Elevated 1-h plasma glucose following 75-g oral glucose load is a predictor of arterial stiffness in subjects with normal glucose tolerance.

AIMS: The study aimed to investigate arterial stiffness in subjects with normal glucose tolerance. METHODS: BMI, systolic blood pressure, fasting plasma glucose, lipid variables, ankle-brachial pressure index and brachial-ankle pulse wave velocity were measured in 2059 subjects from Takasaki city, located approximately 100 km north of Tokyo in Japan. Following a 75-g oral glucose tolerance test, only subjects with normal glucose tolerance were selected. RESULTS: One-hour post-challenge plasma glucose levels were correlated with brachial-ankle pulse wave velocity values (r = 0.340, P < 0.0001). When subjects with normal glucose tolerance were divided into three groups-group 1 (1-h plasma glucose < 8.56 mmol/l, n = 1595), group 2 (1-h plasma glucose ≥ 8.56 and < 10.17 mmol/l, n = 334) and group 3 (1-h plasma glucose ≥ 10.17 mmol/l, n = 130)-the brachial-ankle pulse wave velocity of group 3 (1473 ± 322 cm/s) was significantly higher than that of group 2 (1355 ± 252 cm/s) and brachial-ankle pulse wave velocity of group 2 was also significantly higher than that of group 1 (1275 ± 212 cm/s). CONCLUSIONS: We have identified that, in normal glucose tolerance, arterial stiffness is advanced in subjects with higher 1-h post-challenge plasma glucose in spite of the normal range for BMI, systolic blood pressure, fasting plasma glucose and lipid variables. Higher 1-h plasma glucose level is a risk factor for arterial stiffness in normal glucose tolerance.

Interleukin 3 as a trophic factor for central cholinergic neurons in vitro and in vivo.

We have found that interleukin 3 (IL-3), a growth factor for hematopoietic cells, is a novel trophic factor for mouse and rat central cholinergic neurons. It enhanced neurite outgrowth and elevated choline acetyltransferase activity. The effect seems to be specific for cholinergic neurons, since somatostatin release and glutamic acid decarboxylase and 2',3'-cyclic nucleotide 3'-phosphodiesterase activities were not significantly influenced by IL-3. In vivo, IL-3 was infused into the lateral ventricles of rats after unilateral axotomy of the septohippocampal pathways. Two weeks later, the IL-3-treated animals showed significant numbers of acetylcholinesterase-positive neurons remaining in the septal region.

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations.

BACKGROUND: Early-onset ataxia with hypoalbuminemia is regarded as a variant form of Friedreich ataxia in Japan. Early-onset ataxia with hypoalbuminemia and ataxia with ocular motor apraxia have been considered as the same clinical entity because of the recent identification of a common mutation in the aprataxin gene. A new clinical entity named early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) has been proposed to explain these two diseases. OBJECTIVE: To disclose the clinical features of EAOH and to identify the mutations in the aprataxin gene in six patients in four Japanese families with EAOH. METHODS: The clinical features, laboratory findings, sural nerve biopsy results, and brain MRI or CT findings for these patients were evaluated, and molecular analysis was performed, which involved sequencing of the aprataxin gene directly or use of the subcloning method. RESULTS: Cerebellar ataxia and peripheral neuropathy were noted in all six patients. Ocular motor apraxia was observed in five patients; two of these patients had obvious head thrust. Choreiform movements of the limbs and mental deterioration were observed in five patients. Although foot deformity was noted in five patients, kyphoscoliosis was noted only in one patient. In all patients, hypoalbuminemia and hypercholesterolemia were evident, and brain MRI or CT showed marked cerebellar atrophy. Nerve biopsy revealed depletion of large myelinated fibers in three of the five patients examined. Molecular analysis of the aprataxin gene revealed an insertion mutation (insT at nt167) and two missense mutations (A-to-G transition at nt80 and C-to-T transition at nt95, the former being novel). CONCLUSION: We found clinical heterogeneity in the patients with EAOH in this study. With the disease course, the choreiform movements tended to reduce in degree, and hypoalbuminemia became evident. Molecular analysis identified one insertion and two missense mutations including a novel missense one, which was located at a highly conserved amino acid residue in the aprataxin gene product.

Differential roles of the caudate nucleus and putamen in motor behavior of the cat as investigated by local injection of GABA antagonists.

In order to reveal a functional difference between the two distinctly separate nuclei of the striatum, i.e. the caudate nucleus (Cd) and the putamen (Put), we studied the effects of local bicuculline (BIC) and picrotoxin (PTX) injection into these nuclei on the motor behavior in the cat. The extent of diffusion of the injected BIC could be approximated by determining the extent of spreading of the dye fast green FCF (FCF) mixed with BIC solution since the extent of diffusion of radioactive [3H]BIC mixed with BIC and FCF solution was almost the same as that of FCF.BIC and PTX are GABA antagonists and are assumed to activate efferent neurons of the Cd and Put by removing the action of GABA-ergic inhibitory synapses on them. A total of 28 BIC and 22 PTX injections was made in 20 adult cats, 22 aimed at the Cd and 28 at the Put. Injection of BIC or PTX to either the head or body of the Cd unilaterally induced locomotor hyperactivity without any postural asymmetry or circling tendency. When BIC or PTX was injected into the Put, dystonic movements (dystonia) towards the contralateral side appeared frequently in the neck and trunk. Even though the injected BIC or PTX often spread to the external segment of the globus pallidus, claustrum, or anterior sylvian gyrus, none of these areas was consistently associated with dystonia. These results demonstrate that the Cd and Put are differentially associated with locomotor and postural functions.

Impairment of active avoidance produced after destruction of pedunculopontine nucleus areas in the rat.

Pedunculopontine nucleus areas were lesioned bilaterally in the rat by local injection of kainic acid. When rats so treated were tested for active avoidance behavior in shuttle boxes we found that their avoidance acquisition was completely abolished, whereas their intertrial locomotor activity and escape behavior were not affected. In the lesioned rats, choline acetyltransferase activity in the medial thalamus and substantia nigra decreased, but not in the lateral thalamus, hippocampus, or cerebral cortex. These findings suggest that the cholinergic pedunculopontine-medial thalamus projection plays an important role in memory acquisition in the rat.

Activation of mesencephalic dopamine neurons by chemical stimulation of the nucleus tegmenti pedunculopontinus pars compacta.

Unilateral stereotaxic microinjection of a small amount of kainic acid (KA) into the nucleus tegmenti pedunculopontinus pars compacta (TPC) of male Wistar rats produced constant ipsiversive circling behavior. The rate of the TPC-derived circling was significantly attenuated by blocking agents of dopamine systems, including haloperidol and alpha-methyl-tyrosine (both injected intraperitoneally) and also 6-hydroxydopamine (injected into the bilateral medial forebrain bundles). Administration of norepinephrine antagonists (phenoxybenzamine hydrochloride and DL-propranolol) had no effect on the rate of the TPC-derived circling. Bilateral preinjections of atropine sulfate into the ventral midbrain tegmentum, including the ventral tegmental area and the pars compacta of the substantia nigra, significantly attenuated the rate of the circling. The unilateral KA injection into the TPC dramatically increased the ratio of HVA + DOPAC/dopamine, an indicator of dopamine turnover, in the nucleus accumbens as well as in the striatum bilaterally. The increase of the ratio in the nucleus accumbens was selectively suppressed by pretreatment with atropine sulfate administered into the bilateral ventral midbrain tegmentum. These facts indicate: (1) the TPC-derived circling behavior is mediated by the dopamine system, (2) the chemical stimulation of TPC by KA might produce an activation of midbrain dopamine neurons by excitatory TPC efferents to the dopamine neurons and enhance the dopamine turnover in the nucleus accumbens as well as in the striatum, (3) the excitatory TPC efferents may be muscarinic cholinergic in accordance with previous reports.

Electrophysiological evidence for branching nigral projections to pontine reticular formation, superior colliculus and thalamus.

Neurons of the pars reticulata of the substantia nigra were activated antidromically by stimulating pontine reticular formation, superior colliculus and thalamus. Many nigral neurons (42.6%) were activated antidromically from pontine reticular formation ipsilaterally and about a half of them had branching axons to superior colliculus and/or thalamus.

Effect of stimulation of the putamen on the substantia nigra in the cat.

The function of the putamen has been investigated in the cat by stimulating the nucleus electrically and recording from neurons of the pars reticulata of the substantia nigra. It was found that putaminonigral fibers were, at least partly, inhibitory in nature and that they exerted this inhibition monosynaptically on nigral neurons.

Enhanced survival of cultured dopamine neurons by treatment with soluble extracts from chemically deafferentiated striatum of adult rat brain.

A soluble fraction was extracted from a chemically deafferentiated striatum of adult Wistar rats after unilateral lesioning of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA) injection. The soluble extract from the lesioned side enhanced the survival of cultured mesencephalic dopamine (DA) neurons of 14-day-old rat embryos as evidenced by quantitative counting of tyrosine hydroxylase-like immunoreactive cells. The neurotrophic activity of this striatal extract for DA neurons was highest 14 days after 6-OHDA injection and became negligible in 28 days. The extract showed no promoting effects on cultured gamma-aminobutyric acid (GABA)-containing mesencephalic neurons. These observations indicate that the striatum of adult rats may initiate de novo synthesis of trophic substance(s) for DA neurons but not for GABA neurons when subjected to nigral dopaminergic deafferentiation.

Long-term effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine content in young and mature mice.

Long-term effects of MPTP on striatal dopamine (DA) content and the influence of aging on the recovery were investigated in mice. Male C57BL/6J mice, young (2-month-old) and mature (10-month-old), were used. Two different dosage schedules of MPTP, i.e., 4 doses subcutaneous injections of 20 mg/kg each, and 4 doses subcutaneous injections of 40 mg/kg each, were given to both young and mature mice at 12-h intervals. Assays of striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) content were performed 1 week, 1 month, 2 months, and 3 months after the last injection of MPTP. MPTP produced a marked reduction (-75% to -80%) of striatal DA content in both young and mature mice 1 week after the last injection of MPTP. In young mice, the striatal DA content showed a partial recovery in the subsequent stages studied. In contrast, no apparent recovery occurred in mature mice until as long as 3 months after the last injection. The results suggest that mice have a capacity for partial recovery of the striatal DA contents which was depleted by MPTP, and this capacity for recovery appears to be impaired in mature mice.

Neurophysiological analysis of ataxia in capsular ataxic hemiparesis.

A quantitative analysis of ataxia and the readiness potential were studied in four cases of ataxic hemiparesis resulting from a small infarct in the posterior limb of the internal capsule. The ataxia appeared to be the result of involvement of the corticopontine tract originating from the precentral region (areas 4 and 6) at this level. The voluntary movements of the affected limbs were characterized by slowness and irregularity similar to those seen in cerebellar ataxia. The weakness per se was not such that it could account for the ataxia. The dentato-rubro-thalamo-cortical system did not appear to be significantly involved on the basis of normal readiness potentials.

A large Japanese SPG4 family with a novel insertion mutation of the SPG4 gene: a clinical and genetic study.

We studied a large Japanese family with autosomal dominant pure hereditary spastic paraplegia (ADPHSP) clinically and genetically. To date, seven loci causing ADPHSP have been mapped to chromosomes 14q, 2p, 15q, 8q, 12q, 2q, and 19q. Among these loci, the SPG4 locus on chromosome 2p21--p22 has been shown to account for approximately 40% of all autosomal dominant hereditary spastic paraplegia (ADHSP) families. Very recently, Hazan et al. identified the SPG4 gene encoding a new member of the AAA (ATPases associated with diverse cellular activities) protein family, named spastin. We found a novel insertion mutation (nt1272--1273insA) in exon 8 of the SPG4 gene in the present family. Our study is the first to confirm the causative mutation of the SPG4 gene in Japanese. Clinically, it is noteworthy that the disease progression in the patients of this family was slow in spite of the late onset, and more than half of the patients showed severe constipation in addition to pure spastic paraplegia.

A detachable balloon procedure for a traumatic internal carotid-internal jugular fistula: report of a case.

A case of a traumatic fistula between the internal carotid artery and the internal jugular vein is reported. The fistula was treated by detachable balloon occlusion and clipping of the internal carotid artery.

Familial osteodysplasia associated with trigeminal neuralgia: case report.

A 24-year-old woman suffering from left trigeminal neuralgia presented with the familial occurrence of skeletal anomalies simulating Hajdu-Cheney syndrome. She was of a short stature and had low-set ears, protrusion of the bilateral temporal and occipital bones, platybasia, basilar impression, and dental anomaly. Vertebral angiography disclosed marked displacement to the left and dorsally of the basilar artery, which was confirmed during the operation to have compressed the left trigeminal nerve in the cerebellopontine angle narrowed by the unusually protruded bony structure. Cases of Hajdu-Cheney syndrome have occasionally been reported, a few combined with facial spasm, but Hajdu-Cheney syndrome with trigeminal neuralgia is very rare. The patient's family members were surveyed. The possible cause of the neuralgia with its relation to the osteodysplasia is briefly discussed.

Nonsuture microvascular anastomosis using an Nd-YAG laser and a water-soluble polyvinyl alcohol splint.

Anastomosis of rat common carotid artery was performed without sutures, using a neodymium (Nd)-YAG laser at 20 W for 100 msec; this power and exposure had been found optimal in preliminary experiments. An intraluminal intervascular splint made of water-soluble polyvinyl alcohol, which dissolved and disappeared within a few minutes after recirculation of blood, was used for precise "intima-to-intima" coaptation. No stay sutures or glue were required during the procedure. There was a 92% patency rate 24 hours after surgery, and the anastomosed vessels were still patent on the 7th and 30th postoperative days. Complications such as aneurysm formation or stenotic change were negligible. The fusion of the muscle layer and collagen fibers of the media in the anastomosis was confirmed histologically. A tensile strength test immediately following operation and 1 week later showed that this anastomosis was significantly better than that achieved with the usual manual suture method. The major advantages of this technique, combined with use of a water-soluble polyvinyl alcohol splint, are rapidity, consistency of results, and firm fusion with no residual foreign body.

Ossified spinal meningioma en plaque.

Ossified spinal meningiomas alone are uncommon lesions and spinal meningiomas en plaque are even more. A rare case is presented of ossified meningioma en plaque in the midthoracic spine, which was totally removed. Characteristics of this tumor with reference to relatively pathognomonic neuroimagings are discussed. Microsurgical outcome of this type of tumor is expected to be good.

Choriocarcinoma arising from the pituitary fossa with extracranial metastasis: a review of the literature.

Since Askanazy's first report on a case of primary intracranial choriocarcinoma in 1906, more than 60 cases have been reported so far. We add to that a case of intrasellar choriocarcinoma with suprasellar extension: A 12-year-old girl showed cranial nerve palsies, hypopituitarism, and abnormally high titers of human chorionic gonadotropin (HCG) in blood and in cerebrospinal fluid (CSF). She died 3 months after surgery. At autopsy, an intra- and suprasellar choriocarcinoma, which penetrated through the clivus into the cerebellopontine angle and metastasized remotely to the lungs, was confirmed. This rare case is presented with a thorough review of the literature.

Preventive superficial cervical plexus block for postoperative cervicocephalic pain in neurosurgery.

Eighty-six (54%) of a series of 160 patients who underwent neurosurgery experienced postoperative cervicocephalic pain. We performed a superficial cervical plexus block (SCPB) immediately after operation in the subsequent 240 patients, in which the incidence of postoperative cervicocephalic pain was reduced to 27% (65 patients), and the intensity of pain was apparently milder. SCPB is a worthwhile procedure to prevent postoperative cervicocephalic pain.

[A new family of Machado-Joseph disease--an abnormal decrease in signal intensity of the putamen in magnetic resonance imaging].

The propositus (case 1) was a 40 year-old man. He had begun to note unsteady walking at age 26. He was found to have cerebellar ataxia and pyramidal signs in addition to minor features such as progressive external ophthalmoplegia, gaze nystagmus, bulging eyes, intention fasciculation-like movements of facial and lingual muscles, and limb dystonia. These findings were categorized into type II form of the disease. One sister (case 3) aged 37 years, and one brother (case 4) aged 44 years of the propositus had also type II form of the disease. His uncle (case 2) had the same cerebellar and extrapyramidal signs accompanied with peripheral nerve signs such as muscle wasting, weakness, hypo-tonus and decreased deep tendon reflexes, and a diagnosis of type III form of the disease was made. In the T2-weighted magnetic resonance imaging (1.5 T, TR 2000 or 3000 msec, TE 120 msec) of the three patients (case 1, 3 and 4), dorsolateral part of the putamen showed decreased signal intensity. Although hypo-intensity of the putamen is often observed in normal elderly people over 50 years old, it is considered to be abnormal when it exists in relatively young people as in this family members.

[Neck clipping of an aneurysm at the basilar artery-anterior inferior cerebellar artery via presigmoid-transmastoideal approach].

A 51-year-old man presented severe disturbance of consciousness and massive subarachnoid hemorrhage. Angiography disclosed an aneurysm at the ventral bifurcation of the basilar and anterior inferior cerebellar arteries. Neck clipping and additional wrapping/coating were performed via the presigmoid-transmastoideal approach with successful result. The operative procedure was described and advantages of this approach were discussed.