the young, due to higher organ affinity of halothane. From our data we conclude that age significantly affects uptake and elimination of volatile anaesthetics and the control of anaesthesia is easiest with isoflurane in paediatric patients.

Adult↗

[The circulatory effects of Org NC 45 (Norcuron) on three different anesthetic methods in patients with healthy hearts].

Patients under neurolept, halothane or enflurane anaesthesia received Org NC 45 for muscle relaxation. Systolic, diastolic, mean arterial pressure and heart rate were monitored throughout the study. All patients showed a fall in heart rate after Org NC 45, but this was significant (p less than 0,05) only during neurolept and enflurane anaesthesia. There was no significant change in blood pressure after Org NC 45.

Adult↗

Comparative investigations on the cardiovascular effects of Org NC45 and pancuronium in dogs.

Cardiovascular effects of Org NC 45 and pancuronium were examined in seven anaesthetized dogs. Systemic circulatory effects were measured after increasing doses administered as a single i.v. bolus. Cardiac effects were measured after intracoronary (i.c.) injection of the equivalent dose of the respective neuromuscular blocking agent, which produced 90% neuromuscular blockade. Org NC 45 i.v. did not cause any significant cardiovascular changes, whereas pancuronium i.v. produced significant and dose-related increases in heart rate, left ventricular (LV) dP/dtmax and cardiac output (CO). After i.c. injection of equipotent doses, neither drug induced any significant change in haemodynamic measurements. This implies that neither drug exerted a direct influence on cardiac contractility, the increases in LV dP/dt max and CO following pancuronium being dependent on heart rate.

Animals↗

Muscular relaxation with atracurium, vecuronium and duador under balanced anaesthesia.

The neuromuscular effects of three new nondepolarizing neuromuscular blocking drugs, atracurium, vecuronium and Duador, were investigated in surgical patients under balanced anaesthesia. (The numbers of patients in each study are given in the tables.) There were no significant differences in the neuromuscular effects of the three agents. None showed any cumulation after repeated administration of maintenance doses. Muscular relaxation for upper abdominal surgery was adequate as long as the isometric twitch tension (P) was no more than 25% of control. Conditions for tracheal intubation were satisfactory within less than 3 min after the start of injection. Spontaneous recovery of P to 90-95% of control, after the last dose of neuromuscular blocker was the fastest with vecuronium (35.8 +/- 2.4 min) and about the same with atracurium (54.3 +/- 2.4 min) and Duador (54.2 +/- 4.7 min). The T4/T1 ratio at the time of greater than 90% recovery of P was 0.44, 0.52 and 0.56 with vecuronium, Duador and atracurium, respectively, indicating the need for the reversal of the residual neuromuscular block. This could be accomplished within 2 min by the i.v. injection of edrophonium 0.5 mg kg-1, preceded by atropine 0.01 mg kg-1. No side-effects were observed with vecuronium. Atracurium caused mild to moderate histamine release in four of 50 patients included in this study, all of whom received an initial dose of 0.5 mg kg-1. The initial dose of Duador caused a 16.7% increase in heart rate. The findings indicate that the three new muscle relaxants merit further clinical trial. In our opinion, until the results of such studies become available, atracurium should not be used in patients with a history of allergic diathesis and Duador in those in whom increased heart rate may be harmful.

Androstanes↗

[Premedication with flunitrazepam, lormetazepam or pethidine-promethazine. Psychometric study of subjective conditions].

In the course of a clinical study oral administration of two different diazepine derivatives as well as i.m. injection of pethidine and promethazine have been explored with a view to their anxiolytic, sedating and hypnotic action. The study involved 128 patients, randomized into four groups. Group 1 received flunitrazepam 1,5-2 mg p.o. only the evening before operation to group 2 flunitrazepam 1,5-2 p.o. was administered the evening before and the morning of the operation, group 3 were given lormetazepam 2-2,5 mg p.o. at the same time as group 2, in group 4 nitrazepam, 5 mg p.o. the evening before operation and pethidine, 50-100 mg combined with promethazine, 25 mg was given i.m. 60 min before surgery. In group 1 anxiolytic and sedating effect of flunitrazepam were not persistent enough to provide the patient with adequate premedication until the onset of surgery. Intensive sedation and fatigue as well as minimum recollection were observed under medication 2, however, increase in anxiety and depression as well as deterioration of mood were not prevented. Under medication 3 patients felt less exhausted and fatigued than under medication 2, but likewise anxiety and depression increased in the course of the operating day. Group 4 emerged as the last effective premedication both with regard to sleep during the previous night and the conditions of the day of the operation itself.

Adult↗

Relative roles of heart rate and ventricular stroke volume for the regulation of cardiac output during controlled hypotension with sodium nitroprusside in man.

The effects of N-allyl clonidine (St 567, alinidine), (0.5 mg/kg i.v.) a substance with specific bradycardic action at the sinus node, were studied on a total of thirteen patients in neuroleptanaesthesia and during controlled hypotension with sodium nitroprusside (SNP). Invariably, the fall in blood pressure was associated with an increase in heart rate (20.0 +/- 4.3+; P less than 0.01), presumably due to an activation of the arterial baroreceptor reflex. Alinidine decreased heart rate to the original level but no fall in cardiac output occurred a ventricular stroke volume and the calculated left ventricular stroke work were increased compensatorily (35.9 +/- 7.2% and 35.9 +/- 6.7%, P less than 0.01, respectively). In patients who received alinidine before the onset of controlled hypotension (n = 5) SNP failed to elicit an increase in heart rate. It is concluded that in patients under neuroleptanaesthesia tachycardiac does not play an important role for the maintenance of an adequate cardiac output during controlled hypotension with SNP.

Adult↗