Biomedical subjects

C Zöllner

Publications and source records attributed to C Zöllner.

At least 19 recordsLinked to original sources

PubMed2007

Opioids.

Opioids are the most effective and widely used drugs in the treatment of severe pain. They act through G protein-coupled receptors. Four families of endogenous ligands (opioid peptides) are known. The standard exogenous opioid analgesic is morphine. Opioid agonists can activate central and peripheral opioid receptors. Three classes of opioid receptors (mu, delta, kappa) have been identified. Multiple pathways ofopioid receptor signaling (e.g., G(i/o) coupling, cAMP inhibition, Ca++ channel inhibition) have been described. The differential regulation of effectors, preclinical pharmacology, clinical applications, and side effects will be reviewed in this chapter.

Amino Acid Sequence↗

PubMed2004

Rapid upregulation of mu opioid receptor mRNA in dorsal root ganglia in response to peripheral inflammation depends on neuronal conduction.

S.c. painful inflammation leads to an increase in axonal transport of opioid receptors from dorsal root ganglia (DRG) toward the periphery, thus causing a higher receptor density and enhanced opioid analgesia at the injured site. To examine whether this increase is related to transcription, the mRNA of Delta- (DOR) and mu-opioid receptor (MOR) in lumbar DRG was quantified by real time Light Cycler polymerase chain reaction (LC-PCR), and correlated to ligand binding in DRG and sciatic nerve. In normal DRG, DOR mRNA was seven times less abundantly expressed than MOR mRNA. After induction of unilateral paw inflammation, mRNA content for DOR remained unchanged, but a bi-phasic upregulation for MOR mRNA with an early peak at 1-2 h and a late increase at 96 h was found in ipsilateral DRG. As no changes were observed in DRG of the non-inflamed side, this effect was apparently not systemically mediated. A significant increase in binding of the MOR ligand DAMGO was detected after 24 h in DRG, and after early and late ligation in the sciatic nerve, indicating an enhanced axonal transport of MOR in response to inflammation. The early increase in MOR mRNA could be completely prevented by local anesthetic blockade of neuronal conduction in sciatic nerve. These data suggest that mRNA of the two opioid receptors DOR and MOR is differentially regulated in DRG during peripheral painful inflammation. The apparently increased axonal transport of MOR in response to this inflammation is preceded by upregulated mRNA-transcription, which is dependent on neuronal electrical activity.

Anesthetics, Local↗

PubMed2001

Continuous cardiac output measurements do not agree with conventional bolus thermodilution cardiac output determination.

PURPOSE: To evaluate the performance of two different continuous cardiac output monitoring systems based on the thermodilution principle in critically ill patients. METHODS: Nineteen cardiac surgical patients were randomly assigned to continuous cardiac output monitoring using one of the two systems under study (group I, IntelliCath(TM) catheter, n=9; group II, Opti-Q(TM) catheter, n=10). Each patient was studied over a period of three hours. Conventional bolus thermodilution cardiac output measurements were carried out every 15 min leading to 13 measurements in each patient. The continuous cardiac output values were compared with the bolus thermodilution measurements. Bias (mean difference between continuous and bolus thermodilution) and precision (SD of differences) were calculated as a measure of agreement between the respective continuous method and conventional bolus thermodilution. RESULTS: The range of measured cardiac outputs was 3.8-15.4 L*min(-1) (IntelliCath(TM)) and 3.5-8.3 L*min(-1) (OptiQ(TM)). Bias and precision was 0.06 +/- 0.76 L*min(-1) (IntelliCath(TM)) and -0.04 +/- 0.74 L*min(-1) (OptiQ(TM)), respectively. There was no difference in bias between the two systems (P=0.38). +/- 2 SD of the differences (i.e., 95% of the differences) did not fall within the predetermined limits of agreement of +/- 0.5 L*min(-1). CONCLUSIONS: There was no difference between the two systems regarding the agreement with conventional bolus thermodilution as the standard. A discrepancy between bolus and continuous thermodilution cardiac output measurement techniques above the clinically acceptable limits suggest that they are not interchangeable.

Adult↗

PubMed2000

Control of mu opioid receptor expression by modification of cDNA 5'- and 3'-noncoding regions.

Removal of a 712 base pair (bp) sequence following the coding region of a human micro opioid receptor (hmuOR) cDNA unexpectedly increased expression of the receptor protein. A series of 3'-noncoding region deletion mutants revealed that at least three discrete regions following the stop codon influenced receptor expression levels. Deletion of the 205-bp 5'-noncoding region immediately preceding the Kozak sequence doubled receptor expression relative to wild type, and simultaneous deletion of 5'- and 3'-noncoding regions increased expression several fold. The hmuOR noncoding regions may participate in a regulatory mechanism that controls the number of cell surface receptors.

3' Untranslated Regions↗

PubMed2000

Beat-to-beat measurement of cardiac output by intravascular pulse contour analysis: a prospective criterion standard study in patients after cardiac surgery.

OBJECTIVE: To evaluate the accuracy of a new pulse contour method of measuring cardiac output in critically ill patients. DESIGN: A prospective criterion standard study. SETTING: Cardiac surgery intensive care unit in a university hospital. PARTICIPANTS: Nineteen cardiac surgery patients requiring intensive care treatment with pulmonary artery catheters after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pulse contour cardiac output monitor uses transpulmonary bolus thermodilution measurements to calibrate the system. In each patient, the pulse contour cardiac output values were compared with conventional thermodilution. The method described by Bland and Altman and linear regression analysis were used for comparison. The mean difference (bias) +/- standard deviation of differences (precision) was 0.31 +/- 1.25 L/min for pulmonary bolus thermodilution cardiac output versus pulse contour cardiac output and 0.21 +/- 0.73 L/min for pulmonary bolus thermodilution cardiac output versus transpulmonary bolus thermodilution cardiac output. Linear regression (correlation) analyses were pulse contour cardiac output = 0.97 thermodilution + 0.53 (r = 0.88), and transpulmonary cardiac output = 0.87 thermodilution + 1.09 (r = 0.96). There was a small increase 60 minutes after recalibration but not a statistically significant difference between pulse contour cardiac output and pulmonary bolus thermodilution cardiac output (p = 0.52). CONCLUSIONS: Bias and precision are acceptable, and the system provides results that agree with conventional thermodilution. This study demonstrates the clinical applicability of the pulse contour cardiac output monitoring system.

Adult↗

PubMed1999

Mutation of human mu opioid receptor extracellular "disulfide cysteine" residues alters ligand binding but does not prevent receptor targeting to the cell plasma membrane.

The mu opioid receptor, a primary site of action in the brain for opioid neuropeptides and opiate drugs of abuse, is a member of the seven transmembrane, G protein-coupled receptor (GPCR) superfamily. Two cysteine residues, one in each of the first two of three extracellular loops (ECLs), are highly conserved among GPCRs, and there is direct or circumstantial evidence that the residues form a disulfide bond in many of these receptors. Such a bond would dramatically govern the topology of the ECLs, and possibly affect the position of the membrane-spanning domains. Recent findings from several laboratories indicate the importance of the ECLs for opioid ligand selectivity. These conserved cysteine residues in the mu opioid receptor were studied using site-directed mutagenesis. Little or no specific binding of radiolabled opiate alkaloid or opioid peptide agonists or antagonists was observed for receptors mutated at either "disulfide cysteine" residue. Each mutant mu opioid receptor was expressed in both transiently- and stably-transfected cells, in some cases at levels comparable to the wild type receptor. The two point mutants possessing serine-for-cysteine substitutions were also observed to successfully reach the cell plasma membrane, as evidenced by electron microscopy. Consistent with related work with other GPCRs, the mu opioid receptor apparently also employs the extracellular disulfide bond. This information now permits accurate molecular modeling of extracellular aspects of the receptor, including plausible scenarios of mu receptor docking of opioid ligands known to require specific extracellular loop features for high affinity binding.

Amino Acid Substitution↗

PubMed1999

Evaluation of a new continuous thermodilution cardiac output monitor in cardiac surgical patients: a prospective criterion standard study.

OBJECTIVE: To evaluate the accuracy of a new continuous cardiac output monitor in critically ill patients. DESIGN: Criterion standard study. SETTING: Cardiac surgery intensive care unit in a university hospital. PATIENTS: Twenty cardiac surgical patients requiring intensive care treatment with pulmonary artery catheters after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cardiac output was monitored continuously with a modified pulmonary artery catheter that has a heating filament on the outside of the catheter. Four modes of data processing with different response times ("Normal," "Fast," "FastFilter," and "Urgent" modes) used by the monitoring system. A total of 240 determinations of cardiac output were performed using conventional bolus thermodilution technique; these results were compared with those obtained using three of the four continuous measuring modes available ("Normal," "FastFilter," and "Urgent"). Cardiac output ranged from 3.47 to 15.77 L/min (bolus thermodilution). The mean (bias) +/- SD of differences (precision) for all measurements was 0.40+/-1.26 L/min in the Normal mode (cardiac output <10 L/min: 0.34+/-0.66 L/min), 0.53+/-1.27 L/min in the FastFilter-mode (cardiac output <10 L/min: 0.60+/-0.75 L/min), and 0.63+/-1.34 L/min in the Urgent mode (cardiac output <10 L/min: 0.57+/-0.82 L/min). CONCLUSIONS: Continuous cardiac output measurement using the thermodilution technique is reasonably accurate, reliable, and applicable in routine clinical practice. The values obtained using the Normal mode of the monitor agreed significantly better with the conventional thermodilution method than the results of the two other modes studied (FastFilter and Urgent). In addition, measurements in two patients with cardiac output values of >10 L/min did not agree with the results of the bolus thermodilution method.

Adult↗

PubMed1998

[Retrospective analysis of transpulmonary and pulmonary arterial measurement of cardiac output in ARDS patients].

OBJECTIVES: To investigate the agreement (and its potential dependency on extra-vascular lung water) between transpulmonary (TPID) and standard pulmonary artery (PAID) thermodilution cardiac output measurements. METHODS: One hundred and sixty simultaneous cardiac output measurements using transpulmonary and pulmonary artery thermodilution techniques were retrospectively compared in 18 patients with acute respiratory distress syndrome. In addition, extravascular lung water was determined using a double indicator technique (temperature and indocyanine green). RESULTS: Mean (+/- SD) difference ("bias") was 0.03 L/min (+/- 1.04 L/min), linear regression analysis resulted in TPID = 0.87 PAID + 1.16 (r = 0.91). Mean extra vascular lung water was 1625 mL (minimum-maximum: 403-3266 mL) and therefore markedly elevated as could have been expected in patients with ARDS. Bias (PAID-TPID) was not dependent on extravascular lung water. CONCLUSIONS: Transpulmonary and pulmonary artery thermodilution methods can be used interchangeably. The results demonstrate for the first time in humans that transpulmonary thermodilution provides valid cardiac output values in patients with markedly increased fluid content of the lungs.

Adult↗

PubMed1995

Evaluation of a new continuous thermodilution cardiac output monitor in critically ill patients: a prospective criterion standard study.

OBJECTIVE: To evaluate the accuracy of a new continuous cardiac output monitor (one based on the thermodilution principle) in critically ill patients. DESIGN: Criterion standard study. SETTING: Multidisciplinary intensive care unit in a university hospital. PATIENTS: Fourteen critically ill patients, with different diseases, requiring pulmonary artery catheterization. INTERVENTIONS: In two patients with a left ventricular assist system, a defined, sudden 1 L/min change in cardiac output was carried through to evaluate the in vivo response time of the continuous cardiac output monitoring system. In the remaining 12 patients, cardiac output was altered by varying the dose of catecholamines, by volume loading, or by varying the level of sedation. In four patients, a rapid infusion of cold saline was given through a central venous catheter to test the performance of the system under these conditions. MEASUREMENTS AND MAIN RESULTS: Cardiac output was monitored continuously. A total of 163 (13 to 18 per patient) bolus determinations of cardiac output were performed, using the conventional thermodilution technique and simultaneously using the indocyanine green dye dilution technique. The range of cardiac output was 3.8 to 15.6 L/min. The results of the continuous thermodilution method were compared with the results of the bolus thermodilution and the dye dilution methods, respectively. The mean difference (bias) +/- SD of differences (precision) was 0.35 +/- 1.01 L/min for continuous vs. bolus thermodilution and 0.34 +/- 1.01 L/min for continuous thermodilution vs. indocyanine green dye dilution. Linear regression (correlation) analyses were y = 0.95x + 0.76 (r2 = .91) for continuous and bolus thermodilution and y = 0.93x + 0.87 (r2 = .91) for continuous thermodilution and dye dilution. The 75% in vivo response time was 10.5 mins. The infusion of cold isotonic saline led to erroneous continuous cardiac output values. When the conventional bolus thermodilution and dye dilution techniques were compared, mean difference was -0.01 +/- 0.54 L/min and the results of linear regression analyses were y = 0.97x + 0.22 (r2 = .97). CONCLUSIONS: Continuous cardiac output measurement using the thermodilution technique is reasonably accurate and is reliable and applicable in routine clinical practice, and therefore may add to patient safety. However, the response time is too slow for the immediate detection of acute changes in cardiac output. Some clinical conditions such as the rapid infusion of cold solutions can interfere with the continuous cardiac output measurement. Conventional bolus thermodilution and indocyanine green dye dilution methods showed good agreement and can be used interchangeably.

Adult↗

PubMed1995

Thermodilution cardiac output may be incorrect in patients on venovenous extracorporeal lung assist.

Cardiac output measurement is part of routine monitoring in critically ill patients. In patients on extracorporeal lung assist, thermodilution cardiac output measurement may lead to erroneous results caused by indicator loss into the extracorporeal circuit. Seven patients on venovenous extracorporeal lung assist were studied using different extracorporeal blood flows. We compared conventional thermodilution cardiac output determinations with dye dilution cardiac output measurement, with dye injection into the pulmonary artery. The latter method is not affected by the extracorporeal circuit. The conventional thermodilution method overestimated cardiac output up to a maximum of 300%, providing results up to 10 L/min higher than true cardiac output. The mean difference between thermodilution and true cardiac output as determined by dye dilution with pulmonary artery indicator injection was 3.0 +/- 2.41 L/min. There was no correlation between thermodilution cardiac output values and true cardiac output (r = 0.06). We conclude that conventional thermodilution is not a suitable method for cardiac output measurement in patients on extracorporeal lung assist, especially if high extracorporeal blood flows are applied.

Adult↗

PubMed1993

[Myiasis in female travelers to the tropics].

Myiasis is a rare disease in Europe and the USA; it is defined by the development of parasitic, mostly tropical maggots in the human body. They are best identified by the pattern of their terminal spiracles and the shape of their stigmal plates. In spite of the size of the larvae of Cordylobia anthropophaga, there is only low-grade inflammation; the clinical course is benign.

Aged↗

PubMed1988

The motor innervation of the tympanic muscles in the guinea pig.

The number and the location of the motor neurons innervating the stapedius or tensor tympani muscles in the guinea pig were identified by retrograde axonal transport of the tracer horseradish peroxidase. Tracer injections were made either into the stapedius or tensor tympani muscle and effected the retrograde labeling of neurons in the ipsilateral brain stem. These findings showed that the stapedius motor neurons lie outside the traditionally recognized facial nucleus and are present in two cell columns: ventromedial and dorsomedial to the facial nucleus. These labeled neurons are dissimilar to cells within the facial nucleus, i.e. they are smaller and more fusiform in shape. The tensor tympani motor neurons were found outside the trigeminal motor nucleus. At a rostral level they were located in a region ventral and ventrolateral to the latter nucleus. These labeled neurons were smaller than the trigeminal motor neurons and polygonal in shape. In the animals studied there were about six times more tensor tympani motor neurons than stapedius motor neurons.

Animals↗

PubMed1988

Effects of topical anesthetics on tympanic membrane structure.

Topical application of a local anesthetic agent can induce adequate insensibility to pain, and therefore can avoid the use of general anesthesia or invasive infiltration techniques for myringotomy or the insertion of a tympanostomy tube. A comparative study was conducted on a guinea pig animal model to determine the effects of three agents on the structure of the tympanic membrane: 5% tetracaine base dissolved in dimethylsulfoxide (DMSO), pure DMSO, and Bonain's solution. Survival times ranged from 1 day to 3 months. Following removal from the animals, membranes were embedded in Spurr and cut in semithin sections. Signs of mild or severe external otitis were frequent; to avoid non-specific results, infected specimens were not evaluated. Bonain's solution caused loss of the epidermis and mucosal epithelium within 1 day of treatment. The connective tissue layers of the drum were severely hyperplastic after a survival time of 1 month. Tetracaine base in DMSO caused a loss of epithelium and mucosal cells in 3 days. Regeneration started within 7 days and a restitution to integrity was seen after 3 months in drums treated with tetracaine base or DMSO alone.

Administration, Topical↗

PubMed1988

[Implantation of 125 iodine seeds in the dog vocal cord. An experimental morphologic study].

Following the first positive therapeutic results of T1a vocal chord cancer with 125iodine seeds in man (brachytherapy), we were concerned with the effects of this low-energy photon source on healthy laryngeal tissue. In the larynx, changes in the area of the vocal chord and the cartilaginous laryngeal structures were investigated in particular. These experimental studies were performed on the larynx of the dog. Through direct laryngoscopy, two 125iodine seeds were implanted in the anterior third of each vocal chord in 8 dogs; the resulting prick canals were sealed with fibrin glue. During survival the correct position of the seeds was radiologically monitored. After survival periods of 1, 3, 6, and 12 months the larynges were fixed by perfusion, removed, imbedded in paraplast, and stained with H. E., Azan, and E. v. G. After this protracted irradiation with 125iodine seeds only slight and for the most part reversible pathological changes had occurred. One month after implantation, only a perivascular infection was found in the vocal chord. After three months an inhibition of the fibrin organization around the seeds was observed as well as a localized dyschylia with broadening of the gland ducts. Additionally, a circumscribed dysplasia of the squamous epithelium, swelling of the capillary endothelium, atrophy of muscular fibres around the seeds, and telangiectasia of blood vessels were discernable. 6 and 12 months after implantation, only the muscular atrophy and the telangiectasia of the blood vessels remained detectable, in addition to a reduced inhibition of the fibrin organisation by connective tissue.

Animals↗

PubMed1988

[A lidocaine base for surface anesthesia of the tympanic membrane].

An anatomical study was conducted to determine the effects of 10% lidocain base (dissolved in DMSO) on the structure of the tympanic membrane. Survival times ranged from 1 day to 3 months. Membranes were embedded in plastic and cut in semithin sections. Within 1 and 3 days mild swelling of the epithelium was seen; 1 month after treatment the connective tissue layers of the lamina propria were severely hyperplastic. 2 months after lidocain-Base application additional collagen fibres, loosely packed and less regularly, appeared in the submucosal connective tissue layer. However, normal appearance of the drums was noticeable after 3 months survival.

Anesthesia, Local↗

PubMed1988

[A rare nasopharyngeal tumor: Hodgkin's disease].

Primary cases of Hodgkin's disease in the nasopharynx are extremely rare. The authors report on two such cases: A 27 year old male had a large tumour, lined with a smooth mucous membrane, in the nasopharynx. The results of examinations of the neck, thorax, and abdomen were normal. The tumour was removed through the palate. Histological findings confirmed the diagnosis of lymphocyte-prominent Hodgkin's disease (subtype paragranuloma). 11 years ago a nasopharynx tumour was removed by adenotomy from a 57 year old female. A diffuse hyperplasia of the lymphatic tissue was diagnosed at the time. Recently cervical lymph nodes appeared, and a second tumorous lesion was discovered in the nasopharynx. Histological examination of the tumour and cervical lymph node indicated lymphocyte-prominent Hodgkin's disease (subtype paragranuloma). On re-examining histological sections from the tumour removed 11 years ago, the authors again saw the types of change indicative of Hodgkin's disease. The probable course and outcome of lymphocyte-prominent Hodgkin's disease of the nasopharynx, especially of the paragranuloma subtype of the disease, are discussed. Treatment of both patients included adjuvant extended-field radiotherapy.

Adult↗

PubMed1987

Sensitivity and specificity of brain stem potentials as a means of differentiating cochlear and retrocochlear disorders (acoustic neuromas).

Between 1980 and 1985 we examined a fairly large group of patients for retrocochlear disorders. Every patient was examined by at least two procedures, registration of brain stem potentials and CT; we had also magnetic resonance images taken of some of these patients. We diagnosed a total of 37 acoustic neuromas in 34 of the patients examined. From our study a conclusion can be drawn about the sensitivity and specificity of brain stem potentials as evidence of an acoustic neuroma. The rate of false negative diagnoses is about 6%. The false positive rate is considerably higher, and it is discussed in detail. The clinical utility of brain stem potentials is illustrated with two case histories. Because of the method's low false negative rate, cochlear disorders diagnosed by registering brain stem potentials need not as a rule be confirmed by modern imaging procedures.

Adult↗

PubMed1987

[Middle ear implants (Tübingen type) of Al2O3 ceramics. Follow-up to 6 years after surgery].

Since 1980 we have been using Al2O3 ceramic implants in some reconstructions of the ossicular chain. We began interposing a small autologous cartilage perichondrium disk between implants of this type and the ear-drum after having observed the first cases of imminent extrusion and of extrusion. Thus about half the implants in our first follow-up study. in 1984, were shielded by a cartilage disk; in 1984 91 patients (108 ears) were examined. 64 of the same patients (66 ears) consented to be re-examined in a second follow-up study in 1986. Of the 66 Al2O3 ceramic implants in the smaller sampling 43 had a cartilage overlay, and 23 did not. The implants without a cartilage overlay had been in situ for 3 to 6 years, and on average for 59 months; those with a cartilage overlay had been in situ for 3 to 6 years, and on average for 59 months; those with a cartilage overlay had been in situ for 2 to 5 years, and on average for 39 months. Both studies show the feasibility of markedly reducing the risk of imminent extrusions and extrusions, which occur when the cavum tympanum is poorly ventilated and the ear-drum retracts. The extrusion rates for Al2O3 middle-ear implants with and without a cartilage overlay were 5% and 16% respectively from 1980 to 1986. The great majority of ears examined showed a residual air-bone-gap of 0 to 20 dB in the frequency range between 0.5 and 2 kHz. Our audiometric results were essentially the same in 1984 and 1986.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗