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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 145 records · Page 8Linked to original sources

[A case of a premenopausal woman with advanced breast cancer treated with aromatization inhibition in combination with luteinizing hormone-releasing hormone agonist].

A 44-year-old premenopausal woman having local recurrence and pleural and bone metastases of breast cancer was treated with aromatization inhibition in combination with Luteinizing Hormone-releasing Hormone (LH-RH) agonist. The dominant site of metastasis was a painful local lesion invading the chest wall. A partial response by reducing the size of the local lesion was attained 3 months after initiation of treatment. This result suggested that treatment using aromatization inhibition in combination with LH-RH agonist would be effective in premenopausal breast cancer. To confirm the effectiveness of this treatment, comparative study between aromatization inhibition in combination with LH-RH agonist aromatization inhibition alone and anti-estrogen in combination with LH-RH agonist are needed.

Adult↗

[Similarities in calcium and magnesium metabolism between amyotrophic lateral sclerosis and calcification of the spinal cord in the Kii Peninsula ALS focus].

Current epidemiological surveys in the Western Pacific area and Kii Peninsula have suggested that low calcium (Ca), magnesium (Mg) and high aluminum (Al) and manganese (Mn) in river, soil and drinking water may be implicated in the pathogenetic process of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD). The condition of unbalanced minerals was experimentally mimicked in this study using rats. Male Wistar rats, weighing 200 g, were maintained for 90 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca-Mg diet, (D) low Ca-Mg diet with high Al. In the groups maintained on unbalanced mineral diets, calcium and magnesium contents of the bones were lower than those fed with standard diet. On the other hand, Ca content of CNS showed higher values in the unbalanced diet groups (especially in spinal cord of the low Ca-Mg plus high Al diet group) than those in the standard diet group. This was determined by neutron activation analysis (NAA) at Research Reactor Institute, Kyoto University. Also, Ca content in soft tissues of rats given unbalanced mineral diets was higher than those on standard diet. Mg content of soft tissues and spinal cord of rats was markedly lower in the low Ca-Mg plus high Al diet group than the other three groups as determined by inductively coupled plasma emission spectrometry (ICP). Six Kii cases with amyotrophic lateral sclerosis (ALS) also showed higher Ca and lower Mg contents in the CNS tissues than those of neurologically normal controls. As of today, calcification of the spinal ligaments (CSL) has been reported in only 120 cases in the world and 28 cases of CSL in the Kii Peninsula have been found in the same foci as ALS. We analyzed Mg content of 7 spinal bones and 10 ligaments of the CSL and Ca content of 5 spinal bones compared with controls. The CSL showed lower values of Mg contents in bones and ligaments compared to controls. The Ca content in bones of CSL was significantly lower than that of controls. These results suggest that the environmental factor may contribute to the pathogenesis of CSL due to low Ca and Mg intake as well as for ALS.

Aged↗

Effects of low calcium and magnesium dietary intake on the central nervous system tissues of rats and calcium-magnesium related disorders in the amyotrophic lateral sclerosis focus in the Kii Peninsula of Japan.

Current epidemiological investigations in the Western Pacific including the Kii Peninsula of Japan, have suggested that environmental factors contribute to the pathogenetic process of amyotrophic lateral sclerosis (ALS) and parkinsonism dementia (PD). The condition of unbalanced minerals (a low content of calcium and magnesium, and a high content of aluminum) found in soil and drinking water in all three ALS foci was experimentally mimicked in our studies using rats. In rat groups maintained on unbalanced mineral diets, the calcium and magnesium contents of bones were lower than those fed a standard diet. In addition, the calcium content of CNS tissues showed higher values in the unbalanced diet groups (especially in the spinal cord of the low calcium and magnesium plus high aluminum diet group) than those in the standard diet group. The calcium content of other soft tissues as well as the CNS of rats fed unbalanced mineral diets was also higher than those on the standard diet. The magnesium content of soft tissues and spinal cord of rats was markedly lower in the low calcium and magnesium plus high aluminum diet group than in the other groups. Examination of tissues from six Kii Peninsula patients with ALS showed an average magnesium concentration in 26 CNS regions (cortical gray matter, white matter, basal ganglia, brain stem, spinal cord) significantly lower than that for five neurologically normal controls. The average calcium concentration in gray matter of ALS cases was significantly higher than that of controls. Interestingly, only 120 cases of calcification of spinal ligaments have been reported worldwide, and of these, 26 of 28 cases of calcification of spinal in the Kii Peninsula have been found to overlap the same geographic focal region as ALS. We analyzed the magnesium content of seven spinal vertebrae and 10 spinal ligaments of patients with calcification of spinal ligaments and the calcium content of five spinal bones compared with controls. The calcification of spinal ligaments patients had lower values for magnesium contents of bones and ligaments compared to controls and the calcium content of bones in these patients was significantly lower than that of controls. These data suggest that low dietary intake of calcium and magnesium over an extended period of time may contribute to the pathogenesis of patients with ALS and calcification of spinal ligaments.

Amyotrophic Lateral Sclerosis↗

[Efficacy of nasal bi-level positive airway pressure ventilation in a patient with olivo-ponto-cerebellar atrophy suffering from sleep apnea syndrome].

Sleep apnea with neuromuscular disorders has been successfully treated with bi-level positive airway pressure ventilation (BiPAP), which, unlike continuous positive airway pressure ventilation (CPAP), creates pressure difference between expiratory and inspiratory phases. Hence if the respiration of patients stops longer than a pre-set duration, BiPAP can automatically force them to breath through a nasal mask. We report a 60-year-old woman with olivo-ponto-cerebellar atrophy (OPCA), whose mixed-type sleep apnea was difficult to treat with conventional CPAP. We therefore tried BiPAP on this patient at night. Nocturnal CO2 retention was nearly resolved, and unexpectedly daytime PaCO2 was also corrected with marked improvement of daytime somnolence. BiPAP is totally non-invasive, and may be one of the most effective treatments in patients with OPCA suffering from sleep apnea.

Female↗

[Phase I study of S-1. S-1 Study Group].

We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).

Administration, Oral↗

[Binocular functions in amblyopia and strabismus].

Regarding the changing trends in the concept, definition, etiological classification, and criteria for diagnosis of amblyopia, we reviewed a total of 4,693 cases of amblyopia seen during the past 37 years. The amblyopia was divided into four types: strabismic, anisometropic, ametropic, and form vision deprivative. There was a definite trend for the incidence to decrease and for the diagnosis to be made during earlier age in recent years. Although favorable recovery of visual acuity is obtained after treatment of amblyopia and strabismus, there are difficulties in obtaining good binocular functions in early-onset amblyopia and strabismus. This feature was evaluated in regard to motion perception asymmetry (MPA) and binocular depth from motion (DFM). Many cases of early-onset amblyopia and strabismus showed no disparity stereopsis, or position stereopsis, in spite of the presence of DFM. The MPA appeared to be closely related to early-onset esotropia regardless of age, while it disappeared and motion perception became symmetric 4 to 5 months after birth in normal infants. The DFM seemed to play an important role in maintaining good motor alignment for several years after surgery. I developed a checkerboard pattern stimulator in 1978. This method proved to be useful in developing binocular functions and motor alignment by applying simultaneous bifoveolar stimulation and anti-suppression. Extensive exposure to the stimulation was essential for therapeutic success.

Adolescent↗

[A study of nursing systems in transition in developed countries].

The present study was designed to investigate nursing systems in other countries in comparison with the current system in Japan, and thereby assess how nursing personnel should be in order to improve the quality of nursing. The study focused on the actual situation of the nursing system and licensed practical nurses (LPNs) or second-level nurses similar to LPNs in other countries. The survey was conducted in regard to six countries considered to be advanced in the development of nursing activities and likely to provide useful suggestions for the future direction of nursing in Japan: Australia, Canada, France, Sweden, the United Kingdom and the United States. Questionnaires were sent to the heads or staff of a total of 29 organizations, including WHO Collaborating Centers and professional organizations for nursing, in these countries. Nineteen organizations responded (response rate: 65.5%), and an effective response with completed questionnaire forms was obtained from 15 organizations. In addition, an interview survey was conducted on three nursing administration and education experts in the United States in order to acquire clear understanding of the actual state of nursing in health care practice. The results were as follows: 1. Six countries (Japan included) excluding France had LPNs. Educational preparation for LPNs has been discontinued in the United Kingdom. 2. The number of nurses per 1,000 population was lowest in Japan: the total number of registered nurses (RNs) and LPNs in Japan was less than the number of RNs in the United Kingdom. Only in Japan the proportions of LPNs and RNs were similar, while in other countries of number of LPNs was one-third to one-fourth of the number of RNs. 3. In the five other countries having LPNs, the nurse's competency or scope of practice was clearly defined for both LPNs and RNs. In contrast, no clear line was drawn between the two in Japan. 4. The length of education required for LPNs ranged from 11 to 14 years (including the period of compulsory education) and was shortest in Japan (11 years). The educational requirement for admission to LPN school in Japan was 9 years of compulsory education (graduation from junior high school), whereas in other countries it was at the level of senior high school graduation. 5. Four countries had conversion programs for LPNs to become RNs, and the conversion courses were positioned within the framework of higher education comparable to the university level. 6. In the United Kingdom, where the educational preparation for LPNs has been discontinued, nurses are included in a single higher level profession. At the same time there was found to be a need to train and educate auxiliary personnel in order to maintain multi-level care services. Because of the increasing tendency toward advanced medical technology and highly specialized medical care associated with the rapidly increasing care needs in the community, the current educational preparation for LPNs in Japan in unsatisfactory as a training and educational system for nursing manpower to cope with the current situation. The above findings suggest that the education system for LPNs be reviewed with a view to discontinuing it and consolidating nursing education in Japan.

Australia↗

[A case of acute inflammatory demyelinating neuropathy associated with autoimmune-type chronic active hepatitis].

We presented a case of acute inflammatory demyelinating polyneuropathy associated with autoimmune chronic active hepatitis (AI-CAH). This is the third case report of neuropathy in AI-CAH. A 64-year-old male with chronic liver dysfunction was admitted to the hospital because of high fever, distal weakness and sensory disturbance of all extremities, bilateral facial weakness and dysphagia. On neurologic examination, there was bilateral weakness of the upper and lower facial muscles, bulbar palsy and severe distal weakness of all extremities. The deep tendon reflexes were absent and the sensation of touch, pinprick, temperature, and vibration was impaired bilaterally symmetrically in all extremities. Serum biochemistry revealed hyperproteinemia, hypergammaglobulinemia and elevated liver enzymes. Rheumatoid factor, antinuclear antibody anti-smooth muscle antibody were positive. Serological tests for hepatitis B surface antigen and its antibody hepatitis B core antibody, and hepatitis C antibody were all negative. Serum anti-GM1, anti-GD1b, anti-GQ1b and anti-MAG antibodies were negative. Liver biopsy findings were consistent with AI-CAH with marked lymphocytic infiltration in the portal tracts. Albuminocytologic dissociation was noted in CSF. Motorconduction velocity of the median, ulnar and facial nerves were markedly reduced with temporal dispersion. No motor response was evoked in the lower extremities. Needle electromyography revealed denervation and reinnervation potentials in the arm and leg. The sural nerve biopsy showed segmental de- and re-myelination and deposition of IgG components in endoneurium. Neurological symptoms and liver dysfunction improved with corticosteroid treatment. In this case, hypergammaglobulinemia associated with an exacerbation of AI-CAH may be responsible for the acute inflammatory demyelinating neuropathy through an unknown autoimmune mechanism.

Acute Disease↗

[Neurosarcoidosis with an alternating and recurrent external ophthalmoplegia].

We report a 62-year-old woman who was admitted to our hospital because of abrupt onset of ptosis, and alternating and recurrent bilateral external ophthalmoplegia in a short period without pupillary sphincter muscle abnormality. She had been suffering from uveitis of unknown origin for four years before admission, which was improved with the local administration of steroid. Her brain CT and MRI showed a parasellar mass lesion, and cerebral angiography revealed total occlusion of the right internal carotid artery with little arteriosclerotic change in other blood vessels. She was diagnosed as having sarcoidosis because of elevated serum creatinine kinase and lysozyme levels, and the pathological finding of granuloma in muscle biopsy. The oral administration of prednisolone resulted in disappearance of her external ophthalmoplegia completely in ten months. We postulate that in this patient, the alternating and recurrent external ophthalmoplegia in a short period was related to ischemic neuropathy caused by vascular lesion of neurosarcoidosis.

Cranial Nerve Diseases↗

Status of microchimerism in recipients 15 years after living related kidney transplantation.

To study the relevance of microchimerism to the long-term outcome of renal allografting, we analyzed the frequency of microchimerism in kidney transplant recipients who had stable graft function for 15 years or longer. Among the 104 recipients who underwent kidney transplantation between 1971 and 1980, 27 renal allografts (26%) are still functioning. Among these 27 patients, 13 recipients whose donor was still alive and cooperative were investigated for the presence of microchimerism in the peripheral blood and for their immunological status. Microchimerism was tested using the polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) method. To test the sensitivity of PCP-SSCP, the peripheral blood obtained within 5 weeks after transplantation (four kidney transplants, three liver transplants) was also examined. Microchimerism was detectable in five patients within 5 weeks of transplantation (kidney transplantation, 3/4; liver transplantation 2/3. However, in the patients studied 15 years after transplantation, microchimerism was detected in only one recipient (1/13). In this chimeric patient, mixed lymphocyte response revealed high responsiveness against donor antigen. In contrast, some patients who did not have chimerism showed donor-specific hyporesponsiveness in mixed lymphocyte response assay and did not develop antidonor antibody, according to flow cytometric analysis. Microchimerism is an infrequent state in the long-term survivors of kidney allografting, and this state is irrelevant to donor-specific unresponsiveness.

Adult↗

Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorders.

The dopamine D2 receptor gene is a candidate gene for schizophrenia because the potency of certain neuroleptics correlates with their affinity for this receptor. Case-control studies in 291 schizophrenics, 78 patients with affective disorders, and 579 controls on an association of a molecular variant of S311C of the dopamine D2 receptor with psychiatric disorders were conducted. The frequency of individuals with S311C was significantly higher in schizophrenics with the absence of negative symptoms (17.1%, P < 0.00001), but similar in schizophrenics with the presence of negative symptoms (5.7%, P = 0.46) when compared with the controls (4.1%). The frequency of S311C was significantly higher in familial schizophrenics from one local area but not in those from other areas. It was significant that S311C was frequently present in patients with mood-incongruent psychotic affective disorders (33.3%, P < 0.0001), but not in those with other affective disorders. These data suggest that S311C might be one of the genetic factors for symptomatic dimensions of delusions and hallucinations and might be involved in underlying clinical heterogeneity in schizophrenia and affective disorders.

Adult↗

Dose escalation study of carboplatin with fixed-dose etoposide plus granulocyte-colony stimulating factor in patients with small cell lung carcinoma. A study of the Lung Cancer Study Group of West Japan.

BACKGROUND: We performed a Phase I-II trial to determine the maximum tolerated dose of carboplatin (CBDCA) with a fixed dose of VP-16 and granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC) patients. METHODS: Treatment consisted of a starting dose of CBDCA, 400 mg/m2 (i.v., Day 1); VP-16, 100 mg/m2 (i.v., Days 1-3), and G-CSF, 2 micrograms/kg (s.c., Days 4-17) every 4 weeks for four cycles. The dose of CBDCA was escalated in increments of 50 mg/m2 until Grade IV toxicity on the World Health Organization scale developed in two-thirds or more of the patients. RESULTS: Seventy-five previously untreated patients with pathology confirmed SCLC were entered into the trial. Seventy-one patients were eligible and 70 patients were evaluated for response. Forty-five patients had limited disease (LD) and 26 had extensive disease (ED). The response rate of the 70 patients who could be evaluated was 81%, with 23% attaining a complete response (CR) and 58% attaining a partial response (PR). The response rate was 80% in LD patients (CR, 23%; PR, 57%) and 85% in ED patients (CR, 23%; PR, 62%). The major dose-limiting toxicity was thrombocytopenia. Nephrotoxicity, neurotoxicity, and ototoxicity were uncommon. The doses of CBDCA that resulted in unacceptable thrombocytopenia were 700 mg/m2 in patients younger than 70 years and 500 mg/m2 in patients older than 70 years. Overall median survival time (MST) was 9 months. MST of LD patients and ED patients were 11 months and 7 months, respectively. The dose-limiting toxicity of CBDCA with a fixed dose of VP-16 and using G-CSF as bone marrow rescue was age-related thrombocytopenia. The maximum tolerated dose of CBDCA was 650 mg/m2 if patients were younger than 70 years and 450 mg/m2 if they were 70 years or older. CONCLUSIONS: When we retrospectively compared our results with those using standard chemotherapy regimens, we saw no therapeutic benefit from increasing planned doses of CBDCA up to 700 mg/m2 in combination with G-CSF in patients with SCLC.

Aged↗

Synergistic effect of donor-specific blood transfusion and a short course of deoxyspergualin in rat kidney transplantation.

Deoxyspergualin (DSG), an analogue of spergualin produced by B. laterosporus, has a strong immunosuppressive effect in various transplantation models. We have investigated the mechanism of donor-specific prolongation of survival time in rat kidney grafting by donor-specific blood transfusion (DST) and a short course of DSG. Lewis (LEW) kidney allografts were transplanted into fully allogeneic BN rats. Fresh, whole LEW blood 1.0 ml, was injected i.v. into BN rats 2 days prior to transplantation. Then, DSG, 6 mg/kg per day, was administered by i.m. injection on days 0, 1, and 2 after transplantation. The recipients were divided into five groups: group 1 (n = 6) no treatment: group 2 (n = 6) DST only; group 3 (n = 7) DSG only; group 4 (n = 7) DST and DSG; and group 5 (n = 6), third party (ACI rats) blood transfusion and DSG. Lymphocytes (cervical lymph nodes) and serum were harvested from BN recipients on day 7 postgrafting. For suppressor cell assays, lymphocytes from BN recipients in each group were added as a third cell to the mixed lymphocyte reaction (MLC) between nontransplanted BN lymphocytes (responder) and LEW or other third party (PVGC, ACI, WKA rats) lymphocytes (stimulator). Antidonor lymphocytotoxic antibody (ADLA) was checked by microcytotoxicity assays. Median survival times (MST) for each group were: group 1, 10 days; group 2, 10 days; group 3, 13 days; group 4, 75 days; and group 5, 13 days. Remarkable prolongation of MST was only noted in group 4. In the suppressor cell assay, group 4 showed significant suppression (40%; P > or = 0.05); the other groups did not show any suppression. This suppressive activity in group 4 was effective only during the MLC between BN and LEW, not during the MLC of third party-BN combinations. Thus, suppressor cells from DST/DSG-treated BN recipients appear to be donor-specific. In the microcytotoxicity assay, the only group that showed any ADLA was group 2, which was not treated with DSG. These results clearly show that both induction of donor-specific suppressor cells and inhibition of ADLA production are associated with the remarkable donor-specific prolongation of kidney allograft survival in DST/DSG-treated recipients.

Animals↗

Removal of anti-A/B antibodies for successful kidney transplantation between ABO blood type incompatible couples.

A growing shortage of cadaveric donors has prompted expansion of the criteria for acceptable living donors. Because of this, ABO-incompatible kidney transplantation has been carried out. To remove anti-A and/or anti-B antibodies, the recipients received one or two sessions of double filtration plasmapheresis (DFPP) and three or four sessions of immunoadsorption prior to transplantation until the anti-A IgG/IgM titers and/or anti-B IgG/IgM titers decreased to 1:16 or less. Our immunosuppressive protocol involved treatment with the drugs methylprednisolone, cyclosporine, azathioprine, anti lymphocyte globulin and deoxyspergualin. The patient survival was 98% at 1 month, 98% at 3 months, 94% at 6 months, and 92% at 1-5 years. Graft survival was 92% at 1 month, 88% at 3 months, 85% at 6 months, 81% at 1 year, and 76% at 5 years. Both DFPP and/or immunoadsorption eliminated anti-ABO antibodies from ABO-incompatible kidney transplant recipients effectively and safely. The results of the ABO-incompatible kidney transplantation were acceptable and not different from those of ABO-compatible cases.

ABO Blood-Group System↗