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Biomedical subjects

M Akizuki

Publications and source records attributed to M Akizuki.

At least 55 records · Page 3Linked to original sources

Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the molecular weight of drugs.

To clarify the relationship between the direct transport from the rat nasal cavity to the cerebrospinal fluid (CSF) and the molecular weight of the drug, the transport of fluorescein isothiocyanate-labelled dextran (FD) with various molecular weights was investigated. FDs (average molecular weights 4,400 (FD4); 9,400 (FD10); 18,900 (FD20); 40,500 Da (FD40)) were administered nasally or intravenously to rats, and the concentrations in the plasma and the CSF were measured and compared. None of the FDs were detected in the CSF after intravenous administration. However, FD4, FD10 and FD20 were observed to appear in the CSF after nasal administration, whereas the concentration in the plasma was much lower than that after intravenous administration. FD40 was not detected even after nasal administration. In addition, the concentration of these FDs in the CSF decreased with the increase in the molecular weight of FDs. These findings show that drugs with a molecular weight up to at least 20,000 Da can be directly transported from the nasal cavity to the CSF and that the transport of FDs to the CSF is dependent on their molecular weights.

Administration, Intranasal↗

Development of anti-Sm and anti-DNA antibodies followed by clinical manifestation of systemic lupus erythematosus in an elderly woman with long-standing Sjögren's syndrome.

A 69-year-old Japanese women who had been followed up for 10 years as a primary Sjögren's syndrome, is reported. She suddenly developed serological and clinical characteristics of systemic lupus erythematosus (SLE): anti-Sm and anti-dsDNA antibodies followed by nephrotic syndrome and pancytopenia. This case suggests that the diagnosis of primary Sjögren's syndrome should be considered as tentative in certain cases and that the development of serological characteristics precede and are associated with the development of clinical symptoms of SLE.

Aged↗

[A case of adult onset Still's disease complicated with adult respiratory distress syndrome and disseminated intravascular coagulation].

A 71 year-old man with adult onset Still's disease was admitted to our hospital because of fever, sore throat, myalgia and macular nonpruritic salmon pink eruption. He was treated with prednisolone, 40 mg daily and these symptoms disappeared. When the dose of prednisolone was reduced to 30 mg daily, he began to notice fever. 5 days later he developed adult respiratory distress syndrome (ARDS). The dose of prednisolone was increased to 50 mg daily and oxygen administration was started. All symptoms began to improve immediately and the dose of prednisolone was decreased to 40 mg daily. 10 days later he noticed fever and skin rash. Laboratory investigation showed platelet counts of 69,000/mm3, a ferritin of 37,000 ng/ml, and increased fibrinogen degradation product, indicating increased activity of adult onset Still's disease associated with disseminated intravascular coagulation (DIC). The dose of prednisolone was again increased to 60 mg daily, and 100 mg of nafamostat mesilate was administrated intravenously. All above symptoms associated with adult onset Still's disease and DIC disappeared. The dose of prednisolone was gradually decreased and the clinical course was uneventful with daily administration of 10 mg of prednisolone. Although there are a couple of case report which described the association of adult onset Still's disease with either ARDS or DIC, the association of adult onset Still's disease with both ARDS and DIC have not been reported yet.

Aged↗

[Efficacy of beraprost sodium on Raynaud's phenomenon in patients with systemic sclerosis].

Raynaud's phenomenon is an important clinical manifestation in patients with systemic sclerosis (SSc). No effective therapy, however, has been established for this phenomenon. Beraprost sodium, a stable prostacycline (PGI2) analogue, has been reported to improve hemorrheological impairment in patients with rheumatic diseases. In this study, we, therefore, examined the efficacy of beraprost sodium on Raynaud's phenomenon in 30 patients with SSc. Sixty micrograms per day of beraprost sodium was found to be effective in 14 patients (47%) in the period of 15.0 +/- 12.5 weeks. Raynaud's phenomenon in patients who responded to beraprost sodium was characterized by infrequent nail fold thrombosis and narrower hand areas affected by Raynaud's phenomenon, with mild secondary symptoms such as pain. These results indicate that beraprost sodium is effective for mild forms of Raynaud's phenomenon in patients with SSc.

Adult↗

[The validity and reliability of a Japanese version of Arthritis Impact Measurement Scales in patients with rheumatoid arthritis].

A Japanese version of Arthritis Impact Measurement Scales (Japanese-AIMS) was developed after the original AIMS Version 2 (AIMS 2). We then conducted a Quality of Life measurement of 691 patients with Rheumatoid Arthritis (RA) with this newly developed questionnaire. Based on the data collected, the validity and reliability of the Japanese-AIMS was examined. The validity of the Japanese-AIMS, which was assessed by the examination of internal consistency among items and through factor analysis, was almost comparable with that of the original AIMS 2. QOL scales were also validated using internal standards based on the subject's responses to other items in the questionnaire. The test-retest reliability, which was the correlation of scale scores between two tests administered 4-5 weeks apart, was slightly lower than the original one. We conclude that the validity and reliability of the Japanese AIMS were comparable with those of the original one, though there could be possibly improved by the minor revision of phrasing. The large scale QOL measurement study with RA patients is under way, using the Japanese-AIMS with minor revision.

Activities of Daily Living↗

[Three cases with systemic rheumatic diseases who developed pulmonary lesions suggestive of bronchiolitis obliterans organizing pneumonia].

Three cases with systemic rheumatic diseases who developed lung diseases compatible with BOOP were reported. Underlying diseases of these patients were: RA (1 case), SLE (2 cases). Respiratory symptoms were observed in one case such as dry cough at the time of diagnosis of BOOP. Chest radiography showed multiple infiltrates in 2 cases, bilateral reticular shadow in one case. In one case characteristic finding described as wandering shadow was observed. TBLB was done in 3 cases. Pathohistological findings were compatible with BOOP. Repeated Bacteriological examinations failed to demonstrate specific organisms implicated for lung lesions. Cytological studies of sputum and TBLB specimens were all negative for malignancy. Antibiotic agents including anti-tuberculosis drugs were not effective for pulmonary diseases. Moderate doses of prednisolone were effective in 3 cases. Although the open lung biopsy has been recommended for establishment of diagnosis of BOOP, in patient with systemic rheumatic diseases this invasive procedure is not always easily performed. Further characterizations of clinical and laboratory features are indicated for noninvasive diagnosis of BOOP.

Adult↗

[Quality of life, subjective health status and health and life satisfaction in rheumatoid arthritis].

A Japanese version of Arthritis Impact Measurement Scales (AIMS) was developed after the original AIMS Version 2 and utilized for Quality of Life (QOL) measurement in 691 patients with Rheumatoid Arthritis (RA). Various medical (physical and laboratory) examinations, which are widely used in the clinical settings for the assessment of RA activity and severity, were also performed by physicians. Interrelationships between QOL, patient subjective health status, and health and life satisfaction were analyzed with the following results: 1: The effect of QOL impairment by RA upon patients' subjective health rating and health satisfaction were not constant over the range of severity of disease status. Pain was found to lower overall subjective health and health satisfaction regardless of RA class. On the other hand, while the deterioration of mobility aspects of QOL had negative effects upon patients' subjective health status and satisfaction among less-disabled RA patients, any of physical aspects of QOL, including the degree of mobility impairment, showed no significant association with patients' subjective health status and satisfaction in the more disabled. 2: Psychological aspects of QOL (mood and tension) had significant associations with patients' subjective health status and satisfaction. In the less severe group, mood impairment had a significant effect on subjective health and satisfaction, while in the more severe group tension showed a significant association. It was indicated that management of psychological aspects of QOL is important in RA patients to improve and advance their subjective health status and satisfaction. 3: Although social aspects of QOL, i.e. social support, social life and job status, showed no significant relationship to subjective health rating and health satisfaction, those with less disease severity who lacked social support and who had a jobless state were likely to have lower disease acceptance and life satisfaction, while those with more severe disease who had less social interaction manifested lower life satisfaction. These results suggested that social aspects of QOL, while not directly associated with subjective health rating, could be important factors affecting disease acceptance and life satisfaction.

Adult↗

[Interstitial lung disease in patients with connective tissue diseases].

Interstitial lung disease is a significant prognostic factor in connective tissue diseases. To further clarify clinical and immunological features of interstitial lung disease, we studied 894 consecutive patients with connective tissue diseases first evaluated between 1970 and 1993. Interstitial lung disease was found in 101 of 181 (56%) patients with systemic sclerosis, 92 of 183 (50%) with overlap syndrome, 35 of 76 (46%) with polymyositis/dermatomyositis, and 13 of 444 (3%) with systemic lupus erythematosus (p < 0.05, systemic lupus erythematosus vs. other connective tissue diseases). The presence of interstitial lung disease correlated with decreased survival in systemic sclerosis and in polymyositis/dermatomyositis, but not in overlap syndrome or in systemic lupus erythematosus. Interstitial lung disease in patients with connective tissue diseases was classified into two types: acute (n = 8) and chronic (n = 233). Among the 8 patients with acute disease, 4 (all with dermatomyositis) died of respiratory failure and 3 (all with systemic lupus erythematosus) responded to corticosteroids. Among the 233 patients with chronic interstitial lung disease, 20 had polymyositis/dermatomyositis with anti-aminoacyl tRNA synthetase antibodies and 40 had overlap syndrome with anti-U1 RNP antibodies. Respiratory failure in these patients was not frequent and occurred late in the course of the disease. As a cause of death, respiratory failure was associated with autoantibodies to topoisomerase I and aminoacyl tRNA synthetase but not anti-U1 RNP. Autoantibodies to aminoacyl tRNA synthetases were detected before the development of interstitial lung disease in 9 patients with polymyositis/dermatomyositis. We conclude that the clinical features of interstitial lung disease associated with connective tissue diseases vary with the type of connective tissue disease, and that analysis of autoantibodies can be useful in establishing a diagnosis and in forecasting the course and outcome.

Adult↗

Clinical significance of antibodies to native or denatured 60-kd or 52-kd Ro/SS-A proteins in Sjögren's syndrome.

OBJECTIVE: To evaluate the clinical significance of antibodies to native or denatured (anti-n or anti-d) 60- or 52-kd Ro/SS-A proteins (60K or 52K) in Sjögren's syndrome (SS). METHODS: The presence of antibodies to denatured and native Ro/SS-A proteins was determined by immunoblotting and immunoprecipitation, respectively. Salivary gland dysfunction was evaluated by salivary function scintigraphy. RESULTS: The incidence of anti-d-60K without anti-d-52K was lower among patients with systemic lupus erythematosus with SS (SLE/SS) and among those with primary SS, compared with patients who had SLE without SS, whereas anti-d-52K without anti-d-60K was more common in SLE/SS patients and primary SS patients than in SLE patients without SS. All of the patients with anti-Ro/SS-A had anti-n-60K. Serologic abnormalities and salivary gland dysfunction were associated with anti-n-60K in SS, whereas Hashimoto's thyroiditis in SS was related to anti-d-60K. Anti-d-52K was not associated with any extraglandular or glandular symptoms in SS. CONCLUSION: The data indicate that anti-n-60K, which appears to recognize conformational epitopes, is associated with clinical features of SS characterized by glandular dysfunction.

Autoantibodies↗

Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the dissociation of the drug.

We aimed to clarify the relationship between drug dissociation (sulphisomidine) and its direct transport from the nasal cavity to the cerebrospinal fluid (CSF). Rat nasal cavities were perfused in a single pass system with buffers (pH 5.5, 6.5, 7.4, 8.7 and 9.4). Plasma and CSF were collected and the concentration of sulphisomidine was measured. Nasal clearance increased with the increase in the un-ionized fraction of the drug. The ratio of the drug concentration in CSF to that in the nasal perfusion fluid (the index of the degree of the drug transport from the nasal cavity to CSF), was changed in accordance with the un-ionized fraction of drug. These results show that both the nasal absorption and the drug transport conform to the pH partition theory.

Absorption↗

Recurrent annular erythema with anti-SSA/Ro and anti-SSB/La antibodies localized on palms and fingers in an elderly man.

A 69-year-old Japanese man with recurrent annular erythema localized on palms and flexor surface of fingers with anti-SSA/Ro and anti-SSB/La antibodies, is reported. The present case indicates that even in an elderly man with atypical localization, annular erythema with autoimmunity may be considered and serological analysis should be performed. Systematic studies will be required to understand the relationship between 'recurrent annular erythema associated with anti-SSB/La antibodies' in Japanese, subacute cutaneous lupus erythematosus (SCLE) and 'annular erythema associated with Sjogren's syndrome'.

Aged↗

[Detection of autoantibodies in sera from patients with rheumatoid arthritis].

Although Rheumatoid Arthritis (RA) is categorized in the systemic autoimmune diseases, specific autoantibodies in RA have been reported to be rare. We have investigated autoantibodies found in sera from patients with RA and examined their clinical significance. Immunoprecipitation techniques using 32P-labeled or 35S-labeled HeLa cell extracts and immunoblotting were utilized to detect autoantibodies in sera from 42 patients with RA and 58 patients with other connective tissue diseases as controls. Certain autoantibodies were detected in 33 of 42 patients (79%) with RA by any of the assay systems mentioned above. Anti-SSA/Ro, anti-SSB/La, anti-7-2RNP, and anti-Sm antibodies were found in 13 (29%), 3 (7%), 4 (10%), and 1 (2%) patients with RA, respectively. All 3 patients with anti-SSB/La and 9 with anti-SSA/Ro revealed Sjögren's syndrome besides RA. However, all 4 patients with anti-7-2RNP and one patient with anti-Sm showed no evidence of scleroderma nor SLE. Besides of these known autoantibodies, we have also detected 4 new antibodies which reacted with a 60kD protein in 15 (36%), 45kD in 10 (24%), 75kD in 8 (19%), 180kD in 4 patients (10%) with RA. These autoantibodies were not found in other connective tissue diseases except one of SLE for anti-60kD and one of dermatomyositis for anti-75kD, and therefore appeared to be specific for RA patients. Anti-45kD antibodies were associated with low prevalence of anti-nuclear antibodies, and anti-180kD antibodies were associated with lymphadenopathy and Sjögren's syndrome. Thus, it was demonstrated that patients with RA develop a variety of autoantibodies as well as those with other connective tissue diseases.

Arthritis, Rheumatoid↗