[5-Year-Follow-up of the MEmbeR Multicenter Study on Medical-Occupational Rehabilitation]. / 5-Jahres-Follow-Up der multizentrischen Evaluationsstudie zur medizinisch-beruflichen Rehabilitation (MEmbeR).

In Germany, medical-occupational rehabilitation represents an essential link between rehabilitation programs focusing either on medical or occupational rehabilitation. Its main objective is return to work. The current study presents the vocational integration 5 years after medical-occupational rehabilitation and determines possible prognostic factors for long-term occupational integration. To evaluate the effectiveness of medical-occupational rehabilitation, a 5-year-follow-up interview was conducted with participants (n=105) of the multicenter study on medical-occupational rehabilitation (MEmbeR). As a main result, 76% of the participants were still employed 5 years after medical-occupational rehabilitation and the return to work rate was 57%. Prognostic factors for long-term occupational integration could not be identified. However, a low degree of disability, an unrestricted capacity for teamwork as well as an unrestricted ability to judge might be beneficial factors for a successful reintegration. The high amount of participants who returned to work 5 years after medical-occupational rehabilitation, supports the concept of medical-occupational rehabilitation. However, more studies are needed to identify further factors influencing the outcome.

[Positional paper of the German working group "cardiopulmonary exercise testing" to ventilatory and metabolic (lactate) thresholds]. / Ventilatorische und metabolische (Laktat-)Schwellen. Positionspapier der Arbeitsgemeinschaft Spiroergometrie.

Thresholds in cardiopulmonary exercise testing are necessary for the evaluation of motivation and cooperation in exercise, for training programs, in transplant medicine, preoperative evaluation and medical assessments. There is a hardly comprehensible number of terminologies concerning these thresholds and their definitions. This hampers the comparison of protocols and studies and leads to incertainties in terminologies and interpretations of cardiopulmonary exercise tests. Based on literature a definition of thresholds was undertaken. Thresholds should be regarded from a conceptional and an operational (methodological) point of view. The conceptional model means, that there are two ventilatory thresholds (VT1 and VT2) and two metabolic thresholds (lactate threshold [LT] 1 and 2 ). These thresholds are pathophysiologically based. Both threshold concepts determinate the beginning and the end of the aerobic-anaerobic transition. The lactate thresholds determine the metabolic changes, whereas the ventilator thresholds 1 and 2 represent the ventilatory response to the metabolic changes. VT1 represents the subsequent increase of ventilation and CO2-output relative to oxygen uptake as a consequence of an increase of lactate and a necessary lactate buffering. VT2 is characterized by an exceeding of lactate-steady-state, resulting in excess lactate, metabolic acidosis and overproportional rise of ventilation. The operational concept describes the method, which is used for determination of the different lactate and ventilatory thresholds. In a further step this can be completed by indicating the exercise protocol which was applied.

[Prevention of psychic disorders]. / Prävention psychischer Störungen.

Prevention aims to avoid the occurrence of psychiatric illness and disability caused by psychic disorders. The relevant interventions refer to the individual, the family context and other environmental factors. Universal and primary prevention target the entire population or a part of this (i. e. students). Secondary and selective intervention should prevent the manifestation of psychiatric disorders in vulnerable individuals (i. e. children with behavioral problems). Tertiary measures aim at preventing the worsening or recurrence of symptoms in individuals who already suffer from mental illness. Within the past 25 years protective and risk factors that reduce or increase the probability of occurrence of mental disorders have increasingly been identified. This results in improved prevention. The present article gives an overview of preventive measures against the most common mental disorders in the light of the current evidence base.

The effects of venlafaxine on cognitive functions and quantitative EEG in healthy volunteers.

Antidepressants that selectively block serotonin uptake may cause unwanted effects on cognitive functions such as impairment of vigilance and memory. A double-blind, randomized, placebo-controlled cross-over trial was performed to examine the effects of venlafaxine, a selective serotonin and noradrenaline reuptake inhibitor (SSNRI), on cognitive functions and quantitative EEG (qEEG) in humans. 12 healthy male subjects aged 23-32 years (26+/-3 years mean+/-sd) orally received 37.5 mg venlafaxine b.i.d. for 7 days and subsequently 75 mg b.i.d. for another 7 days. After a 14-day wash-out phase, placebo was administered to the subjects for 14 days under randomized double-blind cross-over conditions. Venlafaxine did not influence cognitive functions such as choice reaction, memory, psychomotor performance and subjective mood. Placebo resulted in an increase in slow alpha power (p<0.05) whereas venlafaxine had no effect on qEEG. In conclusion, multiple dosing with venlafaxine did not influence cognitive functions in healthy humans.

The pharmacokinetics of zinc from zinc gluconate: a comparison with zinc oxide in healthy men.

OBJECTIVE: Zinc supplementation is beneficial in some clinical conditions such as age-related macula degeneration (AMD). It has been suggested that zinc absorption is influenced by the form in which zinc is ingested. Therefore, the pharmacokinetics of zinc gluconate (organic) were compared with those of zinc oxide (inorganic). METHODS: 12 healthy male subjects aged between 21 and 31 years (24 years median) orally received daily doses of 20 mg metal zinc as zinc gluconate and 17.4 mg metal zinc as zinc oxide under randomized crossover conditions for 14 days each with at least 14 days as a washout. Zinc plasma concentrations were measured by means of inductively coupled plasma-atomic emission spectroscopy. RESULTS: C(max) was found 18.3% (10.3 - 26.3%) higher following multiple-dose administration of zinc gluconate as compared to zinc oxide (mean; 0.95% confidence interval of the relative differences between both treatment conditions; p < 0.05). AUC(0-24h) was noted 8.1% (1.9 - 14.3%) higher after zinc was given as zinc gluconate when compared to zinc oxide (p < 0.05) whereas t(max) did not differ between both treatment conditions. CONCLUSIONS: Zinc absorption in humans could be improved by zinc complexation with gluconate.

The effects of moclobemide on autonomic and cognitive functions in healthy volunteers.

BACKGROUND: Moclobemide, a reversible and selective inhibitor of the MAO-A isoenzyme, is marketed as an antidepressant that lacks autonomic and cognitive side effects. However, only few and inconclusive quantitative data on the effects of moclobemide on autonomic and cognitive functions have been reported in the literature. Therefore, a double-blind, randomized, placebo-controlled crossover trial was performed. METHODS: Twelve healthy male volunteers (age 22-29 years) received orally 150 mg moclobemide b.i.d. and placebo for 14 days each. Heart rate variability (HRV) and skin conductance response (SCR) following sudden deep breath were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. Measurements were performed before the start of drug administration and repeatedly on the last treatment day. RESULTS: Parameters of HRV and SCR were not changed by multiple dosing with moclobemide (P > 0.05). Neither cognitive functions such as flicker fusion frequency, memory, choice reaction time, and psychomotor performance nor qEEG was significantly influenced, but subjective tiredness was decreased at all time points of measurement after multiple dosing with moclobemide (P < 0.05). CONCLUSIONS: In conclusion, moclobemide does not appear to influence autonomic functions or cognitive functions when given subchronically to healthy humans. In contrast, changes in subjective mood hint at a subtle activating effect.

The effects of St John's wort extract on heart rate variability, cognitive function and quantitative EEG: a comparison with amitriptyline and placebo in healthy men.

AIMS: To compare the effects of multiple dosing with St John's wort (Hypericum perforatum) extract and amitriptyline on heart rate variability, cognitive function and quantitative EEG (qEEG) with placebo in healthy humans. METHODS: A randomized, double-blind, cross over study of 12 healthy male volunteers. Subjects orally received capsules with 255-285 mg St John's wort extract (900 micro g hypericin content), 25 mg amitriptyline and placebo three times daily for periods of 14 days each with at least 14 days between. The doses of amitriptyline and St John's wort extract are comparable with respect to their antidepressant activity. Compliance was confirmed by coadministration of 10 mg of riboflavin with each capsule and detection of urinary vitamin B2 on treatment day 11 with high performance liquid chromatography. Measurements of heart rate variability, psychometric tests and qEEG were performed before start of medication and repeatedly on the last treatment day. RESULTS: St John's wort extract did not affect heart rate variability (HRV) whereas amitripytline significantly decreased it: the difference in the percentage number of adjacent RR intervals> 50 ms (pNN50) was 8.6 (-2.6, 19.9; mean; 95% confidence interval) between St John's wort extract and placebo and -17.6 (-24.7, -10.4) between amitriptyline and placebo. Neither St John's wort extract nor amitriptyline had an influence on cognitive performance such as choice reaction, psychomotor coordination, short-term memory and responsiveness to distractive stimuli. Amitriptyline but not St John's wort extract decreased self rated activity (P < 0.05). Both drugs caused significant qEEG changes. St John's wort extract increased theta power density. Amitriptyline increased theta as well as fast alpha power density. CONCLUSIONS: Multiple doses of St John's wort extract do not affect heart rate variability nor cognitive function. Chronic administration of amitriptyline causes a decrement of HRV and subjective sedation but it does not impair cognitive performance.

Influence of clinical factors, diet, and drugs on the human upper gastrointestinal glutathione system.

BACKGROUND: Glutathione (GSH) and the cytosolic glutathione S-transferases (GSTs) protect the gastrointestinal mucosa against the toxic effects of a wide variety of compounds, such as reactive oxygen species and electrophiles. AIMS: We wished to investigate the distribution along the upper gastrointestinal mucosa and the influence of clinical variables on components of the GSH system to learn more about factors which control its cytoprotective properties. METHODS: Antral and duodenal biopsies of normal appearing mucosa were collected from 202 patients (104 males, 98 females; mean age 62 years) undergoing upper gastrointestinal endoscopy. GSH content was examined by high pressure liquid chromatography, GST enzyme activity by 1-chloro-, 2, 4-dinitrobenzene conjugation, and levels of the GST classes alpha, pi, and theta by western blot. RESULTS: GSH, GST enzyme activity, and GST alpha levels were significantly lower (p<0.001) in the antrum than in the duodenum (antrum v duodenum: GSH 23.0 (0.7) v 35.0 (1.0) nmol/mg protein; GST activity 626 (19) v 832 (22) nmol/mg protein/min; GST alpha 4.5 (0.5) v 20.0 (0.7) microg/mg protein) while GST pi content was significantly higher (p<0.001) in antral than in duodenal biopsies (16.5 (0.7) v 11.2 (0.5) microg/mg protein). Antral GSH and GST activities were markedly lower in males compared with females (p<0.01). Some drugs (cisapride, diuretics, cortisol, analgesics) increased GST pi and GST alpha content but cytostatic drugs suppressed duodenal GST activity. High intake (>3 days a week) of vegetables enhanced duodenal GST alpha and GST pi and high intake of fruits the antral content of GST theta 1. CONCLUSIONS: The gastrointestinal GSH system represents the antitoxic barrier of the mucosa; its activity is influenced by localisation, sex, and drugs, and its enzymes are stimulated by a high intake of vegetables and fruits.

[Psychopharmacotherapy in the 20th century]. / Psychopharmakotherapie im 20. Jahrhundert.

Neuroleptics, antidepressants, mood stabilizers and anxiolytics are the most frequently prescribed drugs in psychiatric therapy. Their introduction came largely in the past five decades. This review summarizes the history that led to their discovery and introduction to the market in the 20th century.

The effects of reboxetine on autonomic and cognitive functions in healthy volunteers.

RATIONALE: Though reboxetine, a selective noradrenaline reuptake inhibitor, causes autonomic and cognitive adverse events there is a paucity of appropriately designed studies on the cognitive and autonomic effects of the drug in the literature. OBJECTIVE: To compare the effects of reboxetine on cognitive and autonomic functions with those of placebo in healthy humans. METHOD: A randomised, double-blind, crossover study of 12 healthy male volunteers aged 25 (21-27; median, range) years. Subjects orally received 4 mg reboxetine and placebo twice daily for periods of 14 days each with at least 14 days in between. Vasoconstrictory response of cutaneous vessels (VR) and skin conductance response (SCR) following sudden deep breath were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. RESULTS: Reboxetine decreased SCR and prolonged the dilation phase of VR (P<0.05). It did not affect cognitive functions such as flicker fusion frequency, choice reaction, memory and psychomotor coordination but increased slow beta (beta1) power density in the qEEG. Tiredness (n=12), dry mouth (n=9), delayed urination (n=3) and constipation (n=1) were noted with reboxetine. CONCLUSION: Sustained peripheral and/or central sympathetic activation accounts for the prolongation of VR. The decrease of SCR and typical side effects suggest a relevant antimuscarinic drug action. Chronic administration of reboxetine at therapeutic doses causes autonomic dysfunction and subjective sedation but does not impair cognitive and psychomotor abilities in healthy humans.

Effects of nitroglycerine on cerebral blood flow velocity, quantitative electroencephalogram and cognitive performance.

BACKGROUND: Despite the widespread use of nitroglycerine, little is known of its cerebral haemodynamic effects. The present study was undertaken to evaluate the effects of nitroglycerine on cerebral circulation and cognitive function in normal volunteers. DESIGN: Twelve healthy male volunteers (age 25 +/- 3 years; mean +/- SD) received continuous intravenous infusions of nitroglycerine at 1 mg h-1 and 2 mg h-1 rates as well as placebo (0.9% saline) under randomized, double-blind cross-over conditions on three different occasions. A 10-min quantitative EEG (qEEG) was recorded before, during and repeatedly after infusion. Blood flow velocity in the left arteria cerebri media (MCA) was measured simultaneously by means of transcranial Doppler sonography. Cognitive performance was assessed with a computerized test battery. RESULTS: Administration of nitroglycerine caused a significant reduction of mean blood flow velocity in the left MCA. In parallel a significant increase of absolute power density < 4 Hz was noted. The latter effect was dose dependent. Cognitive functions, such as attention and memory, were not altered. CONCLUSIONS: The decrease in cerebral blood flow velocity in the left MCA may be due to vasodilatation and/or reduction in perfusion. The concomitant increase of slow wave power in the qEEG may indicate an impairment of brain function.

[Pruritus during treatment with an estrogen-gestagen combination]. / Pruritus unter einer Estrogen-Gestagen-Kombination.

HISTORY AND CLINICAL FINDINGS: A 51 year old female patient complained about marked pruritus of the whole integument. Since seven years she had been taking a two phase combination of estrogens and gestagen because of climacteric symptoms. 24 years ago severe pruritus occurred especially at the hands during the last trimenon of her first pregnancy whereas 7 years later during the subsequent pregnancy pruritus was absent. Physical examination revealed multiple excoriations over the whole body. No other relevant pathological findings were noted. INVESTIGATIONS: Laboratory findings, chest X-ray and abdominal sonography were normal. TREATMENT AND COURSE: Neither oral administration of an antihistaminic drug nor topical application of betamethasone improved the situation to a relevant extent. For 12 months the occurrence of pruritus had not been referred to hormonal treatment by the physicians in charge. Complete cessation of pruritus was seen within a few days after the patient had stopped hormonal medication on her own. CONCLUSION: Patients should be asked for pregnancy associated pruritus or jaundice before receiving drug combinations with estrogens and gestagens. In case of a positive history, the physician should inform them about possible side effects such as pruritus and icterus.

Regional drug information service.

BACKGROUND: Drug information centers (DICs) were established in Europe more than two decades ago. The majority of German DICs were created in the 90s. The regional University hospital-based DIC, which offers services to physicans, is now in operation for three and a half years . OBJECTIVE: To evaluate the types of enquiries received and the profile of the users of a drug information service. METHODS: The working procedure at a regional center in Dresden, Germany, is described. The topics for consultation (adverse reactions, pharmacokinetics, etc.) are presented, and the types of drugs involved are classified according to the Anatomical Therapeutic Chemical (ATC) classification. Users are grouped by medical specialty. Future plans for the DIC are discussed. RESULTS: A total of 516 enquiries were received. Questions concerning therapeutic use (34%), adverse drug reactions (28%), pregnancy/lactation (16%), and pharmacokinetics/dosage (15%) were asked most frequently. Cardiovascular drugs (20%), systemic antiinfectives (19%) as well as drugs targeting the central nervous system (15%) and alimentation/metabolism (9%) were the predominant foci of enquiries. The major users of the DIC were internists (19%), general practitioners (19%), pediatricians (18%), and gynecologists (11%). CONCLUSIONS: The types of questions and users of this service were generally similar to those recorded at many other European DICs. The service has begun producing educational bulletins on drug-related topics of clinical relevance.

Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration.

The effects of subcutaneously administered scopolamine on quantitative electroencephalogram (qEEG) and cognitive performance were evaluated and correlated with pharmacokinetic parameters in a randomized, double-blind placebo-controlled crossover study of 10 healthy male volunteers. Changes in qEEG and cognition were determined for 8 hours after drug administration. Scopolamine produced dose- and time-dependent impairments of attention and memory and a time-dependent increase in delta power (1.25-4.50 Hz) and a decrease in fast alpha power (9.75-12.50 Hz) on qEEG compared with placebo. Maximum serum concentrations of scopolamine occurred 10 to 30 minutes after drug administration. Mean peak serum concentrations (free base) were 3.27, 8.99, and 18.81 ng/mL after administration of 0.4, 0.6 mg, and 0.8 mg scopolamine, respectively. Elimination half-life was approximately 220 minutes. The findings indicate temporary changes in qEEG and psychometric tests, and support the possible use of such a testing model for impaired cognitive functions such as age-related memory disturbances.

Pharmacokinetics and safety of propiverine in patients with fatty liver disease.

OBJECTIVE: The present study was designed to assess the pharmacokinetics of propiverine after single and multiple dosing in patients with and without fatty liver disease. METHODS: The serum concentration-time curves of propiverine and its main metabolite propiverine-N-oxide were investigated in 12 patients with mild to moderate impairment of liver function (mean antipyrine clearance 26.0 ml x min(-1)) and in 12 controls (antipyrine clearance 42.8 ml x min(-1)). Subjects were treated orally with propiverine hydrochloride (Mictonorm) for 5 days (15 mg t. i. d.) to reach steady state. RESULTS: No significant differences were observed for propiverine and its main metabolite with regard to peak serum concentration (Cmax), area under the serum concentration-time curve (AUC) and elimination half-life (t1/2). Adverse events were reported by 12 patients. Five patients with fatty liver disease and seven patients with normal liver function complained of dry mouth and/or blurred vision. All adverse events reported were transient and mild. CONCLUSION: No pharmacokinetic differences relevant for safety were observed, comparing patients with and without fatty liver disease following repeated oral administration of propiverine. Thus there seems to be no need to adjust the dose in patients with mild to moderate impairment of liver function.