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Biomedical subjects

M Gastpar

Publications and source records attributed to M Gastpar.

At least 37 records · Page 2Linked to original sources
PubMed2001

Chronic mu-opioid receptor stimulation in humans decreases muscle sympathetic nerve activity.

BACKGROUND: Opioid-addicted patients undergoing detoxification provide a unique opportunity to assess the effects of chronic opioid receptor stimulation on the sympathetic nervous system. We tested the hypothesis that chronic oral methadone intake decreases resting efferent sympathetic nerve activity to muscle (MSA). Furthermore, we assessed whether this effect is reversed by mu-opioid receptor blockade during antagonist-supported detoxification under general anesthesia. METHODS AND RESULTS: Fifteen young patients (30+/-1 years old, mean+/-SEM) with a long history of mono-opioid addiction and under oral methadone substitution therapy (65+/-10 mg/d for 21+/-6 months) were selected. Peroneal MSA (microneurography) and catecholamine plasma concentrations (high-performance liquid chromatography) were assessed in the awake state and compared with those of age-matched healthy control subjects. The effects of mu-opioid receptor blockade by naloxone (12.4 mg IV) were determined during propofol anesthesia. Compared with healthy volunteers, resting MSA (4+/-2 versus 22+/-2 bursts/min, P<0.0001) and antecubital venous norepinephrine plasma concentration (100+/-64 versus 256+/-48 pg/mL, P=0.01) were markedly decreased in addicted patients despite similar arterial blood pressure and heart rate. Opioid receptor blockade markedly increased MSA (5+/-2 to 24+/-3 bursts/min) and norepinephrine (49+/-12 to 305+/-48 pg/mL) and epinephrine (13+/-2 to 482+/-67 pg/mL) arterial plasma concentrations as well as mean arterial pressure (82+/-4 to 108+/-3 mm Hg) and heart rate (70+/-3 to 86+/-4 beats/min). CONCLUSIONS: Chronic mu-opioid receptor stimulation by methadone decreases resting MSA in humans.

Adult↗
PubMed2001

Somatic comorbidity of addicts: does hospitalization yield relevant findings?

The aim of this prospective study was to examine the severity and character of somatic comorbidity when addicted patients were admitted to hospital for detoxification. The study was conducted at a university-based psychiatric clinic. Somatic comorbidity was registered by laboratory, radiological and electrocardiographic parameters and by the amount of non-psychiatric consultations. Besides the number of patients with dual diagnosis interpreted as combination of addictive and psychiatric diseases was registered. A total of 111 consecutive patients (32 women) was divided into patients with alcohol dependence and patients with other addictive diseases including polydrug abuse and opiate dependence. Patients with alcohol dependence were characterized by an elevated heart rate and higher values for gamma-glutamyltransferase. No significant differences between groups could be found for the rate corrected QT interval and cardiothoracic ratio. Although viral liver disease was diagnosed in both groups patients with a history of injecting drug use were at greatest risk for hepatitis C. About one-third of all patients required consultant non-psychiatric treatment. Concomitant heart and pulmonary diseases were more pronounced in the alcohol dependence group. The findings emphasize that hospitalization of addicted patients yields relevant somatic morbidity which has an impact on cost and requires medically supervised detoxification programs.

Adult↗
PubMed2000

[Psychotherapy research in psychiatry. Results of a survey of psychiatric clinics].

This paper concerns advances in the integration of psychotherapy in psychiatric education and clinical practice and whether they go along with increasing research activities. To find answers, a survey on psychotherapy research was carried out in all German psychiatric hospitals and departments by means of a questionnaire. The results indicate that psychotherapy research is done nearly exclusively in university hospitals. About half of them had already published psychotherapy studies and two thirds of them are presently carrying out studies, mostly including prospective, randomized clinical trials. These studies cover the whole spectrum of psychiatric disorders: substance abuse, schizophrenic and affective disorders, anxiety, and obsessive compulsive and personality disorders. To improve psychotherapy research conditions further, efforts are necessary to increase scientific exchange, financial support, and the integration of institutions outside the universities.

Curriculum↗
PubMed2000

Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic, and cardiovascular patterns.

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.

Adult↗
PubMed2000

Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients.

Steady state plasma concentrations of the (L)- and (D)-enantiomers of trimipramine (TRI), desmethyltrimipramine (DTRI), 2-hydroxytrimipramine (TRIOH) and 2-hydroxydesmethyl-trimipramine (DTRIOH) were measured in 27 patients receiving between 300 and 400 mg/day racemic TRI. The patients were phenotyped with dextromethorphan and mephenytoin, and the 8-hour urinary ratios of dextromethorphan/dextrorphan, dextromethorphan/3-methoxymorphinan, and (S)-mephenytoin/(R)mephenytoin were used as markers of cytochrome P-450IID6 (CYP2D6), CYP3A4/5 and CYP2C19 activities, respectively. One patient was a CYP2D6 and one was a CYP2C19 poor metabolizer. A stereoselectivity in the metabolism of TRI has been found, with a preferential N-demethylation of (D)-TRI and a preferential hydroxylation of (L)-TRI. CYP2D6 appears to be involved in the 2-hydroxylation of (L)-TRI, (L)DTRI and (D)-DTRI, but not of (D)-TRI, as significant correlations were measured between the dextromethorphan/dextrorphan ratios and the (L)-TRI/(L)-TRIOH (r = 0.45, p = 0.019), the (L)-DTRI/(L)-DTRIOH (r = 0.47, p = 0.014), and the (D)-DTRI/(D)-DTRIOH (r = 0.51, p = 0.006), but not with the (D)-TRI/(D)-TRIOH ratios (r = 0.29, NS). CYP2C19, but not CYP2D6, appears to be involved in the demethylation pathway, with a stereoselectivity toward the (D)-enantiomer of TRI, as a significant positive correlation was calculated between the mephenytoin (S)/(R) ratios and the concentrations to dose-to-weight ratios of (D)-TRI (r = 0.69, p = 0.00006). CYP3A4/5 appears to be involved in the metabolism of (L)-TRI to a presently not determined metabolite. The CYP2D6 poor metabolizer had the highest (L)-DTRI and (D)-DTRI concentrations to dose-to-weight ratios, and the CYP2C19 poor metabolizer had the highest (L)-TRI and (D)-TRI concentrations to dose-to-weight ratios of the group.

Adult↗
PubMed2000

Cognitive-motor performance of methadone-maintained patients.

Fifty-four methadone-maintained patients and 54 healthy controls, matched for age, gender and educational attainment, completed a battery of six cognitive-psychomotor performance tests. Results of previous studies were replicated in four areas. An attention task was performed less well by patients [mean difference more than 0.7 standard deviations (SD)] as was a tachistoscopic perception task (0. 3 SD). On a simple-choice reaction test, patients showed higher speed in decision making and motor reaction as well as an increased number of decision errors (0.3 SD each). Performing a tracking test, patients showed less deviations (0.4 SD) combined with more time needed (0.8 SD). Our data go beyond previous (seemingly inconsistent) research findings by showing that patients did less well by more than 0.6 SD when on higher speed levels. Absolving a test on visual structuring, more patients than controls achieved a 100% accuracy level (52 vs. 30%), but at the same time patients were slower (0.6 SD) than controls. An inferior test performance of patients in methadone maintenance treatment has been confirmed in some areas, especially in attention. However, the fairly moderate size of these effects and the fact that in the majority of measures the observed variance was better explained by sociodemographic features than by group membership lead on the conclusion that belonging to the group of methadone patients alone is not necessarily sufficient to predict an impairment in cognitive-psychomotor skills. To conclude, assessment of fitness for certain tasks or occupations should be done individually for each patient and should take into account comorbidity, including the extent of alcohol and other drug use.

Adult↗
PubMed1999

Treatment of alcohol withdrawal syndrome with gabapentin.

Four in-patients with moderate alcohol-withdrawal syndromes benefited from treatment with gabapentin administered in an add-on fashion to clomethiazole. In comparison with the amount of clomethiazole required as estimated using a specially developed score during previous detoxifications of these patients at our hospital, gabapentin (400 mg q.i.d.) clearly reduced the amount of clomethiazole needed now Gabapentin, an anticonvulsant with favorable pharmacokinetic properties and tolerability, and with no known risk of dependence, may therefore be a useful new drug in the treatment of alcohol withdrawal. We believe that the potential value of gabapentin in alcohol withdrawal deserves further controlled studies.

Acetates↗
PubMed1999

Competence to give informed consent to clinical studies. Statement by the taskforce on "ethical and legal questions" of the Association for Neuropsychopharmacology and Pharmacopsychiatry ("Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie [AGNP]").

Over the last 50 years, patient autonomy has become an increasingly important part of the principles of medical ethics, or rather of the ethics of the doctor-patient relationship. While the principle of charity and the associated paternalism became less important, the patient's active consent became more and more relevant (Sass, 1989; Bayer, 1998; Nedopil, 1998). This development was inevitably also accompanied by a demand for more detailed information prior to medical interventions (Appelbaum and Grisso, 1988; Weisstub, 1990; Kreussler, 1997; Ulsenheimer, 1995; Laufs, 1997; Sommer, 1997) and for complete information on medical procedures subsequent to interventions (e. g. Bender, 1997). Determination of a person's competence to give informed consent is a central problem in the assessment of his expression of consent to a medical intervention. The capacity to adequately express consent can be impaired at certain stages of life and during some illnesses. Patients in borderline situations, children, mentally ill patients and old people with dementia may either be limited in their capacity to give informed consent, or be completely unable to do so. This results in special ethical problems when such groups are included in research projects.

Clinical Trials as Topic↗
PubMed1999

DEPRES II (Depression Research in European Society II): a patient survey of the symptoms, disability and current management of depression in the community. DEPRES Steering Committee.

The first pan-European survey of depression in the community (DEPRES I) demonstrated that 17% of the general population suffer from depression (major depression, minor depression, or depressive symptoms). This article describes findings from a second phase of DEPRES (DEPRES II), in which detailed interviews based on a semi-structured questionnaire (78 questions) were conducted with 1884 DEPRES I participants who had suffered from depression and who consulted a healthcare professional about their symptoms during the previous 6 months. The mean time from onset of depression was 45 months, and the most commonly experienced symptoms during the latest period were low mood (76%), tiredness (73%) and sleep problems (63%). During the previous 6 months, respondents had been unable to undertake normal activities because of their depression for a mean of 30 days, and a mean of 20 days of work had been lost to depression by those in paid employment. Approximately one-third of respondents (30%) had received an antidepressant during the latest period of depression. Significantly more respondents given a selective serotonin reputake inhibitor found that their treatment made them feel more like their normal self than those given a tricyclic antidepressant, and fewer reported treatment-related concentration lapses, weight problems, and heavy-headedness (all P < 0.05). Approximately two-thirds of respondents (70%) had received no antidepressant therapy during the latest period of depression, and prescription of benzodiazepines alone, which are not effective against depression, was widespread (17%). There is a need for education of healthcare professionals to encourage appropriate treatment of depression.

Antidepressive Agents↗
PubMed1999

Identification of depressed patient types in the community and their treatment needs: findings from the DEPRES II (Depression Research in European Society II) survey. DEPRES Steering Committee.

DEPRES II (Depression Research in European Society II), the first in-depth, pan-European survey of depression in the community, provided an opportunity to identify depressed patient types and their treatment needs. Cluster analysis applied to data generated from DEPRES II interviews revealed six depressed patient types with clearly differentiated profiles. The patient type with moderately impaired depression has episodic depression and minimal disability. By contrast, severe depression associated with anxiety presents with chronic symptoms, including anxiety and panic, and causes considerable disruption to normal life and employment. Depression associated with chronic physical problems and depression associated with social problems are characterized by chronic physical illness and relationship or financial difficulties, respectively, and sufferers are pessimistic about recovery. Depression associated with sleep problems is associated with symptoms of tiredness and broken or inadequate sleep, and is commonly caused by stress. Tiredness is also a principal symptom of depression associated with tiredness or fatigue, but sufferers' ability to sleep is unaffected. All patient types would benefit from antidepressant therapy. The depressed patient types identified from the DEPRES II data make intuitive sense, but now need to be tested for face validity in the primary care setting.

Cluster Analysis↗
PubMed1998

Choreoathetoid movements associated with rapid adjustment to methadone.

Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.

Adult↗
PubMed1998

Alternative strategies of opiate detoxification: evaluation of the so-called ultra-rapid detoxification.

This study was done in order to examine the hypothesis that so-called ultra-rapid opiate detoxification provides a mild, short, and safe withdrawal. A total of 22 patients who were addicted to opiates exclusively underwent ultra-rapid detoxification. Each patient was pretreated with methadone. During general anesthesia lasting about six hours with methohexital or propofol, naloxone was administered with doubling of the dose every 15 minutes with a starting bolus dose of 0.4 mg. The total bolus dose of 12.4 mg, delivered within 60 minutes, was followed by a naloxone infusion of 0.8 mg/h until the next morning. On the day of anesthesia naltrexone (50 mg/d) treatment was initiated. When withdrawal symptoms occurred, specific medications, e.g., clonidine, were added. After determining baseline values, withdrawal symptoms were investigated during a further four weeks by means of established clinical scales. The results document marked withdrawal symptoms for at least one week after detoxification. The intensity of withdrawal symptoms during the first seven days of treatment was significantly (p<0.05) more marked than during baseline. None of the patients underwent a life-threatening complication and only one patient failed to complete the detoxification procedure. Finally, about 75% of the patients could be referred for further treatment. In this study ultra-rapid detoxification provided a safe withdrawal procedure with high rates of completed withdrawals and referrals for further treatment, respectively. However, in contrast to previous reports, many patients suffered from middle-grade withdrawal symptoms over several days. Due to the risks of general anesthesia and the expense associated with this treatment, only patients addicted to opiates alone and for whom other detoxification strategies are unsuitable should undergo a ultra-rapid detoxification procedure.

Adolescent↗
PubMed1998

Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after mu-opioid receptor blockade in opioid-addicted patients during barbiturate-induced anesthesia for acute detoxification.

BACKGROUND: Acute displacement of opioids from their receptors by administration of large doses of opioid antagonists during general anesthesia is a new approach for detoxification of patients addicted to opioids. The authors tested the hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular stimulation mediated by the sympathoadrenal system. METHODS: Heart rate, cardiac index, and intravascular pressures were measured in 10 patients addicted to opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and concentrations of catecholamine in plasma were measured in the awake state, during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(-1)) before administration of naloxone, and repeatedly during the first 3 h of mu-opioid receptor blockade. Naloxone was administered initially in an intravenous dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg) at 15-min intervals until a total dose of 12.4 mg had been administered within 60 min; administration was then continued by infusion (0.8 mg/h). RESULTS: Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304 pg/ml), whereas concentration of norepinephrine in plasma only increased to a minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P < 0.05). Cardiac index increased by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching maximum 45 min after the initial injection of naloxone. In parallel, systemic vascular resistance index decreased (-40%). Systolic arterial pressure significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic arterial pressure did not change. CONCLUSIONS: Despite barbiturate-induced anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids induces profound epinephrine release and cardiovascular stimulation. These data suggest that long-term opioid receptor stimulation changes sympathoadrenal and cardiovascular function, which is acutely unmasked by mu-opioid receptor blockade. Because of the attendant cardiovascular stimulation, acute detoxification using naloxone should be performed by trained anesthesiologists or intensivists.

Adult↗
PubMed1997

[Early and differential diagnosis of 1,000 patients examined in a memory clinic].

The results from 1000 patients included in a consecutive sample of older persons showing signs of "age-related memory deficits" clearly demonstrate the necessity for a wide spectrum of differential diagnostic competence. The patients included in the study were diagnosed in succession by an interdisciplinary team of psychiatrists, neurologists, geriatric medical specialists, psychologists and gerontologists. The diagnostic process for clarification of DSM-III-R and ICD-10 criteria are discussed in detail. In all, 49.6% of the patients were diagnosed as suffering from dementia of the Alzheimer type, 31% from vascular dementia and 10% from a mixed form. In all, 12.5% of the patients were somatically ill and 31.4% displayed other psychiatric conditions, 50% of which were evaluated as being treatable with psychotherapy. The results are primarily discussed for their relevance to the reality of current treatment.

Adult↗
PubMed1997

The effect of hypericum extract on cardiac conduction as seen in the electrocardiogram compared to that of imipramine.

The electrocardiographic effects of high-dose hypericum extract were compared to the effects of imipramine hydrochloride on ECG recordings in a randomized, double-blind, multicenter treatment study of 209 patients suffering from depression. ECGs were recorded before and after a six-week treatment period with either hypericum extract or imipramine. At the end of the study ECGs of 84 patients treated with hypericum extract and 76 patients treated with imipramine were suitable for an analysis of conduction intervals and pathological findings. In the first ECG analysis comparing high dose hypericum extract with imipramine, a prolongation of the conduction intervals PR, QRS and QTc was found for imipramine. In contrast, a small acceleration of conduction was seen for the high-dose hypericum extract. The comparison of ECGs at the beginning and after six weeks of treatment showed a significant increase in first degree AV-blocks and abnormalities of repolarization under imipramine but a significant reduction of such pathological findings under treatment with hypericum extract. It should be emphasized that this favorable feature of safe cardiac activity was achieved with 1800 mg of hypericum extract. The reduction in pathological ECG features after treatment with hypericum extract may have resulted mainly from the change of medication, probably tricyclics, to hypericum extract. Our results indicate that for the treatment of patients with a pre-existing conductive dysfunction or elderly patients, high-dose hypericum extract is safer with regard to cardiac function than tricyclic antidepressants.

Adult↗