[Rasagiline in daily clinical use. Results of a treatment study of Parkinson patients with a combination treatment]. / Rasagilin im klinischen Alltag. Ergebnisse einer Anwendungsbeobachtung bei Parkinson-Patienten mit einer Kombinationstherapie.

Rasagiline (Azilect) is a potent, highly selective and irreversible inhibitor of monoamine oxidase type B of the second generation. Rasagiline is indicated for the treatment of Parkinson's disease (PD) as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations. The efficacy and tolerability of rasagiline has been demonstrated in large-scale, controlled clinical studies in patients with early PD as well as with more advanced PD. This multicentred post-marketing observational study included an investigation of the efficacy and tolerability of rasagiline in a large patient population under conditions of the daily routine in neurologic practice with a special attention on the collection of data regarding a patients' subjective evaluation of quality of life. A total of 754 patients with Parkinson's disease were enrolled, 545 of the patients (63% male patients, mean age 68 years, mean duration of PD 6 years, Hoehn & Yahr stage II to III in 69% of the patients) started rasagiline 1 mg/day as adjunct therapy for up to 4 months. The PD symptoms were rated by the physicians using the Columbia University Rating Scale (CURS) and the clinical fluctuations subscale of the Unified Parkinson's Disease Rating Scale (UPDRS, part IV B). Different aspects of quality of life were rated by the patients using the self-rating Parkinson's Disease Questionaire (PDQ-39). In addition, patients documented the number of hours spend in the OFF-state in "24-hour" home diaries prior to each of the assessment visits. During the treatment period rasagiline was most frequently co-administered with levodopa/DCI (81.7%) and/or dopamine agonists (65.8%). The mean treatment duration was 117.4 (+/-36.4) days, during which PD medication remained unchanged in 86.6% of the cases. The improvement rates in each of the CURS items ranged between 31.1% to 48.4% and the total score was reduced by 22% under the therapy of rasagiline. In the motor part (tremor, rigidity, bradykinesia) the total score was reduced from 6.2 to 4.8, within the other items from 14.7 to 11.5. The proportion of patients without OFF-periods increased from 33.3% to 49.5%. Determined from "24-hours" home diaries, time spend in the OFF-state during wake time decreased from 120 minutes to 45 minutes. In all 8 aspects of quality of life rated by the patients an reduction of the disability could be documented. The PDQ-39 total score was reduced from 36.4 by 7.3 points (20.1%). In total, 29 of the 545 patients who received rasagiline as combination therapy had switched directly from previous combination therapy with selegiline. In this subgroup CURS total score improved from 17.0 to 12.9 points during treatment. The proportion of patients without OFF-periods increased from 36% to 48% and the daily time spent in the OFF-state was reduced from 45 minutes to 30 minutes. The PDQ-39 total score improved by 6.5 points (22.2%). All in all, adverse events were reported by 8.4% of the patients. In conclusion this post-marketing observational study has shown that in patients with pre-existing combination therapy the add-on medication of rasagiline resulted in improvements of motor and non-motor functions. Furthermore, motor complications were significantly reduced and led to an improved quality of life in the self-estimation of the patients. This also applies to those patients with selegiline pre-treatment.

Fluoride uptake and remineralisation of enamel lesions after weekly application of differently concentrated fluoride gels.

There is only little information on the remineralising capability of regularly applied highly concentrated fluoride gels. The aim of this in situ study was to test the hypothesis that weekly application of a 1.25% fluoride gel results in a significantly higher fluoride uptake and a significantly higher mineral gain compared to a 0.5% fluoride or a placebo gel, respectively. Thirty-six subjects were included in this double-blind, three-way, crossover, placebo-controlled study and randomly assigned to a treatment scheme. Two weeks before the study, between treatment periods as well as during the study periods, subjects were instructed to abstain from any fluoride source other than the study medication. At the beginning of each of three 4-week periods specimen holders, each containing 10 bovine enamel slabs, were placed in the subjects' mouths. During the experimental periods the volunteers brushed the specimens with placebo gel, 0.5% fluoride gel or 1.25% fluoride gel once a week. Fluoride uptake was significantly higher after treatment with the 1.25% fluoride gel than after treatment with the 0.5% fluoride gel (p = 0.007) or the placebo gel (p < 0.001). Treatment with 0.5% fluoride gel led to a significantly higher fluoride uptake compared to placebo treatment (p < 0.001). Changes in mineral gain and lesion depth were not statistically significantly different between the three groups. Under the present experimental conditions repeated application of highly concentrated fluoride gels did not promote remineralisation significantly.

Oxaceprol--a randomised, placebo-controlled clinical study in osteoarthritis with a non-conventional non-steroidal anti-inflammatory drug.

OBJECTIVE: To evaluate efficacy of therapy with oxaceprol in the treatment of symptomatic osteoarthritis of knee or hip. METHODS: A 3-week prospective, multicentric, randomised, double-blind, placebo-controlled study with 167 patients aged between 40 and 75 years with painful and radiologically confirmed knee or hip osteoarthritis. Patients were randomly assigned to receive oxaceprol 1200 mg/day or placebo for 3 weeks. At inclusion, osteoarthritis symptoms were minimum pain following exercise (standardised as pain after climbing 12-15 stairs) of 40 to 90 mm on a 100 mm pain scale and difficulties in climbing stairs. Efficacy criteria were changes in pain shown in a visual analogue scale (VAS), in the Lequesne index, and in assessments of joint limitation, joint complaint and therapeutic success. The primary end point was the pain following exercise. The confirmatory analysis was based on the Full Analysis data set using the t-test for independent samples. RESULTS: Baseline characteristics of both groups were comparable. In the primary endpoint a clinically relevant and statistically significant superiority of oxaceprol as compared to placebo could be demonstrated (mean improvement in pain following exercise was 16.6 mm in the oxaceprol and 4.5 mm in the placebo group, p = 0.002). The safety and tolerability was good, showing no statistically significant difference between oxaceprol and placebo. CONCLUSION: A statistically significant and clinically relevant efficacy of oxaceprol was shown. The good safety and tolerability of oxaceprol was confirmed.

Safety monitoring of a polyvalent immunoglobulin preparation: documentation of 15,548 administrations.

UNLABELLED: Between 1997 and 2002, a post-marketing surveillance study was conducted throughout Germany to evaluate Intraglobin F in a replacement therapy for primary and secondary immunodeficiency diseases. A total of 15,548 individual administrations in 1,705 patients were documented. METHODS: The study was conducted as a multicenter project involving 72 outpatient and inpatient treatment centers in Germany. The study variables were recorded during the routine treatment of patients with congenital or acquired immunodeficiencies. No additional variables outside the normal routine were recorded as is mandatory in post-marketing surveillance studies. RESULTS: The rate of adverse drug reactions (ADR) was 0.064% in 15,548 administrations or 0.59% with reference to 1,705 treated patients; eight non-serious adverse events (AE) were considered to have a "probable" and one further AE a "possible" causal association with the use of Intraglobin F. Only one AE assessed as "serious" was classified as "probably" treatment-related. The efficacy of Intraglobin F was rated by the treating physicians as "very good" or "good" in 91.8% of the evaluated patients. CONCLUSIONS: This post-marketing surveillance study has demonstrated the safety of Intraglobin F. The statistical results obtained with the data are supported by the overall assessment of the treating physicians who rated the tolerability of Intraglobin F as "very good" or "good" in 98.5% of the patients. No new or unexpected risks were observed.

Alfacalcidol in the therapy of renal bone disease.

Parathyroid hormone increases due to hypocalcemia even in the early phases of renal insufficiency. At the same time, hyperphosphatemia develops due to decreasing renal excretion which, in turn, intensifies secondary hyperparathyroidism. The cornerstones for prevention and therapy of renal osteopathy are, therefore, efficient lowering of phosphate levels and the early substitution of vitamin-D3 metabolites. In a post marketing surveillance (PMS) of almost 2,000 dialysis patients with renal osteopathy, the course of therapy with Alfacalcidol (Bondiol) was observed over a 6-month period. In 55.9% of cases, Alfacalcidol was administered at a daily dose of 0.25 microg. In 26.6% of patients, Alfacalcidol was administered every second day at a dose of 0.25-1 microg/d. In 16.1% of patients, Alfacalcidol was administered as pulse-therapy, mostly at a dose of 1-2 microg once or twice per week. To lower phosphate levels, 54.8% of patients received calcium compounds, 9.2% aluminium compounds, and 21.7% aluminium compounds in combination with calcium compounds. 14.3% of patients did not receive phosphate binding agents. Two thirds of patients had received active vitamin-D3-metabolites prior to commencing therapy with alfacalcidol, most frequently calcitrol. In 58.1%, the dialysis solution used had a calcium concentration of 1.5 mmol/l (44.8%) or lower; whereas in 41.9%, a higher calcium concentration was used--mostly 1.75 mmol/l (3 8%). During the observation period, serum concentrations of calcium and phosphate remained constant, suggesting that the risk of hypercalcemia due to therapy with Alfacalcidol was not increased. It was found that elevated alkaline phosphatase and parathyroid hormone levels could be significantly lowered (statistically). These effects could be observed both in patients who had been previously treated with vitamin-D3-metabolites and in patients without prior therapy. Efficacy and tolerability of therapy with Alfacalcidol was assessed to be very high by the attending nephrologists.

Oxaceprol is a well-tolerated therapy for osteoarthritis with efficacy equivalent to diclofenac.

The therapeutic equivalence and safety of treatment for 21 days with 400 mg t.i.d. oxaceprol (n = 132) and 50 mg t.i.d. diclofenac (n = 131) were assessed in a multicentre, randomised, double-blind study of a mixed population of patients with osteoarthritis of the knee and/or hip. In a per-protocol analysis of efficacy, the mean Lequesne index decreased by 2.5 points in the oxaceprol group (n = 109) and by 2.8 points in the diclofenac group (n = 109). The 95% confidence interval for the end-point difference revealed therapeutic equivalence. This was confirmed by assessments (visual analogue scale) of pain at rest, weight-bearing pain, pain on standing and pain on movement, all of which decreased to a similar extent under both treatments. The pain-free walking time increased in both groups from 10 min to 25 min by the end of the treatment period. Mobility was also increased to a similar extent by both drugs. The physicians assessed treatment as good or very good in 45-46% of patients in both groups. In all patients who received treatment, 28 and 37 adverse events were reported by 25 out of 132 (18.9%) and 33 out of 131 (25.2%) patients treated with oxaceprol and diclofenac, respectively. In 15 patients (11.4%) with 15 adverse events in the oxaceprol group and 25 patients (19.1%) with 27 adverse events in the diclofenac group, a relation to the medication was considered probable. The difference between the groups was statistically significant (p = 0.04106) for the number of these adverse events. Oxaceprol is therapeutically equivalent to diclofenac, but better tolerated than diclofenac in the treatment of osteoarthritis.

Oxaceprol is as effective as diclofenac in the therapy of osteoarthritis of the knee and hip.

In this multicentre (five centres in Germany), randomised, double-blind, comparative study, 150 patients with painful degenerative joint disease according to EULAR criteria received either oxaceprol (200 mg three times daily) or diclofenac (25 mg three times daily) for 20 days. Joint function, the primary variable, assessed according to Lequesne's indices, improved equally in both treatment groups to a clinically relevant degree. Joint mobility improved by approximately 60% in both groups. By the end of therapy in both groups, the period of pain-free walking time had more than doubled and subjectively evaluated pain perception (VAS) was reduced by almost 50% without any significant differences between the treatments. The incidence of adverse drug reactions was similar in both groups but oxaceprol induced milder symptoms. Oxaceprol is as effective and better tolerated than diclofenac in the treatment of osteoarthritis.

Study of the long-term action of a Ginkgo biloba extract on vigilance and mental performance as determined by means of quantitative pharmaco-EEG and psychometric measurements.

The action of a Ginkgo biloba extract (rökan, Tanakan, G.B.E.) in promoting blood flow has been demonstrated in several animal and human pharmacological studies. The aim of this present study was to estimate the action of the substance on the central nervous system in order to be able to assess its potential use as a therapeutic agent in geriatric patients with cerebral insufficiency. Quantitative pharmaco-EEG is the method of choice for studying the vigilance-promoting effects of a drug. It is incomparable for confirming the findings of behavioural and psychometric studies. 60 volunteers of either sex participated in the double-blind trial. They were aged 57-77 years and showed mental deterioration corresponding to their age. They were randomly divided into three experimental groups: 20 subjects received 3 X 40 mg/day G.B.E., 20 received 5 mg nicergoline and 20 received a placebo of similar appearance. The subjects underwent an extensive series of examinations before and 4, 8 and 12 weeks after the start of medication. Analysis of the EEG results for the whole group revealed no significant advantage of G.B.E. over the two reference substances with regard to vigilance. However, a subclassification of the subjects showed that the vigilance of those persons with a more unfavourable initial situation measured in the resting EEG could be clearly improved by chronic G.B.E. medication. This increase in vigilance was reflected at the behavioural level by an improvement of reaction times in the G.B.E. group by comparison with the reference substances.(ABSTRACT TRUNCATED AT 250 WORDS)

[Studies on the effect of Harmonicum Much on sleep using polygraphic EEG recordings]. / Untersuchung der Wirkung von Harmonicum Much auf den Schlaf mit Hilfe polygraphischer EEG-Aufzeichnungen.

The effects of 60 and 120 mg valerian (1 resp. 2 capsules Harmonicum Much) have been investigated by computer analysis of sleep stages (sleep profiles) and psychometric methods ( questionnaires ). EOG, EMG of cervical muscles, ECG and EEG (two-sided: centro-occipital and fronto-central - have been recorded from 6 male and 5 (3) female healthy volunteers. Amplified signals have been analysed on-line (power spectral analysis) and the sleep profiles have been calculated accordingly. After one night for adaptation, each subject took orally placebo, 60 and 120 mg valerian (1 resp. 2 capsules Harmonicum Much) according to a randomized double-blind repeated measures-design. The sleep investigations have been carried out by distance of a week for each condition (dosage per subject). In the morning following this night, the subjects completed a mood scale. Both dosages showed a decrease of sleep stage 4 and a slight reduction of REM-sleep. Contrary, a slight increase of sleep stage awake, 1 and 2 could be observed. A further increase of sleep stage 3 could be identified. After application of 120 mg valerian , the frequency of REM-phases (in %) declined during the first half of the night, whereas during the second part of the night, a surplus appeared. Changes or the Beta-intensity of the EEG during REM-sleep show a stronger hypnotic effect for the 120 mg dosage than for 60 mg. Maximum effect was observed between 2 and 3 hours post medicationem . Results of the mood scale are indifferent between the experimental conditions, which indicate no negative (side-) effects neither by drug nor by testing methods.

[Influence of a Pentifylline-Nicotinic Acid Combination on Vigilance and Mental Performance (author's transl)]. / Beeinflussung von Vigilanz und mentaler Leistungsfähigkeit durch eine Pentifyllin-Nicotinsäure-Kombination.

The effect of a single dose of 4 sugar-coated tablets of Cosaldon (1-hexyl-3,7-dimethylxanthine (pentifylline) + nicotinic acid) was shown by quantitative pharmaco-EEG investigations and psychometric tests in 12 volunteers aged 58 to 75 years, who were in a good physical condition. The design was randomized, double-blind and cross-over designed against placebo. EEG and psychometric tests were made before medication and repeated each hour up to 6 h after medication. Each turn was split up into a resting-EEG (R-EEG) and a vigilance-EEG (V-EEG) lasting 3 min each; the psychometric tests were made immediately afterwards. An increase of the vigilance, shown by an increased EEG-power, was found after Cosaldon administration as compared to placebo. Furthermore, the delta and theta intensity decreased to a statistically significant degree, while the intensity within the alpha-1-scope increased. The strongest effect as compared to placebo could be observed 4 h after medication. The statistical significance was shown for the V-EEG-condition, the R-EEG showed only minor changes. The effects in the occipital region were stronger than in the more frontal parts. In accordance with the results of the EEG, the psychological tests showed remarkable improvements in performance which reached their maximum between 2 and 4 h after medication.