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H Mitsumoto

Publications and source records attributed to H Mitsumoto.

At least 37 records · Page 2Linked to original sources
PubMed2001

Objective measures of the efficacy of noninvasive positive-pressure ventilation in amyotrophic lateral sclerosis.

The impact of noninvasive positive-pressure ventilation (NIPPV) on pulmonary function studies, quality of life, and survival was assessed in patients with amyotrophic lateral sclerosis. NIPPV did not change the rate of decline of the forced vital capacity (FVC) and forced expiratory volume in the first second (FEV(1)) (2.31 and 2.09 percent-predicted points per month, respectively). NIPPV resulted in a drop of FEV(1) by 5.94 percent-predicted points (P = 0.07), and of maximal inspiratory pressure by 6.33 percent-predicted points (P = 0.11). The change in FEV(1) and FVC pre- and postintervention correlated with the corresponding change in maximal inspiratory pressure. Fatigue and mastery scores were improved by NIPPV. Median survivals in patients intolerant and tolerant of NIPPV were 5 and 20 months, respectively (P = 0.002). Although NIPPV has no impact on the rate of decline of lung function and may have deleterious effects on spirometric measures, it may improve quality of life and survival.

Aged↗
PubMed2001

Role of brain-derived neurotrophic factor in wobbler mouse motor neuron disease.

Brain-derived neurotrophic factor (BDNF) is neuroprotective for motoneurons undergoing degeneration, including those in natural motor neuron disease (MND) in wobbler mice. To assess the role of BDNF in this model of MND, endogenous BDNF immunoreactivity was analyzed by semiquantitative video-image analysis. Affected cervical spinal cord motoneurons had significantly greater BDNF immunoreactivity compared to motoneurons of healthy littermates (P = 0.01) and affected lumbar spinal cord motoneurons (P = 0.008 at age 4 weeks; P = 0.005 at age 8 weeks). Neuronal nitric oxide synthase (n-NOS) immunocytochemistry revealed increased immunoreactivity in the affected cervical spinal cord motoneurons. Exogenous BDNF treatment partially inhibited the increased NOS activity, as quantitatively measured by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry. The mean number of NADPH-d(+) motoneurons in the cervical anterior horn decreased from 3.5 +/- 1.2 to 1.5 +/- 1.2 (P = 0.002). The increase in endogenous BDNF immunoreactivity in the affected spinal cord may be compensatory in diseased motoneurons, yet it appears to still be inadequate because exogenous BDNF treatment is required to suppress increased NOS activity in degenerating motoneurons. Our study indicates that BDNF is important in halting nitric oxide (NO)-mediated motor neuron degeneration, which has potential implications for the treatment of neurodegenerative disorders.

Animals↗
PubMed2001

Effects of cardiotrophin-1 (CT-1) in a mouse motor neuron disease.

Cardiotrophin-1 (CT-1) has potent survival-promoting effects on motor neurons in vitro and in vivo and may be effective in treating motor neuron diseases (MND). We investigated the effects of CT-1 treatment in wobbler mouse MND. Wobbler mice were randomly assigned to receive subcutaneously injected CT-1 (1 mg/kg, n = 18, in two experiments) or vehicle (n = 18, in two experiments) daily, 6 times/week for 4 weeks after clinical diagnosis at age 3 to 4 weeks. Cardiotrophin-1 treatment prevented deterioration in paw position and walking pattern abnormalities. Grip strength declined steadily in the vehicle group, whereas in the CT-1 group it declined at week 1 but increased thereafter to exceed baseline strength by 5% (P = 0.0002) at week 4. Running speed was faster with CT-1 (P = 0.007). Biceps muscle twitch tension, muscle weight, mean muscle fiber diameter, and intramuscular axonal sprouting were significantly greater with CT-1 treatment than with vehicle treatment. Histometry revealed a trend that indicated CT-1 modestly increased the number of immunoreactive motor neurons, as determined by both choline acetyltransferase and c-Ret antibodies, and reduced the number of phosphorylated neurofilament immunoreactive perikarya (P = 0.05). The number of large myelinated motor axons significantly increased with treatment (206 versus 113, P = 0.01). We conclude that CT-1 exerts myotrophic effects as well as neurotrophic effects in a mouse model of spontaneous MND, a finding that has potential therapeutic implications for human MND.

Animals↗
PubMed2001

Development, analysis, refinement, and utility of an interdisciplinary amyotrophic lateral sclerosis database.

The current status of evaluation and management provided by individual healthcare professionals (HCP) at amyotrophic lateral sclerosis (ALS) centers and clinics needs to be analyzed. This paper describes one ALS center's experiences with the development, analysis, refinement, and utility of an interdisciplinary, HCP-driven ALS database. The purpose and conceptual framework of the database, the general data that needed to be collected, and the types of reports that needed to be generated were determined, and, in collaboration with a computer programmer, data entry and database management systems were developed. Data were collected on 234 patients between September 1996 and August 1998, and were analyzed by a biostatistician. Based on review of the biostatistician's report and discussion of problems encountered with the systems, the database was then refined. Benefits of the database system included: systematization of data collection and reporting, reduction of redundant data collection by individuals, decreased variability of evaluation methods and management decisions from patient to patient, and increased availability of a variety of uniform patient information to assist team members in making care decisions. Ongoing refinement will ensure that this HCP-driven ALS database continues to be informative, practical and effective for decision-making and enhancing delivery of care.

Adult↗
PubMed2001

Clinical trials: present and future.

The past decade has seen a major expansion of clinical trials in amyotrophic lateral sclerosis (ALS). However, the perfectly-designed ALS trial remains elusive. Attempts to track the progression of the disease are affected by continual improvements in the care of patients. Comparing the effectiveness of different drugs is difficult because different primary endpoints are used in different studies. We also need to decide how much benefit we are aiming to achieve when studying a new treatment. The interpretation of animal models has also proved problematic, with results not being replicated in human studies. Moreover, promising phase I/II trial results have often not been confirmed by phase III studies. Our patients, meanwhile, are anxious to try any medication that may help. The ALS research community has learned a great deal from past trials and this will be greatly beneficial when evaluating the novel and combination therapies currently being developed. Effort must also be directed towards the search for objective markers for ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2001

The use of non-invasive positive pressure ventilation (NIPPV) in ALS patients. A need for improved determination of intervention timing.

We present our experience with 27 patients with symptoms of alveolar hypoventilation, a precursor to respiratory failure, to demonstrate variability in symptoms, physiologic status and outcome of intervention. They represent 27 consecutive patients who tolerated NIPPV for more that 4 hours per 24-h period for more than 2 weeks. All patients received neurological consultation, electromyography and met criteria for ALS according to El Escorial diagnostic criteria. To assess respiratory status, spirometry was measured in sitting and when possible, in the supine positions. Resting arterial blood gases were available in 22 patients. Orthopnea was the most common symptom at the time of institution of NIPPV. No correlation existed between age at institution of NIPPV, duration of effective use of this technology or vital capacity and duration of effective use of NIPPV. The lack of correlation between vital capacity at the institution of NIPPV and duration of its effectiveness suggest that more sensitive indicators for the onset of alveolar hypoventilation must be defined, particularly since the principal benefit from its use is relief of symptoms of alveolar hypoventilation.

Adult↗
PubMed2000

Novel mutations in spastin gene and absence of correlation with age at onset of symptoms.

Autosomal dominant hereditary spastic paraplegia is genetically heterogeneous, with at least five loci identified by linkage analysis. Recently, mutations in spastin were identified in SPG4, the most common locus for dominant hereditary spastic paraplegia that was previously mapped to chromosome 2p22. We identified five novel mutations in the spastin gene in five families with SPG4 mutations from North America and Tunisia and showed the absence of correlation between the predicted mutant spastin protein and age at onset of symptoms.

Adenosine Triphosphatases↗
PubMed2000

The ALS patient care database: goals, design, and early results. ALS C.A.R.E. Study Group.

OBJECTIVE: The ALS Patient Care Database was created to improve the quality of care for patients with ALS by 1) providing neurologists with data to evaluate and improve their practices, 2) publishing data on temporal trends in the care of patients with ALS, and 3) developing hypotheses to be tested during formal clinical trials. BACKGROUND: Substantial variations exist in managing ALS, but there has been no North American database to measure outcomes in ALS until now. METHODS: This observational database is open to all neurologists practicing in North America, who are encouraged to enroll both incident and prevalent ALS patients. Longitudinal data are collected at intervals of 3 to 6 months by using standard data collection instruments. Forms are submitted to a central data coordinating center, which mails quarterly reports to participating neurologists. RESULTS: Beginning in September 1996 through November 30, 1998, 1,857 patients were enrolled at 83 clinical sites. On enrollment, patients had a mean age of 58.6 years +/-12.9 (SD) years (range, 20.1 to 95.1 years), 92% were white, and 61% were men. The mean interval between onset of symptoms and diagnosis was 1.2+/-1.6 years (range, 0 to 31.9 years). Riluzole was the most frequently used disease-specific therapy (48%). Physical therapy was the most common nonpharmacologic intervention (45%). The primary caregiver was generally the spouse (77%). Advance directives were in place at the time of death for 70% of 213 enrolled patients who were reported to have died. CONCLUSIONS: The ALS Patient Care Database appears to provide valuable data on physician practices and patient-focused outcomes in ALS.

Activities of Daily Living↗
PubMed2000

Use of palatal lift and palatal augmentation prostheses to improve dysarthria in patients with amyotrophic lateral sclerosis: a case series.

STATEMENT OF PROBLEM: Amyotrophic Lateral Sclerosis (ALS) is a progressive, adult onset neurodegenerative disorder manifesting itself as a loss of motor capabilities and untimely death. The dysarthria seen in patients with ALS who have bulbar symptoms causes severe problems with communication. The struggle to be understood comes at a time when progressive cumulative disabilities make communication with family, friends, and healthcare workers vital. The use of palatal lift/augmentation prostheses for dysarthria in ALS is not a frequently requested procedure by neurologists. PURPOSE: The purpose of this retrospective outcomes study was to evaluate the effectiveness of this treatment on improving speech function and intelligibility in this group of patients. This study also reviews the history, incidence, pathogenesis, and speech characteristics of the patient with ALS. METHODS: A retrospective study of 25 patients treated with a prosthesis was performed using chart reviews and phone/office interviews to evaluate the efficacy of a palatal lift and/or augmentation prosthesis to improve speech in ALS patients. RESULTS: Twenty-one patients (84%) treated with a palatal lift demonstrated improvement in their dysarthria, specifically in reduction of hypernasality, with 19 (76%) benefiting at least moderately for 6 months. Of the 10 patients treated with a combination palatal lift and augmentation prosthesis, 6 (60%) demonstrated improvement in articulation. A majority of patients indicated it was easier to speak with less effort involved when wearing the prosthesis. CONCLUSION: On the basis of this preliminary retrospective study, the use of a palatal lift/augmentation prosthesis should be considered in ALS patients with dysarthria.

Adult↗
PubMed2000

Improving the quality of life for people with ALS: the challenge ahead.

In tandem with recent progress in basic and clinical research in amyotrophic lateral sclerosis (ALS), clinical care and management has improved substantially. Key processes and practices have been established and are specified in current ALS Practice Parameters; the international ALS databases identify the current status of care and management given by physicians. A number of prospective clinical management research studies are now well underway to establish the effective utility of enteral feeding, assistive ventilatory device, and exercise in patients with ALS. One of the main research objectives in the clinical management of ALS is to improve patients' quality of life. For patients with ALS, only comprehensive multidisciplinary care can effectively improve their overall quality of life from diagnosis to death. This paper will briefly review a number of factors that must be considered if we are to improve the quality of life for these patients, including comprehensive medical management, patient education, the importance of hope, the role of the health care professional, and the patients themselves.

Attitude to Health↗
PubMed2000

Spiritual well-being of the individual with amyotrophic lateral sclerosis.

BACKGROUND: A study was conducted to: (1) establish the feasibility and reliability of the Spiritual Well-Being Scale (SWBS) and its religious (RWB) and existential well-being (EWB) subscales in a sample of individuals with ALS; (2) describe the spiritual and religious practices, and spiritual well-being in these individuals; and (3) examine the relationship between spiritual well-being and quality of life. METHOD: A random sample of 60 individuals completed the SWBS at the beginning and end of an ALS clinic visit. Subjects were classified into early, middle or late stage of ALS, using vital capacity and total ALS Functional Rating Scale scores. A subsample completed the Sickness Impact Profile (SIP). RESULTS: The SWBS and its RWB and EWB subscales were found to have high internal consistency and test-retest reliability. There were no statistically significant differences in SWB, RWB or EWB scores among the three stages of ALS. RWB scores were significantly higher than EWB scores overall and within the middle and late stages. Strong negative correlations were found between physical and psychosocial dimension SIP subscores and RWB scores, suggesting that religious well-being may impact quality of life, or vice versa.

Attitude to Health↗
PubMed2000

Amyotrophic lateral sclerosis with multiple sclerosis: a clinical and pathological report.

We report a 62-year-old woman with a past history of painful central visual loss who developed progressive quadriparesis and bulbar palsy. Neurological examination revealed widespread upper and lower motor neuron signs in the bulbar region and extremities. Electromyography demonstrated widespread active and chronic motor axon loss. Magnetic resonance neuroimaging studies revealed enhancing callosal and periventricular white matter lesions and cervical and thoracic cord hyperintensities. Cerebrospinal fluid analysis was consistent with multiple sclerosis. The patient died of respiratory failure two years after presentation, and autopsy revealed multifocal demyelination involving the corpus callosum, cerebellum and spinal cord as well as pathologic findings typical of amyotrophic lateral sclerosis. A review of the literature confirms the exceedingly unusual combination of amyotrophic lateral sclerosis with multiple sclerosis.

Autopsy↗
PubMed1999

1H-MRS evidence of neurodegeneration and excess glutamate + glutamine in ALS medulla.

OBJECTIVE: To determine whether short echo-time (TE) proton magnetic resonance spectroscopic imaging (1H-MRSI) can detect in vivo differences in signal intensities of specific metabolites in the medulla of patients with ALS compared with healthy individuals and whether these metabolites could be useful surrogate markers of disease. BACKGROUND: 1H-MRSI can detect N-acetylaspartate + N-acetylaspartylglutamate (abbreviated NAx), which is localized to neurons, and glutamate (Glu) + glutamine (Gln), abbreviated Glx, which may be important in ALS pathogenesis. The medulla is an ideal region to study ALS because of its high density of nuclei and fiber tracts that frequently undergo degeneration, even when more rostral brain regions show minimal pathology. METHODS: Ten patients with ALS and seven healthy control subjects underwent short TE 1H-MRSI on a 1.5 T clinical imaging system. Signal intensities of NAx and Glx were normalized to creatine-phosphocreatine and compared between groups. RESULTS: Compared with normal subjects, the medulla of patients with ALS had 17% lower NAx (p = 0.03) and 55% higher Glx (p = 0.02) signals. Bulbar symptoms, represented by the ALS Functional Rating Scale, correlated with Glx (r = -0.68, p = 0.03) but not NAx (r = 0.22, p = 0.53). CONCLUSION: There is in vivo 1H-MRSI evidence of neuronal degeneration or loss and excess Glu + Gln in the medulla of patients with ALS. Although this cross-sectional study cannot identify which change occurred first, the higher Glx signal in the medulla of patients with more dysarthria and dysphagia is consistent with the hypothesis of Glu excitotoxicity in ALS pathogenesis. Longitudinal 1H-MRSI studies of the medulla (and other brain regions) in more patients with ALS are required to confirm these findings and to determine whether such metabolite changes will be useful in monitoring disease progression, in clinical diagnosis, and in understanding the pathogenesis of ALS.

Adult↗
PubMed1999

Neurotrophic factors and neuro-muscular disease: II. GDNF, other neurotrophic factors, and future directions.

This is the second of two reviews in which we discuss the essential aspects of neurotrophic factor neurobiology, the characteristics of each neurotrophic factor, and their clinical relevance to neuromuscular diseases. The previous paper reviewed the neurotrophin family and neuropoietic cytokines. In the present article, we focus on the GDNF family and other neurotrophic factors and then consider future approaches that may be utilized in neurotrophic factor treatment.

Animals↗