Tetsuo Ando

Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia type 6.

Using a molecular diagnostic approach, we investigated 101 kindreds with autosomal dominant cerebellar ataxias (ADCAs) from the central Honshu island of Japan, including spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2), Machado‐Joseph disease (MJD), dentatorubral and pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 6 (SCA6). In our unselected series, MJD was the most common type of ADCA, accounting for 33.7% followed by DRPLA (19.8%), SCA2 (5.9%) and SCA6 (5.9%). No SCA1 mutations were identified. We analysed the clinical features of six molecular confirmed SCA6 kindreds: in each family, there was an expanded allele in the αdA‐voltage dependent calcium channel comprising between 23 and 25 CAG repeats. The mean age at onset of symptoms was 43 ± 13 years. The clinical features consisted predominantly of cerebellar ataxia, dysarthria and horizontal nystagmus, which was generally consistent with ADCA type 3. However several new clinical features were found in some patients: dramatic anticipation, rapid disease progression, severe ataxia associated with action tremor or action myoclonus, and very early onset, which are not described as the classical features of ADCA type 3.

Cervical spondylotic amyotrophy. Magnetic resonance imaging demonstration of intrinsic cord pathology.

Study Design. Three case reports. Objective. To elucidate the pathophysiology of cervical spondylotic amyotrophy. Summary of Background Data. Cervical spondylotic amyotrophy is the clinical syndrome in cervical spondylosis characterized by severe muscular atrophy in the upper extremities, with an absent or insignificant sensory deficit. Pathophysiology of this particular syndrome has not been well understood. Methods. Three cases of cervical spondylotic amyotrophy are presented in which magnetic resonance imaging confirmed the intrinsic cord disease as the cause of the syndrome. Results. The patients had segmental muscular atrophy of the proximal upper extremities, with an absent or insignificant sensory deficit. After initial disease progression, the symptoms stabilized for years. Sagittal T2‐weighted magnetic resonance images showed multisegmental linear high‐signal intensity within the compressed spinal cord. These high‐signal intensity lesions appeared to be located at the anterior horns on axial images. The spinal cord compression was less severe in the neck‐neutral position, but spinal canal stenosis increased when the neck was extended. Conclusions. The results suggest that one pathophysiology of this syndrome may be multisegmental damage to the anterior horns caused by dynamic cord compression, possibly through circulatory insufficiency.

Differential response to corticosteroid therapy of MRI findings and clinical manifestations in spinal cord sarcoidosis

Abstract Spinal cord sarcoidosis is a rare disorder whose natural history and therapeutic outcome are not fully known. We examined four patients with spinal cord sarcoidosis both clinically and radiologically, particularly in relation to corticosteroid treatment. The initial manifestation was cervical myelopathy in three and uveitis in one. All four patients progressed slowly until corticosteroid therapy was initiated. The cervial spine was involved in all patients. Magnetic resonance imaging (MRI) showed spinal cord swelling with T2-weighted high intensity and linear leptomeningeal and patchy or diffuse intramedullary enhancement with gadolinium diethylene triaminepentaacetic acid. With corticosteroid therapy, dramatic improvement was seen on MRI, including disappearance or marked reduction of swelling and enhancement. Plasma levels of angiotensin-converting enzyme (ACE) were also markedly improved. In contrast, the clinical symptoms were little improved in one patient, unchanged in two, and rather worsened in one patient. Recurrence was seen on MRI at the maintenance dose in all four patients, without any dramatic change in clinical manifestation. MRI findings and plasma ACE are well correlated with active leasion of the spinal cord sarcoidosis, providing a useful marker for recurrence, but do not parallel the clinical manifestations.

Motor conduction studies in Miller Fisher syndrome with severe tetraparesis.

Some patients with Miller Fisher syndrome (MFS) have a severe tetraparesis such as that observed in Guillain–Barré syndrome (GBS). To determine whether pathophysiologic differences exist between the tetraparesis in MFS and that in GBS, we compared clinical and motor conduction findings in 4 MFS patients who developed severe tetraparesis with those in 5 MFS patients without tetraparesis, and 14 GBS patients. MFS patients with or without tetraplegia had normal motor conduction velocities, distal motor latencies, compound muscle action potential (CMAP) amplitudes, and F‐wave latencies. CMAP amplitude tended to be lower in tetraparetic MFS patients than in MFS patients without tetraparesis, but not significantly. F‐wave occurrence was slightly reduced in 1 MFS patient with tetraparesis and 1 MFS patient without tetraparesis. Motor conduction parameters were abnormal in 13 of 14 patients with GBS, and showed demyelinating features in 10. Our results suggest that the pathophysiology of tetraparesis in MFS differs from that in GBS.

Bioaccumulation of mercury in a vestimentiferan worm living in Kagoshima Bay, Japan

The present study reports on the mercury concentrations of the vestimentiferan worm, Lamellibrachia satsuma, (Annelida: Pogonophora) found near hydrothermal vents at a depth of 80-100 m in the northern parts of Kagoshima Bay. The vestimentiferan worms had total mercury concentrations of 238 ng/g in the anterior muscle of the body and 164 ng/g in the posterior trophosome. Methylmercury constituted only 7.6% of total mercury detected anteriorly and 16.3% posteriorly. The mean total mercury concentration in filtrated ambient seawater of the worm habitat was 1.1 ng/l. The worm should accumulate mercury in seawater by a one-step into the anterior and posterior parts as 2.2 x 10(%) and 1.5 x 10(5) times those of the filtered ambient seawater, respectively. The bioaccumulation factor of mercury by the worms with only their respiration would be actually larger than that by other marine animals through food webs. The high bioaccumulation factor of mercury in the worms suggest the following two possibilities: (i) the biological half-life of organomercury in the worm could be exceptionally long; or (ii) the lifetime of vestimentiferan worms examined in the present study could be extremely long. Various metals in one specimen of the worm were analyzed by using ICP-MS, and then gold as well as silver were detected in the worm. Gold was detected for the first time from marine animals.

Detection of localized methylmercury contamination by use of the mussel adductor muscle in Minamata Bay and Kagoshima Bay, Japan.

Based on our previous finding that the concentrations of total mercury in mussel adductor muscle approximated those of methylmercury, we compared concentrations of total mercury in the adductor muscle of the mussel Mytilus galloprovincialis, collected from four sites around Minamata City from 1993 to 1995 and four sites in Kagoshima Bay from 1997 to 1998, to assess the level of localized methylmercury contamination. Though the input of mercury from the chemical plant had stopped by around 1970, concentrations of total mercury in the mussel adductor muscle were higher at two sites (26-121 ng/g, n = 135) near the main fallout of wastewater from the chemical plant in Minamata Bay than at the other sites, i.e. two sites 1-5 km from the former sites in Minamata City (6-28 ng/g, n = 52), and all sites in Kagoshima Bay (2-30 ng/g, n = 287). The localized methylmercury contamination around the chemical plant in Minamata Bay was documented also by our sensitive analysis of mercury concentrations in seawater and sediment samples. The survey of concentrations of total mercury in the mussel adductor muscle seems to be useful for monitoring the methylmercury contamination in coastal areas.

Latent Copper Deficiency in Patients Receiving Low-Copper Enteral Nutrition for a Prolonged Period

BACKGROUND Copper deficiency has been reported in patients supported with long-term enteral nutrition. Occasionally, this leads to anemia and leukopenia. There is no detailed report relating to the onset time of copper deficiency and how the symptoms develop. This report describes the relation between copper deficiency symptoms and duration of enteral nutrition. METHODS The study included 55 patients, with 82 measurements, at the neurologic ward of Nagoya Daini Red Cross Hospital. The mean age was 71 +/- 11 years. The daily average dosage of energy was 938 kcal/d. A commercial nutrient for enteral administration that contains 0.13 mg/1000 mL copper was used. Baseline measures on individual patients were taken every month. Blood was collected at 8 am before and after the start of enteral nutrition. Levels of copper, zinc, ceruloplasmin, hemoglobin, and white blood cells were measured. RESULTS The serum level of copper in the patients was 94.0-181.0 microg/dL before the start of enteral nutrition. The level of serum copper remained within the normal range for about 3 months. The level of serum copper in the patients decreased gradually and was less than the normal level after 3 months, with the exception of 1 patient. The serum level of copper in the patients was 3.0-123.0 microg/dL 3 months after the start of enteral nutrition. The levels of serum copper were below normal in 25 cases out of 82 measurements. However, the number of patients with symptoms of copper deficiency was only 2. Copper deficiency symptoms appeared at 41 and 77 months, the average being 59 months. CONCLUSIONS Almost all patients showed a latent copper deficiency about 3 months after the start of enteral nutrition. However, only a few patients developed overt symptoms of copper deficiency.

Survey of the Effects of a Column for Adsorption of β2-Microglobulin in Patients With Dialysis-Related Amyloidosis in Japan

Dialysis‐related amyloidosis is a serious complication of long‐term hemodialysis. Its pathogenic mechanism involves accumulation of β2‐microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of β2‐microglobulin, has been available since 1996 to treat dialysis‐related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis‐related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9 ± 7.7 years age, who had undergone dialysis for 25.9 ± 6.2 years and Lixelle treatment for 3.5 ± 2.7 years. Based on self‐evaluation by patients, worsening of symptoms was inhibited in 84.9–96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis‐related amyloidosis in most patients.

Effects of methylmercury on the lipid components in rats.

The effects of methyl mercury chloride on the variation of both the content and fatty acid composition of lipads in the liver, kidney and brain of rats is retorted. Methyl mercury is identified as an extremely toxici substance for man and his environment. Though the toxic effects of mercury have been widely studied from biochemical, physiological, and pathological points of view, there are very few reports which give clear elucidation of the mechanism for the occurrence of neuroinclear elucidation of the mechnism for the occurrence of neuroin-toxication.

Effect of Polydextrose Intake on Constipation in Japanese Dialysis Patients: A Triple-Blind, Randomized, Controlled Trial.

The objective of the present study was to evaluate bowel habits induced by ingestion of 10 g polydextrose (PDX) fed to Japanese hemodialysis (HD) patients. This was a randomized, placebo-controlled, triple-blind, parallel-group controlled, 8-wk study. A total of 50 HD outpatients capable of self-management (51-79 y of age) were recruited at H Clinic, Japan. Inclusion criteria for participation in the study were ingestion of one or more laxative tablets for more than 3 mo and having received HD for more than 6 mo. The participants were randomly assigned to 2 groups: A (0 g polydextrose/d; control), B (10 g polydextrose/d; PDX). The primary outcome measure was stool frequency. Secondary outcomes were stool consistency, abdominal pain, intestinal bloating and clinical biochemistry indexes. PDX had no significant effect on blood biochemistry indexes. The PDX group showed significant improvements in bowel function (stool frequency increased from 3.0 times per week to 7.5 times per week) and reported no laxation problems (abdominal distention, cramps, and diarrhea) (p<0.01). Regular consumption of the PDX products increased dietary fiber intake to recommended levels and improved bowel habits.