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Background: Peripheral arterial disease affects five per cent of men and women by late middle age. Approximately 25% of those affected will develop critical limb ischaemia (rest pain, ulceration and gangrene) within five years. Naftidrofuryl is a vasoactive drug which may be beneficial in the treatment of critical limb ischaemia., Objectives: To determine whether naftidrofuryl, when administered intravenously, is effective in alleviating symptoms and reducing progression of disease in patients with critical limb ischaemia., Search Methods: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2012) and CENTRAL (2012, Issue 4). We searched the reference lists of articles. We also contacted pharmaceutical companies for any unpublished trials., Selection Criteria: All randomised controlled trials of critical limb ischaemia in which participants were randomly allocated to intravenous naftidrofuryl or control (either pharmacological, inert placebo or conservative therapy) were included. People with intermittent claudication were not included., Data Collection and Analysis: Sixteen trials were identified, but eight were excluded because of poor methodology. The eight included trials involved a total of 269 participants from five different countries. The following outcomes were reported: pain reduction, rest pain/necrosis, progression of disease in terms of incidence of surgical reconstruction/amputation, mortality and side effects. On extraction of the data, odds ratios and mean differences were estimated where appropriate., Main Results: Treatment with naftidrofuryl tended to show reduction of pain evaluated by both analogue score and analgesic consumption, but the effect was statistically non-significant (mean difference (MD): 0.42; 95% confidence interval (CI)1.19 to 0.35). Similarly, improvement in rest pain or skin necrosis occurred, but these effects were also non-significant. The effect on mean ankle systolic pressure was inconclusive., Authors' Conclusions: Based on the results of these trials, it cannot be confirmed that intravenous naftidrofuryl is effective in the treatment of people with critical limb ischaemia. However, these results were based on trials of generally low methodological quality which had only a small number of participants, the duration of treatment was extremely short, and the methods varied between the trials. The wide range of endpoints effectively precluded any meaningful pooling of the results. Intravenous naftidrofuryl was withdrawn as a treatment for severe peripheral arterial disease in 1995 because of reported side effects.

Two groups of tinnitus patients (n=93) were recruited, one of which was treated with standard infusion therapy and further acute medical intervention, while the other obtained an additional psychotherapeutic intervention. Questionnaires and interviews were taken at beginning of the treatment, and 9 days and 3 years after treatment. The accompanying psychotherapeutic intervention consisted primarily of client-centered counseling, guided relaxation techniques from clinical hypnosis, and some standard and tinnitus-related methods for a better coping with stress. After 9 days, both treatment groups showed significant improvement in several psychological characteristics. However, there was no evidence for the superiority of the combined treatment with psychological intervention. Psychotherapeutic treatment accompanying the acute medical treatment probably shows better effectiveness in an ambulant setting with both patients and medical healthcare professionals rating it as 'very helpful'. This pilot study has contributed initial results for the integrated treatment of the acute tinnitus and has helped in the development of further therapeutic strategies as well as an evidence based concept for further evaluation. This study received one of the two scientific first prizes of the "German Tinnitus League".

Background: Testicular cancer has a favorable prognosis in the majority of patients due to the excellent susceptibility to chemotherapy with cisplatin, etoposide and bleomycin (BEP), which is commonly administered over 3-4 cycles of treatment., Case Report: A 22-year-old male failed to achieve complete response after unconventional treatment with 6 courses of BEP for intermediate-risk metastasized testicular cancer. The patient developed chemotherapy-induced digital necrosis and substantial loss of digital function after this excessive treatment. This condition resolved with infusional alprostadil combined with oral clonidin and pentoxifyllin., Result: Infusional alprostadil adds substantial clinical benefit to combined vasoactive therapy in chemotherapy-induced vascular toxicity, even after the onset of digital necrosis.

Naftidrofuryl (CAS 31329-57-4) is used, mainly in elderly patients, in the treatment of various vascular disorders. The aim of this study was to evaluate and compare the pharmacokinetics of naftidrofuryl after single oral administration of a 200 mg naftidrofuryl tablet (Praxilene) in caucasian male and female subjects with renal impairment versus healthy volunteers. This prospective and open study was conducted in three parallel groups: Group A = healthy subjects with a Cl(CR) > 80 ml/min, Group B = uraemic patients with a 20 < or = Cl(CR) < 40 ml/min, Group C = uraemic patients with a Cl(CR) < 20 ml/min. Blood samples were taken over a period of 32 h after dosing. The mean values (+/-SD) of the pharmacokinetic parameters of naftidrofuryl for group A were as follows: tmax: 1.3 h (median), Cmax: 174 +/- 46 ng/ml, t(1/2 beta): 4.4 +/- 1.1 h, AUC(0-infinity): 1541 +/- 384 ng x h/ml; for group B: tmax: 2.5 h (median), Cmax: 239 +/- 94 ng/ml, t(1/2 beta): 5.0 +/- 1.2 h, AUC(0-infinity): 2361 +/- 751 ng x h/ml; for group C: tmax: 3.0 h (median), Cmax: 236 +/- 104 ng/ml, t(1/2 beta): 5.0 +/- 2.1 h, AUC(0-infinity): 2488 +/- 2003 ng x h/ml. The statistical analysis was performed on the pharmacokinetic parameters with one-way ANOVA in order to compare each group. No significant difference between each group was observed. In conclusion, renal insufficiency did not appear to influence the pharmacokinetic profile of oral naftidrofuryl.

In the present study, we investigated the effects of a single and a repeated (5 days) administration of naftidrofuryl, a serotonin 5-HT2 receptor inhibitor having neuroprotective properties, on functional brain physiology in male healthy elderly subjects, using quantitative electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Twelve subjects aged 60 +/- 3.8 years completed the quantitative EEG study, where the effects of 400 and 600 mg were assessed, and 12 other subjects (aged 56 +/- 4.7 years) completed the fMRI study, where the effect of 400 mg was assessed on the brain activation induced by the continuous performance test (CPT). Naftidrofuryl induced a transient reduction in alpha activity followed by a specific synchronisation of the 9.5- to 11-Hz EEG activity most pronounced after repeated administration. Such regimen also increased the CPT-induced brain activation visualized by way of fMRI. The results of the present study can be interpreted at the functional level that naftidrofuryl induced an improved level of vigilance or an increased capacity of alertness in healthy elderly subjects., (Copyright 2003 S. Karger AG, Basel)

Enzymatic retinyl ester hydrolysis is a key reaction for maintaining cellular retinol homeostasis. The ability of naftidrofuryl and erythromycin to inhibit retinol liberation by retinyl ester hydrolase (REH) in vitro suggests an ability to interfere with vitamin A metabolism in vivo, particularly during hepatic processing. To address this question, systemic and local response to these agents were studied in Brown Norway (BN) and Long-Evans (LE) rats. The study was conducted in two parts: a drug-loading phase and a washout phase. Analysis of variance of the time course changes in plasma retinol during the post-treatment period (Days 10-18) showed rat strain (p < 0.04) and time (p < 0.001; strain-by-time interactive effect, p < 0.001) to be significant factors, but drug exposure (p = 0.19) was not significant. Endpoints included hepatic REH activity, size and composition of the liver vitamin A stores, and retinoid content of the kidneys. Rats recovering from naftidrofuryl dosing demonstrated a lower REH activity than did animals recovering from erythromycin treatment (p < 0.009). The major side effect of erythromycin is vitamin A accumulation in the liver (p < 0.001) and reductions in retinol reserves (p < 0.02) were among the consequences of naftidrofuryl treatment. In the kidney of LE rats, there were higher concentrations of vitamin A (p < 0.003) secondary to naftidrofuryl exposure. Together our data suggest that clinically achievable concentrations of the drugs, given as a continuous infusion, produce aberrations in vitamin A metabolism.

Background: Hearing loss resulting from exposure to permanent or repeated amplified music in professional musicians and music consumers is described in literature. The risk of hearing loss does not exist only after prolonged exposure to music. Short-term exposure to very high sound levels, for example in concerts, can also cause hearing loss and tinnitus., Patients: The retrospective study includes 24 patients who required rheologic therapy between 1994 and 1997 due to a music related acoustic trauma. The type, intensity, and length of music exposure as well as the distance and the position to the source of noise were examined. The type of hearing damage and its development during rheological treatment was studied by pure-tone audiometry., Results: In the majority of examined patients (67%) the hearing loss developed on the basis of one-time exposure at a rock concert or pop concert, followed by hearing loss from attending discotheques (17%) or parties (12%), and music exposure from personal cassette players (4%). The majority of patients showed a maximum hearing loss of 40-60 dB (A) in a frequency between 3 kHz and 4 kHz. Pure-tone audiometry in 58% of the patients exhibited a unilateral threshold in a frequency between 3 kHz and 4 kHz combined with ipsilateral tinnitus of the same frequency. Twenty-one percent of the patients showed a symmetric bilateral threshold and tinnitus between 3 kHz and 4 kHz. In 8% there was a unilateral tinnitus, and in 13% a bilateral tinnitus without any hearing loss. All patients improved their hearing loss during rheologic treatment. Improvement in the tinnitus was only achieved in 33% of the examined cases., Conclusion: The risk of permanent hearing loss resulting from short-term exposure to amplified music is low compared to the risk of continuous tinnitus. Given the lack of acceptance of personal ear protectors, the risk of acute hearing damage due to amplified music could be reduced by avoiding the immediate proximity to the speakers.

Background: Using a disease specific questionnaire, the CLAU-S, we undertook a double blind, placebo controlled study in patients with intermittent claudication to determine whether the increase in the pain-free walking distance, previously demonstrated with naftidrofuryl, is reflected as an improvement in the patients' quality of life., Patients and Methods: 287 patients, with stable intermittent claudication for at least 3 months were entered into the study. Following an initial one month placebo run-in, patients were randomised to either naftidrofuryl, at a dosage of 200 mg three times daily, or matching placebo, for 6 months. All patients completed the self-administered CLAU-S questionnaire which is divided into 6 dimensions, before the start of treatment, at 3 and 6 months. Statistical analysis was undertaken on an intention-to-treat (ITT) basis which included all patients know to have taken at least one dose of the drug and to have provided key data on at least one occasion after baseline. For each of the CLAU-S dimensions the two groups were compared with respect to difference between the initial and final values., Results: 255 patients (133 naftidrofuryl, 122 placebo) were eligible for the ITT analysis. Significant improvements, in favour of the active medication, were seen for the dimensions "daily living", "pain", "disease specific anxiety" and "mood". A multivariate analysis of covariance, which took into account such factors as initial score, age and sex confirmed the global superiority of naftidrofuryl (p = 0.004)., Conclusions: In this placebo controlled study, using a disease specific questionnaire, naftidrofuryl has been shown to significantly improve several aspects of the quality of life of patients with intermittent claudication.

Purpose: To evaluate the effects of an S2 specific antiserotonine agent (Naftidrofuryl) on the optic nerve head blood flow in glaucomatous patient., Patients and Method: 11 glaucomatous subjects were enrolled in the study. After administration of 200 mg naftidrofuryl twice daily for 7 days: values of optic nerve head blood flow (Fonh), velocity and volume were recorded in the temporal rim and cup of the optic nerve head. Blood flow measurements were performed by laser doppler flow-metry at day 0 and day 7 before and one and two hours after drug administration., Results: Our study showed a significant improvement of perfusion pressure (p = 0.02) at day 7 and an increase of mean ophthalmique artery pressure (p = 0.03)., Discussion: Our preliminary results on a small number of patients and a short follow-up indicate that the use of naftidrofuryl may enhance optic nerve head blood flow in glaucomatous patients. Further studies may confirm these results.

The present study was devised to determine whether the pattern of hearing loss has any meaning for prognosis in patients with sudden hearing loss. The audiograms and clinical records of 145 patients with sudden deafness between 1991 and 1993 were reviewed. Forty-eight of the patients were females and 97 were males. All patients had been hospitalized and treated with intravenous infusions of naftidrofuryl. The best recovery rate was seen in patients with low-tone hearing losses (68.8% complete and 25% partial recoveries), whereas in patients with high-tone and flat losses the recovery rates were 41.9% and 45.5% respectively for complete recovery and 52.4% and 36.3% for incomplete recovery. The entire group showed an overall recovery rate of 52.4% for complete recovery and 30.3% for incomplete recovery. Immediate treatment resulted in a positive effect on prognosis. Patients under 30 years of age had a somewhat better recovery rate than did older patients. Pre-existing risk factors (diabetes, hypertension, etc.) or accompanying symptoms of vestibular disturbances did not influence prognosis, whereas patients with pre-existing inner ear deafness or with a recurrence of sudden deafness showed relatively lower recovery rates. The possible reasons responsible for exceptionally good prognosis of low-tone hearing losses are discussed.

Crystalluria is important in the evaluation of patients with urinary stone and is more frequently encountered in elderly than in younger adults. After noting that calcium oxalate monohydrate crystalluria was higher in elderly patients, we undertook a study to determine if oral treatment with naftidrofuryl oxalate, a drug frequently prescribed for elderly patients in France, was associated with crystalluria. The presence of early morning crystalluria was assessed in non-stone-forming patients hospitalized in a geriatric department. We studied 251 patients without a history of nephrolithiasis (mean age; 81.6 +/- 8.5 years) of whom 49 had been treated orally with naftidrofuryl oxalate at a mean dosage of 485 +/- 120 mg/24h. We identified and quantified the crystals in one early morning urine sample kept at room temperature. The frequency of crystalluria in elderly patients without stones who were not taking naftidrofuryl oxalate was 31.7% compared with only 6% in the general adult population. In this group, mainly calcium phosphate crystals were found. In patients who received naftidrofuryl oxalate, the frequency of crystalluria was 51% of which the major component was calcium oxalate monohydrate and not calcium phosphate. Naftidrofuryl oxalate may enhance crystal formation in elderly patients. This should be taken into account, particularly when other predisposing factors for nephrolithiasis are present, and a preventive increase in fluid intake considered.

We investigated the action of oral naftidrofuryl, a serotonin (5-HT2)antagonist, on atheromatous plaque formation, endothelial function, and neutrophil activity in cholesterol-fed (1% for 12 weeks) rabbits. Cholesterol feeding caused almost complete (84 +/- 4%) coverage of the aortic surface with atheromas and a marked intimal thickening. The endothelium-dependent relaxation to acetylcholine (ACh 1 nM-10 microM) and substance P (30 nM) was considerably reduced, whereas the relaxing effect to the endothelium-independent nitric oxide donor linsidomine (SIN-1) (100 microM) was unchanged. Treatment of hypercholesterolemic rabbits with naftidrofuryl (50 mg/kg body weight) resulted in a marked (54 +/- 6%, p < 0.05) reduction in aortic plaque formation. Endothelium-dependent relaxation to ACh was significantly improved in rings of both thoracic aorta: 33 +/- 5 versus 14 +/- 5% (p < 0.05) and abdominal aorta 68 +/- 9 versus 37 +/- 10% (p < 0.05). Similar results were obtained with substance P, but the responses to SIN-1 were unchanged. Zymosan-induced, luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMN) was markedly stimulated in cholesterol-fed rabbits. Naftidrofuryl reduced this hyperreactivity to that of control rabbits. There was no change by naftidrofuryl in any of these parameters in control rabbits, precluding a direct action of the compound in nonhypercholesterolemic conditions. These data demonstrate significant endothelium-protective actions of long-term oral naftidrofuryl in cholesterol-fed rabbits that involve inhibition of cholesterol-induced neutrophil activation.

We report two cases of acute renal failure in patients with arteriosclerosis obliterans treated by intravenous infusion of naftidrofuryl oxalate. At renal biopsy the histological lesions were identical with those found in ARF due to hyperoxaluria of other causes, revealing tubular epithelial necrosis and massive intratubular precipitation of calcium oxalate monohydrate (C1) crystals. A second study was then conducted in four other patients with arteriosclerosis obliterans to evaluate serum and urinary levels of oxalate, and crystalluria during the intravenous administration of 800 mg of naftidrofuryl oxalate per day for 10 days. During the course of treatment, the serum and urinary oxalate levels were found to increase substantially, with the gradual onset of massive C1 crystalluria. These results indicate that naftidrofuryl oxalate was responsible for the acute renal failure in the first two patients. High intravenous doses of naftidrofuryl oxalate must be used cautiously, with close surveillance of renal function.

Naftidrofuryl is commonly used in treatment of peripheral vascular disease. Its vasodilator action has been partly explained by its inhibitory effect of 5-HT2 receptors on peripheral arteries in vitro. The purpose of this study was to test in vivo whether naftidrofuryl selectively inhibits 5-hydroxytryptamine (5-HT)-mediated constriction of large arterioles in the peripheral microcirculation. This constriction appears to be 5-HT2 receptor-mediated. Three separate protocols were used to test the effects of naftidrofuryl: chronic injection (15 mg/kg, i.p., twice daily for 5-6 days; n = 7), acute intravenous (i.v.) infusion (15 mg/kg over 30 min; n = 7), or topical application (5 x 10(-8) M, n = 6; 5 x 10(-7) M, n = 5; 5 x 10(-6) M, n = 5; 10(-5) M, n = 7). Male Sprague-Dawley rats (145-185 g body weight) were anesthetized with sodium pentobarbital (50 mg/kg) and the cremaster muscle was prepared for intravital video microscopy. Diameter response of arterioles (70-120 microns) to increasing concentrations of locally applied 5-HT (10(-8)-10(-4) M) was assessed. In rats receiving no drug treatment, 5-HT caused vasoconstriction of arterioles beginning at 10(-6) M and reaching approximately 40% constriction at 10(-4) M. These vasoactive responses were not altered by chronic daily doses or an acute infusion of naftidrofuryl. 5-HT responses obtained with and without naftidrofuryl applied directly into the cremaster-bath also had little effect on the arteriole response at each of the four concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS)

80 patients with idiopathic sudden hearing loss existing no longer than 10 days were included in a randomised reference-controlled study. The therapeutic value of Ginkgo EGb 761 (Tebonin) + HAES was compared to that of Naftidrofuryl (Dusodril)+HAES. The main mechanisms of action of EGb 761 are a vasoregulating activity (increased blood flow), the platelet activating factor antagonism and a prevention of membrane damage caused by free radicals. Naftidrofuryl has antiserotonergic and therefore vasodilatory properties. The statistical analysis of the audiometric data was performed in measuring the relative hearing gain as described by Eibach 1979. After one week of observation, 40% of the patients in each group showed a complete remission of hearing loss. This was also observed by other authors who had compared other drugs. Therefore, in these cases, it is most likely that spontaneous recovery is the most important factor. After two and three weeks of observation, measuring the relative hearing gain, there was a significant borderline benefit of EGb 761 (p = 0.06) without any side effects. Some patients of the reference group developed side effects such as orthostatic dysregulation or headache or sleep disturbances. Minimising side effects should be one of the most important goals in therapy of sudden hearing loss until the efficiency of infusion therapy is proved.

The aim of the present study was to investigate the influence of long term intravenous administration of naftidrofuryl (Dusodril-Lipha Arzn) twice daily in a dose of 200 mg in continuous, 4-hour infusion in 500 ml 0.9% NaCl to the patients suffering from a peripheral arterial occlusive disease (PAOD) in a clinical condition with special attention paid to transcutaneous partial oxygen pressure measurements (tcPO2) and rheographic parameters. Also the effect of treatment with naftidrofuryl on the platelet adhesion to the bovine extracellular matrix, the leukocyte adhesion to nylon fibres, and the number of platelet-leukocyte aggregates has been studied. We have found that after the naftidrofuryl treatment tcPO2 significantly increased from 38.5 +/- 0.8 mm Hg to 54.6 +/- 11.5 mm Hg, and the impedance plethysmography indexes, such as the height of the rheographic wave, the area of the rheographic wave and the rheographic index were also slightly increased. The leukocyte adherence to nylon fibres, the platelet adhesion to the extracellular matrix and the total number of platelet-leukocyte aggregates were significantly reduced after the treatment with Dusodril. On the basis of this study it seems that the observed influence of naftidrofuryl on leukocyte function in patients with PAOD is an additional mode of action of this drug that can be of new clinical value in the treatment of patients with a peripheral occlusive arterial disease. It seems that tcPO2 measurements in ischaemic legs can be recommended as a very sensitive method of monitoring the efficacy of vasoactive drugs in patients with PAOD.

The case of a 7-year-old boy who suffered a convulsion during parenteral infusion of naftidrofuryl is reported. The effectiveness of adding naftidrofuryl to infusions designed to increase cochlear blood flow in cases of sudden hearing loss has been keenly debated in the otologic literature. Several hazards are associated with this drug, especially when the infusion is performed too fast. We recommend an individual decision for each patient suffering from cochleo-vestibular disorder based on the neurological and cardiological risk factors and the therapeutic possibilities.

Eighty patients with idiopathic sudden deafness existing no longer than 10 days were included in a prospective randomized double-blind study. Patients were treated for 10 days with infusions of either 10% low-molecular weight dextran or the combination of low-molecular weight dextran with naftidrofuryl. Before treatment and after 10 days hearing loss in the affected ear was determined at 0.5, 1, 2, 3, 4 and 6 kHz. The mean hearing loss was then calculated as the average from these values. During monotherapy with low-molecular weight dextran the mean hearing loss decreased from 40 to 27 dB compared to 38 to 17 dB when naftidrofuryl treatment was added (p < 0.01 between groups). A significant benefit of naftidrofuryl on hearing loss was also found at frequencies between 0.5 and 3 kHz. Furthermore, patients reported better improvement of tinnitus when naftidrofuryl was combined with dextran. Two patients receiving dextran alone developed side effects: one had an allergic reaction causing withdrawal of treatment, which the other case had vertigo, nausea and headache with spontaneous recovery. The results of the study showed that treatment with naftidrofuryl in addition to hemodilution with low-molecular weight dextran was of therapeutic benefit in the therapy of sudden deafness without increasing the rate of side effects.

Treatment with intravenous naftidrofuryl may be complicated by ventricular arrhythmias. A case of slow ventricular tachycardia occurring in a 65-year-old man with a dilated cardiomyopathy following an accidental overdose of naftidrofuryl (2 x 200 mg ampules in 250 ml of 5% glucose solution in 2 hours) prescribed for complicated arterial disease of the lower limbs is reported. This sustained ventricular tachycardia converted spontaneously after several hours. This case emphasises the risk of arrhythmogenic effects of this drug and indicates the need for careful monitoring when it is used intravenously in patients with underlying heart disease.

In 30 patients undergoing femoro-distal bypass the effect of papaverine and praxilene on blood flow in the graft was measured. The mean resting flow was 129 ml min-1 (range: 91-167) and after papaverine was 202 ml min-1 (142-262) and after praxilene was 205 ml min-1 (143-267). Praxilene has a similar effect to papaverine in the augmentation of blood flow, and further investigation is needed to see if long-term praxilene administration might improve graft survival.

To analyze the effects of naftidrofuryl oxalate (LS-121) on the central nervous system exposed to critical hypoxia, survival duration was employed as a parameter of the protective effects of the drug against hypoxia-induced death. In the control group (no drug administration), the electroencephalogram (EEG) was flattened promptly after changing to hypoxia from aerobic conditions, and it was impossible to recognize precisely what time the EEG disappeared because of vigorous body movements. Arterial blood pressure (BP) was clearly recognized, and rats never recovered after BP decreased to 0 mmHg, although the electrocardiogram (ECG) was still recorded. Thus, survival duration recognized by measuring the time from the onset of hypoxia to the time when BP became 0 mmHg was considered to be a good indicator. After LS-121 (10 mg/kg) administration, survival duration was significantly prolonged compared to the control. Combination therapy of LS-121 (25 mg/kg) and bifemelane hydrochloride (BI) (25 mg/kg) also revealed the prolongation of survival duration. Neither idebenone (10 mg/kg) nor nicergoline (10 mg/kg) showed significant changes in survival duration. These findings suggest that LS-121, either with or without BI, could improve cerebrovascular disorders induced by hypoxia.

The nutritional blood flow to the tissue is the principle factor determining the outcome of reconstructive procedures in plastic surgery. Beside vasoconstriction, thrombocytes aggregation, leukocytes activation, followed by production of oxygen free radicals and release of proteases, impaired fluidity of erythrocytes and swelling of the microvascular endothelium are responsible for impaired perfusion following ischemia/reperfusion. Therefore, vasoactive drugs known to improve nutritional blood flow are of particular interest in the prevention and therapy of skin flap necrosis. Several methods have been employed to quantify nutritional blood flow in skin flaps but none of them have elucidated the mechanisms underlying potential tissue protection by these drugs. We have developed two skin flap models in the hairless mouse, in which nutritional blood flow can be directly assessed at capillary level by means of intravital microscopy. In the arterial skin flap model, the efficacy of three vasoactive drugs (naftidrofuryl [4.5 mg/kg/day], pentoxifylline [17.0 mg/kg/day] and buflomedil [3.0 mg/kg/day]) to prevent and/or reduce tissue necrosis was investigated. Buflomedil provided the most efficient tissue protection, a phenomenon also verified in a random skin flap model. It was demonstrated that preoperative application of buflomedil preserves functional vascular density in the distal part of skin flaps more efficiently compared to postoperative application. However, there were no significant differences in amount of skin necrosis between the two groups. The tissue protection effect was also observed in random pattern flaps rendered ischemic for six hours after flap elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

Two good comparable groups of patients (group 1 treated with 10% HES 200/0.5 + Naftidrofuryl; and group 2 treated with 6% HES 200/0.5 + Naftidrofuryl) with sudden hearing loss were compared with respect to their hearing recovery, hemorheological parameters and intravasal detectable HES fraction. The results showed an overall improvement of the hemorheological features. No difference between the two groups could be found wether in the hearing improvement nor the investigated parameters. We therefore conclude, that HES 6% is a good alternative to HES 10% for hemodilution therapy in cochleo-vestibular disorders.

This study was a 6-month open trial of the effects of naftidrofuryl fumarate (600 mg/day orally) on the clinical and electrophysiological signs of diabetic polyneuropathy in 15 patients. A scored clinical evaluation and an indexed electrophysiological examination were done at inclusion, and after 3 and 6 months. Mean clinical score and electrophysiological index was improved after 3 months of therapy, the improvement persisting at 6 months, with no change in control of diabetes. These results could be related to the vasodilating properties of the drug, causing an increase in nerve temperature, or to a specific neurotropic action, as recently demonstrated in rats. Controlled studies are necessary to confirm these results, and explore the mechanism of this improvement.

35 normal tension glaucoma patients were followed during 8 to 11 month. 12 patients received 2 x 200 mg/day Naftidrofuryl, a serotonine S2 receptor antagonist. As controles, another 23 patients were followed without treatment. The treated group, compared with the 23 non treated patients showed a significant increase in visual acuity (p = 0.001), a significant increase of the MS (p = 0.03), and a non significant decrease of the MD and CLV on the Octopus visual field (p, NS). The physiology and physiopathology of serotonine and S2 receptor antagonist are discussed.

In a controlled double-blind study, 78 patients with moderate senile dementia were randomly assigned to 3-months' treatment with 200 mg naftidrofuryl twice daily in slow-release form or with placebo. The patients were selected on the basis of the EACG (Echelle d'Appréciation Clinique en Gériatrie), which was also used as main criterion for confirmatory analysis of the efficacy of naftidrofuryl. A further main criterion was the SGRS (Stockton Geriatric Rating Scale). Secondary criteria examined were visual memory as tested in the Benton test, verbal memory as tested in the Rey test and numerical memory as tested in the digit-span test. The patients' concentration was tested in the Zazzo test. The tests were performed before the patients were admitted to the study and after 1 and 3-months' treatment. Confirmatory analysis of the primary criteria showed a significant treatment difference in favour of naftidrofuryl in the form of improvement in the global symptoms of senile dementia both in the EACG and in the SGRS, the scores in the naftidrofuryl group improving by 15% compared with only 5% in the placebo group. This was paralleled by a significant improvement in visual and verbal memory in the naftidrofuryl group in comparison with placebo. The naftidrofuryl patients also showed a greater improvement in concentration than the placebo group. One patient in the naftidrofuryl group suffered briefly from gastro-intestinal symptoms. There were no changes in routine laboratory parameters studied.

Early atherosclerosis can be easily dedected in arteries accessable to ultrasound. The main localisations are the carotid and femoral arteries, which can be deseased alone or together. The progression seems to be higher in the femoral vessels. There is the impression that the growth can be influenced by drugs which lower blood cholesterol or are partial inhibitors of serotonin receptors (S 2).

After a wash-out period of four weeks 51 patients with mild to moderate senile dementia were treated with either 600 mg naftidrofuryl (n = 23) daily per os or placebo (n = 28) over an eight-week period. When classified according to Hachinski's score, 24 patients were found to be suffering from senile dementia of Alzheimer's type (SDAT), whereas 27 patients presented with vascular dementia (MID). During wash-out and the treatment period the somatic and social symptoms of the disease were assessed by the AGP score. Cerebral performance was evaluated by a battery of tests measuring memory, concentration, psychomotor coordination and degree of depression. Electrical activity of the brain was estimated by a power-spectral analysis of EEG. In the total study group, the naftidrofuryl group showed a significantly better improvement in the results of the psychometric test battery, which was the primary variable during treatment. A parallel development was to be found in the AGP score and electrical brain function. When results of subgroups were analyzed according to the etiopathogenetic background of patients with SDAT, it was possible to show that naftidrofuryl affected psychopathometry and EEG-parameters while patients with MID responded to naftidrofuryl with changes in AGP score and EEG variables. These findings indicate the importance of etiopathologic features in performing studies with nootropic drugs in obtaining information on possible different actions in patients with different kinds of senile dementia.

Fourteen children and adolescents aged between four and 17 years with genuine sudden hearing loss were analyzed in a retrospective study. The symptoms of hearing loss, tinnitus and vertigo were similar to those found in adults. The study's findings suggest that younger children particularly below the age of 14, will not suffer from these symptoms. Consequently, the disease was frequently diagnosed in younger children after the parents had observed defective hearing. In an 13-year-old child it was not possible to provoke a caloric vestibular response. As in the case of the other children (below 14 years of age) this patient did not complain of vertigo. -The prognosis of sudden hearing loss in children is poor. Thus 22% (two out of nine) of all patients treated with drugs became deaf. Moreover, 29% (four out of 14) of all patients examined (with and without therapy) remained deaf after sudden hearing loss. It is concluded that, due to this poor prognosis, a therapeutic attempt should be performed analogous to the treatment given to adults.

Three seconds after 0.08 g of Naftidrofuryl administered through the right carotid artery during an operation for carotid stenosis a right temporal sharp wave discharge occurred followed by diffuse polyspike activity occurring every 3to4 seconds with concomitant myoclonus. Rare episodes of this type are recorded in the literature when it has been used in neuroradiology. The authors state this agent should be forbidden by intracarotid injection.

Naftidrofuryl hydrogen oxalate was used for 4 1/2 years in 216 patients with chronic arterial occlusive disease in a surgical clinic. An increase of 1 to 10 times the walking distance could be obtained in over 77% of cases in Fontaine's stage II by a genuine combination treatment with active vascular muscle training and continuous intravenous drip lasting for an average of 28 days. The continuous drip treatment was made possible by a specially designed infusion rucksack 19% of the cases still showed a moderate effect on the walking capacity. By elimination of pain at rest and healing of trophic disorders, it was possible to transfer over 68% of the patients in Stages III and IV to Stage II.

There are many drugs marketed for the purpose of altering vascular blood flow in various regions, especially of the central nervous system and in peripheral arterial insufficiency. More than 50 different methods are described for the treatment of sudden deafness. Considerations of the therapy of sudden deafness are influenced by the fact that the cause of the disease is unknown. The dysfunction of the hair-cells of the organ of CORTI is thought to be caused by a deficit of oxygen due to disorders of micro-circulation in the inner ear. The infusion of vaso-active drugs in the early state of disease can lead to a remarkable improvement of hearing whereas the prospect of improvement without treatment remains uncertain. Nevertheless it may be difficult to distinguish the beneficial effects of vasodilator agents from spontaneous improvement. Naftidrofuryl oxalate (dusodril) has been in use for many years and proved its therapeutic value in many studies. It is regarded as non-toxic and is used extensively in Europe. Side effects are only reported rarely, and include decrease of cerebral blood flow, abdominal distension, diarrhoea, oesophageal ulceration, epileptic seizures, aphasia, disturbances of consciousness, hypotension, hypertensive crisis, vertigo and dizziness, depression of cardiac conduction, thrombophlebitis, and allergy. This case report of allergic reaction in a young female patient demonstrates that the intravenous application of this drug may lead to severe complications.

The effectiveness of a 72 h. intra-arterial prostacyclin infusion has been compared to that of naftidrofuryl oxalate (Praxilene) in a double blind study of 29 patients with ischaemic rest pain in 30 legs. Long-term relief of symptoms was achieved in 14 legs (47%) and major limb amputation avoided in 18 (60%). No significant difference was demonstrated between the results of prostacyclin infusion and those of Praxilene.

In a prospective randomised clinical study on 80 patients with idiopathic sudden hearing loss the therapeutic value of nimodipine was evaluated. Nimodipine is a 4-5-dihydropyridine calcium antagonist with selective spasmolytic and vasodilatory properties on cerebral vessels. The mean improvement of hearing (250, 500, 1000, 2000, 4000 Hz) amounted to 16.5 +/- 11.3 dB as compared with 18.6 +/- 10.2 dB achieved by standard treatment with hydroxyethyl starch (HAES) and naftidrofuryl. The difference is not significant (p greater than 0.2). These results together with the low rate of side effects indicate nimodipine as a therapeutic alternative in cases of hypertension, cardiac failure and allergic predisposition. The possible role of spontaneous recovery on one side and of specific parameters such as rheologic abnormalities or type of audiogram are discussed. They are important for a more sophisticated therapeutic approach towards sudden hearing loss.

The effect of 2-(diethylamino) ethyl-tetrahydro-alpha-(1-naphthyl-methyl)-2-furanpropionate (naftidrofuryl, Praxilene) on an in vivo preparation of mouse cerebral blood vessels was investigated. Naftidrofuryl significantly reduced the arteriolar constriction produced by topical application of serotonin or dinoprost (prostaglandin F2 alpha). Local application of 10(-5) mol/l naftidrofuryl reduced both the constrictions to serotonin or dinoprost, when applied simultaneously with either constrictor. However, 10(-7) mol/l naftidrofuryl only inhibited serotonin. Moreover, 30 min after intraperitoneal injection, 160 mg/kg naftidrofuryl inhibited constrictions by either serotonin or dinoprost but 40 mg/kg only inhibited serotonin. 10 mg/kg also inhibited serotonin. The results are compatible with reports of a relatively selective action of naftidrofuryl on the serotonin S2 receptor. Moreover, while naftidrofuryl has long been suggested as a drug which could enhance cerebral blood flow or improve cerebral ischemia, the present observations suggest an antispasmodic effect on cerebral vessels in vivo.

The effect of a hemodilution therapy for sudden sensorineural hearing loss was analysed comparing the results of a prospective randomised double blind study and a retrospective study at the Frankfurt university. The prospective study consists of a treatment group receiving infusions with hydroxyethyl starch-pentoxifyllin and a control group with infusions with normal saline. Another patient group receiving hydroxyethyl starch-pentoxifyllin-naftidrofuryl infusions was analysed retrospectively. The overall therapy results are in the same range for all 3 groups. However patients with a hemoglobin value above 14 mg % in the control group had a poorer result compared to the other groups. The patient group with systolic blood pressure above 130 mm Hg treated with hydroxyethyl starch-pentoxifyllin had a significant hearing improvement over normal saline and hydroxyethyl starch-pentoxifyllin-naftidrofuryl. With increasing systolic blood pressure, patients in the control and hydroxyethyl starch-pentoxifyllin-naftidrofuryl groups had a statistically significant lower therapy result.

Analysis of 548 cases of sudden deafness shows impressively the importance of an infusion therapy with drugs improving the circulation which should be started as soon as possible. The greatest success could be made in the deep frequencies, whereas in the high frequencies the results were lower by nearly 8 decibels. Patients with sudden deafness on both sides or recurrent sudden deafness showed significantly less improvement of hearing than patients with first-time sudden deafness on one side. Remarkable is the continuous growth of sudden deafness in the low frequencies only, a phenomenon which was rarely seen one generation ago. Can this be interpreted as a change in the pattern of sudden deafness?

Unlabelled: The aim of this study was to investigate if PGE1 i.v.-therapy after active physical training further increases the walking distance in PAOD stage IIb according to Fontaine. 48 outpatients with intermittent claudication underwent a standardized active walking training of about 6 months twice weekly. Afterwards patients were randomly given once daily an i.v. infusion of 60 micrograms PGE1 (3 ampoules prostavasin) or 600 mg naftidrofuryl. The therapy lasted for 3 weeks with the exception of Saturdays and Sundays. Besides laboratory and doppler parameters, painfree and maximum walking distance (treadmill, 10% incline, 3.5 km/h) were determined., Results: Under active physical training the patients' walking distance increased significantly to more than double the baseline levels. Further significant increase of the painfree walking distance was seen after a 3 week treatment with PGE1 from 136 to 270 m (99%) as well as with naftidrofuryl from 117 to 230 m (97%). While this difference was not significant there was a significant difference in favour to PGE1 after the follow-up period (p less than 0.01). In the PGE1-group the painfree walking distance showed a further increase (from 270m to 306m) whereas it decreased in the naftidrofuryl-group (from 230m to 210m). At the same time under PGE1 the ankle/arm index increased significantly in comparison to naftidrofuryl (p less than 0.01). Side effects differed significantly in respect of the frequency and severity. In the PGE1-group in 20.8% of the patients side effects occurred, whereas in 91.6% of the patients in the naftidrofuryl-group side effects were observed. In no case therapy had to be discontinued because of side effects.