Comparison of whole blood and plasma potassium concentrations in dogs using the Reflovet system.

BACKGROUND: The Reflovet system is designed for chemical analysis of whole blood. However, plasma or serum is recommended for potassium analysis because of possible interference from RBC potassium. Because RBC potassium concentration is low in most canine erythrocytes, however, there should be little or no interference. OBJECTIVE: The objective of this study was to compare potassium results obtained in whole blood and in plasma from dogs using the Reflovet system. METHODS: Blood samples were collected from 104 dogs into lithium-heparin tubes. The potassium concentration was measured in whole blood, and subsequently the PCV was measured. Samples were centrifuged and the potassium concentration was measured in plasma. Comparisons were made using Deming's regression and Bland-Altman difference plots. RESULTS: There was very good correlation between results of potassium measurements in whole blood and plasma (r = 0.93). Potassium values were moderately lower in whole blood: Potassium(blood) = 0.912 x Potassium(plasma)+ 0.119. Hemolysis had a negligible effect on the results, but the difference increased with the PCV value. In more than 90% of samples, the difference between the 2 measurements was

Prevalence of orthostatic hypotension in Parkinson's disease.

OBJECTIVES: To investigate the prevalence of orthostatic hypotension and the nature of the postural events related to a fall in blood pressure in patients with Parkinson's disease. METHODS: Blood pressure was measured first in a supine position after a rest of at least 15 minutes and every minute during 10 minutes of an active standing up procedure. Orthostatic hypotension was considered as present when a fall of at least 20 mm Hg of systolic blood pressure was recorded. Postural events which occurred during the standing test were identified from a questionnaire and self reporting. Statistical analysis was performed to determine the relation between orthostatic hypotension and disease characteristics (duration, severity) and the use of antiparkinsonian drugs. Ninety one consecutive patients with Parkinson's disease (48 women, 43 men, mean age 66 (SD 9) years) participated to the study. RESULTS: A fall of at least 20 mm Hg of systolic blood pressure was found in 58.2% of the patients. Orthostatic hypotension was asymptomatic in 38.5% and associated with postural events in 19.8% of the patients. Symptomatic (but not asymptomatic) orthostatic hypotension was related to duration and severity of the disease and with the use of higher daily levodopa and bromocriptine doses. The analysis of the relation between the postural symptoms (and the need for standing test abortion) with the fall in systolic blood pressure allowed the identification of six clinical criteria specific of orthostatic hypotension. A direct relation between the postural changes in systolic blood pressure and the number of clinical events in this clinical scale was found. CONCLUSION: The frequency of orthostatic hypotension in Parkinson's disease is high and it is possible to establish a clinical rating scale which could be used to assess the effects of drugs employed in the management of orthostatic hypotension.

Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study.

OBJECTIVE: To study the effect of the levorotatory form of 5-hydroxytryptophan on the cerebellar symptoms of Friedreich's ataxia. DESIGN: Cooperative double-blind study of the levorotatory form of 5-hydroxytryptophan vs placebo. SETTING: Twelve centers in research hospitals. PATIENTS: Twenty-six patients were included; 19 completed the study (mean +/- SD age of patients, 25.9 +/- 8.1 years). Of these 19 patients, eight were treated with placebo and 11 were treated with the drug. MAIN OUTCOME MEASURES: A semiquantitative scale for kinetic and static ("postural") cerebellar functions and quantitative measurements of time in standard tests that evaluated stance, speech, writing, and drawing. RESULTS: In the active treatment group, a significant decrease of the kinetic score was observed (P = .03), indicating an improvement in coordination. CONCLUSIONS: These results demonstrated that the levorotatory form of 5-hydroxytryptophan is able to modify significantly the cerebellar symptoms in patients with Friedreich's ataxia. However, the effect is only partial and not clinically major.

Abnormal vestibuloocular reflex cancellation in multiple system atrophy and progressive supranuclear palsy but not in Parkinson's disease.

We have measured the gain of the vestibuloocular reflex (VOR) in darkness and its cancellation by fixation in 37 patients with Parkinson's disease (PD), 26 patients with multiple system atrophy (MSA), 11 patients with progressive supranuclear palsy (PSP), and 19 normal volunteers. The capacity to cancel the VOR by fixation (VOR cancellation) was significantly reduced in the MSA and PSP patients compared with the PD and normal subjects (p < 10(-4)). A VOR cancellation < 90% (i.e., the mean VOR cancellation of the normals--2 SD) was present in four PD patients, 23 MSA patients, and 11 PSP patients. This criteria distinguished PD and MSA with a 89% sensitivity and a 89% specificity. Our results demonstrate that the VOR cancellation is impaired in most patients with MSA and PSP but not with PD. In MSA patients, the abnormal VOR cancellation is probably not related to the nigrostriatal dopaminergic deficit and more likely reflects a cerebellar dysfunction. Impaired VOR cancellation is a clinical criteria to differentiate MSA and PSP from PD.

Sublingual apomorphine: a new pharmacological approach in Parkinson's disease?

Apomorphine, a potent dopamine agonist with mixed D1 and D2 properties, has long been recognized to have antiparkinsonian effect. Its oral administration is limited by both its hepatic first pass metabolism and adverse side effects (nausea, vomiting, azotemia). It is now widely used by subcutaneous route for the treatment of severe "off" periods seen with levodopa treatment. However, the use of penjects can be difficult in some patients with severe tremor or akineto-rigid symptoms during "off" periods. Our group has recently investigated the effect of sublingual administration of apomorphine in patients suffering from Parkinson's disease. Sublingual apomorphine was shown to reduce extrapyramidal symptoms. The main characteristics of the pharmacodynamic effects of sublingual apomorphine in parkinsonians and the relationship between pharmacodynamic and pharmacokinetic effects are discussed. Sublingual apomorphine has the advantage of being easier to administer than subcutaneous injection. For the moment, the long-term use of sublingual apomorphine is limited by two major problems: first, time for dissolution and switch "on" (which is longer than after subcutaneous route) and secondly, the occurrence of local side effects (stomatitis). Further clinical studies using either more efficient (tablets with faster dissolution) and better tolerated sublingual formulations or other dopamine agonists should be carried on before recommending this approach in the treatment of Parkinson's disease.

A randomised controlled study comparing bromocriptine to which levodopa was later added, with levodopa alone in previously untreated patients with Parkinson's disease: a five year follow up.

This pilot study was performed to compare the occurrence of long term motor complications in Parkinson's disease when the introduction of levodopa was delayed by an initial treatment with high doses of bromocriptine alone. The trial was a prospective randomised controlled study comparing 31 previously untreated patients with Parkinson's disease initially given bromocriptine alone to which levodopa was later added (group B/D) and 29 other previously untreated patients with Parkinson's disease immediately given levodopa alone (group D). The end point was the occurrence of the first motor complications (wearing off or dyskinesia). Group B/D patients received bromocriptine (52 (SEM 5) mg/day) for 2.7 years, to which levodopa was later added (471 (SEM 46) mg/day). Group D patients received a comparable dose of levodopa alone (569 (SEM 47) mg/day). Both had similar disability scores at the end of the study. Motor complications were fewer and appeared later in group B/D than in group D (56% after 4.9 (SEM 0.5) years of treatment v 90% after 2.7 (SEM 0.5) years, p < 0.01). Wearing off appeared later (p < 0.01) in group B/D (4.5 (SEM 0.6) years) than in group D (2.9 (SEM 0.6) years). Peak dose dyskinesia occurred less often in group B/D patients (three v 14 cases, p < 0.01). This study showed that a three year initial monotherapy with high doses of bromocriptine followed by addition of levodopa delayed the occurrence of long term motor complications usually found in patients with Parkinson's disease treated with levodopa alone from the beginning.

Naltrexone, an opiate antagonist, fails to modify motor symptoms in patients with Parkinson's disease.

One month of adjunct treatment with naltrexone (100 mg/day) was compared with placebo in a double-blind, randomized, cross-over design in two groups of patients with Parkinson's disease. The first group was composed of 10 patients with a moderate motor impairment insufficiently controlled by monotherapy with bromocriptine. The second group was composed of eight patients with L-dopa-induced peak-dose dyskinesia. Naltrexone as compared with placebo did not demonstrate any significant change in motor function in either group. These negative clinical results do not support a significant role of endogenous opioid systems in the pathophysiology of motor impairment in Parkinson's disease.

[Cognitive evaluation of patients with Alzheimer-type dementia by French revised version of the Hierarchic Dementia Scale]. / L'évaluation cognitive des patients présentant une démence de type Alzheimer par la version française révisée de la hierarchic dementia scale. Echelle hiérarchisée de la démence (EHD).

The revised French version of the Hierarchic Dementia Scale (HDS) was assessed in 88 DAT patients (30 men, 58 women, mean age: 70, MMS from 0 to 26). The HDS consisted of 20 subtests which covered the entire range of cognitive functions; each subtest was hierarchically organized. This scale has been validated by the authors in 149 control subjects (Démonet et al., 1990). The goals of the present study were to validate this scale in DAT patients in comparison with the MMS scores and to specify the cognitive impairments of our pathologic population. Results showed that the scores on the HDS were highly correlated with the MMS scores (p < .0001). Some subtests of the HDS (memory subtests and mental control) allow good discrimination between mild demented patients and controls (sensibility = 80.8 p. 100, specificity = 96 p. 100). Conversely some subtests allowed a cognitive follow-up of patients for whom the MMS was no longer useful (MMS scores from 0 to 10). In conclusion, it appears that this scale is useful for drawing cognitive profile of DAT patients and to approach the heterogeneity of dementia.

Normal activation of the supplementary motor area in patients with Parkinson's disease undergoing long-term treatment with levodopa.

Regional cerebral blood flow (rCBF) changes in cortical motor areas were measured during a movement of the dominant right hand in 15 patients with Parkinson's disease deprived of their usual levodopa treatment, in 11 patients with Parkinson's disease undergoing long-term treatment with levodopa, and in 15 normal volunteers. The supplementary motor areas were significantly activated in the normal subjects and in the patients receiving levodopa but not in the patients deprived of levodopa. The contralateral primary sensory motor area was significantly activated in all three groups. The ipsilateral primary sensory motor cortex was not activated in the normal subjects and the non-treated patients but was in the patients treated with levodopa. It is concluded that the supplementary motor area hypoactivation which is observed in akinetic non-treated patients with Parkinson's disease is not present in patients undergoing long-term treatment with levodopa. This result suggests that (a) levodopa improves the functional activity of supplementary motor areas in Parkinson's disease and (b) there is no pharmacological tolerance to this effect. The ipsilateral primary motor cortex activation observed in the patients treated with levodopa could be related to levodopa-induced abnormal involuntary movements.

Migrating motor complex of the intestine and absorption of a biliary excreted drug in the dog.

The role of the migrating motor complex (MMC) of the small intestine in the absorption of an enterally administered marker (tolfenamic acid, TA) used to investigate enterohepatic recycling was studied in the fasted dog. TA was rapidly and extensively absorbed in the duodenum as well as in the ileum. In contrast, the conjugated form of TA (CTA) was not absorbed in the duodenum but only in the ileum, i.e., after bacterial hydrolysis. By administering CTA in the duodenum at different phases (I and II) of the MMC, it was shown that CTA had to be propelled from the duodenum to the ileum by the motor activity of the MMC. Under these conditions, the peak plasma TA concentration was only observed when phase II of the MMC present in the duodenum at the time of CTA administration arrived in the ileum. The estimated mean transit time of CTA from the duodenum to ileum was 45 min and the mean hydrolysis time of CTA to TA was about 75 min. It was concluded that 1) in the fasted dog, a relatively long delay must exist between bile excretion of a conjugate and the reabsorption of its free moiety in the ileum and 2) a realistic physiological model of enterohepatic recycling must take into account the MMC pattern of the intestine when drugs are administered to animals in the fasted state.

Effect of side and rate of stimulation on cerebral blood flow changes in motor areas during finger movements in humans.

We measured, using single photon emission computed tomography, the regional CBF (rCBF) changes in the motor areas of 24 right-handed normal volunteers during the performance of a motor task consisting of sequential finger-to-thumb opposition. Twelve of them performed the task with their right and their left hands consecutively with a fast frequency and large amplitude. The other 12 subjects performed the task with their right hand only at a slow frequency and small amplitude. The contralateral primary sensorimotor areas (S1/M1), supplementary motor area (SMA), and ipsilateral cerebellum were significantly activated during right and left finger movements performed at fast frequency and large amplitude. No significant difference was found between the rCBF changes induced by the right dominant and left nondominant hands. When the task was performed with a slow rate and small amplitude, the SMA was significantly activated while no significant changes were observed in the contralateral S1/M1 or in the ipsilateral cerebellum. These results demonstrate (a) that hand dominance evokes no differences in the activation of the main motor areas and (b) that the frequency and amplitude of the movement have a major effect on the quantitative and qualitative aspect of activation of motor areas in humans.

Effects of yohimbine on plasma catecholamine levels in orthostatic hypotension related to Parkinson disease or multiple system atrophy.

Different pathophysiological mechanisms may underly orthostatic hypotension (OH) observed in neurological degenerative disorders. The present study investigates the responses to the pharmacological activation of sympathetic pathways induced by yohimbine (0.2 mg/kg orally) through measurements of plasma catecholamine levels in parkinsonian patients with (n = 9) or without OH (n = 11), in patients with multiple system atrophy (MSA) plus OH (n = 9), and in controls (n = 6). Basal norepinephrine plasma levels in parkinsonian patients with OH (71 +/- 11 pg/ml) were significantly lower (p < 0.05) than in parkinsonian patients without OH (280 +/- 25 pg/ml) or in controls (259 +/- 48 pg/ml). In patients with MSA plus OH, basal catecholamine plasma levels were in the normal range (344 +/- 54 pg/ml). Yohimbine significantly increased norepinephrine (p < 0.05) but not epinephrine plasma levels in all groups. However, the increment obtained in parkinsonian patients with OH (+53 +/- 18 pg/ml) remained significantly lower (p < 0.05) than in parkinsonian patients without OH or in controls (+638 +/- 140 and +457 +/- 103 pg/ml, respectively) as well as in MSA plus OH (+633 +/- 142 pg/ml). Yohimbine failed to modify the blood pressure and heart rate at the dose used. The results suggest that the yohimbine test is useful to elucidate the site of the dysfunction of the efferent sympathetic pathways in these two conditions. In Parkinson disease with OH, the lesion is both central and postganglionnic, whereas in MSA it is only centrally located.

Lack of yohimbine effect on ambulatory blood pressure recording: a double-blind cross-over trial in parkinsonians with orthostatic hypotension.

Yohimbine is an alpha 2-adrenergic antagonist which has been proposed for the treatment of orthostatic hypotension (OH). We investigated in a double-blind placebo-controlled crossover trial the effects of yohimbine (2 mg tid) on blood pressure (BP) and heart rate (HR) using ambulatory monitoring of blood pressure (AMBP) in 17 patients (69 +/- 5 years) with Parkinson's disease (PD) suffering from non drug-induced OH. At the end of each sequence of 4 weeks, mean systolic (SBP) and diastolic (DBP) BP and HR (+/- SD), BP variability (coefficient of variation of the mean) and nychtemeral rhythm were calculated for day-time (09:00-19:00 h) and night-time (23:00-06:00 h). OH related to PD was characterized by: i) loss of the nychtemeral rhythm of BP (night/day ratio: 1.18 +/- 0.14) but not of HR (night/day ratio: 0.87 +/- 0.04), ii) high variability of BP during day-time and iii) post-prandial hypotension (12 out of 17 patients). There was no significant difference in AMBP parameters between baseline, yohimbine and placebo periods. This study shows that AMBP is a simple and reproducible method to assess the effects of drugs used in the management of OH on BP parameters (mean values and variability) and that yohimbine is not effective to correct OH of PD. Future studies must investigate other more selective alpha 2-adrenergic antagonists.

[Ambulatory monitoring of blood pressure in orthostatic hypotension of Parkinson disease]. / Enregistrement ambulatoire de la pression artérielle dans l'hypotension orthostatique de la maladie de Parkinson.

Ambulatory recordings of blood pressure (BP) and heart rate were performed using a Spacelabs device during day and night periods in parkinsonian patients with (n = 19) or without (n = 19) orthostatic hypotension. In patients with orthostatic hypotension, the average blood pressure during the night (systolic BP: 137 +/- 5 mmHg; diastolic BP: 80 +/- 3 mmHg) was higher (p < 0.05) than during the diurnal period (systolic BP: 121 +/- 3 mmHg; diastolic BP: 76 +/- 2 mmHg). In parkinsonian patients without orthostatic hypotension, a physiological decrease in BP was recorded during the nocturnal period. In patients with orthostatic hypotension, BP variability was higher (p < 0.05) during the day (systolic BP: 14.6 +/- 1.3%, diastolic BP: 16.5 +/- 1.0%) than during the night (systolic BP: 9.1 +/- 0.8%, diastolic BP: 10.8 +/- 1.1%). The blood pressure load (% of BP values above 140/90 mmHg) during the night was significantly higher (p < 0.05) than during the day for both systolic (41.2 +/- 8.1 vs 19.6 +/- 4.7%) and diastolic BP (24.9 +/- 6.9 vs 16.3 +/- 4.9%). A normal decrease in heart rate was found in both groups during the night. A fall of at least 25 mmHg in systolic BP after meals occurred in 10 patients with orthostatic hypotension and in 1 without orthostatic hypotension. These results indicate that orthostatic hypotension in Parkinson's disease is associated with specific modifications of ambulatory blood pressure including loss of circadian rhythm of BP, increased diurnal BP variability and often post-prandial hypotension.

The anatomy of phonological and semantic processing in normal subjects.

We assessed brain activation of nine normal right-handed volunteers in a positron emission tomography study designed to differentiate the functional anatomy of the two major components of auditory comprehension of language, namely phonological versus lexico-semantic processing. The activation paradigm included three tasks. In the reference task, subjects were asked to detect rising pitch within a series of pure tones. In the phonological task, they had to monitor the sequential phonemic organization of non-words. In the lexico-semantic task, they monitored concrete nouns according to semantic criteria. We found highly significant and different patterns of activation. Phonological processing was associated with activation in the left superior temporal gyrus (mainly Wernicke's area) and, to a lesser extent, in Broca's area and in the right superior temporal regions. Lexico-semantic processing was associated with activity in the left middle and inferior temporal gyri, the left inferior parietal region and the left superior prefrontal region, in addition to the superior temporal regions. A comparison of the pattern of activation obtained with the lexico-semantic task to that obtained with the phonological task was made in order to account for the contribution of lower stage components to semantic processing. No difference in activation was found in Broca's area and superior temporal areas which suggests that these areas are activated by the phonological component of both tasks, but activation was noted in the temporal, parietal and frontal multi-modal association areas. These constitute parts of a large network that represent the specific anatomic substrate of the lexico-semantic processing of language.