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1.
Nervenarzt ; 87(1): 35-45, 2016 Jan.
Article in German | MEDLINE | ID: mdl-26666768

ABSTRACT

Tobacco consumption is one of the major preventable health risk factors. In Germany approximately 110,000 people prematurely die from tobacco-related diseases and approximately 50% of regular smokers are considered to be tobacco dependent. Nevertheless, motivation to quit smoking is low and the long-term abstinence rates after attempts to stop smoking without professional support are far below 10%. As part of the S3 treatment guidelines 78 recommendations for motivation and early interventions for smokers unwilling to quit as well as psychotherapeutic and pharmacological support for smokers willing to quit were formulated after an systematic search of the current literature. More than 50 professional associations adopted the recommendations and background information in a complex certification process. In this article the scientific evidence base regarding the psychotherapeutic and pharmacological treatment options as well as recommendations and further information about indications and treatment implementation are presented. By following these guidelines for treatment of heavy smokers who are willing to quit combined with individual and group therapies on the basis of behavioral treatment strategies and pharmacological support, long-term success rates of almost 30% can be achieved.


Subject(s)
Practice Guidelines as Topic , Psychiatry/standards , Psychotherapy/standards , Tobacco Use Cessation/methods , Tobacco Use Disorder/psychology , Tobacco Use Disorder/therapy , Evidence-Based Medicine , Germany , Guideline Adherence , Humans , Neurology/standards , Tobacco Use Cessation/psychology , Tobacco Use Cessation Devices/standards , Tobacco Use Disorder/diagnosis , Treatment Outcome
2.
Fortschr Neurol Psychiatr ; 79(2): 92-6, 2011 Feb.
Article in German | MEDLINE | ID: mdl-21136345

ABSTRACT

INTRODUCTION: Psychiatry is confronted with increasing requirements in quality management, guidelines and an increasing proportion of elderly, chronic multimorbid patients with psychiatric disorders. The latter give rise to polypharmacy which may lead to drug-drug interactions. Assessment of drug interactions is more and more difficult as the total number of drugs taken increases. In the present study hospital discharge medication was analysed semiautomatically for possible drug-drug interactions. METHODS: In-hospital cases were randomly selected. Discharge medication was analysed using PsiacOnline, a large web-based database for drug interactions. RESULTS: The selection yielded 342 cases from 213 patients (mean age 46.3 years, 53 % females). 86 patients had one psychiatric diagnosis; the other patients had at least two or more diagnoses. The discharge prescription was analysed for 55 different psychotropic drugs from 4 large drug groups (18 antidepressants; 17 antipsychotic drugs; 5 mood stabilisers/epileptic drugs and 13 different hypnotic/anxiolytic drugs). Antipsychotic drugs were the most frequent drugs (n = 334); followed by antidepressants (n = 312) and mood stabilizers (n = 112). 47 patients (13.7 %) were discharged with monotherapy. Mean drug number was 2.7. PsiacOnline revealed 535 hits: 126 (23.6 %) combinations were non-critical, 86 (16.1 %) combinations were critical based on pharmacological properties of the drugs; 232 (43.4 %) combinations were critical according to in vitro studies or animal experiments; critical drug combinations in high-risk patients: 67 × (12.5 %); combinations with reported risks for side effects due to interaction: 17 × (3.2 %) and combinations with documented risks for severe drug interactions: 7 × (1.3 %). CONCLUSION: Although the majority of drug combinations was considered not critical, approximately 3 % of cases had an increased risk for adverse drug actions and a further 1.3 % cases with a severe risk gave evidence that integration of an IT-based pharmacological expert system in a computerised physician order entry (CPOE) should be considered. Suggested beneficial effects need to be shown by an appropriately-designed clinical study.


Subject(s)
Drug Interactions , Psychotropic Drugs/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Databases, Factual , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Online Systems , Patient Discharge , Pharmacogenetics , Polypharmacy , Psychopharmacology , Retrospective Studies , Risk , Young Adult
3.
PLoS One ; 11(4): e0152984, 2016.
Article in English | MEDLINE | ID: mdl-27054571

ABSTRACT

Variation in genes coding for nicotinic acetylcholine receptor (nAChR) subunits affect cognitive processes and may contribute to the genetic architecture of neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in the CHRNA4 gene that codes for the alpha4 subunit of alpha4/beta2-containing receptors have previously been implicated in aspects of (mostly visual) attention and smoking-related behavioral measures. Here we investigated the effects of six synonymous but functional CHRNA4 exon 5 SNPs on the N100 event-related potential (ERP), an electrophysiological endophenotype elicited by a standard auditory oddball. A total of N = 1,705 subjects randomly selected from the general population were studied with electroencephalography (EEG) as part of the German Multicenter Study on nicotine addiction. Two of the six variants, rs1044396 and neighboring rs1044397, were significantly associated with N100 amplitude. This effect was pronounced in females where we also observed an effect on reaction time. Sequencing of the complete exon 5 region in the population sample excluded the existence of additional/functional variants that may be responsible for the observed effects. This is the first large-scale population-based study investigation the effects of CHRNA4 SNPs on brain activity measures related to stimulus processing and attention. Our results provide further evidence that common synonymous CHRNA4 exon 5 SNPs affect cognitive processes and suggest that they also play a role in the auditory system. As N100 amplitude reduction is considered a schizophrenia-related endophenotype the SNPs studied here may also be associated with schizophrenia outcome measures.


Subject(s)
Polymorphism, Single Nucleotide/genetics , Receptors, Nicotinic/genetics , Smoking/adverse effects , Tobacco Use Disorder/genetics , Adult , Electrophysiological Phenomena , Endophenotypes , Female , Germany/epidemiology , Humans , Male , Neuroimaging , Tobacco Use Disorder/epidemiology , Tobacco Use Disorder/pathology
5.
Intensive Care Med ; 24(7): 685-90, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9722038

ABSTRACT

OBJECTIVE: To analyze perioperative and postoperative complications and long-term sequelae following percutaneous dilatational tracheostomy (PDT). DESIGN: A prospective clinical study of patients undergoing PDT. SETTING: Seven intensive care units at a University hospital PATIENTS: 326 intensive care patients (202 male, 124 female; age: 11-95 years) with indications for tracheostomy. INTERVENTIONS: Using tracheoscopic guidance, 337 PDTs were performed according to Ciaglias' method. In 106 decannulated patients, tracheal narrowing was assessed by plain tracheal radiography. RESULTS: Two procedure-related deaths were seen (0.6%). Perioperative and postoperative complications occurred with 9.5% of the PDTs. One of 106 patients, who were followed-up for at least 6 months, showed a clinically relevant tracheal stenosis. Subclinical tracheal stenosis of at least 10% of the cross-sectioned area was recognized in 46 of 106 patients (43.4%). In the univariate analysis, the degree of stenosis was influenced by the age of the patient (p = 0.044), the duration of intubation prior to PDT (p = 0.042) and by the duration of cannulation (p = 0.006). These parameters had no statistical significance in a multiple regression model. CONCLUSION: When performed by experienced physicians, percutaneous dilatational tracheostomy under fiberoptic guidance is a safe method. The risks of early complications and of clinically relevant tracheal stenoses are low. Subclinical tracheal stenoses are found in about 40% of patients following PDT.


Subject(s)
Tracheostomy/adverse effects , Tracheostomy/methods , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Analysis of Variance , Child , Critical Illness , Dilatation , Female , Humans , Male , Middle Aged , Prospective Studies , Regression Analysis , Risk Factors , Time Factors , Tracheal Stenosis/etiology , Tracheostomy/mortality , Treatment Outcome
6.
Brain Res ; 262(2): 225-32, 1983 Mar 07.
Article in English | MEDLINE | ID: mdl-6301634

ABSTRACT

Homogenates of central myelin were treated with ferritin derivatives having different isoelectric points. It was found that considerable amounts of cationic ferritin (pI 8.5-9.5) had access to the extracellular space, but that anionic ferritin (pI 4.0) and native ferritin (pI 4.5) did not. The electrostatic nature of the binding of cationic ferritin was demonstrated by treating the homogenates with poly-L-lysine and 1 M NaCl:both reagents led to a complete displacement of the bound cationic ferritin. Neither extensive trypsination nor neuraminidase treatment showed a significant effect on the intralamellar distribution of the bound cationic ferritin molecules. This suggests that the net negative charge on the extracellular myelin face stems primarily from acidic lipid groups in the membrane.


Subject(s)
Brain/cytology , Ferritins/metabolism , Iron-Binding Proteins , Myelin Sheath/metabolism , Synaptic Transmission , Animals , Freeze Fracturing , Membrane Lipids/metabolism , Membrane Potentials , Myelin Sheath/ultrastructure , Rats , Rats, Inbred Strains , Receptors, Cell Surface/metabolism
7.
Brain Res ; 629(2): 293-9, 1993 Dec 03.
Article in English | MEDLINE | ID: mdl-8111632

ABSTRACT

Slow electrical responses after painful stimulation with carbon dioxide, which is known to specifically activate nociceptors, were recorded from the nasal respiratory epithelium in human volunteers. The negative component of these potentials (negative mucosal potential NMP) has been hypothesized to be a summated receptor potential. The aim of the present study was to characterize the stimulus-response relationship and to demonstrate that the NMP is restricted to the site of stimulation, i.e., to the area of activated nociceptors. Eight healthy volunteers participated in the experiments. The NMP was recorded from the nasal septum and intensity ratings were obtained for each of the applied stimuli. To control for autonomic reflexes, blood flow changes were additionally recorded using a laser Doppler flow meter. Both increasing stimulus duration and increasing concentration produced a significant increase in the subjects' intensity estimates, in the NMP's amplitudes and areas under the curve, but did not change the local blood flow in a dose-related manner. The odorant hydrogen sulphide, which was used as a non-painful control stimulus, did not elicit mucosal potentials or produce blood flow changes. By recording both ipsi- and contralaterally it was also demonstrated that the NMP could only be obtained at the stimulated site, thus supporting the hypothesis that the NMP is a specific peripheral nociceptive correlate.


Subject(s)
Nasal Mucosa/innervation , Nociceptors/physiology , Reflex/physiology , Adult , Autonomic Nervous System/physiology , Blinking/physiology , Electric Stimulation , Electrodes , Female , Humans , Hydrogen Sulfide/pharmacology , Male , Membrane Potentials/physiology , Nasal Mucosa/blood supply , Nasal Mucosa/physiology , Pain Measurement , Regional Blood Flow/physiology , Stimulation, Chemical
8.
Eur J Pain ; 4(1): 107-9, 2000.
Article in English | MEDLINE | ID: mdl-10833560

ABSTRACT

In order to analyse the effects of potent exogenous analgesia with opioids in borderline personality disorder (BPD), we present a case report in which the application of morphine abolished the perception of pain during self-injury and intensified self-injurious activities. On the basis of our observations, we concluded that the use of potent analgesics might aggravate psychopathology in BPD.


Subject(s)
Analgesics, Opioid/adverse effects , Borderline Personality Disorder/psychology , Pain/drug therapy , Self-Injurious Behavior/psychology , Adult , Antidepressive Agents, Second-Generation/therapeutic use , Borderline Personality Disorder/therapy , Female , Humans , Low Back Pain/drug therapy , Pain Measurement , Paroxetine/therapeutic use , Psychotherapy , Self-Injurious Behavior/therapy
9.
Neurosci Lett ; 128(2): 297-300, 1991 Jul 22.
Article in English | MEDLINE | ID: mdl-1945051

ABSTRACT

Negative mucosal potentials (NMPs) were recorded from the nasal respiratory mucosa in rats following retrograde stimulation with CO2 through a tube advanced to the nasopharynx. Local application of capsaicin (3 mg in 0.3 ml solvent, n = 5) and lidocaine (31 mg in 0.3 ml solvent, n = 5) eliminated the NMPs and cortical responses in the EEG. A quantitative reduction in NMPs was found following systemic pretreatment with capsaicin (cumulative dose, 200 mg/kg, n = 4), but not with guanethidine (50 mg/kg s.c., n = 4). Blood flow measurements and NMPs were obtained from the same recording position (n = 4). Onset of blood flow changes (1200-4800 ms) appeared significantly later than the onset of NMPs (120-500 ms). On the basis of these results a sensory neurogenic origin of the NMP is assumed.


Subject(s)
Carbon Dioxide/pharmacology , Nasal Mucosa/physiology , Nociceptors/drug effects , Peripheral Nerves/drug effects , Animals , Capsaicin/pharmacology , Electroencephalography , Evoked Potentials/drug effects , Guanethidine/pharmacology , Lidocaine/pharmacology , Male , Neurons/drug effects , Rats , Rats, Inbred Strains , Stimulation, Chemical , Sympathetic Nervous System/cytology , Sympathetic Nervous System/drug effects , Trigeminal Nerve/physiology
10.
Fortschr Neurol Psychiatr ; 76(1): 7-13, 2008 Jan.
Article in German | MEDLINE | ID: mdl-17899492

ABSTRACT

In psychiatry, there is an increasing use of drugs Off-Label. Especially antidepressants and antipsychotic drugs are prescribed more often outside approved indications. Main problems with Off-Label Use are drug safety, lack of reimbursement by health care providers and insufficient coordination between clinics and primary care psychiatrists. Many, especially older psychotropic drugs are approved for psychopathologic phenomena rather than on ICD-10 categories. According to current judication of the German supreme court for social issues, specific criteria for Off-Label Use have been defined. Now, in social legislation, under particular circumstances Off-Label Use is feasible. Recommendations of expert groups for psychiatry are currently lacking, but are expected in next future for Methylphenidate in treatment of adult attention-deficit-hyperactive disorder (ADHS). Especially important for all psychiatrists is to receive informed consent of the patient before initiation of a drug therapy Off-Label.


Subject(s)
Mental Disorders/drug therapy , Psychiatry/trends , Psychotropic Drugs/therapeutic use , Attention Deficit Disorder with Hyperactivity/drug therapy , Drug Approval , Drug Prescriptions , Drug Utilization , Germany , Hospitals, Psychiatric , Humans , Mental Disorders/psychology , Methylphenidate/therapeutic use , Psychiatry/standards
11.
Stain Technol ; 57(3): 171-5, 1982 May.
Article in English | MEDLINE | ID: mdl-7135430

ABSTRACT

Cationized ferritin molecules, which are positively charged at physiological pH, can be used as a cytochemical marker to visualize negatively charged groups over cell surfaces. The preparation of cationized ferritin, however, is hampered by irreversible aggregation of the ferritins and by poor reproducibility of pI values. In this report we describe an improved method which allows production of ferritin derivatives with different pI values. An elaborate protocol for the preparation of cationized ferritin is given as well as a table for the adjustment of their pI values to between 4.5--10.0.


Subject(s)
Ferritins/analogs & derivatives , Cations , Chemical Phenomena , Chemistry , Dialysis , Erythrocytes/ultrastructure , Ferritins/chemical synthesis , Humans , Hydrogen-Ion Concentration
12.
J Ultrastruct Res ; 84(2): 103-10, 1983 Aug.
Article in English | MEDLINE | ID: mdl-6195352

ABSTRACT

Ferritin derivatives with different pI values and the basic dye ruthenium red have been used as cationic probes to localize anionic sites associated with fenestrated brain capillaries. Cationic ferritin was found in the endothelial basement membrane and the basement membrane of the perivascular cellular linings in amounts far exceeding those observed with anionic derivatives, the degree being greater for the more cationized ferritin molecules. Labeling of the luminal endothelial front with cationic ferritin was only achieved when a serum- or albumin-free medium was applied. Furthermore, the striated collagen fibers were coated with cationic ferritin molecules in a highly ordered fashion. Ruthenium red localized to the same sites. The findings suggest the existence of a perivascular charge filter around fenestrated capillaries of the brain. Some physiological roles of this filter are discussed, as related to its possible function in regulating homeostasis of cerebrospinal fluid.


Subject(s)
Anions , Brain/blood supply , Capillaries , Affinity Labels/metabolism , Animals , Basement Membrane/metabolism , Capillaries/metabolism , Cations , Electrochemistry , Endothelium/metabolism , Ferritins/metabolism , Isoelectric Point , Microscopy, Electron , Rats , Rats, Inbred Strains , Ruthenium Red/metabolism , Surface Properties
13.
Br J Clin Pharmacol ; 38(6): 545-55, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7888293

ABSTRACT

1. The aim of this study was to investigate the sensitivity of pain-related potentials used in experimental pain models to the non-specific effects of the tranquilizer diazepam. Pain-related potentials were recorded after painful stimulation of the nasal mucosa with CO2 and after painful stimulation of the tooth pulp. Acoustically evoked potentials were measured in order to compare their sensitivity to the tranquilizer diazepam with the sensitivity of the pain-related potentials. 2. Twenty volunteers participated in this randomised, double-blind, three-fold crossover study. Measurements were obtained before and 20 min after the administration of the drug. Event-related potentials were recorded after painful stimulation of the nasal mucosa with CO2 (two stimulus intensities: 60% v/v and 70% v/v CO2), after painful stimulation of the tooth pulp (two stimulus intensities: 2.2 x and 3.3 x detection threshold), and after non-painful acoustical stimulation of the right ear. The subjects rated the perceived intensity of the painful stimuli by means of a visual analogue scale. In addition the spontaneous EEG was analysed in the frequency domain and the vigilance of the subjects was assessed in a tracking task. 3. Diazepam reduced significantly the amplitudes of the event-related potentials after painful stimulation of the tooth pulp and after acoustical stimulation. In contrast only a small, statistically non-significant reduction could be found after painful stimulation with CO2. The pain ratings of the painful stimuli were not affected by diazepam. Diazepam reduced the performance of the tracking task. A decrease of arousal could be found in the alpha 2-range, whereas in the beta 2 and the theta-range the power density increased under diazepam. 4. We demonstrated that event-related potentials after painful stimulation of the nasal mucosa with CO2 are less affected by the nonspecific effects of the tranquilizer diazepam than event-related potentials after painful stimulation of the tooth pulp. The effects of diazepam on the tracking task, the spontaneous EEG and the event-related potentials clearly confirm its sedative properties. Diazepam had no analgesic effect measurable by pain intensity estimates.


Subject(s)
Carbon Dioxide/pharmacology , Chemoreceptor Cells/drug effects , Dental Pulp/drug effects , Diazepam/pharmacology , Pain/physiopathology , Acoustic Stimulation , Adult , Cross-Over Studies , Diazepam/blood , Double-Blind Method , Electric Stimulation , Electroencephalography/drug effects , Evoked Potentials/drug effects , Evoked Potentials, Auditory/drug effects , Evoked Potentials, Somatosensory/drug effects , Evoked Potentials, Somatosensory/physiology , Female , Humans , Male , Nasal Mucosa/drug effects , Nasal Mucosa/innervation , Psychomotor Performance/drug effects
14.
Chem Senses ; 20(3): 337-44, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7552043

ABSTRACT

The aim of this study was to determine whether the olfactory system is responsible for the discriminability of the stereoisomers of nicotine. The EOG was recorded after stimulation with different concentrations of undistilled S(-)-, distilled S(-)- and distilled R(-)-nicotine separately in three groups of frogs (Xenopus laevis). The responses to all types of nicotine used in the experiments increased with increasing stimulus concentration. The responses to undistilled S(-)-nicotine were significantly lower compared to responses to distilled S(-)- and R(+)-nicotine, whereas no significant differences could be found when the purified stereoisomers of nicotine [distilled S(-)-nicotine, distilled R(+)-nicotine] were compared. Control measurements of time course and peak concentration employing a UV-detection method demonstrated that the differences between distilled and undistilled S(-)-nicotine could not be explained by different nicotine concentrations. The fact that no differences between the pure nicotine stereoisomers could be found for all concentrations used in our experiments and that experiments in humans revealed similar detection thresholds for both stereoisomers points to a similar receptor affinity of R(+)- and S(-)-nicotine within the olfactory system. At this point, it cannot be determined whether the observed differences in the perception of nicotine enantiomers in humans are due to differences in quality coding by stereospecific receptors on the olfactory sensory cells or by specific receptors on the trigeminal nerve endings.


Subject(s)
Nicotine/pharmacology , Olfactory Mucosa/drug effects , Animals , Electrooculography , Olfactory Mucosa/physiology , Spectrophotometry, Ultraviolet , Stereoisomerism , Xenopus laevis
15.
J Ultrastruct Res ; 84(2): 111-9, 1983 Aug.
Article in English | MEDLINE | ID: mdl-6632049

ABSTRACT

We report on the effect of the net charge of a tracer (ferritin) on its permeability in fenestrated capillaries of the brain. Our experiments show that the charge of this tracer actually influences its interaction with the endothelium. Three phases of tracer-endothelial interaction could be discriminated. Anionic and slightly cationic derivatives (pH 4.5-7.8) do not show any affinity to the luminal endothelial membrane. Ferritin derivatives with a pI value between 7.8 and 9.3 result in the labeling of the fenestrae without coating additional luminal plasmalemmal structures (i.e., coated pits and plasmalemmal vesicles). Tracers with a high positive net charge (pI greater than 9.3) led to their endocytotic uptake and extravasation by some transcytotic mechanism. Extravasated cationic ferritin accumulates in the endothelial basement membrane and binds to striated collagen fibrils. It is suggested that the pericapillary collagen fibrils of fenestrated brain capillaries act as a charge filter with respect to macromolecules.


Subject(s)
Brain/blood supply , Capillary Permeability , Affinity Labels/metabolism , Animals , Capillaries/ultrastructure , Cations , Electrochemistry , Endocytosis , Endothelium/metabolism , Ferritins/metabolism , Isoelectric Point , Microscopy, Electron , Rats , Rats, Inbred Strains , Surface Properties
16.
Zentralbl Chir ; 118(7): 406-11, 1993.
Article in German | MEDLINE | ID: mdl-8372522

ABSTRACT

The so-called percutaneous dilatational tracheostomy-essentially a minimally invasive puncture method-inserting the tracheal cannula by a modified Seldinger-technique is an alternative method to the conventional operative tracheostomy. The percutaneous dilatational tracheostomy was evaluated in a prospective trial (June 92-January 93) on 50 consecutive surgical (n = 36), medical (n = 10), and neurological-neurosurgical (n = 4) critically ill patients (29 m, 21 f; age 14-87 years) with need for prolonged mechanical ventilation. After an average duration of endotracheal intubation of 6 (0-22) days, the procedure was endoscopically guided and controlled via the endotracheal tube. An 8 mm cannula was inserted in each case. Eight patients had severe thrombocytopenia (< or = 50,000 Plt./microL). The percutaneous tracheostomy was always performed with success. The average procedure duration was 8 (5-15) minutes. The perioperative complications were: one patient died of acute cardiac failure independent from the method of tracheostomy, one sustained a temporary subcutaneous emphysema and one a minor bleeding. During a mean duration of cannulation of 21 (0-113) days only one bleeding from the skin margin was observed postoperatively. Infection of stoma site, misplacement of cannula, rupture of the tube cuff, and pneumothorax were not noticed. On 13 decannulated patients stenosis of the trachea was not found in a period of 6-8 weeks following the tracheostomy. As a bedside procedure the percutaneous dilatational tracheostomy is safe and quick and should therefore be the method of choice for critically ill patients who require a tracheostomy.


Subject(s)
Critical Care , Punctures/instrumentation , Tracheostomy/instrumentation , Adolescent , Adult , Aged , Aged, 80 and over , Dilatation/instrumentation , Female , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/therapy , Prospective Studies , Wound Healing/physiology
17.
Eur J Neurol ; 10(6): 743-4, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14641525

ABSTRACT

A 76-year old woman was admitted because of severe gait ataxia and dysarthric speech that had worsened over the last 24 h. The patient was initially suspected of having repeated transitory ischemic attacks (TIAs) as her daughter reported a similar episode that had happened 3 weeks prior to admission. The onset of spontaneous twisting, choreoathetotic movements of both hands and arms and worsening of symptoms one hour after admission together with a history of lithium therapy lead to the correct diagnosis and appropriate treatment.


Subject(s)
Athetosis/chemically induced , Chorea/chemically induced , Lithium/adverse effects , Aged , Depressive Disorder/drug therapy , Diagnosis, Differential , Dysarthria/complications , Female , Humans , Ischemic Attack, Transient/diagnosis , Lithium/therapeutic use , Tomography, X-Ray Computed
18.
Eur J Neurosci ; 8(10): 2080-9, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8921299

ABSTRACT

Patch-clamp recordings revealed the presence of a non-desensitizing cyclic nucleotide-gated channel on human olfactory receptor neurons and a fast-desensitizing non-specific cation channel activated by nucleotides on human supporting cells. Cyclic nucleotide-gated channels on olfactory receptor neurons showed selective channel activation by cAMP (K1/2 = 5 microM) and cGMP (K1/2 = 2 microM), a unitary conductance of approximately 20 pS, a reversal potential of single-channel currents close to 0 mV, a linear current-voltage relationship over the range of -80 to 80 mV and a strong extracellular but a weaker intracellular blocking effect of Ca2+. The channel activity outlasted the cyclic nucleotide pulses for hundreds of milliseconds when higher agonist concentrations (> 50 microM cAMP) were applied. The duration of the response was longer than in cyclic nucleotide-gated channels from other species studied so far. The plateau duration and the decay remained constant for pulses with a length of 50-150 ms, whereas pulses shorter than 50 ms successively reduced the time required by shortening the plateau phase. A larger difference for the K1/2 values of cAMP (K1/2 = 22 microM) and cGMP (K1/2 = 2.5 microM) were found for a small group (n = 3) of cyclic nucleotide-gated channels, pointing to the selective expression of the alpha-subunit in a small subgroup of olfactory receptor neurons.


Subject(s)
Cyclic AMP/physiology , Cyclic GMP/physiology , Ion Channel Gating , Olfactory Receptor Neurons/physiology , Biomarkers/chemistry , Humans , Patch-Clamp Techniques
19.
Crit Care Med ; 28(4): 969-76, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10809268

ABSTRACT

OBJECTIVE: Mu-Opioid receptor blockade during general anesthesia is a new treatment for detoxification of opioid addicted patients. We assessed catecholamine plasma concentrations, oxygen consumption, cardiovascular variables, and withdrawal symptoms after naloxone and tested the hypothesis that variables are influenced by the anesthetic administered during detoxification. DESIGN: Prospective randomized clinical study. SETTING: Intensive care unit of a university hospital and psychiatric ward. PATIENTS: Twenty-five mono-opioid addicted patients with mild to moderate systemic disease (ASA II classification) in a methadone substitution program. INTERVENTION: General anesthesia with either propofol (129+/-7 microg x kg(-1) x min(-1), mean +/- SEM) or methohexital (74+/-14 microg x kg(-1). min(-1)), mu-opioid receptor blockade by naloxone in a stepwise fashion (increasing doses of 0.4 mg, 0.8 mg, 1.6 mg, 3.2 mg, and 6.4 mg at 15 min intervals followed by 0.8 mg x hr(-1) for 24 hrs) and naltrexone 50 mg x day(-1) orally for > or =4 wks. Clonidine was started 180 mins after the first naloxone dose and its infusion rate was individually adjusted to mitigate withdrawal symptoms during weaning and after extubation. MEASUREMENTS AND MAIN RESULTS: During propofol and methohexital anesthesia, naloxone induced a 30-fold increase in epinephrine and a significant three-fold increase in norepinephrine plasma concentrations without a significant difference between groups. This increase in catecholamine plasma concentrations was associated with increased oxygen consumption and marked cardiovascular stimulation with both anesthetics, as shown by increased cardiac index, heart rate, and systolic atrial pressure whereas diastolic pressure remained unchanged. Patients receiving propofol could be extubated significantly earlier after discontinuation of the anesthetics. Although the maximum degree of withdrawal symptoms (Short Opioid Withdrawal Scale) on the day after detoxification was similar with both anesthetics, subsequent withdrawal symptoms decreased significantly more rapidly after propofol anesthesia. CONCLUSIONS: Naloxone treatment, in opioid-addicted patients, induced a marked increase in catecholamine plasma concentrations, metabolism, and cardiovascular stimulation during anesthesia with both propofol and methohexital. Although both anesthetics appear suitable for detoxification treatment, the use of propofol is associated with earlier extubation and, surprisingly, a shortened period of long-term withdrawal symptoms during detoxification.


Subject(s)
Anesthetics, Intravenous , Methohexital , Naloxone/therapeutic use , Narcotic Antagonists/therapeutic use , Opioid-Related Disorders/drug therapy , Propofol , Substance Withdrawal Syndrome/drug therapy , Adult , Anesthesia, General , Catecholamines/blood , Female , Humans , Male , Methadone/therapeutic use , Middle Aged , Narcotics/therapeutic use , Opioid-Related Disorders/blood , Opioid-Related Disorders/rehabilitation , Prospective Studies , Substance Withdrawal Syndrome/blood
20.
Article in English | MEDLINE | ID: mdl-10810264

ABSTRACT

Dilatative percutaneous tracheotomy is more and more indicated in intensive-care medicine. We report on the perforation of the posterior tracheal wall observed in 3 patients after this procedure. In 2 patients the tracheo-oesophageal fistula was closed by the use of a pediculated flap from the infrahyoideal muscle. The third patient died due to the underlying disease. As demonstrated by the 3 cases reported here, this complication cannot be avoided in every case neither by the use of an endoscope nor by extensive personal experience of the physician. The possibility of this complication should be known, because it seems to be typical of this procedure. In the case of perforation of the posterior tracheal wall, active surgical treatment seems to be a successful method to deal with this complication.


Subject(s)
Intraoperative Complications/etiology , Tracheoesophageal Fistula/etiology , Tracheotomy/adverse effects , Adolescent , Aged , Female , Humans , Intraoperative Complications/surgery , Tracheoesophageal Fistula/surgery , Treatment Outcome
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