[Severe orthostatic hypotension and intramedullary tumor: a case report and review of the literature]. / Hypotension orthostatique sévère et tumeur intramédullaire. A propos d'un cas et revue de la littérature.

A 55-year-old woman presented with bilateral neuropathic pain of the upper limbs, motor palsy of the right arm, urinary dysfunction, and postural dizziness. MRI showed an intramedullary cervical tumor with a solid portion extended from C1 to C3 surrounded by a cystic portion. A macroscopic complete resection was performed and histological examination confirmed the diagnosis of ependymoma. Postoperatively, the patient's neuropathic pain and postural dizziness worsened, with syncopal attack while upright because of severe orthostatic hypotension (OH). On physical examination, her supine systolic blood pressure was 130 mmHg and fell to 80 mmHg while sitting with no change in heart rate. We found motor palsy of the left arm, bilateral ataxia, and urinary retention. Three months later, the patient was still bedridden, notably because of the OH. After 6 months, with the association of preventative measures of OH and high doses of a direct alpha1-adrenoreceptor agonist, a vasoconstricting agent, the patient recovered an independent gait permitting her to walk unassisted. The main causes of OH include medication, nonneurogenic causes such as cardiac insufficiency, and central or peripheral neurogenic causes such as diabetic insufficiency. Brainstem tumors are known to provide severe OH but this symptom has been seldom described in a purely spinal cord lesion. We report an interesting case of severe OH that had complicated the surgical treatment of a high cervical spinal cord ependymoma and we review the literature.

Frontotemporal dementia, motor neuron disease and tauopathy: clinical and neuropathological study in a family.

We report a familial disorder occurring in three patients that presented as frontotemporal dementia (FTD). A neuropathological study was performed in a 58-year-old patient, who developed FTD 2 years prior to the onset of motor neuron disease (MND), and died at age 62. Lesions indicative of associated MND were observed: neuronal loss in the anterior horns of the spinal cord, Bunina bodies, axonal spheroids, degeneration of the pyramidal tracts, and of FTD: decreased neuronal density and laminar microvacuolation of layers II and III in the frontal and temporal cortex. Ubiquitin-only-immunoreactive changes were found in the spinal cord and medulla, but were absent from the temporal and frontal cortex. There were also widespread deposits of various neuronal and glial inclusions containing abnormally phosphorylated tau protein, the Western blotting pattern of which was characterized by two major bands of 64 and 69 kDa. There were no abnormalities of the entire coding sequences of microtubule-associated protein tau (MAPT) and copper-zinc superoxide dismutase (SOD(1)) genes. Our results suggest that FTD associated with MND can be caused by a larger spectrum of neuropathological lesions than commonly accepted.

Alfuzosin, an alpha1-adrenoceptor antagonist for the treatment of benign prostatic hyperplasia: once daily versus 3 times daily dosing in healthy subjects.

OBJECTIVE: A new patented prolonged release formulation of the alpha1-adrenoceptor antagonist alfuzosin has been developed for once-daily (OD) administration in benign prostatic hyperplasia (BPH). This study was designed to compare 2 dose regimens: 10 mg OD alfuzosin and 2.5 mg TID alfuzosin at steady state. METHODS: In an open, randomized crossover study with a 9-day washout between treatments, 18 healthy male subjects (50 - 65 years) received OD or TID alfuzosin tablets orally over 5 days. Both formulations were administered according to the schedule recommended for therapeutic use: OD was administered 5 min after the evening meal, TID was administered in the evening, then in the morning and at noon (30 min before meals). On the fifth day, plasma concentrations were quantitated by HPLC with spectrofluorometric detection. RESULTS: The following pharmacokinetic parameters refer to the geometric mean values for both formulations. Mean Cmax value of 10 mg OD alfuzosin was 15.8 ng/ml at a median t(max) of 9.0 h; Cmax was higher and reached earlier from 2.5 mg alfuzosin TID: 19.3 ng/ml, 19.7 ng/ml and 20.3 at 1.0 hour after each dosing, respectively. Mean AUC(0-24) values after OD and TID were 228.3 and 226.0 ng x h/ml, respectively. Based on AUC(0-24) values corrected by the administered daily dose, the relative bioavailability of alfuzosin OD was 75.7% with a 90% confidence interval of 68.0 - 84.3%. Non-corrected AUC(0-24) values were bioequivalent with a ratio estimate of 101.0% and a 90% confidence interval of 90.7 - 112.5%. The higher daily dose compensated for the loss of bioavailability observed with the OD formulation. Mean t1/2z value was longer for the OD (8.9 h) than the TID formulation (6.9 h). Variability between individuals was similar for the 2 formulations. Both dose regimens were well tolerated. CONCLUSIONS: Alfuzosin 10 mg once-daily provides a suitable pharmacokinetic profile for a once-daily administration, equivalent bioavailability between the 2 dosage regimens and a good safety profile justify the use of alfuzosin 10 mg in patients with BPH.

Safety and pharmacokinetics of a single oral dose of amisulpride in healthy elderly volunteers.

OBJECTIVE: Amisulpride is a substituted benzamide neuroleptic, which binds selectively to dopamine D2 and D3 receptors, mainly in the limbic structures. States of delusion and agitation occur frequently in the population aged more than 65 years, especially in demented patients and this sometimes requires the use of neuroleptics. The objectives of this study were to determine the safety and the pharmacokinetic profile of 50 mg of amisulpride administered orally as a single dose to elderly volunteers. METHODS: Twenty healthy volunteers (10 men and 10 women) aged 65 79 years were included in this open trial. Frequent measurements of blood pressure and heart rate were made and ECG and blood samples were performed up to 72 h after drug intake. RESULTS: The overall clinical and cardiovascular safety was satisfactory. The mean Cmax of the racemate amisulpride in elderly people was 64.1+/-6.7 ng ml(-1), and was not different from the value of 56+/-4.1 ng ml(-1) in young subjects. As with the Cmax, the mean values of t1/2 and AUC in elderly people (15.6+/-1.3 h and 667+/-51 ng. ml(-1).h, respectively) were not different to values observed in young subject (respectively 11.7+/-0.5 h and 603+/-25 ng m1(-1) h). CONCLUSION: A single oral dose of amisulpride was well tolerated and showed a similar pharmacokinetic profile in healthy elderly and young subjects. However, these findings should be confirmed after multiple dosing in a larger population in order to establish the lack of need of dosage adjustment in this elderly population.

Influence of age on the pharmacokinetics of naftidrofuryl after single oral administration in elderly versus young healthy volunteers.

The aim of this study was to evaluate and compare the pharmacokinetics of naftidrofuryl (CAS 3200-06-4) after single oral administration of a 200 mg naftidrofuryl tablet (Praxilene) in Caucasian male and female elderly healthy volunteers versus young healthy volunteers. Thirty healthy volunteers were included in a randomised phase I trial in 3 parallel groups of 10 subjects aged 18-35 years (group 1), 60-70 years (group 2) and 70-80 years (group 3). Blood samples were taken over a period of 24 h after dosing for evaluation of the pharmacokinetics of naftidrofuryl. The Cmax, tmax, AUC0-t parameters were measured and t1/2 and AUC0-alpha were calculated by a model independent method. The mean (+/- SD) pharmacokinetic parameters of naftidrofuryl after single oral administration of 200 mg of naftidrofuryl for group 1 were as follows: tmax 3.5 h (median), Cmax 284 +/- 136 ng/ml, t1/2 3.69 +/- 1.30 h, AUC0-t 1865 +/- 905 h.ng/ml and AUC0-inf 2055 +/- 901 h.ng/ml; for group 2: tmax 2.75 h (median), Cmax 282 +/- 165 ng/ml, t1/2 3.03 +/- 1.08 h, AUC0-t 1783 +/- 1147 h.ng/ml and AUC0-inf 1856 +/- 1158 h.ng/ml; for group 3: tmax 2.5 h (median), Cmax 271 +/- 86 ng/ml, t1/2 3.50 +/- 1.29 h, AUC0-t 1742 +/- 544 h.ng/ml and AUC0-inf 1834 +/- 549 h.ng/ml. Statistical analysis was performed on the pharmacokinetic parameters with one-way ANOVA in order to compare each age group. The results of the pharmacokinetic and statistical analysis showed no significant difference between each age group. The mean pharmacokinetic parameters of naftidrofuryl after single oral administration of 200 mg of naftidrofuryl in the whole population were as follows: tmax 2.75 h (median), for Cmax 279 +/- 128 ng/ml, t1/2 3.41 +/- 1.22 h, AUC0-t 1797 +/- 870 h.ng/ml for AUC0-inf 1910 +/- 877 h.ng/ml. In conclusion, advanced age did not appear to influence the pharmacokinetic profile of oral naftidrofuryl, and therefore it is not necessary to adjust the dosage of naftidrofuryl in this population.