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Nausea and/or vomiting are frequent dose-limiting class effects of cholinesterase inhibitors, occurring mostly during the dose-escalation phase. These untoward effects make it difficult to increase rivastigmine dosage above 6 mg daily in most patients. The antiemetic domperidone was given to 22 patients with Alzheimer's disease (9 men, 13 women; mean age 74.5+/-4.6 years; mean age at diagnosis: 73.1+/-5.0 years) in 15-day prophylactic cycles, starting 15 days before each dose escalation of rivastigmine above 6 mg daily. Only four patients (18.2%) experienced nausea, which was so mild that all patients reached >or=9 mg rivastigmine daily and 16 (72.7%) reached and maintained the top dosage (12 mg daily). An improvement or stabilization of Mini Mental State Examination scores was achieved in 54.5% of the patients. The treatment regimen was well tolerated; no patients stopped treatment because of adverse events. Further investigations assessing the role of domperidone in the prevention of rivastigmine-related gastrointestinal disturbances are warranted.

The aims of this study were to assess autonomic nervous function in subjects with recently diagnosed Parkinson's disease (de novo patients) and to evaluate its changes following acute levodopa administration. In 13 patients (8 males, 5 females) and 13 age-matched control subjects, three cardiovascular autonomic function tests (Deep Breathing, Valsalva, Lying to Standing) were performed, the QT interval was calculated on a 12-lead electrocardiogram, and the response of plasma norepinephrine to standing was assessed in basal conditions. The cardiovascular tests and the measurement of the QT interval were repeated in de novo Parkinsonian patients 90 minutes after the administration of levodopa 200 mg per os. The results of the Deep Breathing and Valsalva tests were worse and the QT interval longer in patients than in control subjects (although the differences were not statistically significant). The heart rate increase at 30 seconds after standing up was significantly higher in Parkinsonian patients than in the control group. The response of plasma norepinephrine to standing was similar in both groups. Levodopa administration produced a slight improvement in the Deep Breathing test, a shortening of the QT interval and increased tachycardia on standing. Our data suggest that a mild subclinical impairment of parasympathetic function can be a feature of de novo Parkinsonian patients and that levodopa therapy could have a beneficial effect on this autonomic dysfunction.

The Long-Term Dopa Syndrome (LTDS) is one of the main problems in the management of advanced parkinsonian patients. A transient L-Dopa withdrawal (Drug Holiday, DH) can be useful to improve the drug response after DH, even if this approach presents risks due to patient akinesia. We tried to verify if Apomorphine sc administration during DH (DH with Apomorphine, DHA) can: a) reduce the risks connected with DH: b) maintain the benefits of DH: c) standardize the duration of DH. Twenty-five parkinsonian patients with LTDS were treated with Apomorphine sc during DH (14 days). No patient had any severe side effects. The follow-up at 180 days, conducted using the Unified Parkinson's Disease Rating Scale, demonstrated a significant improvement in the clinical conditions of about 70% of the patients, allowing a 27.1% reduction in daily L-dopa dosage. DHA can represent a valid therapeutical approach for parkinsonian patients with LTDS.

Alzheimer's disease (AD) is a central nervous system disorder characterized by the presence of neurofibrillary tangles, neuritic plaques and dystrophic neurones in susceptible areas of the brain. Few options for treatment of AD symptomatology are available. We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel trial consisting of a 90 day treatment period followed by a 30 day single blind placebo administration and by an optional long term period of treatment up to a year with idebenone in open fashion. Ninety two patients entered the study and nine of them dropped out before the first control. Treatment with idebenone was found effective on memory, attention, and orientation and in slowing down the natural progressive worsening of the disease. The most common side effects associated with this treatment were insomnia, gastralgia, nausea, and anxiety. However, all adverse effects were of mild intensity and did not require specific therapies.

A double-blind, placebo-controlled, randomized study is described of an assessment of the efficacy and relative safety of the ergot alkaloid, dihydroergocryptine, on 52 patients with mild organic brain syndrome over a period of three months using a series of neurophysiological tests. The results indicated that short-term treatment with the alkaloid improved memory impairment. The side-effects were mild and transient in both the dihydroergocryptine and placebo groups and there were no alterations in blood chemistry.

Forty elderly patients (13 men and 27 women, aged 56 to 80 years) were enrolled in a single-blind, randomized, parallel study to assess the efficacy and safety of selegiline (10 mg, once daily) and that of L-acetylcarnitine (500 mg, twice daily) in the treatment of patients with mild-to-moderate Alzheimer-type disorders. The treatments lasted 90 days, after a run-in period of 15 days. An extensive psychometric examination, carried out at baseline and subsequently at every 30 days of treatment, was used for evaluation of efficacy. Drug safety was assessed by noting any adverse effects that occurred during treatment and by performing laboratory tests at the beginning and end of treatment. According to the resulting data, selegiline therapy led to a global improvement in the capacity for the processing, storage, and retrieval of given information. Improvements in verbal fluency and visuospatial abilities were also noted. The marked between-group differences demonstrate that, at the dosage used, selegiline was far more effective than L-acetylcarnitine with respect to the degree of improvement. Finally, tolerability of both drugs was excellent, inasmuch as neither the monitoring for adverse drug reactions nor laboratory tests revealed any abnormalities resulting from therapy.

After a definition of the condition and a discussion of its physiopathological significance, the need to examine the patient as a whole and provide total therapy is emphasised with reference to both the literature and personal cases. It is concluded: 1) that the mesodiencephalic structures, especially the hypothalamus, are of primary importance in human physiological and pathological processes. The hypothalamus is the real brain of the viscera, the functional bridge between the hypophysis, the limbic structures and the upper cortical centres; 2) that doctors should consider the role of the hypothalamus in the diagnosis and therapy of the total person: a) in evaluating the patient's real emotional and psychological situation; b) in realising that the simple administration of a drug to cure the organic symptom really means only partial treatment of the patient himself.

Elderly hypertensive patients with psycho-organic syndrome were treated with nicardipine (40-60 mg daily) alone or combined with hydrochlorothiazide (30 mg). This treatment led not only to a significant reduction in blood pressure but also to improvement in the score of the scales used for psychogeriatric evaluation (SCAG = Sandoz Geriatric Assessment Scale and HAM-D = Hamilton Rating Scale for Depression). These findings appear to confirm the possibility to consider nicardipine a drug of first choice for the treatment of arterial hypertension in the elderly with psycho-organic syndrome.

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.