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Biomedical subjects

R Kohnen

Publications and source records attributed to R Kohnen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Substitution of conventional cyclosporin with a new microemulsion formulation in renal transplant patients: results after 1 year.

BACKGROUND: A new galenic form of cyclosporin A has been developed, based on microemulsion technology. The bioavailability of the compound is relatively independent of food intake and bile flow. It was the purpose of this prospective clinical trial to study the safety of the microemulsion form of cyclosporin A. METHODS: Three hundred and two renal transplant patients, stratified according to transplant age, were switched from the conventional to the new microemulsion formulation of cyclosporin A. A 1:1 conversion ration was used. Measurements included CsA levels, S-creatinine, liver enzymes, uric acid, and blood pressure. Measurements were performed at baseline and on days 4, 8, 15, 29 and months 3, 6 and 12 after conversion. Dose adjustments were performed to achieve through levels of 80-120 ng/ml. RESULTS: Within the 12-month observation period the cyclosporin dose was reduced by 14.7% (from 204 +/- 60 mg/day at baseline to 174 +/- 51 mg/day after conversion, P < 0.001). Acutely, i.e. by day 8, 1:1 dose conversion resulted in a modest increase of mean drug through levels (from 114 ng/ml at baseline to 120 ng/ml, P < 0.01). This increase was accompanied by an increase in serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in uric acid values (P < or = 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decrease (P < 0.05). After 1 month, drug through levels had decreased to baseline (112 ng/ml) and remained there until month 6. They were significantly lower after 12 months (102 +/- 33 ng/ml), P <0.001). Creatinine clearance values increased to above baseline at 6 and 12 months. Within the 1-year period there occurred 24 (= 8%) episodes of biopsy proven rejection and seven episodes of cyclosporin-attributed nephrotoxicity. CONCLUSIONS: The 1:1 conversion from conventional cyclosporin A to the microemulsion formulation s efficacious and safe, but an initial dose reduction of 10% is advised in patients with through levels in the high-normal range.

Administration, Oral↗
PubMed1996

Conversion to microemulsion cyclosporine in stable renal transplant patients: results after one year.

We switched 302 renal transplant patients from the conventional to a new microemulsion formulation of cyclosporine, to study the latter's safety and efficacy. We used a simple 1:1 conversion of the patient's total daily dose. We measured trough drug levels as well as serum creatinine, liver enzymes, uric acid, and blood pressure values at baseline and at days 4, 8, 15, 29, and months 3, 6 and 12 after drug substitution. Dose adjustments directed at trough levels 80-120 ng/ml were performed, starting at day 8. Within the 12-month observation period, the cyclosporine dose was reduced by 14.7% (204 +/- 60 mg/day baseline vs 174 +/- 51 mg/day after conversion, p < or = 0.001). By day 8, the 1:1 dosage conversion resulted in a modest mean increase in drug trough levels (114 ng/ml baseline vs 120 ng/ml, p < or = 0.01). This increase was accompanied by an increase in serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in uric acid values (p < or = 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decreased (p < or = 0.05). After one month, drug trough levels had decreased to baseline (112 ng/ml) and remained there until month 6. They were significantly lower after 12 months (102 +/- 33 ng/ml, p < or = 0.001). Plasma creatinine values decreased to below baseline by month 6 (p < or = 0.001) and month 12 (p < or = 0.001). Twenty-four (8%) biopsy proven rejection episodes and 7 cases of cyclosporine attributed nephrotoxicity occurred in these 302 patients within these 12 months. We conclude, that a 1:1 conversion from conventional to the microemulsion form of cyclosporine is efficacious and safe. However, we advise an initial 10% decrease in dose reduction in those patients whose trough levels are in the high-normal range.

Adult↗
PubMed1995

L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial.

We report the effects of a single bedtime dose of L-dopa 100-200 mg on sleep quality, frequency of periodic leg movements (PLM) and daily living in patients with idiopathic and uremic restless legs syndrome (RLS). Seventeen patients with idiopathic and 11 with uremic (on continuous hemodialysis) RLS were evaluated comparatively by polysomnography, actigraphy and subjective ratings in a randomized, controlled and double-blind crossover trial with L-dopa and placebo for 4 weeks each. Neurophysiologic assessments showed significant reduction of the number of periodic leg movements (p = 0.003) and the PLM-index (p = 0.005) most pronounced during the first 4 hours of bedtime after L-dopa (p = 0.001). Subjective evaluation confirmed improvement of sleep quality (p = 0.002) and showed significantly higher quality of life during daytime (p = 0.030) while the patients received L-dopa therapy. We conclude that L-dopa 100-200 mg proved to be effective in idiopathic RLS and for the first time under controlled conditions in uremic RLS without any severe side effects.

Adult↗
PubMed1995

New actigraphic assessment method for periodic leg movements (PLM).

A new actigraphic method by which periodic leg movements (PLM) can be measured is presented. Data acquistion and analysis were brought into line to distinguish short-lasting repetive leg movements from random motor restlessness. The definition of PLM follows the generally accepted criteria for PLM scoring. Thirty restless legs patients, all also suffering from PLM, were investigated three times by polysomnography, including tibialis anterior surface electromyography and actigraphy. A high correlation (reliability) was found for the number of PLM per hour spent in bed between the two methods. Furthermore, the actigraph records PLM specifically. An index of random motor restlessness is not sufficient for a reliable PLM according. In addition, periodic movements in sleep (PMS) and PLM show comparable variability in general. The actigraphic assessment of PLM, however, gives a better measure because PMS recordings may result in a substantial underestimation of PLM when sleep efficiency is reduced. This method is an ambulatory assessment tool that can also be used for screening purposes.

Adult↗
PubMed1995

Moclobemide versus fluoxetine in the treatment of inpatients with major depression.

Seventy inpatients with a DSM-III-R major depression were included in a double-blind, randomized, clinical trial to compare the efficacy and tolerability of moclobemide versus fluoxetine. After a 3-day placebo run-in phase, treatments were administered for 4 weeks in daily doses of between 300 and 600 mg of moclobemide or 20 to 40 mg of fluoxetine. Efficacy was measured by the Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression, and subjective mood ratings (45-item self-rating scale). Fifty-three patients (mean age, 40 years; 22 men, 31 women) completed the 4-week treatment. Changes between end of treatment and baseline did not differ between both study drugs. The HAM-D responder rate (50% improvement from baseline) was 59% in the moclobemide group and 58% in the fluoxetine group after 4 weeks. Moclobemide, however, acted therapeutically faster than fluoxetine. After 1 week of treatment, the HAM-D scores were significantly lower in patients on moclobemide than in those on fluoxetine (p < 0.005). The earlier efficacy of moclobemide after 1 week was also detected by the patients' subjective mood ratings (p < 0.02). There were no differences between moclobemide and fluoxetine regarding tolerability ratings. These data suggest that both agents have a similar efficacy and tolerability but that moclobemide has an earlier onset of antidepressive action.

Adolescent↗
PubMed1995

Clinical experience transferring kidney transplant patients from Sandimmun to Sandimmun Neoral--results after 3 months.

The new galenic formulation of cyclosporine prepared as microemulsion (Sandimmun Neoral, SN) shows a significantly improved correlation between both trough level (Cmin) and dose. Moreover, since the bioavailability is increased by 20 to 30% on average, it may lead to a drug overexposure in so far malabsorbing patients. In order to assess safety and to establish an appropriate procedure to switch patients safely from conventional Sandimmun to SN, we initialized an open, stratified (transplant age) clinical trial enrolling 302 patients of our outpatient clinic. We used a simple 1:1 conversion of the patient's total daily dose. Trough drug levels, as well as serum creatinine, liver enzymes, uric acid, and blood pressure values were measured at baseline, at days 4, 8, 15, 29, and at month 3 after drug substitution. Within the three month observation period, the cyclosporine dose was reduced by 14.2% (204 +/- 60 mg/day baseline vs. 175 +/- 54 mg/day after conversion, p < 0.05). By day 8, the 1:1 dosage conversion resulted in a modest mean increase in drug trough levels (114 ng/ml baseline vs. 120 ng/ml, p < 0.05). This increase was accompanied by a slight increase in mean serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in mean uric acid values (p < 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decreased (p < 0.05). Parallel to dosage reduction, drug trough levels had decreased after 1 month to baseline (112 ng/ml) and remained there for the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Availability↗
PubMed1995

[Effectiveness of slow release L-DOPA/benserazide in treatment of end-of-dose akinesia in Parkinson disease].

In an open label study 63 patients with idiopathic Parkinson's disease suffering from end-of-dose akinesia were switched from a treatment with a L-DOPA standard formulation to a combined therapy of L-DOPA standard in the morning and L-DOPA slow release (levodopa, benserazide, Madopar Depot) at the remaining single doses. Substitution of L-DOPA standard by L-DOPA slow release took on average 2-4 weeks. Patients were subsequently treated for 6 months. Due to a lower bioavailability of the slow release formulation--the latter is based on the "hydrodynamically balanced system" (HBS)--, the patients remained initially on their time schedule of drug intake but received a higher dose of L-DOPA slow release compared to the preceding L-DOPA standard therapy. In 20 centers 37 men and 26 women were included into the study. 27 males and 20 females completed the 6 month treatment period. Before switching, the patients received 438 +/- 213 mg a day L-DOPA standard, after conversion, the average dose was 617 +/- 323 mg L-DOPA slow release and 107 +/- 95 mg L-DOPA standard a day. Fluctuations during the day and at night which were rated according to a newly developed clinical 5-point rating scale were significantly improved by the treatment regimen from 2.8 +/- 0.9 to 1.4 +/- 1.2. Additionally, parkinsonian symptoms were significantly reduced during the ON-phase as there was a significant decrease of the Webster rating score from 12.0 +/- 4.6 to 7.1 +/- 4.0. Quality of life as measured by subjective ratings of the patients improved. The tolerability of the new formulation of L-DOPA was rated to be good in 51.1% and very good in 48.9%. The results of this open label study suggest that the combination of L-DOPA standard in the morning and L-DOPA slow release formulation at the following time points can be an efficient therapy in parkinsonian patients who suffer form L-DOPA related end-of-dose motor akinesia.

Adult↗
PubMed1995

[Treatment of idiopathic and uremic restless legs syndrome with L-dopa--a double-blind cross-over study].

In a randomized, controlled and double-blind cross-over trial with L-Dopa and placebo we evaluated the effects of a single bedtime dose of L-Dopa 100 to 200 mg on sleep quality and frequency of periodic leg movements (PLM) in 17 patients with idiopathic and in 11 patients with uremic restless legs syndrome (RLS) by polysomnography, actigraphy, and subjective ratings. Treatment with L-Dopa showed significant reduction of the number of periodic leg movements and the PLM-index most pronounced during the first 4 hours of bedtime. Subjective evaluation confirmed improvement of sleep quality. L-Dopa proved to be effective in idiopathic and uremic RLS without any severe side effects.

Administration, Oral↗
PubMed1993

A comparison study of moclobemide and doxepin in major depression with special reference to effects on sexual dysfunction.

A double-blind parallel-group comparison study of moclobemide versus doxepin in 237 patients with major depression confirmed that moclobemide was equal in efficacy and better tolerated than doxepin. It was less sedating and caused fewer anticholinergic adverse events as measured by the UKU side-effect rating scale. Unexpectedly, moclobemide therapy more often than doxepin resulted in increased sexual desire. An exploratory analysis of UKU-measured symptoms of impaired sexual function prior to commencement of the study revealed that moclobemide more often than doxepin led to an improvement of reduced libido and impaired erection, ejaculation and orgasm. This finding is compatible with the assumption that there is a greater likelihood that the anticholinergic reuptake inhibitor doxepin has a higher risk of impairing sexual function than the non-anticholinergic RIMA moclobemide. A single case report of moclobemide-induced sexual hyperarousal supports the alternative assumption that moclobemide has a specific sexually stimulative effect in depression.

Adult↗
PubMed1993

Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study.

We report the results of a multicentre, double-blind, placebo-controlled study of topical therapy with omega-3-polyunsaturated fatty acids (omega-3-PUFA) in 52 patients suffering from moderate plaque-type psoriasis. In each patient, two similar stable psoriatic plaques served as indicator lesions for the study. One indicator lesion was randomly assigned to treatment with topical preparations of highly purified omega-3-PUFA in one of two concentrations (1 or 10%), and the other was treated with placebo. Efficacy assessment was based on changes in local psoriasis severity index, area involved, erythema, desquamation, induration and pruritus. After 8 weeks of treatment, all indicator lesions had improved significantly, compared with baseline. However, no statistically or clinically relevant differences between the omega-3-PUFA-treated and the placebo-treated lesions were found. Therapy was well tolerated and, apart from one patient who developed perilesional eczema, no clinically relevant adverse events occurred. In conclusion, topical omega-3-PUFA were not effective in a randomized, placebo-controlled, double-blind setting. Results of non-blind trials should be (re-)considered with caution.

Administration, Topical↗
PubMed1982

Tranquillizer effects in an experimental analog of verbal examinations.

In an experimental analog of verbal examinations, the call-up situation, the effects of two dosages of a tranquillizing agent (lopirazepam) are compared to placebo treatment. 72 male and female, healthy, young volunteers have been randomly assigned to 12 groups of 6 subjects each. Pulse frequency and performance were registered. The results indicated differential drug effects which were interpreted according to the hypotheses of 'differential effects of social stressors'. If a situation was highly challenging for a subject, the application of a tranquillizer in an adequately high dosage enabled him to perform well in spite of or because of strong increases in pulse frequency.

Achievement↗
PubMed1982

Tranquillizer effects in an experimental analog of group psychotherapy.

In an experimental analog of group psychotherapy situations, the effects of two dosages of a tranquillizing agent (prazepam) are compared with those of placebo treatment. Pulse frequency and psychic strain on 24 healthy young volunteers was measured in different social interactions. Variations of social situations induced great changes both in physiological and in psychological measures. The drug acted differentially as to sex and dosage, but showed no situation-specific action. These and further results indicated that group dynamics are an efficient tool in proving drug effects.

Adult↗