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Biomedical subjects

P Friederich

Publications and source records attributed to P Friederich.

At least 19 recordsLinked to original sources
PubMed2007

[Severe accidental hypothermia with cardiac arrest and extracorporeal rewarming. A case report of a 2-year-old child].

In patients with severe hypothermia and cardiac arrest, active rewarming is recommended by extracorporeal circulation with cardiopulmonary bypass. The current guidelines for resuscitation of the European Resuscitation Council now include the recommendation regarding patients with hypothermia remaining comatose after initial resuscitation to accomplish an active rewarming only up to a temperature of 32-34 degrees C and to maintain a mild hypothermia for 12-24 h. We report the case of a 2-year-old boy who suffered from severe hypothermia after falling into ice-cold water. On discovery cardiac arrest with asystole was present and the first measured temperature was 23.8 degrees C. Resuscitation led to restoration of spontaneous circulation. The patient was rewarmed by extracorporeal circulation with cardiopulmonary bypass to 33 degrees C then mild hypothermia was maintained for a further 12 h. On the third day after the accident the patient was extubated and after a further 9 days was discharged without any sequelae.

Accidents↗
PubMed2006

[Thalidomide for the treatment of recurrent gastrointestinal blood loss due to intestinal angiodysplasias].

Two female patients, 86 and 80 years of age, had been treated with blood transfusions for several years and several months, respectively, due to iron-deficiency anaemia caused by gastrointestinal blood loss. Angiodysplasias were detected and subsequently coagulated in the course of repeated gastroscopies and colonoscopies. Due to the failure of this treatment, treatment with thalidomide was started. Thereafter, the gastrointestinal bleeding stopped and there was no longer any need for blood transfusions. Treatment with thalidomide seems an effective therapy for patients with frequently recurring gastrointestinal blood loss due to angiodysplasias who no longer tolerate conventional and invasive procedures due to their physical condition.

Aged, 80 and over↗
PubMed2006

Inhibition of HERG channels by the local anaesthetic articaine.

BACKGROUND AND OBJECTIVE: Articaine is an amide local anaesthetic widely used in dentistry. Human ether-a-go-go-related gene (HERG) potassium channels constitute potential targets involved in cardiotoxic side-effects of various pharmacological agents including amide local anaesthetics. The aim of this study was to determine the sensitivity of HERG channels to the inhibitory action of articaine and to further evaluate the effect of the mutations Y652A and F656A in the putative drug-binding region of HERG on the sensitivity for articaine. METHODS: We examined the inhibition of wild-type and mutant HERG channels, transiently expressed in Chinese hamster ovary cells by articaine. Whole cell patch-clamp recordings were performed at room temperature. RESULTS: Inhibition of HERG wild-type and HERG Y652A channels by articaine was concentration dependent and reversible. The concentration-response data were described by Hill functions (wild type: IC50 = 224 +/- 6 micromol L-1, Hill coefficient h = 1.17 +/- 0.03, n = 23; Y652A: IC50 = 360 +/- 48 micromol L-1, h = 0.93 +/- 0.08, n = 26). The mutation Y5652A decreased the sensitivity by factor 1.6. The mutation F656A decreased inhibition of inward tail currents by 300 micromol L-1 articaine in 100 mmol extracellular K+ 3-fold. CONCLUSIONS: Our results indicate that the local anaesthetic articaine does not inhibit HERG channels at clinically relevant concentrations. Articaine may therefore constitute a safer alternative for local and regional anaesthesia. The aromatic amino acid F656 rather than Y652 in the S6 region might play a role in interaction of the drug with the channel.

Anesthetics, Local↗
PubMed2006

Decreased levels of mucosal detoxification enzymes in the pouch of patients with familial adenomatous polyposis.

BACKGROUND: Adenomas can develop in the pouch after colectomy with ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP). Glutathione S-transferases (GSTs) have a protective role in carcinogenesis. GST activity is much higher in the ileum than in the colon. The present study examined the hypothesis that the protective capacity of GSTs may be lowered as a result of colonic metaplasia of the ileal pouch. METHODS: Levels of GSTs, glutathione and cysteine, and the degree of inflammation and colonic metaplasia were quantified in biopsies from the pouch and afferent loop of 26 patients with FAP. RESULTS: GST enzyme activity, and levels of GST alpha, glutathione and cysteine in the pouch were significantly lower than those in the afferent loop (308 versus 398 nmol per min per mg protein (P<0.001), 4604 versus 5286 ng per mg protein (P=0.010), 27.1 versus 34.8 nmol per mg protein (P=0.023) and 0 versus 4.8 nmol per mg protein (P=0.009) respectively). No correlation was found between inflammation or colonic metaplasia of the pouch and GST enzyme activity in the pouch. CONCLUSION: After IPAA, GST detoxification activity in the pouch is significantly lower than that in the afferent ileal loop, which may promote tumorigenesis.

Adenomatous Polyposis Coli↗
PubMed2006

[Severe anaphylaxis from rocuronium].

Muscle relaxant drugs are the most frequent cause of anaphylactic and anaphylactoid reactions during anaesthesia. We report a case of a life-threatening anaphylactic reaction during induction of anaesthesia with severe bronchospasm as the first clinical symptom. Mechanical ventilation was nearly impossible. The patient required a multimodal antiallergic therapy and a high-dose catecholamine therapy for stabilization. Rocuronium was identified as the allergic agent using intradermal testing.

Anaphylaxis↗
PubMed2006

[Public access defibrillation. Limited use by trained first responders and laymen].

As ventricular fibrillation is the most frequent initial heart rhythm causing out-of-hospital sudden cardiac arrest, defibrillation is of essential significance. Automated external defibrillators (AEDs) have been available for some years and as a result defibrillation can be carried out by individuals other than physicians and healthcare providers such as trained first responders and untrained lay rescuers. This so-called public access defibrillation nourished hope of progress in the treatment of sudden cardiac arrest. However, several limitations exist, such as low frequency of sudden cardiac arrest in public, rare use of publicly placed AEDs, low cost effectiveness, legal requirements and insufficient public willingness to help. Due to these restrictions of public access defibrillation other measures are more promising than the attempt at general distribution of AEDs. These measures are primary or secondary prophylaxis of sudden cardiac arrest, general knowledge of adequate activation of emergency medical services, implementation of first responder teams equipped with AEDs and particularly a better education in and application of the well-established principles of cardiopulmonary resuscitation.

Cost-Benefit Analysis↗
PubMed2005

[Fast-track surgery in radical retropubic prostatectomy. First experiences with a comprehensive program to enhance postoperative convalescence].

Fast-track surgery is a comprehensive program for the optimization of perioperative care in elective surgery reducing potential postoperative complications and speeding up convalescence. Recent data from randomized colon resection trials emphasize that fast-track surgery is possible in most major operations. Our initial results in radical retropubic prostatectomy fast-track surgery have been encouraging. Fast-track surgery in major urological operations needs validation using randomized trials.

Clinical Trials as Topic↗
PubMed2004

Local anaesthetic sensitivities of cloned HERG channels from human heart: comparison with HERG/MiRP1 and HERG/MiRP1 T8A.

BACKGROUND: Myocardial potassium channels are complexes formed by different subunits. The subunit composition may influence the cardiotoxic action of local anaesthetics. The effects of amide local anaesthetics on HERG channels co-expressed with the putative subunit MiRP1 have not been established. It is also unclear if the common polymorphism MiRP1(T8A) that predisposes individuals to drug-induced cardiac arrhythmia increases local-anaesthetic sensitivity of HERG/MiRP1 channels. This may suggest the presence of genetic risk factors for local-anaesthetic-induced cardiac arrhythmia. METHODS: Whole-cell patch-clamp recordings and site-directed mutagenesis were combined to compare local anaesthetic sensitivities of cloned and mutated human potassium channel subunits. The ion channels were activated by a protocol that approximated ventricular action potentials. RESULTS: The amide local anaesthetics bupivacaine, levobupivacaine and ropivacaine inhibited HERG channels at toxicologically relevant concentrations, with IC(50) values of 20 (SEM 2) micro M (n=29), 10 (1) micro M (n=40) and 20 (2) micro M (n=49), respectively. Hill coefficients were close to unity. There were no indications of qualitative differences in channel inhibition between the three anaesthetics. The putative subunit MiRP1 did not alter local anaesthetic sensitivity of HERG channels. The common single nucleotide polymorphism producing MiRP1(T8A) did not increase local anaesthetic sensitivity of HERG/MiRP1 channels. CONCLUSIONS: Amide local anaesthetics target HERG and HERG/MiRP1 channels with identical potency. The effects on these ion currents may significantly contribute to local-anaesthetic-induced cardiac arrhythmia. MiRP1(T8A) does not seem to confer an increased risk of severe cardiac side-effects to carriers of this common polymorphism.

Amides↗
PubMed2003

Basic concepts of ion channel physiology and anaesthetic drug effects.

Ion channels regulate a diversity of physiological functions such as neuronal signalling, cardiac excitability and immune cell response. All of these systems may be affected during the conduct of general as well as local anaesthesia. Thus, the investigation of anaesthetic action on ion channels has become the focus of an increasing number of laboratory studies. Consequently, the concepts of ion channel physiology are becoming important for understanding the scientific and pharmacological basis of clinical anaesthesia. This brief guide is intended to help in understanding the increasing number of studies concerned with the effects of anaesthetic agents on ionic currents. The generation of ionic currents requires a complex molecular interplay of ions, ion channel proteins and lipid membranes. Anaesthetic agents frequently exhibit more than a single effect on ion channel function. Their effects can be described by quantifying the pharmacological alteration of ion channel activation, conductance and inactivation. Many physiological functions are directly influenced by ion channels. Pharmacological action on ion channels is thus fundamental to effects as well as side-effects of anaesthetic agents. The alteration of ion channel function by anaesthetic agents consequently determines their clinical effects.

Anesthetics↗
PubMed2003

Biophysical properties of Kv3.1 channels in SH-SY5Y human neuroblastoma cells.

Biophysical properties of delayed rectifier K channels in the human neuroblastoma SH-SY5Y were established using patch clamp recordings. The whole cell K+ conductance activated at membrane potentials positive to -20 mV. The midpoint of current activation was 9.6 +/- 5.1 mV, the equivalent charge was 3.7 +/-.6. Whole-cell currents inactivated slightly with time constants of 700 ms and 5 s. The K+ currents were sensitive to micromolar concentrations of TEA and 4-aminopyridine. RT-PCR experiments amplified a cDNA fragment specific for human Kv3.1 channels. Activation gating parameters in outside-out patches were shifted by approximately 14 mV in the hyperpolarizing direction.

4-Aminopyridine↗
PubMed2002

Lidocaine-induced cell death in a human model of neuronal apoptosis.

BACKGROUND AND OBJECTIVE: Clinical studies suggest that lidocaine may induce irreversible neurological damage after spinal application in human beings. The mechanisms underlying the possible cytotoxic action of lidocaine have only been suggested from animal studies. This study aimed to investigate if lidocaine exhibited cytotoxic action in a human model widely used for the study of neuronal apoptosis. This is important to know as it may help one to judge on possible neurotoxic risks imposed by the spinal application of lidocaine. METHODS: The concentration- and time-dependent effects of lidocaine on retinoic acid-differentiated human neuroblastoma SH-SY5Y cells were quantified by trypan blue staining, the release of lactate dehydrogenase, immunocytochemistry and flow cytometry. RESULTS: The local anaesthetic caused a significant increase in the number of cells staining positive for trypan blue, a significant increase of LDH release into the incubation medium, and a significant increase of 7AAD and annexin V binding. Lidocaine induced apoptosis already at 3 mm. At a concentration of 10 mmol 47% of the cells and at 30 mmol 98% of the cell population was necrotic. Both necrosis and apoptosis were time-dependent. CONCLUSIONS: The results demonstrate that lidocaine exhibited neurotoxic effects in a human model established for the study of drug-induced neuronal apoptosis. The results were consistent with the neurotoxic clinical effects of lidocaine. These effects may be produced by more than a single mechanism.

Apoptosis↗
PubMed2002

Ketamine effects on human neuronal Na+ channels.

BACKGROUND AND OBJECTIVE: Similar doses of ketamine are employed in regional and general anaesthesia. In contrast to commonly used local anaesthetic agents, accidental systemic application of local anaesthetic doses of ketamine will not result in seizure, dysrhythmia or cardiovascular depression. However, there is some doubt about the quality of regional analgesia induced by ketamine. As human sodium channels constitute an important molecular target of local anaesthetics, the study was designed to establish concentration-dependent effects of ketamine on conductance, steady-state activation and steady-state inactivation of human neuronal sodium channels. This information--that has, so far, not been published--will help to characterize further local anaesthetic properties of ketamine. METHODS: Whole-cell patch-clamp recordings were made of sodium channels natively expressed in human neuroblastoma SH-SY5Y cells. RESULTS: The sodium channels activated at a threshold of -60 mV and exhibited a maximal peak current at -10 mV. The voltage of half-maximal activation was -20 mV. The Na+ currents depended on the prepulse potential. The voltage of half-maximal inactivation was -80 mV. Ketamine inhibited the sodium conductance in a concentration-dependent manner (IC50 = 1140 micromol). A concentration-dependent hyperpolarizing shift of both steady-state activation and steady-state inactivation accounted for at most 5 mV. CONCLUSIONS: The effects of ketamine on these human ion channels occur at clinical concentrations. They are consistent with the local anaesthetic action of ketamine. Whether ketamine helps to decrease the incidence of severe side-effects during regional anaesthesia needs to be addressed in further clinical studies.

Anesthetics, Dissociative↗
PubMed2002

Bupivacaine inhibits human neuronal Kv3 channels in SH-SY5Y human neuroblastoma cells.

BACKGROUND: Information on molecular targets that may be involved in the neurotoxicity of bupivacaine is limited. Suppression of Kv3 channels has been demonstrated to result in abnormal patterns in the electroencephalogram and in seizures. Inhibition of Kv3 channels by bupivacaine may consequently contribute to its neuroexcitatory side-effects. Data on the effects of bupivacaine on these potassium channels are lacking. We therefore characterized the effects of bupivacaine on human Kv3 channels natively expressed in SH-SY5Y cells. METHODS: Kv3 channels natively expressed in human SH-SY5Y cells were studied using a standard whole-cell patch-clamp protocol. RESULTS: Bupivacaine reversibly inhibited Kv3 channels in a concentration-dependent manner. The half-maximal inhibitory concentration (IC50) for conductance block was 57 microM and the Hill coefficient was close to unity. Bupivacaine accelerated macroscopic current decline by inducing inactivation-like behaviour. The midpoint of current activation was shifted to depolarized potentials in a concentration-dependent and reversible manner by a maximum of 26 mV. The IC50 was 47 microM and the Hill coefficient was 2.4. The free arterial plasma concentrations of bupivacaine that have been estimated to occur during convulsions in man would inhibit the Kv3 channels by at least 40% and would shift the midpoint of current activation by a minimum of 9 mV. CONCLUSIONS: Both inhibition of potassium channels and a depolarizing shift of their activation midpoint would increase neuronal excitability. The effects of bupivacaine on human Kv3 channels are thus compatible with a contributory role of Kv channel alteration in bupivacaine-induced neuronal excitation.

Anesthetics, Local↗
PubMed2001

Ketamine and propofol differentially inhibit human neuronal K(+) channels.

BACKGROUND AND OBJECTIVE: Interaction of intravenous anaesthetic agents with voltage-dependent potassium channels significantly correlates with clinical concentrations. If potassium channels were to play an important part in anaesthesia, one might expect different effects at the molecular level of those anaesthetics that show different clinical effects. Our aim was to analyse the interaction of general anaesthetics with voltage-dependent K channels. METHODS: Whole cell patch-clamp experiments were analysed in detail in order to compare the effects of two clinically diverse intravenous hypnotics, ketamine and propofol, on voltage-dependent potassium channels in human neuroblastoma SH-SY5Y cells. RESULTS: Both anaesthetics inhibited the potassium conductance in a concentration-dependent and reversible manner with IC50-values of 300 microM and 45 microM for ketamine and propofol respectively. Whereas ketamine shifted the midpoint of current activation by maximally 14 mV to more hyperpolarized potentials, propofol had the opposite effect on the activation midpoint. Current inhibition by ketamine increased with voltage but decreased with propofol at higher membrane potentials. Propofol but not ketamine induced concentration-dependent but voltage-independent decline, akin to inactivation, of the voltage-dependent potassium channels. CONCLUSIONS: The anaesthetics differed not only in their clinical profiles but they also showed differential actions on voltage-dependent potassium channels in several ways. This provides additional evidence for the hypothesis that voltage-dependent potassium channels play an important role in anaesthesia.

Algorithms↗
PubMed2001

[Epileptic seizures from etomidate? The human Kv1.1 potassium channel in humans].

OBJECTIVE: It is a matter of dispute whether etomidate exhibits an epileptogenic action. It is also disputed whether frequently observed myocloni induced by etomidate are related to seizure-like activity in the EEG. The clinical effects of anaesthetic agents reflect their molecular action. A possible epileptogenic action of etomidate should, therefore, result from action on a molecular target that has yet to be identified. Suppression of Kv1.1 channels may be associated with epilepsy in men. Inhibition of Kv1.1 channels by etomidate at clinically relevant concentrations would, thus, argue in favour of an epileptogenic action of etomidate. METHODS: Patch-clamp recordings of the pharmacological action of etomidate on cloned and functionally expressed human Kv1.1 channels. RESULTS: Etomidate inhibits human Kv1.1 channels in a concentration-dependent and reversible manner. The IC50-value is 400 microM, the Hill-coefficient is 2. The ratio of free clinical plasma concentrations and the IC50-value is 0.006. At plasma concentrations determined in a clinical setting Kv1.1 channels would be suppressed by less than 0.01%. CONCLUSION: The small effect of etomidate on human Kv1.1 channels at these concentrations questions an epileptogenic action of etomidate caused by inhibition of Kv1.1 channels.

Cells, Cultured↗
PubMed2001

Interaction of volatile anesthetics with human Kv channels in relation to clinical concentrations.

BACKGROUND: Recent evidence shows that inhibition of human Kv3 channels by intravenous anesthetics occurs at clinical concentrations. The effects of volatile anesthetics on these human ion channels are unknown. This study was designed to establish whether minimum alveolar concentrations (MAC) of halothane, enflurane, isoflurane, and desflurane exhibit effects on Kv3 channeLs. To obtain an indication whether these findings may be specific to Kv3 channels, the effects of enflurane and isoflurane on human Kv1.1 channels were also investigated. METHODS: Kv3 channels natively expressed in SH-SY5Y cells and Kv1.1 channels expressed in HEK293 cells were measured with the whole cell patch clamp technique by standard protocols. Concentrations of volatile anesthetics were determined by gas chromatography. RESULTS: Halothane, enflurane, isoflurane, and desflurane reversibly inhibited Kv3 channels in a concentration-dependent manner. Concentrations at half-maximal effect (IC50 values) ranged between 1,800 and 4,600 microM. Hill coefficients were between 1.7 and 2.5. IC50 values for inhibition of Kv1.1 channels were 2,800 and 5,200 microM, and Hill coefficients were 3.9 and 5.6 for enflurane and isoflurane, respectively. CONCLUSION: Volatile anesthetics inhibit human Kv3 channels at clinical concentrations. At 1-3 MAC, inhibition would account on average for 2-12%. Inhibition would be highest with enflurane (between 3% and 22%) and lowest with isoflurane (between 0.2% and 3%). Kv1.1 channels would only be inhibited by enflurane at clinical concentrations (2% at 2 MAC and 8% at 3 MAC). Whether the degree of K channel inhibition by volatile anesthetics may contribute to their clinical action needs further study.

Anesthetics, Inhalation↗