Biomedical subjects

M Steinfath

Publications and source records attributed to M Steinfath.

At least 55 records · Page 3Linked to original sources

PubMed1996

[Is remifentanil an ideal opioid for anesthesiologic management in the 21st century?].

Current trends toward outpatient surgery and closed loop computer controlled drug administration have created a demand for short acting anaesthetic agents. Such agents not only provide the anaesthetist with rapid patient recovery after completion of the procedure, but also with almost immediate intra-operative control over the anaesthetic state of the patient. Shorter acting anaesthetic agents are being developed in several therapeutic areas including volatile anaesthetics, neuromuscular blockers as well as injectable anaesthetics. In the injectable anaesthetic area, propofol has been introduced and offers some significant advantages over the previously existing induction agents. Remifentanil is a novel member in the family of the 4-anilidopiperidine opioid analgesics which also include the traditional agents fentanyl, alfentanil, and sufentanil. Remifentanil undergoes widespread extrahepatic metabolism by blood and tissue nonspecific esterases, resulting in an extremely rapid clearance. Because of its unique metabolic pathway among this group of drugs, remifentanil represents a new pharmacokinetic class of opioids which is named esterase metabolised opioid (EMO). Rapid biotransformation to minimally active metabolites results in short and predictable duration of action with no accumulation of effect on repeated dosing or with continuous infusion. Clinical experiences presented so far indicate that remifentanil can be safely administered in different anaesthetic regimens as well as in the great variety of patients including children and patients with renal, hepatic or cardiovascular diseases. However, its use also presents the anaesthetist with a significant challenge. If remifentanil is the only opioid analgesic administered during anaesthesia, it must be remembered that shortly after the end of the surgical procedure, the patient will not benefit from opioid-based analgesia. This problem must be addressed if remifentanil is to be used for procedures associated with significant postoperative pain. Reducing the infusion rate of remifentanil to analgesic doses suitable for the postoperative pain management or immediate administration of longer acting opioids at the end of anaesthesia might solve this problem. At present it is difficult to predict precisely the future ranking of remifentanil. However, the unique pharmacokinetic profile of remifentanil should make it useful in the various surgical settings and in all circumstances where precise control over the analgesic state are desirable.

Adolescent↗

PubMed1996

In vitro diagnosis of malignant hyperthermia susceptibility with ryanodine-induced contractures in human skeletal muscles.

The in vitro contracture test with ryanodine is a new method to distinguish malignant hyperthermia (MH) susceptible (MHS) from normal (MHN) patients. The purpose of our investigation was to determine whether smaller concentrations of ryanodine than those used previously may result in a better differentiation. We performed a ryanodine contracture test (RCT) using concentrations of 1 and 2 microM in muscle specimens of 41 MHS, 58 MHN, and 19 MH-equivocal (MHE) patients. Nine patients were excluded from the study due to neuromuscular diseases. All contracture levels (i.e., start of contractures, contractures of 0.2 g and 1.0 g) were attained significantly earlier in MHS than in MHN muscles at both concentrations of ryanodine. Using a ryanodine concentration of 2 microM, all contracture levels were reached significantly faster than with 1 microM. There was no overlap in the range of times between groups at all contracture levels with ryanodine 1 and 2 microM. The median threshold times for all MHE patients were always between those of MHS and MHN. Defining arbitrarily threshold times for MHS and MHN, an assignment of MHE patients to either MHS or MHN using 1 or 2 microM ryanodine was possible in most cases. Ryanodine administration at a concentration of 1 microM led to a better distinction of MHS from MHN patients than 2 microM. The RCT with ryanodine 1 microM should therefore be added to the current diagnostic methods.

Adolescent↗

PubMed1996

Effects of the serotonin2 receptor agonist DOI on skeletal muscle specimens from malignant hyperthermia-susceptible patients.

BACKGROUND: Administration of serotonin2 (5-HT2) receptor agonists in pigs triggers malignant hyperthermia (MH) and psychotic-like behavior. Both can be reduced by 5-HT2 receptor antagonists. Furthermore, an increase in the plasma concentration of 5-HT has been found during onset of halothane-induced MH in pigs. Therefore, in this study, the in vitro effects of the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were investigated in muscle specimens from MH-susceptible (MHS) and -negative (MHN) patients. METHODS: After MH classification using the caffeine-halothane contracture test (CHCT), surplus muscle specimens from 23 MHS and 17 MHN patients were used to examine the effects of DOI. In the first study, DOI was added to the bath in a concentration of 0.02 mM. In a second experiment, muscles were preincubated for 60 min with 0.02 mM DOI, and subsequently, halothane was added incrementally to the organ bath (0.11-0.22-0.44 mM) for 15 min according to the CHCT protocol. The in vitro effects of DOI on contracture development and muscle twitch were measured for 120 min in both investigations. RESULTS: Muscle specimens form all patients developed contractures after administration of DOI, characterized by a significantly earlier development of contracture in MHS (16.8 +/- 1.7 min) than in MHN (66.3 +/- 5.8 min) muscles (P < 0.05). There was no overlap between the groups in the range of times. The onset of contracture development after DOI was prolonged by halothane in specimens from MHN patients (89.7 +/- 5.6 min) but not MHS patients. Preincubation with DOI increased the halothane-induced contractures in specimens from MHS patients compared to the results of the CHCT. The contracture development in specimens from MHS patients was larger than from MHN patients. At the end of the experiment, contractures had reached a maximum of 12.9 +/- 1.1 mN in specimens from MHS and 5.3 +/- 0.6 mN in MHN patients (P < 0.05). The additional administration of halothane led to significantly increased contractures in specimens from MHS individuals (15.9 +/- 0.9 mN) at 120 min. However, the contracture development decreased significantly to 3.1 +/- 0.4 mN in MHN muscles. Muscle twitch after DOI administration was reduced significantly in specimens from MHS and MHN patients. CONCLUSIONS: A functional or structural altered serotonin system might be involved in the development of MH in humans.

Adolescent↗

PubMed1996

Is sufentanil a useful opioid for laryngomicroscopy?

BACKGROUND: Alfentanil is commonly used as opioid analgesic for short surgical procedures. Little is known about the usefulness of sufentanil for this purpose. We investigated the effects of alfentanil and sufentanil on haemodynamic characteristics, catecholamine levels, and adrenocorticotropic hormone (ACTH) and cortisol contents during elective laryngomicroscopy and short laryngeal surgery (LM). METHODS: 100 patients (ASA class I or II) were randomly allocated into one of four groups to receive either 10 micrograms/kg alfentanil (group I, ALF 10), 20 micrograms/kg alfentanil (group II, ALF 20), 0.25 micrograms/kg sufentanil (group III, SUF 0.25), or 0.5 micrograms/kg sufentanil (group IV, SUF 0.5) given intravenously before induction of anaesthesia. After administration of the opioid analgesic all patients received 2.0 mg/kg propofol, 15 micrograms/kg vecuronium, and 1 mg/kg succinylcholine. Anaesthesia was maintained as total intravenous anaesthesia with propofol (8 mg/ kg/h) and oxygen (33%) in air. Heart rate (HR), mean arterial pressure (MAP), adrenaline (ADR), noradrenaline (NADR), ACTH, and cortisol were measured before (baseline) and after induction of anaesthesia, at the beginning and cessation of LM, and 2 h after LM. RESULTS: In group I (ALF 10) a significant increase in all variables was observed at the beginning and at the end of LM when compared with baseline. Two hours after LM all parameters were found to be at baseline levels. In groups II and III (ALF 20 and SUF 0.25) a significant increase in HR, MAP and catecholamine levels was observed at the end of LM compared to baseline. ACTH and cortisol contents were unchanged throughout. In group IV (SUF 0.5) HR was significantly reduced after induction, at the beginning and cessation of LM, and 2 hours following operation, whereas MAP was only decreased after induction (P < 0.05 vs. baseline). ADR, NADR, ACTH, and cortisol were similar throughout. If the duration of surgery was shorter than 12 min (20%) in group III (SUF 0.25) and 20 min (44%) in group IV (SUF 0.5), the patients had to be treated with naloxone 10 min after cessation of LM in order to antagonize respiratory depression. This side effect was not observed in group I (ALF 10) and in only one patient (4%) of group II (ALF 20) for whom surgery lasted 5 min. CONCLUSION: Clinical recovery is achieved most rapidly with alfentanil in ultra short surgical procedures. However, if surgery is expected to be longer than about 12 min also sufentanil at a dose of 0.25 micrograms/kg seems to be useful for this kind of surgery.

Adrenocorticotropic Hormone↗

PubMed1996

Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil. An update.

Alfentanil, fentanyl and sufentanil are synthetic opioid analgesics acting at specific opioid receptors. These opioids are widely used as analgesics to supplement general anaesthesia for various surgical procedures or as primary anaesthetic agents in very high doses during cardiac surgery. Fentanyl and sufentanil especially are administered via infusion for long term analgesia and sedation in intensive care patients. Opioid analgesics are mainly administered using the intravenous route. However, other techniques of administration, including epidural, intrathecal, transdermal and intranasal applications, have been demonstrated. Important pharmacokinetic differences between alfentanil, fentanyl and sufentanil have been shown in many reports. Alfentanil has the most rapid analgesic onset and time to peak effect as well as the shortest distribution and elimination half-lives. The volume of distribution and total body clearance of this agent are smaller when compared with those of fentanyl and sufentanil. The pharmacokinetics of the opioid analgesics can be affected by several factors including patient age, plasma protein content, acid-base status and cardiopulmonary bypass, but not significantly by renal insufficiency or compensated hepatic dysfunction. In addition, pharmacokinetic properties can be influenced by changes in hepatic blood flow and administration of drug combinations which compete for the same plasma protein carrier or metabolising pathway. Although comparing specific pharmacokinetic parameters such as half-lives is deeply entrenched in the literature and clinical practice, simply comparing half-lives is not a rational way to select an opioid for specific requirements. Using pharmacokinetic-pharmacodynamic models, computer simulations based on changes in the effect site opioid concentration or context-sensitive half-times seem to be extremely useful for selecting an opioid on a more rational basis.

Aging↗

PubMed1995

Effect of captopril on myocardial beta-adrenoceptor density and Gi alpha-proteins in patients with mild to moderate heart failure due to dilated cardiomyopathy.

In end-stage heart failure due to idiopathic dilated cardiomyopathy beta 1-adrenoceptors are downregulated and Gi alpha-proteins are upregulated. The aim of the present study was to investigate the influence of the angiotensin-converting enzyme inhibitor captopril on beta-adrenoceptor density and Gi alpha-proteins in sequential endomyocardial biopsies. Nineteen patients with mild to moderate congestive heart failure due to idiopathic dilated cardiomyopathy (NYHA Class II-III) were studied before and after 8-11 weeks of therapy. Patients were randomised into a captopril and a control group; 9 patients received captopril 12.5-50 mg per day, (divided in 2-3 doses) p.o. in addition to "conventional" therapy with digoxin and diuretics, and 10 controls received "conventional" therapy only. Echocardiography, spiroergometry, right heart catheterisation and endomyocardial biopsies were performed before (baseline) and after treatment. Compared to baseline, captopril increased total beta-adrenoceptor density by selectively increasing beta 1-adrenoceptors (31.6 vs 41.2 fmol.mg-1; p < 0.05) but had no significant effect on Gi alpha-proteins. The results indicate that treatment with angiotensin-converting enzyme inhibitors partly restores myocardial beta 1-adrenoceptor density, and this action effect may contribute to the clinical improvement of patients with idiopathic dilated cardiomyopathy treated in this way.

Adenosine Diphosphate Ribose↗

PubMed1995

Fluconazole is removed by continuous venovenous hemofiltration in a liver transplant patient.

Fluconazole is effective for the treatment of fungal infections. A continuous venovenous hemofiltration (CVVH) was necessary in a liver transplant patient with anuria. Fluconazole treatment was started after the diagnosis of systemic candidiasis. There was no adverse effect on liver function, and the immunosuppression with cyclosporine was not affected. It is shown for the first time that CVVH effectively removes fluconazole from the blood circulation by a clearance into the hemofiltrate of approximately 21 ml/min. These data suggest that the treatment of fungal infections with fluconazole does not necessitate a reduction of the dosage during CVVH.

Anuria↗

PubMed1995

C1840-T mutation in the human skeletal muscle ryanodine receptor gene: frequency in northern German families susceptible to malignant hyperthermia and the relationship to in vitro contracture response.

In swine, a point mutation in the ryanodine receptor gene can account for all cases of malignant hyperthermia (MH). The frequency of a corresponding mutation in humans (C1840-T) and its relationship to the in vitro contracture profile is unknown. We screened 192 patients from 28 unrelated northern German families for the C1840-T mutation in the human ryanodine receptor gene and tested for MH susceptibility using the in vitro contracture test (IVCT) according to the European MH Protocol. In our patients 106 revealed MH susceptible (MHS), 56 MH nonsusceptible and 30 MH equivocal status following IVCT. In each family one or two individuals had developed clinical signs of MH or a MH crisis. All of these patients were classified MHS. The C1840-T mutation was found in 2 of 28 families (7.1%). All eight individuals of the two families characterized by this mutation revealed MHS status following IVCT. The thresholds for halothane- and caffeine-induced contractures as well as the contracture profiles following cumulative (0.4-10.0 mumol/l every 3 min) and bolus (10 mumol/l) administration of ryanodine were found to be similar in MHS patients with and without the C1840-T mutation. In conclusion, the C1840-T mutation in the human ryanodine receptor gene is a rare abnormality in MHS families. Similar contracture profiles in the presence and absence of this mutation might imply no major functional role with respect to the contracture response. At present, molecular genetic analysis cannot replace IVCT to discover MH susceptibility in humans.

Adolescent↗

PubMed1995

[Effects of serotonin 2 receptor agonists on skeletal muscle preparations in patients with a disposition toward malignant hyperthermia].

In pigs genetically susceptible to malignant hyperthermia (MH), it has been shown that serotonin (5-HT2) receptor agonists can induce MH and "psychotic" behaviour. Both can be prevented by 5-HT2 receptor antagonists. Furthermore, free levels of serotonin in plasma increased concomitantly with clinical and laboratory parameters during halothane-induced MH in pigs. In this study the in vitro-effects of the 5-HT2 receptor agonist1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (DOI) were investigated in muscle specimens of MH-susceptible (MHS) and normal (MHN) patients. METHODS. Muscle biopsies were obtained from 37 patients aged 5-69 years (23.6 +/- 5.3 years) with clinical suspicion for MH. The patients were first classified as MHS, MHN or MHE (MH equivocal) by the in vitro contracture test (IVCT) according to the European MH protocol. After MH classification, surplus muscle specimens were subjected to the DOI study. DOI was added to the organ bath in a concentration of 0.02 mmol/l. The in vitro effects on contracture development and muscle twitch were observed for 120 min. RESULTS. Muscle specimens of all patients developed contractures after administration of DOI. However, DOI produced an earlier development of contracture in MHS (17.0 +/- 1.8 min; n = 17) than in MHN (64.7 +/- 5.9 min; n = 15) muscles. In MHS muscles, contractures were more distinct than in MHN muscles; at the end of the experiment, contractures had reached a maximum of 12.5 +/- 0.9 mN in MHS and 5.1 +/- 0.7 mN in MHN muscles. Muscle twitch following DOI administration was reduced significantly in both MHS and MHN muscles. The results of four MHE muscles were comparable with MHS. CONCLUSION. The present study supports the assumption that an altered serotonin system might be involved in the development of MH. In further studies it should investigated whether 5-HT2 receptors of skeletal muscles from MHS subjects are disordered in function or structure. 5-HT2 receptor agonists should be considered as MH-triggering agents.

Adolescent↗

PubMed1995

The technique of endobronchial lidocaine administration does not influence plasma concentration profiles and pharmacokinetic parameters in humans.

This study investigated plasma concentration profiles, pharmacokinetic characteristics and side-effects of lidocaine following 3 different administration techniques. Sixty ASA I/II patients undergoing elective ENT-operations were randomised into 4 groups. Lidocaine 1% (1 mg/kg) was administered 50 min before the end of the operation, via a regular endotracheal tube (group 1), a suction-catheter deep endobronchially (group 2), or an EDGAR-(Endobronchial-Drug and Gas Application during Resuscitation)-tube characterized by a separate injection channel ending at the orifice of the tube (group 3). For the control group, a regular endotracheal tube was inserted without lidocaine administration (group 4). Anesthesia was induced with propofol (2 mg/kg), sufentanil (0.5 micrograms/kg), and vecuronium (0.08 mg/kg) and continued as total intravenous anesthesia with propofol (8 mg/kg/h) and oxygen in air (FiO2 = 0.33). A control and 13 blood samples were taken up to 180 min after lidocaine administration. Lidocaine plasma concentrations were determined using a fluorescence polarization immunoassay (TDxFLx). Heart rate, blood pressure, endtidal PcO2, and oxygen saturation were similar in all groups investigated. Ventilation was interrupted for 3.6 +/- 0.5 s in group 1 and 10.2 +/- 0.8 s in group 2, to administer lidocaine. Patients from group 3 were ventilated continuously because of a separate injection channel integrated in the EDGAR-tube. Sore throat was significantly increased in group 2 as compared with groups 1, 3 and 4. Asorption of lidocaine in groups 1-3 resulted in maximal mean plasma concentrations ranging from 0.78 to 0.85 micrograms/ml after 16.9 to 22.4 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Alterations of inositol polyphosphates in skeletal muscle during porcine malignant hyperthermia.

Malignant hyperthermia (MH) may result from increased intracellular calcium concentrations. Increased 1,4,5-IP3 concentrations could mediate this increase in Ca2+. In this study we measured inositol polyphosphates in selectively bred MH susceptible (MHS) and MH non-susceptible (MHN) swine. MH crisis was induced by halothane challenge, and dantrolene was administered in order to measure inositol polyphosphates after MH reversal. Muscle biopsies of skeletal muscles of the hind limbs were obtained in random order and inositol polyphosphates determined by high pressure liquid chromatography using a metal dye detection method. Inositol polyphosphates were determined in three groups: (1) MHS vs MHN basal, (2) during MH crisis induced by halothane and (3) following treatment with dantrolene after halothane challenge. Clinical variables (P(_)VO2, P(-)VCO2, PE'CO2 and pH) indicated that MH was readily induced in MHS swine. Basal concentrations of all inositol polyphosphates were higher in MHS swine compared with MHN swine. After halothane challenge, 1,3,4-IP3, 1,3,4,6-IP4 and 1,3,4,5-IP4 concentrations increased in MHS animals compared with the respective baseline values, whereas no changes in MHN animals could be detected. Dantrolene administration decreased inositol polyphosphate concentrations in MHS swine. MHN swine showed no changes in inositol polyphosphates after dantrolene. These findings indicate that inositol polyphosphates may be involved in metabolic changes after triggering and treatment of MH.

Anesthetics, Inhalation↗

PubMed1995

Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene.

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from 17 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 mumol.l-1 ryanodine. After pretreatment with 1 mumol.l-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8 +/- 1.8 min) and MHN (46.0 +/- 4.2 min) muscle specimens than after ryanodine alone (MHS 4.8 +/- 0.7 min. (MHN 13.7 +/- 0.9 min). They were no longer observed in either group after pretreatment with 5 mumol.l-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependently, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.

Adolescent↗

PubMed1994

Radioimmunochemical quantification of Gi alpha in right and left ventricles from patients with ischaemic and dilated cardiomyopathy and predominant left ventricular failure.

An increase of Gi alpha-related pertussis toxin substrates has been observed in the failing myocardium. In order to quantify the protein expression of Gi alpha directly, we developed a fast radioimmunoassay using the iodinated synthetic peptide 125I-KENLKDCGLF. beta-adrenoceptors were studied with 125I-cyanopindolol binding for comparison. Immunoblot experiments using recombinant G-protein alpha-subunits showed that DS4 immunostained the G-protein alpha-subunits with a rank order of potency rGi alpha 1 = rGi alpha 2 > rGo alpha >> rGi alpha 3. The G-protein alpha-subunits recognized by DS4 in human ventricular membranes comigrated with rGi alpha 1 and rGi alpha 2. The radioimmunoassay had a sensitivity of 2.5 micrograms/ml transducin alpha with an interassay variation of less than 10%. The non-labelled peptide selectively competed with the myocardial 40 kDa membrane protein for binding to the antiserum DS4. Radioimmunochemical quantification of Gi alpha from cardiac membranes showed that in left ventricular membranes (LV) from dilated cardiomyopathy (DCM), there was an increase of Gi alpha by 138.5% when related to mg protein and 135% when related to 3H-ouabain binding sites as membrane marker. In LV from ischaemic cardiomyopathy (ICM), the increase was smaller (58.4%) when related to mg protein compared to the increase of Gi alpha when related to 3H-ouabain binding sites as membrane marker (155% v NF). In contrast, in the right ventricles (RV) there was no increase of Gi alpha in ICM or DCM. The numbers of beta-adrenoceptors were reduced in RV and LV of both, ICM and DCM. It is concluded that the radioimmunoassay may become an important tool for studying the expression of Gi alpha-protein levels and changes thereof in pathological conditions. The amount of immunodetectable Gi alpha-proteins is increased in failing LV due to DCM and ICM but not in RV, while beta-adrenoceptor down-regulation occurred in RV and LV in both conditions. These findings might indicate that the liability of the LV but not of RV to express Gi alpha-proteins may be increased in predominant LV heart failure. Alternatively, the underlying mechanism, e.g. sympathetic activation, may be regulated locally in the failing heart producing different changes in adjacent chambers.

Adolescent↗

PubMed1994

[Implications of concomitant therapy with psychotropic drugs in emergency care. Discussion of current literature with reference to a case report].

This case report deals with an acute psychotic suicidal patient who stabbed two nail-scissors straight into his eyes. The extent of the trauma was unknown primarily during emergency treatment, and an intracranial trauma had to be considered. Furthermore, there was no information on the patient's history including medical therapy or abuse of psychotropic drugs like monoamine oxidase inhibitors, tri- or tetracyclic antidepressants, neuroleptic agents, or lithium salts which could have consequences for subsequent drug administration. The emergency aid management of psychotic patients with the possibility of both an intracranial trauma and an existing psychotropic drug therapy is discussed in this case report.

Anesthesia, General↗

PubMed1994

High-purity ryanodine and 9,21-dehydroryanodine for in vitro diagnosis of malignant hyperthermia in man.

Susceptibility to malignant hyperthermia (MH) is currently diagnosed by the in vitro contracture test (IVCT) in skeletal muscle. However, this test does not possess absolute specificity. Thus, in addition to the established procedure, the "ryanodine contracture test" has been proposed to improve discrimination between MH-susceptible (MHS) and normal (MHN) patients. In all previous studies, the ryanodine used was a mixture consisting of high-purity ryanodine (HPR) and 9,21-dehydroryanodine (DHR). Therefore, in this study the effects of both substances were investigated in concentrations of 2, 5 and 10 mumol litre-1. With all concentrations, contractures appeared earlier in MHS than in MHN muscles, but these differences were significant at all contracture levels with HPR only. Moreover, with the smallest concentration (2 mumol litre-1), the best discrimination between MHS and MHN was observed. Classification of MH-equivocal patients (MHE) as MHS or MHN seems to be possible with the use of ryanodine-induced contractures. The contracture test with HPR should therefore be added to the established procedure of the IVCT.

Adolescent↗

PubMed1993

Beta-adrenergic receptors in psoriasis: evidence for down-regulation in lesional skin.

Lesional psoriatic skin displays reduced responsiveness to beta-adrenergic stimulating agents. To elucidate whether the receptor protein itself is responsible for this, lesional and non-lesional psoriatic skin was investigated ex vivo for maximal beta-adrenergic binding density (Bmax) and beta-adrenergic binding affinity (KD). Epidermal crude membrane homogenates (ECMH) were prepared from split-thickness skin biopsies and saturated with the lipophilic beta-adrenergic antagonist (-)-125I-iodocyanopindolol (ICYP) as radioligand. Specific binding was saturable and Scatchard transformation of the binding data revealed a homogeneous class of beta-adrenergic receptors in all nine experiments. The maximal beta-adrenergic binding density was significantly less in lesional than in non-lesional psoriatic skin (Bmax = 49.7 +/- 7.2 fmol/mg protein vs. 67.1 +/- 2.2 fmol/mg protein, n = 9, P < 0.05). The binding affinity was similar in lesional and in non-lesional skin (KD = 9.0 +/- 1.5 pmol/l vs. 8.0 +/- 0.9 pmol/l). These results could at least partially explain the reduced responsiveness of the beta-adrenergic system in lesional psoriatic skin seen after stimulation with beta-adrenergic agonists.

Adult↗

PubMed1993

Changes in cardiac beta-adrenoceptors in human heart diseases: relationship to the degree of heart failure and further evidence for etiology-related regulation of beta 1 and beta 2 subtypes.

Radioligand binding studies were performed to investigate total beta-adrenoceptor density (Bmax) and beta 1 and beta 2 subtype distribution in left ventricular biopsies obtained from 8 prospective transplant donors serving as controls and from 143 patients with different degrees of heart failure (NYHA class II to IV) undergoing aortic or mitral valve surgery due to aortic or mitral stenosis, aortic or mitral regurgitation, as well as combined aortic or mitral valve lesions (stenosis and regurgitation). In 13 other patients, heart failure was due to hypertrophic obstructive cardiomyopathy (N = 6, NYHA III), tetralogy of Fallot (N = 4, NYHA III), or Becker's muscular dystrophy (N = 3, NYHA IV). Bmax was assessed by (-)-(125I)-iodocyanopindolol used as radioligand. Competition experiments with the highly selective beta 1-adrenoceptor antagonist CGP 20712A were performed for determination of beta 1- and beta 2-adrenoceptor subtypes. In biopsies taken from transplant donors, the Bmax was found to be 70.1 +/- 5.8 fmol/mg protein. In all groups investigated the extent of total beta-adrenoceptor downregulation was related to the degree of heart failure. The decrease in Bmax was found to be about 20% (NYHA II), 45% (NYHA III), and 60% (NYHA IV) when compared with controls. There was no significant difference in the reduction of total beta-adrenoceptor density between isolated aortic or mitral valve diseases and combined valve lesions. Independent of the degree of heart failure, selective downregulation of the beta 1 subtype was found in patients with isolated or combined aortic valve diseases, hypertrophic obstructive cardiomyopathy, and Becker's muscular dystrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

[High purity ryanodine for in vitro diagnosis of malignant hyperthermia].

OBJECTIVE AND STUDY DESIGN: The identification of disposition for malignant hyperthermia (MH) is performed by the halothane-caffeine contracture test in skeletal muscle. However, testing currently renders about 14% of the patients MH equivocal (MHE). To reduce this number the "ryanodine contracture test" has been proposed in addition to the established procedure. As all ryanodine preparations used until now are combinations of ryanodine and dehydroryanodine, we investigate in this study the effects of the now available high-purity ryanodine (HPR) in concentrations of 2,5 and 10 mumol/l. RESULTS: With all concentrations contractures appeared significantly earlier in MHS (malignant hyperthermia susceptible) than in MHN (malignant hyperthermia non-susceptible). However, only at 2 mumol/l a time overlap between both groups was not observed. By defining a time interval for MHS and MHN, three of the MHE patients could be assigned to MHS and three to MHN following their ryanodine-induced contractures. CONCLUSION: The ryanodine contracture test should be added to the current diagnostics of malignant hyperthermia.

Adolescent↗