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Biomedical subjects

P Friederich

Publications and source records attributed to P Friederich.

31 records · Page 2Linked to original sources
PubMed2000

Prothrombin gene G20210A mutation and elevated anticardiolipin antibodies in a patient with combined portal-mesenteric vein thrombosis.

A 29-year-old man was admitted to the ICU after emergency laparotomy for portal-mesenteric vein thrombosis. Under continuous intravenous heparin therapy the portal-mesenteric shunt occluded on the first postoperative day. After thrombectomy the heparin dose was increased, and the patient remained free of symptoms (partial thromboplastin time 53 s). Two days later abdominal distension developed concomitantly with ventilatory distress due to a large retroperitoneal hematoma. The patient was mechanically ventilated and underwent the third consecutive laparotomy for the hematoma removal on the fifth day. During the surgical procedure the abdomen was packed with towels to stop multiple bleeding sites. The heparin dose was reduced, aiming for a partial thromboplastin time of 30-35 s. Initial coagulation tests revealed increased levels of anticardiolipin immunoglobulin G. After removal of the surgical towels the patient was successfully weaned from mechanical ventilation and discharged from the ICU. Two weeks later genomic testing revealed that he also had a G20210A mutation of the prothrombin gene. Both, increased levels of anticardiolipin immunoglobulin G and the G20210A mutation of the prothrombin gene predispose to thrombosis. Increased levels of anticardiolipin immunoglobulin G may also cause bleeding. Long-term anticoagulation therapy was started with a vitamin K antagonist, and 2 months later a follow-up showed that the patient had no further symptoms of portal-mesenteric vein thrombosis or bleeding. This case illustrates that the convergence of multiple risk factors, including genetic defects, must be considered in patients suffering from thrombosis in unusual sites

Adult↗
PubMed2000

Stereospecific interaction of ketamine with nicotinic acetylcholine receptors in human sympathetic ganglion-like SH-SY5Y cells.

BACKGROUND: Surprising clinical evidence suggests a block of sympathetic transmission by ketamine. The action of ketamine on nicotinic acetylcholine receptors (nAChRs) in human ganglions is unknown. Because ganglionic transmission depends on nAChRs, such information may help to clarify whether ketamine impairs ganglionic transmission in men. Because racemic ketamine as well as S(+)-ketamine are used clinically, the authors investigated stereospecific effects on human ganglionic nAChRs. Stereospecific psychomimetic effects have been attributed to voltage-dependent Kv channel inhibition; therefore the effects on nAChRs were compared with those on Kv channels present in the same cells. METHODS: Whole-cell currents through nAChRs and K channels were measured in SH-SY5Y cells with the patch-clamp technique by application of acetylcholine (1 mm, nAChRs) or by a step depolarization from a holding potential of -80 mV to +40 mV (K channels). Electrolyte conditions were identical for both currents. RESULTS: Racemic ketamine and the isomers inhibited nAChRs and K channels in a concentration-dependent and reversible manner. Racemic ketamine inhibited nAChRs and K channels, with the anesthetic concentration inducing the half-maximal effect being 1.4 and 300 micrometer, respectively. Only inhibition of the nAChRs was stereoselective. The half-maximal concentrations were 0.8 and 3.6 micrometer for S(+)- and R(-)-ketamine. The K channels were 350 and 70 times less sensitive to the effects of S(+)- and R(-)-ketamine. CONCLUSION: Ketamine at concentrations found during clinical anesthesia exerts stereospecific effects on human ganglionic nAChRs but not on voltage-dependent K channels. Our results support the view that ketamine impairs sympathetic ganglionic transmission. Nonspecific effects on voltage-dependent K channels may underlie psychomimetic side effects.

Anesthetics, Dissociative↗
PubMed1999

Interaction of intravenous anesthetics with human neuronal potassium currents in relation to clinical concentrations.

BACKGROUND: Neuronal voltage-dependent potassium (K) currents are crucial for various cellular functions, such as the integration of temporal information in the central nervous system. Data for the effects of intravenous anesthetics on human neuronal K currents are limited. It was the authors' aim to evaluate the concentration-related effects of three opioids (fentanyl, alfentanil, sufentanil) and seven nonopioids (thiopental, pentobarbital, methohexital, propofol, ketamine, midazolam, droperidol) used in clinical anesthesia on neuronal voltage-dependent K currents of human origin. METHOD: K currents were measured in SH-SY5Y cells using the whole cell patch-clamp technique. Currents were elicited by step depolarization from a holding potential of -80 to -50 mV through +90 mV, and their steady state amplitudes were determined. RESULTS: All drugs inhibited the K currents in a concentration-dependent and reversible manner. Because time dependence of inhibition differed among the drugs, effects were measured after 54-64 ms of the test pulse. The IC50 values (concentration of half-maximal inhibition) for current suppression ranged from 7 microM for sufentanil to 2 mM for pentobarbital. Suppression of the K currents by the opioids occurred at 10-fold lower IC50 values (concentration of half-maximal inhibition) than that by the barbiturates. As estimated from the concentration-response curves, K-current suppression at clinical concentrations would be less than 0.1% for the opioids and approximately 3% for the other drugs. CONCLUSIONS: Effects of intravenous anesthetics on voltage-dependent K currents occur at clinical concentrations. The IC50 values for current inhibition of the nonopioid anesthetics correlated with these concentrations (r = 0.95). The results suggest that anesthetic drug action on voltage-dependent K currents may contribute to clinical effects or side effects of intravenous anesthetics.

Anesthetics, Intravenous↗
PubMed1998

Anesthetic mechanisms in-vitro and in general anesthesia.

1. There is no generally accepted and quantifiable definition of general anesthesia. 2. Ion channels are discussed as examples of in-vitro systems used to investigate anesthetic mechanisms. Experimental evidence has accumulated demonstrating that voltage-gated ion channels and ligand-gated ion channels may be affected by clinically relevant concentrations of general anesthetics. 3. There are many factors modulating the anesthetic sensitivity of ion channels, including membrane lipid, electrolyte environment, ion channel subtype, and the functional state of the network. 4. Neuronal networks relevant to human general anesthesia have to be identified before criteria can be formulated as to which component of any particular ion channel function has to be altered to what extent in order to make a contribution to clinical anesthesia.

Anesthesia, General↗
PubMed1998

Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Letrozole International Trial Group (AR/BC3).

BACKGROUND: The study compares letrozole and aminoglutethimide (AG), a standard therapy for postmenopausal women with advanced breast cancer, previously treated with antioestrogens. PATIENTS AND METHODS: 555 women were randomly assigned letrozole 2.5 mg once daily (n = 185), letrozole 0.5 mg once daily (n = 192) or aminoglutethimide 250 mg twice daily with corticosteroid support (n = 178) in an open-label, multicentre trial. The primary endpoint was objective response rate (ORR), with time events as secondary. ORR was analysed nine months after enrollment of the last patient, while survival was analysed 15 months after the last patient was enrolled. We report the results of these analyses plus an extended period of observation (covering a total duration of approximately 45 months) to determine the duration of response and clinical benefit. RESULTS: Overall objective response rates (complete + partial) of 19.5%, 16.7% and 12.4% were seen for letrozole 2.5 mg, 0.5 mg and AG respectively. Median duration of response and stable disease was longest for letrozole 2.5 mg (21 months) compared with letrozole 0.5 mg (18 months) and AG (14 months). Letrozole 2.5 mg was superior to AG in time to progression, time to treatment failure and overall survival. Treatment-related adverse events occurred in fewer patients on letrozole (33%) than on AG (46%). Transient nausea was the most frequent event with letrozole (7% on 0.5 mg, 10% on 2.5 mg, 10% on AG), rash with AG (11%, 1% on 0.5 mg, 3% on 2.5 mg letrozole). CONCLUSIONS: Letrozole 2.5 mg offers longer disease control than aminoglutethimide and letrozole 0.5 mg in the treatment of postmenopausal women with advanced breast cancer, previously treated with anti-oestrogens.

Administration, Oral↗
PubMed1997

[Gluten as food additive in The Netherlands: cheese forbidden for celiac patients?].

A new coating for cheese, to be introduced in May, consists entirely of natural degradable components. The coating is based on wheat gluten. This increase in the amount of gluten in the Dutch diet may lead to overt coeliac disease in people with a subclinical form of it, and will limit the dietary choices of patients already suffering from the disease.

Celiac Disease↗
PubMed1997

[Etomidate inhibits neuronal potassium channels in humans].

INTRODUCTION: There is no data available on the action of etomidate on ion currents in human neuronal cells. Therefore the effects of etomidate on a human neuronal delayed rectifier potassium current were investigated. METHOD: Outward rectifying potassium currents of human neuroblastoma SH-SY5Y cells were measured using the whole cell patch-clamp technique. Cells were grown in RPMI-medium (+Pen/Strep and FCS) at 37 degrees C and 5% CO2. The holding potential was -80 mV. Potassium currents were evoked by depolarizing the membrane potential to values from -50 mV to +90 mV in 10 mV steps using an EPC-7 patch-clamp amplifier (List medical electronics) and pclamp version 5.71 (Axon instruments). RESULTS: Etomidate differentially inhibited steady-state and peak potassium current with IC50-values of 170 microM for peak current suppression and 120 microM for steady-state current respectively. Etomidate induced inactivation-like behaviour of the potassium current and changed the voltage dependence of potassium current activation. CONCLUSION: The results demonstrate that etomidate has more than one effect on the potassium current, indicating the complexity of general anaesthetic actions on neuronal targets. The actions of etomidate on human neuronal potassium currents may potentially contribute to the myocloni observed with this general anaesthetic agent during induction of anaesthesia.

Anesthetics, Intravenous↗
PubMed1993

Inversion of Ca2+ current modulation during recovery of neuroblastoma cells from pertussis toxin pretreatment.

Human neuroblastoma cells (SH-SY5Y) differentiated by retinoic acid exhibited high threshold-activated N-type Ca2+ currents, which were largely inhibited by the two enkephalins, DAGO and DPDPE, as well as by dopamine and somatostatin. The inhibitory effects were fully abolished after pretreatment of cells with pertussis toxin. After washing out the toxin, the inhibitory effects re-established with a time constant of about 16 h. The recovery of Ca2+ current inhibition was similar for all tested agonists. Unexpectedly, we observed a neurotransmitter-induced stimulation of Ca2+ currents in approximately 10% of all investigated cells during the recovery phase. Such a stimulatory effect by otherwise inhibitory receptors was never seen in control cells. It did also not occur when exogenous purified G-proteins of the Gi family were reconstituted via the patch pipette, suggesting that additional mechanisms may play a role in the appearance of stimulatory effects during the recovery phase after pertussis toxin pretreatment.

Calcium↗
PubMed1990

Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study.

Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.

Adult↗