Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

Utility of the PFA-100 as a screening test of platelet function: an audit of haemostasis laboratories in Australia and New Zealand.

The PFA-100 is a relatively new laboratory instrument, first described in 1995. There have since been numerous studies assessing its utility as a screening tool for platelet dysfunction and/or von Willebrand's disease (VWD). The PFA-100 displays variable sensitivity to different types of platelet disorders, as well as to antiplatelet medication (e.g. aspirin), with similar caveats for monitoring of primary haemostasis-promoting therapies in platelet dysfunction. There is therefore considerable uncertainty regarding its utility within this context, and we have accordingly performed an audit of usage among participants of the Royal College of Pathologists of Australasia Quality Assurance Program. Of 105 laboratories surveyed, 40 responded that they performed platelet function testing, with 26 (65%) further indicating they utilized the PFA-100. We report a wide variety of laboratory usage among these users, including numbers of tests performed [annual median (range) = 270 (15-6000)], sources of requests (clinical sources and localities), testing criteria and follow-up action. Most tests were completed within 4 h of collection, as recommended by the manufacturer, and most tests were performed as a replacement, or as a preliminary screen of platelet function (i.e. classical aggregation). Most abnormal findings, however, were attributed to antiplatelet medication such as aspirin.     

Physiological analysis of simple rapid movements in patients with cerebellar deficits.

Patients with cerebellar deficits made elbow flexion movements as rapidly as possible for three different angular distances. Electromyographic activity of biceps and triceps and the kinematics of the movements were analysed. Results were compared with those of normal subjects making both rapid and slow movements. In the patients, the first agonist burst of the biceps was frequently prolonged regardless of the distance or speed of the movement. The most striking kinematic abnormality was prolonged acceleration time. The pattern of acceleration time exceeding deceleration time was common in patients but uncommon in normal subjects. The best kinematic correlate of the duration of the first agonist burst was acceleration time. Altered production of appropriate acceleration may therefore be an important abnormality in cerebellar dysfunction for attempted rapid voluntary movements.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Ipsilateral blepharospasm and contralateral hemidystonia and parkinsonism in a patient with a unilateral rostral brainstem-thalamic lesion: structural and functional abnormalities studied with CT, MRI, and PET scanning

A patient developed progressive right hemidystonia in childhood. Subsequently, left-sided blepharospasm, slurred and stuttering speech, and right-sided rigidity and bradykinesia, responsive to dopamine agonists, appeared. Investigation with computed tomography and magnetic resonance imaging (MRI) at age 43 years revealed a left-sided calcified rostral brainstem-thalamic lesion of uncertain aetiology. Although no structural lesion was seen in the striatal regions, L-[18F]-fluorodopa uptake was severely diminished in the left striatum but normal on the right. Dopamine receptor binding identified by [11C]-methylspiperone was in the normal range on both sides.     

Transient depletion of nucleus accumbens dopamine content may contribute to initial akinesia induced by MPTP in common marmosets

Acute treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused an initial profound akinesia and other motor deficits. However, over the following months akinesia gradually disappeared although the animals remained clumsy and poorly coordinated. At 10 days following MPTP treatment there was a profound decrease in the dopamine, HVA and DOPAC content of the caudate nucleus, putamen and nucleus accumbens. By 3-4 months following MPTP treatment the animals had largely recovered from their akinesia, but the caudate nucleus and putamen dopamine, HVA and DOPAC content remained low. In contrast, the dopamine content of the nucleus accumbens had returned towards normal and the metabolite levels were higher than at 10 days. No overall alterations in 5HT or 5HIAA levels were observed at either time point. The transient and reversible nature of dopamine loss in the nucleus accumbens may contribute to the initial profound akinesia exhibited by common marmosets treated with MPTP. The restoration of dopamine levels in the nucleus accumbens may be partially responsible for the subsequent recovery of motor function that occurs in MPTP-treated marmosets.