Relationship of physical activity with physical function and health-related quality of life in patients having undergone allogeneic haematopoietic stem-cell transplantation.

In this study, we investigated the differences in physical activity before and after transplantation, and the relationship between physical activity and physical function and health-related quality of life (QOL) in 30 patients who underwent allogeneic haematopoietic stem cell transplantation (allo-HSCT). Duration and intensity of physical activity were quantified using a three-dimensional accelerometer. Physical function was quantified by handgrip and knee-extensor strength, with the 6-minute walk test (6MWT) used as a measure of exercise capacity. Health-related QOL was assessed using the 36-item Short-Form Health Survey. The proportion of daily activities performed at an intensity >3.0 metabolic equivalents (METs) increased significantly after allo-HSCT (p < .05). Daily activity time performed at an intensity of 1.6-2.9 METs significantly correlated only with left knee strength (p < .05). In contrast, the total number of daily steps and the proportion of activity performed at 1.6-2.9 METs and >3.0 METs were positively correlated with the 6MWT (p < .05). Additionally, physical functioning and general health subscales in health-related QOL positively correlated with daily activities performed at >3.0 METs (p < .05). Physical activity was associated with 6MWT and health-related QOL. These findings have implications for rehabilitation planning for patients undergoing allo-HSCT.

Cardiac involvements in myasthenia gravis associated with anti-Kv1.4 antibodies.

BACKGROUND AND PURPOSE: There is no general consensus as to whether autoimmune myasthenia gravis (MG) is associated with heart diseases, despite the fact that myocarditis, a serious cardiac involvement treatable by immunotherapy, is a complication of MG. It has been observed previously that MG patients with clinically suspected myocarditis had anti-Kv1.4 antibodies. The purpose of this study was to disclose the association between anti-Kv1.4 antibodies and cardiac involvements in MG patients. METHODS: Anti-Kv1.4 antibody was detected by an immunoprecipitation assay using (35) S-labeled rhabdomyosarcome cellular extract as the antigen source. Cardiac findings including electrocardiography (ECG) and clinical features of clinically suspected myocarditis in MG patients with anti-Kv1.4 antibodies were investigated. Ultrasound echocardiography (UCG) of ex vivo chick embryos was performed to determine the suppressive effects of sera with or without anti-Kv1.4 antibodies on heart muscle functions. RESULTS: Seventy (10.8%) of 650 MG patients had anti-Kv1.4 antibodies and 60% of them had abnormal ECG findings with high frequencies of T-wave abnormality and QT prolongation. Clinically suspected myocarditis was found in eight MG patients with anti-Kv1.4 antibodies but in none of the MG patients without anti-Kv1.4 antibodies. Most patients showed rapid deterioration with lethal arrhythmias such as ventricular tachycardia, sick sinus syndrome, or complete atrial ventricular block and severe heart failure. It was concluded using UCG of ex vivo chick embryos that MG serum with anti-Kv1.4 antibodies suppressed heart muscle functions. CONCLUSION: It has been demonstrated that anti-Kv1.4 antibodies are possible markers for cardiac involvements in MG patients.

Safety and feasibility of physical therapy in cytopenic patients during allogeneic haematopoietic stem cell transplantation.

This study aimed to investigate the safety and feasibility of physical therapy in cytopenic patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT), and to investigate the effect of physical therapy on physiological functions and quality of life (QOL) in allo-HSCT patients. The study cohort included 321 patients who underwent allo-HSCT. To investigate the safety and feasibility of physical therapy during cytopenia, patients were assigned to the physical therapy group (n = 227) or the control group (n = 94). To determine the effects of physical therapy, patients were divided according to the frequency with which they underwent physical therapy (n = 51 per group). Handgrip strength, knee extensor strength and a 6-min walk test were used as measures of physiological function. Short-Form 36 was used to assess QOL. The physical therapy group had higher rate of achieving engraftment and lower death rate than the control group (P < 0.05). After HSCT, the high-frequency physical therapy group showed significantly less decline than the low-frequency physical therapy group with respect to physical functioning of QOL (P < 0.01). Physical therapy is quite beneficial and can be performed safely and feasibly in cytopenic patients during allo-HSCT.

Ganglioside complexes containing GQ1b as targets in Miller Fisher and Guillain-Barre syndromes.

BACKGROUND: Serum antibodies to GQ1b are associated with Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) with ophthalmoplegia. Antibodies to ganglioside complexes (GSCs) have not yet been examined in a large population of patients with MFS or GBS. This study aimed to determine the clinical significance of antibodies to GSCs in MFS and GBS. METHODS: The study investigated serum anti-GSC antibodies and the clinical features in 64 MFS patients, 53 GBS patients with ophthalmoplegia (GBS-OP(+)) and 53 GBS patients without ophthalmoplegia (GBS-OP(-)). RESULTS: Thirty patients with MFS (47%), 25 with GBS-OP(+) (47%) and none with GBS-OP(-) had antibodies to GSCs containing GQ1b or GT1a. Patients with MFS and GBS-OP(+) were subdivided according to the antibody reactivities; patients with antibodies specific to GQ1b and/or GT1a (without anti-GSCs antibodies) were placed in Group 1, those with antibodies against GSCs with a total of two sialic acids in the terminal residues, such as GQ1b/GM1, were placed in Group 2, and those with antibodies against GSCs with a total of three sialic acids in the terminal residue, such as GQ1b/GD1a, were placed in Group 3. In MFS, sensory disturbances were infrequent in Group 2 compared with the other groups (p<0.0001). Antibodies specific to GQ1b were observed more often in MFS than in GBS-OP(+) (p = 0.0002). CONCLUSIONS: IgG antibodies to GSCs containing GQ1b or GT1a were closely associated with the development of ophthalmoplegia in GBS, as well as MFS. Both GQ1b and clustered epitopes of GSCs containing GQ1b or GT1a may be prime target antigens for MFS and GBS-OP(+).

Anti-ganglioside complex antibodies associated with severe disability in GBS.

Ganglioside complexes (GSCs) are known as target antigens in Guillain-Barré syndrome (GBS). To elucidate the clinical importance of the anti-GSC antibodies in GBS, we investigated serum antibodies to GSCs containing two of the gangliosides, GM1, GD1a, GD1b and GT1b, and analyzed clinical features of anti-GSC-positive GBS patients. Thirty-nine (17%) of 234 GBS patients had IgG anti-GSC antibodies. Anti-GSC-positive GBS had antecedent gastrointestinal infection and lower cranial nerve deficits more frequently than control GBS. The presence of antibody specificity to GD1a/GD1b and/or GD1b/GT1b was significantly associated with severe disability and a requirement for mechanical ventilation.

Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GvHD: an analysis of the JSHCT.

A nationwide retrospective study for the clinical outcomes of 99 patients who had received thymoglobulin at a median total dose of 2.5 mg/kg (range, 0.5-18.5 mg/kg) as a second-line treatment for steroid-resistant acute GvHD was conducted. Of the 92 evaluable patients, improvement (complete or partial response) was observed in 55 patients (60%). Multivariate analysis demonstrated that male sex and grade III and IV acute GvHD were associated with a lower improvement rate, whereas thymoglobulin dose (<2.0, 2.0-3.9 and ⩾4.0 mg/kg) was NS. Factors associated with significantly higher nonrelapse mortality included higher patient age (⩾50 years), grade IV acute GvHD, no improvement of GvHD and higher dose of thymoglobulin (hazard ratio, 2.55; 95% confidence interval, 1.34-4.85; P=0.004 for 2.0-3.9 mg/kg group and 1.79; 0.91-3.55; P=0.093 for ⩾4.0 mg/kg group). Higher dose of thymoglobulin was associated with a higher incidence of bacterial infections, CMV antigenemia and any additional infection. Taken together, low-dose thymoglobulin at a median total dose of 2.5 mg/kg provides a comparable response rate to standard-dose thymoglobulin reported previously, and <2.0 mg/kg thymoglobulin is recommended in terms of the balance between efficacy and adverse effects.

Anti-ganglioside complex antibodies in Miller Fisher syndrome.

BACKGROUND: Some ganglioside complexes (GSCs) are target antigens for serum antibodies in patients with Guillain-Barré syndrome (GBS). Anti-GSC antibodies may be associated with particular clinical features of GBS. OBJECTIVE: To investigate antibodies to GSCs in the sera of patients with Miller Fisher syndrome (MFS) characterised by elevation of the IgG anti-GQ1b antibody. RESULTS: In all, 7 of 12 (58%) consecutive patients with MFS were found to have IgG antibodies to GSCs containing GQ1b, of whom 5 had IgG antibodies to GQ1b-GM1 complex (GQ1b/GM1) and 2 had antibodies to GQ1b/GD1a; 4 of 5 patients without sensory symptoms had anti-GQ1b/GM1 antibodies. CONCLUSIONS: At least three different specificities in MFS-associated antibodies, GQ1b-specific, anti-GQ1b/GM1-positive and anti-GQ1b/GD1a-positive, were observed. In patients with MFS not only GQ1b itself but also clustered epitopes of GSCs, including GQ1b, may be considered to be prime target antigens for serum antibodies. A tendency to escape sensory disturbances is shown by anti-GQ1b/GM1-positive MFS.

Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation.

Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After HCT, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P<0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P<0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients.

A novel mutation in the gene for the adult skeletal muscle sodium channel alpha-subunit (SCN4A) that causes paramyotonia congenita of von Eulenburg.

BACKGROUND: Paramyotonia congenita (PMC) of von Eulenburg is an autosomal dominant muscular disease characterized by exercise- and cold-induced myotonia and weakness. To date, 18 missense mutations in the adult skeletal muscle sodium channel alpha-subunit (SCN4A) gene have been identified to cause a spectrum of muscular diseases, including PMC of von Eulenburg, PMC without cold paralysis, potassium-aggravating myotonia, and hyperkalemic periodic paralysis. However, no obvious correlations can be made between the location or nature of amino acid substitutions in SCN4A and its clinical phenotypes. OBJECTIVE: To describe clinical and genetic features of a family with PMC of von Eulenburg. RESULTS: A Japanese family with cold-induced myotonia and weakness was diagnosed as having PMC of von Eulenburg. This phenotype was identified to be caused by a novel mutation that substituted a glutamic acid residue for a highly conserved glycine residue in the fourth transmembrane segment (S4) of domain IV. This predicted a decrease in positive charge specific for the S4. CONCLUSION: In addition to the G1456E identified in this study, 4 mutations that cause a decrease in positive charge in the S4/D4 are associated with the phenotype of PMC of von Eulenburg. This provides an important genotype-phenotype correlation in sodium channelopathies.

Familial paroxysmal dystonic choreoathetosis: clinical findings in a large Japanese family and genetic linkage to 2q.

BACKGROUND: Paroxysmal dystonic choreoathetosis (PDC) is a rare familial movement disorder that has been mapped to chromosome 2q31-36. OBJECTIVE: To study the first Japanese family with PDC clinically and genetically. PATIENTS AND METHODS: We studied a large Japanese family in which at least 17 members in 6 generations have been affected by PDC. We interviewed and examined 26 family members, 8 of whom revealed choreoathetosis-like and dystonialike involuntary movement and 1 of whom revealed no involuntary movement but only muscle stiffness such as the aura of paroxysmal dystonic choreoathetosis (PDC). Genetic linkage studies of this family were carried out with polymorphic DNA markers. RESULTS: The attacks of involuntary movement or muscle stiffness were precipitated by ovulation, menstruation, emotional stress, or caffeine or alcohol ingestion. Magnetic resonance imaging of the brain revealed no abnormalities. Clonazepam therapy was effective for reducing the attacks, and ingestion of garlic was believed by patients to be effective for softening the attacks. An affected woman with only muscle stiffness showed remission after hysterectomy for hysteromyoma. This woman also had the disease haplotype and transferred it to her typical PDC-affected daughter. Maximal pairwise logarithm of odds scores exceeding 2.00 were obtained at D2S2250, D2S1242, D2S377, D2S2148, and D2S126. The PDC gene was demonstrated by linkage analyses to be located in a 15.3-centimorgan interval lying between D2S371 and D2S339 based on pairwise and multipoint logarithm of odds scores and obligate recombination events in affected individuals. CONCLUSIONS: Linkage of PDC to chromosome 2q32-36 was confirmed in a Japanese family. The clinical characterizations of this family with PDC include that ovulation seems also to be a precipitating factor of the attacks and that hysterectomy seems to be effective for softening the attacks. Although low-dose clonazepam treatment was most effective, garlic use was believed by affected members to be effective for softening the attacks. Furthermore, based on the results of clinical and genetic analyses, we suggest that muscle stiffness without involuntary movement may represent a forme fruste of PDC.

Guillain-Barré syndrome associated with IgG monospecific to ganglioside GD1b.

The authors examined serum antiglycolipid antibodies in 445 patients with Guillain-Barré syndrome (GBS). Among them, nine had anti-GD1b IgG antibodies with no reactivity to other glycolipids tested. All those patients had sensory disturbance, and none had the primary axonal form. Anti-GD1b IgG antibodies may bind to primary sensory neurons and paranodal myelin, where GD1b is localized, and be involved in the pathogenesis of sensory disturbance and demyelination. However, more study is needed to substantiate the roles of anti-GD1b IgG antibodies.

Guillain-Barré syndrome with IgM antibody to the ganglioside GalNAc-GD1a.

We analyzed the characteristics of 29 Guillain-Barré syndrome (GBS) patients with IgM anti-GalNAc-GD1a antibodies. Fourteen of them had had an antecedent cytomegalovirus infection (CMV group) and 12 gastrointestinal infection (G-I group). Most of the G-I group patients (nine of 12) were subsequent to Campylobacter jejuni infection. Electrophysiological results in both groups patients predominantly indicated demyelinating neuropathy. The CMV group patients were characterized by slow progression and frequent facial and sensory deficits. IgM antibodies in their sera recognized an epitope shared by GalNAc-GD1a and GM2. The G-I group patients frequently showed motor type of GBS with cranial nerves spared. IgM antibodies specific to GalNAc-GD1a were present in their sera.

Degeneration of rabbit sensory neurons induced by passive transfer of anti-GD1b antiserum.

Systemic infusion of high-titer anti-GD1b antiserum to two rabbits pre-inoculated with keyhole limpet hemocyanin and Freund's complete adjuvant was performed. The two rabbits had low-titer anti-GD1b antibody in sera. Although no apparent clinical signs were observed, pathological examinations showed vacuolar degeneration with macrophage infiltration in a few axons in the dorsal columns of the spinal cords from the two rabbits. No such pathological changes were observed in the other two pre-inoculated rabbits infused with normal rabbit sera. Anti-GD1b antibody therefore may cause degeneration in rabbit sensory neurons with central axons extending to the dorsal column.

Alzheimer's disease with asymmetric parietal lobe atrophy: a case report.

A 52-year-old, right-handed female presented with visuospatial dysfunction including left hemineglect, incomplete Balint's syndrome, and environmental agnosia, together with left-sided motor symptoms such as unskillful movement, dystonic postures, and myoclonus in the left hand, without significant dementia. Symptoms progressed to akinetic mutism prior to her death 10 years after onset of illness. Imaging studies such as MRI, SPECT, and PET studies showed severe, predominantly right-sided involvement of parietal and parieto-occipital areas. The motor signs might originate from the right parietal lesions such as area five or somatosensory area. Neuropathologic studies including immunocytochemistry showed tau-positive neurofibrillary tangles and abundant neuritic plaques with amyloid deposits, confirming the diagnosis of Alzheimer's disease. An analysis of serum apolipoprotein E revealed epsilon3/epsilon3 homozygosity. This case represents a variant of Alzheimer's disease conspicuous for progressive motor signs and visuospatial dysfunction with a striking laterality, reflecting asymmetric parietal involvement. Alzheimer's disease with asymmetric parietal atrophy is difficult to be clinically distinguished from corticobasal degeneration characterized by progressive unilateral motor signs and focal cortical signs.

Painful small-fibre multifocal mononeuropathy and local myositis following influenza B infection.

A 47-year-old man experienced multifocal mononeuropathy and putative ganglionopathy associated with influenza B infection, characterized by aching and dysesthesia in the right arm and left leg with normal deep sense. He displayed muscle atrophy in the affected limbs, which might have resulted from local myositis or a disorder similar to neuralgic amyotrophy. Sural nerve biopsy revealed a severe loss of unmyelinated and thinly myelinated fibres, consistent with a small fibre neuropathy, without evidence of angiopathy or inflammation. We could not detect any other cause of the neuropathy except influenza B. In this case, it may be inferred that small-diameter neurons in the dorsal root ganglia and thinly- or nonmyelinated fibres were selectively involved through a post-infectious immune process. To our knowledge, small fibre neuropathy following influenza B has never been reported.

New cyclic depsipeptide antibiotics, clavariopsins A and B, produced by an aquatic hyphomycetes, Clavariopsis aquatica. 1. Taxonomy, fermentation, isolation, and biological properties.

Clavariopsins were isolated from the fermentation broth of Clavariopsis aquatica AJ 117363. Clavariopsins are cyclic depsipeptide antibiotics with the molecular weight of 1,153 and 1,139. Clavariopsins showed in vitro antifungal activity against not only Aspergillus fumigatus but also, although to a lesser extent, A. niger and Candida albicans.

New cyclic depsipeptide antibiotics, clavariopsins A and B, produced by an aquatic hyphomycetes, Clavariopsis aquatica. 2. Structure analysis.

The structures of new cyclic decadepsipeptides, clavariopsins A and B, were determined to be cyclo[-(R)-2-hydroxyisovaleryl-L-pipecoyl-L-MeVal-L-Val-L-MeAsp-L-MeIle-L-MeIle-Gly L-MeVal-L-Tyr(OMe)-] and cyclo[-(R)-2-hydroxyisovaleryl-L-pipecolyl-L-Val-L-Val-L-MeAsp-L-Melle-L-MeIle-Gly-L-MeVal-L-Tyr(OMe)-], respectively, by spectroscopic analyses, especially using 2D NMR techniques. The absolute stereochemistry was elucidated by the advanced Marfey's method and chiral HPLC analysis.

EEG topographical analysis of spatial disorientation.

BACKGROUND: We examined EEG topography while subjects experienced spatial disorientation (SD) such as vection and somatogravic illusion (SGI). METHODS: Five healthy male subjects were exposed to a rotating image evoking vection (Experiment 1) and to a 0.58 G linear forward acceleration evoking SGI (Experiment 2). The data were analog-to-digital converted with an epoch length of 1 s and a sampling frequency of 256 Hz. Polynomial coefficient vectors were calculated for the following analyses of EEG under the illusion: a) objective evaluation of topographical difference by two-way MANOVA; b) visual inspection of the power spectra maps; and c) logarithmic deviation ratio topography (log DRT). RESULTS: MANOVA demonstrated significant differences in EEG topography in the high alpha band while the vection was evoked. No significant difference was revealed in any bands for SGI. Characteristic patterns common to all subjects were hardly identified on the power spectra maps. By log DRT under vection, a decrease of power was observed in the centro-parietal area on the left side in one subject, on the right in another subject, and in the mid-right frontal area in a third subject compared with the control with eyes open. As for SGI, log DRT revealed a decrease of power in the occipital area in most of the trials as the magnitude was reduced by a visible horizon. CONCLUSIONS: MANOVA revealed a significant change in EEG topography while the subjects felt vection. Log DRT reflected characteristic patterns under vection and SGI. Thus EEG topography may be useful for the study of SD.

Visual influence on the magnitude of somatogravic illusion evoked on advanced spatial disorientation demonstrator.

BACKGROUND: The somatogravic illusion (SGI) is a kind of spatial disorientation caused by a linear sustained acceleration. Pilots believe that visual cues, such as a visible horizon or texture flow, reduce this illusion. This study was performed to evaluate the influence of visual stimuli on the SGI using the Advanced Spatial Disorientation Demonstrator (ASDD). METHODS: There were eight healthy males who were exposed to a 0.58 g x axis linear acceleration on the ASDD, where the direction of the resultant gravitoinertial force was equivalent to 30 degrees pitch-up. One of the following visual stimuli was presented during each acceleration: BLANK (no visual cues); HORIZON (a visible horizon without motion); and TEXTURE (vertical lines moving toward the subject evoking vection). The subjective magnitude of the SGI in ordinal scale was observed; and in interval scale, the deviation of the moving point kept at the subjective horizon was observed. The differences among visual stimuli were analyzed. RESULTS: The subjective magnitude of the SGI (p < 0.01) and the deviation of the moving point (p < 0.05) were significantly smaller in HORIZON than in BLANK and TEXTURE. No difference was demonstrated between BLANK and TEXTURE. The linear vection produced by the TEXTURE stimulus did not affect the SGI. CONCLUSION: The data indicated that the presence of a visible horizon reduced the magnitude of the SGI. On the other hand, the presence of a vection stimulus did not influence the magnitude of the SGI.

[Esophageal dilatation in a patient with myotonic dystrophy: a correlative study on CT and pathologic findings].

We reported a 63-year-old woman with myotonic dystrophy (MD), who had frequent swallowing disturbances and died from suffocation asphyxia. Her esophagus on CT image 30 minutes after taking semi-solid meal showed dietary remnants in the middle portion of esophagus with entire esophageal dilatation. At autopsy, there was marked atrophy in the striated muscles in the upper part and smooth muscles in the lower part of the esophagus. The site of dietary stagnation on CT image was identical to the atrophic smooth muscle layer seen at autopsy. We speculate that one of the causes of esophageal motor dysfunctions is smooth muscle atrophy. The dietary stagnation in the esophagus may increase a risk of the asphyxia. Therefore we need to keep patients at the straight position during and after dietary ingestion to prevent respiratory problems.