Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results of a multicentre, randomized, double-blind, placebo-controlled study

INTRODUCTION: A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of alpha-dihydroergocryptine (alpha-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable. PATIENTS AND METHODS: Sixty-two patients (32 males, 30 females, mean age +/- SD 64 +/- 10) were randomized to alpha-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8 +/- 9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample. RESULTS: The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, alpha-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, alpha-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (alpha-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of alpha-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between alpha-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent. CONCLUSION: The results indicate that alpha-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients.     

Hydrosoluble medicated nail lacquers: in vitro drug permeation and corresponding antimycotic activity

Background Two nail lacquers, containing ciclopirox (CPX) or amorolfine (MRF), based on water‐insoluble polymers are currently considered mainstays of topical treatment of onychomycosis. The present study aimed at evaluating the antimycotic activity of a new water‐soluble nail lacquer containing CPX (CPX/sol), easily removable by washing with water and applicable to periungual skin. Objectives To compare transungual permeation of CPX with that of MRF in the same hydroxypropyl chitosan‐based nail lacquer (MRF/sol) and with a nonwater‐soluble reference (Loceryl^®; Galderma International, La Défense, France), and to evaluate the antimycotic activity of CPX/sol and Loceryl^® against the most common fungal strains that cause onychomycosis. Methods In vitro drug permeation experiments with CPX/sol, MRF/sol and Loceryl^® were carried out through bovine hoof slices. Experimental permeates from CPX/sol and Loceryl^® underwent in vitro susceptibility testing against clinical isolates of dermatophytes, moulds and yeast. Results MRF transungual flux from MRF/sol lacquer was significantly higher when compared with Loceryl^®. CPX was able to permeate hoof membranes more easily compared with MRF. CPX and MRF concentrations in the subungual fluids collected after application of CPX/sol or Loceryl^® were sufficient to inhibit fungal growth, with the exception of Candida parapsilosis. Smaller amounts of fluid containing CPX were required for complete inhibition of fungal growth. Efficacy index values were significantly higher for CPX/sol. Conclusions Application of the CPX/sol nail lacquer allows rapid nail penetration of CPX, providing CPX levels sufficient to inhibit fungal growth for a prolonged period of time (30 h) after application of lacquer dose. CPX/sol nail lacquer appeared superior to the market reference Loceryl^® in terms of both vehicle (hydroxypropyl chitosan) and active ingredient (CPX) as witnessed by its higher efficacy on all nail pathogens.     

Acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in human immunodeficiency virus patients: an open label study

Antiretroviral toxic neuropathy causes morbidity in human immunodeficiency virus (HIV) patients under dideoxynucleoside therapy, benefits only partially from medical therapy, and often leads to drug discontinuation. Proposed pathogeneses include a disorder of mitochondrial oxidative metabolism, eventually related to a reduction of mitochondrial DNA content, and interference with nerve growth factor activity. Carnitine is a substrate of energy production reactions in mitochondria and is involved in many anabolic reactions. Acetyl carnitine treatment promotes peripheral nerve regeneration and has neuroprotective properties and a direct analgesic role related to glutamatergic and cholinergic modulation. The aim of this study was to evaluate acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in HIV patients. Twenty subjects affected by painful antiretroviral toxic neuropathy were treated with oral acetyl-l-carnitine at a dose of 2,000 mg/day for a 4-week period. Efficacy was evaluated by means of the modified Short Form McGill Pain Questionnaire with each item rated on an 11-point intensity scale at weekly intervals and by electromyography at baseline and final visit. Mean pain intensity score was significantly reduced during the study, changing from 7.35 +/- 1.98 (mean +/- SD) at baseline to 5.80 +/- 2.63 at week 4 (p = 0.0001). Electrophysiological parameters did not significantly change between baseline and week 4. In this study, acetyl-l-carnitine was effective and well tolerated in symptomatic treatment of painful neuropathy associated with antiretroviral toxicity. On the contrary, no effect was noted on neurophysiological parameters.     

Indenolol in hypertension

After a complete washout 14 hypertensive inpatients were given placebo for 3 days. Undistinguishable 30- or 60-mg indenolol tablets were then given twice daily for 14 days in a double-blind, randomized manner. Supine and standing arterial pressure and heart rate were measured at rest three times a day. Indenolol decreased systolic and diastolic arterial pressure as well as heart rate in subjects in supine and standing positions. Placebo had no effect. The effect of indenolol on systolic arterial pressure was dose and time related, but independent of the intensity of hypertension. No dose-effect relationship was found on diastolic arterial pressure. Decrease of heart rate was dose and time related, although bradycardia was never noted. Indenolol was well tolerated.     

Far lateral lumbar disc herniation part 1: Imaging,neurophysiology and clinical features

Far lateral lumbar disc herniations (FLLDH) represent a separate category of disc pathology which includes both intraforaminal and extraforaminal lumbar disc herniations, that are characterized by a peculiar clinical presentation, diagnostic and treatment modalities as compared to the more frequent median and paramedian disc hernias. Surgical treatment often represents the only effective weapon for the cure of this disease and over the years different approaches have been developed that can reach the region of the foramen or external to it, with different degrees of invasiveness. The diagnosis is more demanding and still underestimated as it requires a more detailed knowledge in the spine anatomy and dedicated radiological studies. Computerized tomography and in particular magnetic resonance imaging are the appropriate tools for the diagnosis of FLLDH. Despite the widespread use of these diagnostic tests, many cases of FLLDH are overlooked due to insufficiently detailed radiological examinations or due to the execution of exams not focused to the foraminal or the extraforaminal region. Neurophysiological studies represent a valid aid in the diagnostic classification of this pathology and in some cases they can facilitate the differential diagnosis with other types of radiculopathies. In the present study, a comprehensive review of the clinical presentation, epidemiology, radiological study and the neurophysiological aspects is presented.     

Plasma levels of beta-amyloid (1-42) in Alzheimer's disease and mild cognitive impairment

We compared plasma levels of beta-amyloid 1-42 (pg/ml) found for 146 sporadic Alzheimer (AD) patients, 89 subjects with mild cognitive impairment (MCI) and 89 age-matched controls (CT). AD patients had significantly lower levels (38, 54, 52; p<0.01), unrelated to severity of the disease as assessed by MMSE score, age, sex or APOE4 status. Twenty cases investigated at two time points 18 months apart did not demonstrate further decreases. Thus, the reduction in beta-amyloid 1-42 may be a marker for AD status, specifically, a transition from normal status or MCI to AD, rather than a marker for neurodegenerative processes occurring in the disease.     

In Vitro Activity of Nifuratel on Vaginal Bacteria: Could It Be a Good Candidate for the Treatment of Bacterial Vaginosis?

Bacterial vaginosis is characterized by a shift of the physiological flora to a diverse spectrum of bacteria, where Gardnerella vaginalis and Atopobium vaginae are the most important markers. In this study, the antimicrobial activity of nifuratel against G. vaginalis, A. vaginae, and lactobacilli was compared with that of the two currently used antibiotics metronidazole and clindamycin. Results suggest that nifuratel has a better spectrum of activity, being highly active against G. vaginalis and A. vaginae without affecting lactobacilli.     

Amineptine in the management of the depressive syndromes

The antidepressant activity of amineptine was evaluated in 34 patients in a double-blind study vs clomipramine. Clinical results, assessed using the Hamilton rating scale for depression, failed to show any significant difference in the activity of the two drugs. Amineptine was however much better tolerated than clomipramine. The antidepressant activity of amineptine was further investigated in an open multicenter study carried out in 351 depressed patients. The significant reductions in the scores of the Hamilton rating scale for depression and the final clinical evaluations (87% favorable results, 69% of which excellent or good) confirmed the therapeutic efficacy of amineptine. Tolerance was excellent also in elderly, at risk patients.     

Effect of dihydroergokryptine administration on serum prolactin and growth hormone levels in normal,hyperprolactinaemic and acromegalic subjects: Evidence of potent and long-lasting pituitary dopamine receptor stimulation

Summary The endocrine effects of a relatively potent dopaminergic agent, dihydroergokryptine, have been studied in normal subjects, and in hyperprolactinaemic and acromegalic patients. A single 6 mg oral dose of the drug caused a marked, long lasting fall in prolactin (PRL) plasma levels in healthy subjects, in hyperprolactinaemic patients and in normoprolactinaemic acromegalics. Growth hormone (GH) levels decreased in l-DOPA — responder, acromegalic patients, but dihydroergokryptine did not affect GH levels in normal volunteers or in l-DOPA non — responder, acromegalic patients. The PRL-and GH- lowering activity of 6 mg dihydroergokriptine was significantly greater than that of 6 mg dihydroergocristine, and was similar to that of an oral dose of 500 mg l-DOPA.     

Computerized image analysis of nails affected by fungal infection: evaluation using digital photographs and manually defined areas

Despite the relevant increase in clinical trials on the efficacy of various systemic and/or topical antifungal agents in onychomycosis therapy, the evaluation of the results is largely subjective. The aim of this study was to set up and ensure an objective, reproducible and reliable method to measure nail plate involvement in onychomycosis. In order to validate a specifically designed software for the computerized image analysis of affected areas of the nail, standardized clinical pictures of onychomycosis were prepared by six different clinicians using a sample of 11 affected nails. Diseased areas and total nail plates were measured both on the clinical pictures and on their drawings traced by the different clinicians on transparent tapes adhering to sample nails. The computerized procedure was undertaken by a trained operator who was not a dermatologist. The variation coefficients of measurements on clinical pictures (automatically detected) and on drawings were compared. In addition, the agreement between automatic evaluation and drawing was evaluated by means of Bland-Altman analysis. To consider the effect of possible variations linked to different operators using the computerized method, 11 clinical pictures (one for each clinical case considered) were selected and submitted to computerized image analysis by six different trained operators. The computerized detection of affected nail areas showed a coefficient of variation (vc=8.5%) lower than that observed on drawings (vc=14.7%). The two methods showed appreciable agreement, as demonstrated by Bland-Altman plot. The coefficient of variation of image analysis conducted by six different operators was very low for the total area calculation (vc=0.9%) and acceptable for pathological area detection (vc=4.8%). Based on the results obtained, we conclude that automatic evaluation is a reliable and helpful method for the measurement of the clinical involvement of the nail plate in onychomycosis and for the evaluation of therapies, since it can increase the objectivity and reproducibility of data. However, in a minority of difficult cases, expert dermatological evaluation is needed.