[Efficacy and safety of etofibrate in patients with non-proliferative diabetic retinopathy]. / Wirksamkeit und Sicherheit von Etofibrat bei Patienten mit nicht proliferativer diabetischer Retinopathie.

INTRODUCTION: Diabetic retinopathy is the leading cause of vision loss or blindeness in working-age adults in the developed and developing countries. No curative treatments are available for diabetic retinopathy and the most common symptomatic treatment, laser photocoagulation, provides only partial and temporary relief from the progressive vascular damage caused by this disease. Etofibrate (Lipo-Merz) is an orally-administered treatment for lipid disorders that combines fibrate and nicotinic acid in a slow-release formulation. PATIENTS AND METHODS: This report describes the results of a double-blind, randomised, placebo-controlled study, performed to evaluate the efficacy and safety of etofibrat in patients with type 2 diabetes mellitus and concomitant diabetic retinopathy. They received either placebo or 1000 mg/day etofibrate for up to 12 months. Efficacy analyses were based on visual acuity assessment and blinded expert ratings of ocular fundus pathology, as well as laboratory analyses of serum lipid parameters. RESULTS: The evaluable population comprised 296 patients, 148 in each treatment group, of whom 89% completed the study and 73% completed according to protocol. After 12 months of treatment, a significantly larger population of etofibrate-treated patients than placebo-treated patients showed improvements in ocular pathology (46% versus 32%, respectively, p < 0.001); similar findings were already apparent after 6 months of treatment (43% versus 31%, respectively p < 0.001). Etofibrate treatment also produced significant improvements in total cholesterol, LDL-cholesterol and HDL-cholesterol in comparison to the placebo treatment group. Safety evaluations (adverse events, laboratory parameters) did not reveal any clinically significant adverse effects of etofibrate in comparison to placebo. CONCLUSION: Etofibrate provides a safe and effective treatment for ocular pathology resulting from type 2 diabetes mellitus.

Effects of a spleen peptide preparation as supportive therapy in inoperable head and neck cancer patients.

Patients with inoperable head and neck cancer were treated with a spleen peptide preparation (Polyerga) in a phase III randomized, placebo-controlled double-blind study during chemotherapy (cisplatin/carboplatin, 5-fluorouracil) to investigate further the efficacy of this peptide preparation as supportive treatment under chemotherapy. Immunological changes as well as quality of life aspects were examined. Forty patients were included in this study. The peptide preparation had a significant stabilizing effect on the peripheral blood lymphocyte status during chemotherapy cycles (Student t-test, p = 0.05) and tended to stabilize the shift of granulocyte count (Student t-test, p = 0.18). In addition, the group receiving the verum showed a remarkable stabilization of body weight (Mann-Whitney U-test, p = 0.17) during chemotherapy treatment and the generally observed increase of fatigue-inertia during the chemotherapy cycles was significantly reduced (Student t-test, p = 0.01).

Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study.

BACKGROUND/AIMS: In the current state of knowledge of the pathophysiology of hepatic encephalopathy, a reduction in hyperammonemia is the most important evidence of effective treatment. Therefore, the therapeutic efficacy of oral L-ornithine-L-aspartate, which improves impaired ammonia detoxification, was investigated in patients with cirrhosis, hyperammonemia and stable, overt, chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a randomized, double-blind, placebo-controlled clinical trial. METHODS: Oral L-ornithine-L-aspartate was administered three times daily at fixed times for 14 consecutive days in a total dose of 18 g per day. The design was chosen to prevent an increase in ammonia induced by a protein meal of 0.25 g/kg body weight, given at the start of the daily treatment period. Efficacy variables were: fasting and postprandial ammonia concentration, Number-Connection-Test time, mental state grades, and a Portosystemic Encephalopathy Index. Analyses were based on the total study sample of 32 placebo- and 34 L-ornithine-L-aspartate-treated patients as well as on the subgroup samples in the overt (20 placebo- and 23 L-ornithine-L-aspartate-treated) and subclinical hepatic encephalopathy (12 placebo- and 11 L-ornithine-L-aspartate-treated) patients. RESULTS: Number Connection Test performance times (p<0.01) as well as fasting (p<0.01) and postprandial (p<0.05) venous blood ammonia concentrations in the L-ornithine-L-aspartate-treated group showed improvement in comparison to placebo. Also, the mental state grade (p<0.05) and the Portosystemic Encephalopathy Index (p<0.01), improved to a much greater degree in the L-ornithine-L-aspartate group than in the placebo group. Adverse events were observed in neither the placebo nor the L-ornithine-L-aspartate-treated patients. CONCLUSION: Oral L-ornithine-L-aspartate is a safe, well-tolerated treatment with a good compliance rate and a beneficial therapeutic effect in patients with cirrhosis and stable, overt, chronic hepatic encephalopathy.

Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study.

One hundred twenty-six patients with cirrhosis, hyperammonemia (>50 micromol/L), and chronic (persistent) hepatic encephalopathy (HE), which developed spontaneously without the existence of known precipitating factors, were enrolled in a randomized, double-blind, placebo-controlled clinical trial of intravenously administered L-ornithine-L-aspartate (OA). Patients with subclinical (grade 0, West-Haven criteria) hepatic encephalopathy (SHE), characterized by a prolonged number connection test A (NCT-A) time, and manifest HE (grades I and II, West-Haven criteria) were included in the investigation. The trial was planned as a confirmatory clinical trial OA administered in a dose of 20 g/d, as well as placebo, were dissolved in 250 mL of 5% fructose and infused intravenously for a period of 4 hours during 7 consecutive days with a superimposed protein load at the end of the daily treatment period. Primary variables were postprandial venous ammonia and NCT-A performance time measured following OA or placebo infusions to evaluate the net effect of the treatment on the prevention of the protein-induced hyperammonemia, and on parameters such as NCT-A influenced by hyperammonemia. Mental state gradation, portal systemic encephalopathy index (PSEI), and fasting ammonia levels were estimated as additional efficacy parameters. The data presented are based on the total study sample (intent-to-treat analysis), which included 63 patients in the placebo group and 63 patients in the OA group. Of the 126 patients, 114 met all the criteria for inclusion and completed the trial and treatment as outlined in the protocol (treated-per-protocol analysis). During baseline, the placebo and treatment groups were homogeneous with regard to mental states, NCT-A performance time, fasting venous blood ammonia levels, and Child-Pugh criteria. Although a slight improvement occurred in the placebo group, NCT-A performance times (P < .001) and postprandial venous ammonia concentrations in the OA-treated group showed improvements in comparison with placebo. In addition, venous fasting blood ammonia concentration (P < .01), mental state gradation (P < .001), and PSEI (P < .01), which includes the mental state gradation, NCT-A time, and postprandial venous ammonia in this trial, improved to a much higher degree in the OA group than in the placebo group. In subgroups retrospectively classified according to their initial mental state gradation, OA showed differential but uniformly significant efficacies in patients with manifest HE with respect to ammonia-lowering, improvement in NCT times, and mental state gradation. In patients with initial SHE, OA revealed differences between the medications in the psychometric test used. Adverse events consisting of mild gastrointestinal disturbances were observed in 3 of the OA-treated patients (5%). OA infusion appears to be a safe, effective treatment of chronic (persistent) manifest HE in cirrhotic patients. Additional investigations are required to assess the efficacy of OA in patients with SHE, as well as in patients with more severe grades of HE.

Possibilities of scar treatment after thoracic surgery.

During a ten year observation period it was found that scar formation after thoracic surgery is influenced by various factors: metabolism, operative technique and factors of a general nature. On the basis of these findings, a study was carried out to investigate the effect of the scar-specific Contractubex gel (Merz+Co., D-Frankfurt/Main), containing 10% onion extract, 50 U sodium heparin per g of gel and 1% allantoin, in the treatment of children who underwent thoracic surgery and to evaluate its effect on scar development. Before and during the six-month treatment period, both macromorphology and scar colour were assessed; furthermore, a global evaluation of the therapeutic result was made. Additionally, the scars were characterized after a six-month treatment-free follow-up period. The results of 38 Contractubex-treated and 27 untreated patients were compared. In the treated scars, the global evaluation of the therapeutic result was better than in the untreated scars. In the Contractubex group, the rating was "good" and "very good" in 84% of cases, as compared to 59% of the untreated cases. In the treated group, the increase in scar size was markedly lower than in the untreated patients. The treated scars showed a tendency towards quicker paling than the untreated scars. In the treated group, the conversion of primary physiological scars to unphysiological scars (hypertrophic or keloidal scars) was less frequent than in the untreated group. The tolerability of the product was very good in 37 of the 38 treated patients, and good in one patient. All scar-specific effects of Contractubex continued to persist after the end of treatment.

Efficacy of tromantadine and aciclovir in the topical treatment of recurrent herpes orofacialis. Comparison in a clinical trial.

In a double-blind study, 198 patients experiencing recurrent herpes orofacialis were randomly assigned to treatment with either tromantadine hydrochloride (ViruMerz Serol, CAS 53783-83-8) or aciclovir. All patients performed an up to 5-day course of topical treatment beginning on average within 2 h after the first signs of recurrence. The herpes efflorescences and symptoms were assessed daily by the same physician for 14 days, except on weekends, and by the patients each day during the whole observation time. Rapid healing was achieved with both medications. Efficacy was assessed by rating the course of vesicle eruptions, duration until beginning of incrustation and the clinical course of the symptoms (burning, tension, pain). Equivalence between the medication groups was shown by comparative analysis of all evaluation criteria. The global efficacy and tolerability of both medications was rated by the physician as well as by the patients as "good" or "very good" in more than 80% of the cases. The results of this trial show equivalence of both medications in the treatment of recurrent herpes orofacialis, and confirm the good dermal tolerability of the drugs.

Memantine in the treatment of mild to moderate dementia syndrome. A double-blind placebo-controlled study.

The efficacy and the tolerability of memantine (1-amino-3,5-dimethyladamantane hydrochloride, Akatinol Memantine, CAS 41100-52-1) were investigated in patients with mild to moderate dementia syndrome in a randomized two-centre placebo-controlled clinical study. The test substance was administered at a dose of 10 mg/d from day 1 to day 3 and then at a dose of 2 x 10 mg/d from day 4 to the end of treatment after 42 days. Altogether, 88 patients were recruited to the study; their average age was 71.5 years. The efficacy of memantine was judged on the basis of the baseline/6 week differences in the total sum scores of the Clinical Assessment Geriatric Scale (SCAG), the Gottfries-Bräne-Steen Scale (GBS), the SCAG and GBS subscales and the global assessment of the change in the patient's condition. The effects of memantine on performance were studied with the aid of psychomotor tests and a behaviour investigation relating to activities of daily living (ADL). The tolerability of memantine was assessed on the basis of the doctor's global assessment and of entries on structured documentation forms (DOTES/TWIS). Further safety parameters--in the form of clinicochemical tests and measurements of blood pressure and heart rate--were also monitored during the study. On both the psychopathological measurement level (SCAG, global assessment of the change in the patient's condition) and the behavioural level (GBS), confirmatory statistical analysis brought to light significant differences between memantine and placebo (p less than or equal to 0.05), these differences showing a superiority of memantine. The tolerability of memantine was good in the main. The observed adverse reactions were not serious and, except in 3 patients, were rated as causing little or no impairment. The present clinical study demonstrates the efficacy of memantine in patients suffering from mostly moderate dementia syndrome. Clinical and statistically relevant improvements in the dementia-induced disturbances were found on the both the psychopathological level (SCAG, CGI) and the behavioural level (GBS). On the performance level also, the ADL behaviour investigation detected a highly significant improvement in the quality of performance of instrumented activities of daily living under memantine. Also the time taken to carry out these tasks was significantly reduced in comparison with placebo.

Randomized double-blind trial of tromantadine versus aciclovir in recurrent herpes orofacialis.

The present study represents the first randomized, double-blind trial comparing the clinical efficacy of tromantadine (Viru-Merz) vs aciclovir. Both medication groups contained 60 patients. The inclusion criteria required that patients show a history of recurrent manifestations of herpes orofacialis and that they not be recruited later than 24 h following the initial prodromal symptoms. Medication was dispensed randomly in identical tubes to cover a treatment period of up to 5 days. The patients were instructed to keep the tubes close at hand, to initiate therapy as soon as possible after experiencing the first symptoms of the recurrence and to visit the company physician within 24 h after the onset of symptoms. The herpes lesions were assessed daily by the same doctor for 14 days, except on weekends. The data of 119 patients (59 treated with tromantadine, 60 treated with aciclovir) were evaluated. The average time between the first signs of a new recurrence and the beginning of treatment was 7 hours in both treatment groups. The course of the healing process was rated by 4 subjective symptoms (itching, burning, skin tautness and pain) and by the following objective criteria: number of days in the vesicular stage and duration of complete healing, abortive lesions and new lesions. The results of these assessments showed no differences between the medication groups. Global clinical efficacy and tolerance were rated as being "very good" and "good" in more than 83% by patients and doctor in both groups. The results show that it is the early application of the virustatic that is important for successful treatment--regardless of the choice of agent tested.

[Comparative study of the central nervous system effect of the beta receptor blockaders pindolol and bisoprolol]. / Vergleichende Untersuchung zur zentralnervösen Wirkung der beta-Rezeptorenblocker Pindolol und Bisoprolol.

In a total of 36 volunteers with cardiac hyperreaction, investigations were carried out on the effect of bisoprolol (designated tradename: Concor), pindolol and placebo on central nervous functions with the aid of a reaction test, spiral aftereffect, tremor test and mood and sleep questionnaires. In the randomized double-blind study performed with 3 independent groups the volunteers received placebo, 2 X daily 10 mg of pindolol or 1 X daily 10 mg of bisoprolol for a period of 14 days. Bisoprolol is a new highly beta 1-selective adrenoceptor blocker with moderate lipophilia and without intrinsic sympathomimetic activity (ISA). When compared to placebo neither of the beta-adrenoceptor blockers induced any significant changes in mood, vigilance, tremor and reaction times. Moreover, under bisoprolol no negative effect on sleep quality or feeling refreshed after sleep was determined. Under pindolol, on the other hand, a significant impairment of sleep quality was observed after acute dosage and a decrease in feeling refreshed after sleep, continuing up to day 14 of treatment. It is presumed that, as bisoprolol and pindolol have comparable lipophilia, the different intensity with which the two preparations act on the central nervous system is connected with the ISA of pindolol. In the selected doses bisoprolol had a stronger effect on diastolic blood pressure and heart rate than pindolol and placebo.

[Tolerance of nitrefazole in alcoholics with liver disease. A 4-week placebo-controlled double-blind study]. / Verträglichkeit von Nitrefazol bei leberkranken Alkoholikern. Vierwöchige Plazebo-kontrollierte Doppelblind-Studie.

Liver damage is one of the most common organ manifestations of chronic alcoholism. The recovery process following abstinence should not be impaired by therapy with alcohol sensitizing drugs. In a double-blind multicentre-study (controlled against placebo) the liver tolerance of Nitrefazole which is indicated as an alcohol sensitizing agent for therapy of alcoholics, was tested during the first four weeks of a planned longterm therapy. A total of 62 patients with alcoholic liver disease--demonstrated clinically and in the laboratory--were tested. The patients received 800 mg of Nitrefazole (4 capsules a 200 mg), respectively 4 placebo capsules of identical appearance, once a week in the presence of the doctor. In both treatment groups there was a significant (p less than or equal to 0.01) decline of the previously pathologically altered laboratory values, especially concerning gamma-GT, GPT, GOT. The physical and mental condition which was additionally evaluated by the doctor improved within both treatment groups. The improvement of the liver functions due to abstinence is not delayed or impaired by Nitrefazole .

Variability of evoked-potential response to regularly repeated stimulation with checkerboard pattern-reversal and flashlight in healthy volunteers.

Pattern-reversal and flash-evoked potentials (EP) were analyzed in 20 healthy male volunteers (age 40-49 years) to investigate the response variability to monotonously repeated stimulation. The EPs were recorded over O2-T6. Each stimulus train consisted of 256 sweeps. The digitized signals were averaged in four consecutive, non-overlapping blocks, each consisting of 64 sweeps. The subjects were classified according to Q-factor analysis on the basis of five primary personality factors. Two-factorial analyses of variance (repeated measurement) were calculated on the baseline differences with the personality type as grouping factor. The amplitudes of the pattern-reversal EP were increased, those of the flash EP, with one exception, decreased as the stimuli were successively repeated. Differential effects of the personality type on the latencies of the positive components of both VEPs were observed.

Diurnal periodicity of lateral asymmetries of the visual evoked potential in healthy volunteers.

Visual evoked potential (VEP) was analyzed in 24 healthy male volunteers (age: 25-35 years) between 7.00 a.m. and 4.00 p.m. to evaluate possible diurnal variation in hemispheric differences of the response to a diffuse or 1 degree flash and checkerboard pattern-reversal (stimulation: binocular). VEP was recorded over O1-A1 and O2-A2, and 64 exposures were averaged during each session. After diffuse and 1 degree flash stimulation the amplitudes of early components (latencies less than 140 ms) were higher over the right hemisphere (O2-A2) than over the left (O1-A1) in the morning. These differences disappeared during the afternoon. Late components (latencies greater than 250 ms) exhibited higher amplitudes over the left than over the right hemisphere during the whole experiment. With checkerboard pattern-reversal stimulation such a time-dependent change in the amplitudes of VEP between both hemispheres was not measurable.