BACKGROUND: Pituitary pars intermedia dysfunction (PPID), a neurodegenerative disease leading to reduced dopamine production, is a common disease in aged horses. The treatment is based on administration of the dopamine agonist pergolide. This drug has been related to valvular fibrosis in humans, but the cardiovascular effect of this drug has not yet been investigated in horses.
OBJECTIVE: To determine whether pergolide induces valvular disease in horses or affects the cardiac function.
METHODS: Standard, tissue Doppler (TDE) and two-dimensional speckle tracking (STE) echocardiography were performed in horses with diagnosed PPID based on adrenocorticotropic hormone dosage. Measurements taken in horses treated with pergolide were compared with those from untreated horses with nonparametric t-tests. Furthermore, measurements from follow-up examinations performed at least three months after the initial exam were compared with a Wilcoxon signed rank test for repeated measurements in each group.
RESULTS: Twenty-three horses were included. None of the 12 horses under treatment developed valvular regurgitation. Furthermore, no differences in the measurements of the left ventricular systolic or diastolic function could be seen between the group of horses with treatment and those without treatment. Measurements taken in the follow-up exam did not differ compared to those taken in the initial exam in both groups.
CONCLUSIONS: No changes of the left ventricular function assessed by TDE and STE could be shown in a small population of horses with confirmed PPID. Treatment with pergolide did not affect the ventricular function nor induce valvular disease.

OBJECTIVE: The nutritional status of 36 patients with equine pituitary pars intermedia dysfunction (PPID) under pergolide treatment was investigated.
METHODS: The body condi tion score (BCS) and feeding were determined at the beginning of the study and after 60 and 120 days. Sampled blood for control of pergolid therapy were used for insulin and glucose measurement. A standardized questionnaire regarding the symptoms of the disease, including hypertrichosis and weight change, was completed by the owners.
RESULTS: The mean BCS (scale of 1 = cachexia to 9 = grossly obese) was 3.1 ± 0.8 (large horses 2.7 ± 0.8, ponies 3.5 ± 0.8). The mean energy requirement of the large horses was estimated to be 74 ± 10 MJ of metabolizable energy, but the intake amounted only to 65 ± 15 MJ. There was a significant correlation between the BCS and the estimated energy intake in percent of requirements in the large horses. The energy requirements of the ponies were generally met. The patients were fed a mean of 2.0 ± 0.7 meals of roughage per day (total roughage intake per day 0.2-2.1 kg/100 kg body weight) and a maximum of one meal of concentrates. Sixteen ponies and one large horse did not receive any concentrates, whereas five ponies and 14 horses were fed concentrates (mean amount for ponies 0.15 kg and for large horses 0.8 kg). The requirements for zinc, copper, selenium and vitamins A and E were not met in the majority of patients. Blood glucose levels were within the reference range in all samples, but insulin levels were elevated in seven animals at least at one sampling point. The serious underweight of some of the patients was not recognized as a problem by some of the owners.
UNASSIGNED: Owners of PPID patients need more guidance on body condition scoring, amount of feed, number of meals, and logistics of feeding to avoid malnutrition of their animals.

Impulse control behaviors (ICBs) are impulsive-compulsive behaviors often associated with dopamine replacement therapy in Parkinson\'s disease (PD). Although remission can occur in ICB, only four reports on the ratio of remission and the persistence of ICB have been published, and the associated factors with ICB remission or persistence have been little known. Therefore, we conducted a longitudinal assessment of the remission, persistence, and development of ICB and those associated factors in patients with PD.
We retrospectively investigated a PD database at Aomori Prefectural Central Hospital, Japan. One hundred and forty-eight patients with PD who could be followed up for 2 years were enrolled. ICB was assessed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson\'s disease. Motor severity (Hoehn and Yahr scale and United Parkinson\'s Disease Rating Scale), cognitive function (Mini-Mental State Examination), and other clinical variables (sex, age, onset age, disease duration, olfactory dysfunction, and dyskinesia) and medications used to treat PD were assessed. Univariate analyses were performed.
Seven patients were excluded because of the exclusion criteria, and 141 patients were analyzed. Thirty patients (21.3%) had ICB at baseline, and these patients also had significantly higher use of pergolide. The ICB remission rate was 60%, the ICB persistence ratio was 40%, and the ICB development ratio was 12.6% over 2 years. Statistically, younger age and pergolide use were associated with ICB persistence. Being male, having dyskinesia, and rotigotine, entacapone, zonisamide, and istradefylline use were associated with ICB development.
This study suggests that younger age and pergolide use may be the new associated factors with ICB persistence and that entacapone, zonisamide, and istradefylline use may be associated with the development of ICB. Drug profiles and medication practices in Japan may explain the association of these factors with ICB.

Serotonergic drugs, such as pergolide, have been associated with the development of cardiac valvular myxoid thickening and regurgitation in humans and more recently in rats. These effects are potentially mediated by the 5-hydroxytryptamine (5-HT)(2B) receptor (5-HT(2B)R). Therefore, we sought to determine whether cyproheptadine, a 5-HT(2B)R antagonist, might prevent toxic valvulopathy in an animal model of pergolide-induced valvular heart disease. For this purpose, 50 male Wistar rats received daily intraperitoneal injections of pergolide (0.5 mg/kg, n = 14), pergolide (0.5 mg/kg) combined with cyproheptadine (10 mg/kg, n = 12), cyproheptadine (10 mg/kg, n = 12), or no injections (control, n = 12) for 20 wk. Echocardiography was performed blindly at baseline and at 10 and 20 wk followed by pathology. At baseline, no differences between groups were found with echocardiography. At 20 wk, aortic regurgitation was present in all pergolide-treated animals, whereas it was less frequently observed in the other groups (P < 0.0001). For the other valves, this difference was less pronounced. On histopathology, not only aortic but also mitral valves were thicker, myxoid, and exhibited more 5-HT(2B)R-positive cells in pergolide-treated animals compared with the other groups. Moreover, regurgitant aortic and mitral valves were thicker than nonregurgitant aortic and mitral valves. In conclusion, we found that cyproheptadine prevented pergolide-induced valvulopathy in rats, which was associated with a reduced number of 5-HT(2B)R-positive valvular cells. This may have important clinical implications for the prevention of serotonergic drug-induced valvular heart disease.

The aim of this study was to evaluate the safety and tolerability of overnight switching from ergot-derived dopamine agonists such as cabergoline to equivalent doses of pramipexole in patients with Parkinson\'s disease. The safety of overnight switching to pramipexole from cabergoline, which has a long plasma half-life and may cause dopaminergic excess after switchover, has not been established. Twenty-two consecutive patients with Parkinson\'s disease were included, 18 of them on cabergoline treatment. Patients were assessed with the Unified Parkinson\'s Disease Rating Scale (UPDRS) given just prior to switching as well as after 2, 4, 8, and 12 weeks of treatment. Eight patients (36.4%) experienced adverse events, of whom two were withdrawn from the study. Generally, however, significant improvement in the UPDRS was obtained after 2 weeks and improvement was maintained up to 12 weeks of treatment. Therefore, our study showed that overnight switching from ergot-derived dopamine agonists including cabergoline to dose-equivalent pramipexole was safe when associated with good patient compliance.

BACKGROUND: Cabergoline is an ergotic dopamine agonist with D2 receptor activity and a very long half-life. This pharmacological profile may result in clinically different effects. Small clinical trials indicate that overnight switching from 1 agonist to another can be performed safely.
OBJECTIVE: To determine safety and efficacy of overnight switching from dopamine agonists to cabergoline in patients with advanced Parkinson disease (PD).
METHODS: Patients with advanced PD and motor complications not optimally controlled by levodopa and a stable dose of bromocriptine, pergolide, pramipexole, and ropinirole were converted to cabergoline overnight. Patients were assessed by using an on-off diary, Unified Parkinson Disease Rating Scale (subscales I-IV), Parkinson\'s Disease Quality of Life 8 (PDQ-8), an ad hoc sleep questionnaire and an ad hoc off-period severity questionnaire. All rating scales were administered just before conversion and after 2, 6, and 12 weeks of treatment, when patients were on an optimal dose of cabergoline. Adverse effects were assessed at every visit following a check list.
RESULTS: One hundred twenty-eight patients were included in the trial. Forty were on pergolide (mean dose, 2.8 mg/d), 38 on pramipexole (mean dose, 2.1 mg/d), and 32 on ropinirole (mean dose, 8.1 mg/d). Patients on bromocriptine (n = 18) were excluded from the analysis because of the small sample size. Three patients reported serious side effects (respiratory arrest, dyskinesias, and face edema and abdominal pain). Twenty-eight patients reported 41 adverse events. Twelve patients were withdrawn due to adverse effects (hallucinations [n = 5], dyspnea [n = 1], dizziness [n = 4], and vascular problems [n = 2]). A significant improvement in assessed parameters was obtained (P < 0.0001). Mean levodopa dose remained unchanged. After 12 weeks, the mean dose of cabergoline was 3.2 mg, and 25% of patients were taking the drug twice a day.
CONCLUSIONS: Switching from pergolide, ropinirole, and pramipexole to cabergoline in an overnight schedule is safe. The observed clinical improvement may be related to a placebo effect, to the use of low doses of dopamine agonists, or to a direct effect of cabergoline.

OBJECTIVE: To investigate the prevalence and risk factors of heart valve disease in patients having PD treated with pergolide.
METHODS: Prospective observational study.
METHODS: Patients were recruited at the Hôpital de la Pitié-Salpêtrière, Paris, France. Patients Ninety-six patients having PD treated with pergolide for longer than 3 months vs 50 control subjects. Intervention Standardized echocardiography performed by an investigator blinded to treatment status. Main Outcome Measure Moderate to severe regurgitation in at least 1 heart valve.
RESULTS: One hundred thirty-three echocardiograms (86 in the pergolide-treated group and 47 in the control group) were analyzed in the study. Moderate to severe regurgitation was found in 15 patients treated with pergolide (17.4%) and in 2 control subjects (4.3%) (odds ratio [OR], 4.75; 95% confidence interval [CI], 1.02-22.1; P = .03). Moderate to severe regurgitation was associated with the cumulative dose of pergolide (OR, 1.37; 95% CI, 1.04-1.81 per 10-mg/kg increase; P =.03). Including the present study, the meta-analysis comprised 7 trials (394 patients treated with pergolide and 280 controls). The overall OR for moderate to severe regurgitation was 3.1 (95% CI, 1.7-5.6; P < .001) in the pergolide-treated group. Risk differences were correlated with the mean cumulative dose of pergolide (r = 0.90, P < .001).
METHODS: Using an end point of moderate to severe heart valve regurgitation, we performed a meta-analysis of patients having Parkinson disease (PD) treated with pergolide mesylate vs control subjects by searching PubMed (January 1, 1966, to April 1, 2007) and the Cochrane databases to identify English-language prospective observational studies that reported echocardiographic data.
CONCLUSIONS: Heart valve disease is independently associated with the use of pergolide treatment in patients having PD and correlates with its cumulative dose. Trial Registration clinicaltrials.gov Identifier: NCT00202657.

The objective of this study was to investigate neurochemical and metabolic changes in the motor cortex in a group of de novo Parkinson\'s disease (PD) patients before and after 6 mo treatment with the dopamine agonist pergolide. Proton magnetic resonance spectroscopy (1H-MRS) has been used to study striatal and cortical metabolism in PD and other parkinsonisms. So far, no studies evaluating possible brain metabolic changes in PD patients before and after dopaminergic therapy have been reported. De novo PD patients (11) and controls (11) underwent clinical evaluation (UPDRS-III motor evaluation) and a first single-voxel 1H-MRS of the motor cortex. 1H-MRS studies were performed using the PROBE-SV System implemented on a 1.5 Tesla Scanner (GE Medical System, Milwaukee, WI). Pergolide was administered up to a dose of 1 mg t.i.d. After 6 mo follow-up, all patients were clinically evaluated and a second single-voxel 1H-MRS was performed. Lower values of Cho/Cr and NAA/Cr ratios were observed in the motor cortex of PD patients compared with controls (P < 0.02 and P < 0.01, respectively). After 6 mo therapy with pergolide (1 mg t.i.d), PD patients showed an improvement in motor performances (P < 0.05) and an increase in Cho/Cr ratios in the motor cortex at the second 1H-MRS evaluation (P < 0.05) was reported. In conclusion, cortical NAA/Cr and Cho/Cr ratios may be impaired in de novo PD. Dopaminergic therapy capable of improving motor function may restore the Cho/Cr ratio in the motor cortex.

暂无摘要。

OBJECTIVE: To evaluate the relationship of the severity of restless legs syndrome (RLS) as assessed by a subjective, patient-rated scale (International RLS Study Group Rating Scale, IRLS), and of periodic leg movements in sleep (PLMS) as an objective parameter, in two different patient populations.
METHODS: Data of 200 unmedicated patients with idiopathic RLS were evaluated. Group 1 (n=100) consisted of selected patients participating in the Pergolide European Australian RLS (PEARLS) study. Group 2 (n=100) represented an outpatient RLS population investigated in a Sleep Disorders Center. Additionally, Group 1 was also evaluated after a 6 week double-blind treatment period, where 47 patients received pergolide and 53 patients placebo.
RESULTS: In unmedicated patients, IRLS scores correlated with the PLMS-arousal index (r=0.22, p=0.033) but not with the PLMS index in Group 1 while no correlation was found in Group 2. The change of the IRLS score under treatment in Group 1 correlated significantly both with the change of the PLMS index (r=0.42, p<0.001) and the change of the PLMS-arousal index (r=0.38, p<0.001).
CONCLUSIONS: The IRLS adequately reflects treatment changes of PLMS indices. In unmedicated patients, the IRLS correlates with PLMS indices probably only in selected RLS populations with predefined PSG criteria and high PLM activity.
CONCLUSIONS: The IRLS is an appropriate subjective rating scale for measuring treatment effects in RLS.