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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 145 records · Page 8Linked to original sources

A non-arthropathic dose and its disposition following repeated oral administration of ofloxacin, a new quinolone antimicrobial agent, to juvenile dogs.

A non-arthropathic dose and disposition of ofloxacin, a potent new quinolone antimicrobial agent, were assessed in male juvenile (3-month-old) dogs, when administered orally at 5, 10 and 20 mg/kg/day once daily for 8 consecutive days. Ofloxacin concentrations in sera and articular cartilages were analyzed by high-performance liquid chromatography (HPLC). Macroscopically, arthropathy characterized by fluid-filled vesicles in articular surface of the humerus and femur was observed in animals receiving 10 and 20 mg/kg/day of ofloxacin, but not in those given 5 mg/kg/day. At 20 mg/kg/day, arthropathy of comparable severity also occurred on day 2. Microscopically, the cavity formation in the middle zone of the articular cartilage was first identified and then necrotic chondrocytes were found numerous around the cavity, followed by appearance of chondrocyte clusters. In pharmacokinetics, peak serum concentration (Cmax) and area under the concentrations (AUC0-24) were increased in a dose-dependent manner. However, no remarkable differences in these two parameters were noted between a single and repeated treatments, suggesting no accumulation of the drug. The articular ofloxacin concentration 2 hr after treatment was approximately 1.8 (day 2) to 2.0 times (day 8) higher than the serum concentration. Based on these results, a non-arthropathic dose of ofloxacin in male juvenile dogs following an 8-day treatment is considered to be 5 mg/kg/ day, and its Cmax, AUC0-24 and articular cartilage concentrations 2 hr after treatment were 3.4 microg/ml, 35.1 microg-hr/m/ and 7.0 microg/g, respectively, under these experimental conditions. Thus, arthropathy due to ofloxacin may be predicted by monitoring serum drug concentration.

Administration, Oral↗

Chondroblastoma of a metacarpal bone mimicking an aneurysmal bone cyst: a case report and a review of the literature.

Chondroblastoma of the metacarpal bone has been extremely rare and only seven cases have been reported in the English literature. Here we reported the eighth case of a chondroblastoma that developed on the first metacarpal bone of the right hand of a 21-year-old man. Radiographs showed an expansile osteolytic lesion with a multilocular appearance. In MR images, the lesion showed low intensity in T1 and high intensity in T2-weighted images with multiple fluid-fluid levels, which are findings resembling those of an aneurysmal bone cyst. From the pathological findings, however, it was recognized as a chondroblastoma with aneurysmal bone cyst-like change. Good clinical results was obtained by the subtotal resection of the metacarpal bone with a columnar-shaped iliac bone graft.

Adult↗

Esophageal inflammatory pseudotumor mimicking malignancy.

A 54-year-old man with a complaint of dysphagia was found to have a prominent stricture in the proximal esophagus. A biopsy of the stenotic area indicated sarcoma, leading to subtotal esophagectomy. The surgically removed esophagus demonstrated a well-defined intramural mass, consisting of a mixture of fibroblastic cells with bland cytological appearances and inflammatory cells. Reflux esophagitis which was present distal to the stricture seemed to play a role in the development of this inflammatory pseudotumor.

Adult↗

Health status, life habits, and social background among the JPHC study participants at baseline survey. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases.

A self-reported questionnaire on the health status, life habits, and social background was conducted at baseline in the Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases (JPHC study). This report presents the outcome of the study regarding past or family history of various diseases, medical treatment, life habits such as physical labor or sports, and social background among study participants. In both cohorts I and II, prevalent past and family history included hypertension, stroke, and cancer, whereas the prevalence of coronary heart diseases was historically low. The prevalence of a past history of hypertension and stroke was higher in the northern part of Japan, Ninohe, and Yokote, and lower in Okinawa, compared to the other districts. The prevalence of participants with a history of stomach cancer and liver cancer was higher in Arikawa than in other districts. The frequency of participants who took medication from doctors ranged from 20% to 30%, higher in the Tohoku areas, and lower in Okinawa compared to the other districts. All districts showed a high rate of over 70% for the participation rate for basic health examination conducted by the local government, The rate was particularly high in the Tohoku area where a high prevalence of a history of hypertension was found. The frequency of persons who had a chance to participate in sports or physical exercise was high in Okinawa and Suita subcohort 2, although the mean total physical activity (both at work and for leisure time) was lowest in the latter subcohort. No substantial differences were found in compositions of personality among districts. The frequency of more active and positive persons, however, was relatively higher in urban areas and lower in Okinawa compared to the other districts. The association between the differences of health status, life habits, and social background and the occurrence of various lifestyle-related diseases will be clarified in a follow-up study within the JPHC study.

Adult↗

Effect of platinum coordination complex (PtCx) on citrate uptake by rat renal brush border membrane vesicles (BBMV): direct effect of carboplatin.

Inhalation of platinum, as soluble salts, is known to cause respiratory distress and severe dermatitis in workers. Platinum coordination complexes are widely used in the treatment of a variety of solid tumors. However, the clinical use of cisplatin (CDDP) (the most useful agent) is limited by the development of nephrotoxicity. High dose accidental exposure to soluble platinum in platinum refineries and pharmaceutical factories could induce occupational nephrotoxicity. Carboplatin (CBDCA), a second-generation platinum coordination complex, is highly effective against a variety of malignancies at doses five- to ten-times higher than CDDP. At therapeutic doses, CBDCA is less nephrotoxic than CDDP. Additionally, urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In our previous study, the preincubation of rat renal brush border membrane vesicles (BBMV) with 5 mM cisplatin for 4 and 8 hours significantly inhibited the citrate uptake compared with that of the control BBMV. In this study, we exposed BBMV to 100 mM carboplatin (twenty-times higher concentration than cisplatin) and examined the citrate uptake characteristics to clarify the toxic mechanism of platinum coordination complexes. The preincubation of BBMV with 100 mM carboplatin for 8 hours also significantly inhibited the citrate uptake compared with that of the control BBMV, but the alterations were not as severe as those with 5 mM cisplatin.

Animals↗

Effect of platinum coordination complex (PtCx) on citrate uptake by rat renal brush border membrane vesicles (BBMV): cisplatin-intoxicated rats.

Platinosis with severe dermatitis and/or asthma is broadly defined as the effects of soluble platinum salts on people exposed to them occupationally. Platinum coordination complexes are widely used in the treatment of a variety of solid tumors. However, the clinical use of cisplatin, the most useful agent, is limited by the development of nephrotoxicity. Thus, an accidental exposure to soluble platinum at a high dose in platinum refineries and pharmaceutical factories could induce occupational nephrotoxicity. Urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In our previous studies, we found that the preincubation of rat renal brush border membrane vesicles (BBMV) with cisplatin and carboplatin, a second-generation platinum coordination complex, significantly inhibited the citrate uptake compared with that of the control BBMV. In this study, we performed in vivo experiments in cisplatin-intoxicated rats to elucidate the toxic mechanism of cisplatin. And our results showed that the citrate uptake was significantly inhibited in cisplatin-intoxicated rats at 1 min compared with that of control rats.

Animals↗

The nutritional status of elderly bed-ridden patients receiving tube feeding.

Long-term enteral feeding by tube has become a frequently used procedure in elderly patients. However, only a few studies dealing with the nutritional assessment of such patients are currently available. This study was designed to clarify this issue. Anthropometric and biochemical variables, energy expenditure and dietary intake were investigated in 44 hospitalized bed-ridden patients with and without tube feeding over 65 years of age and 41 age-matched free-eating elders in a nursing home. All patients with tube feeding received enteral nutrition by nasogastric tube. The body weight, body mass index, mid-upper-arm circumference, arm muscle circumference and serum level of albumin were significantly lower in the patients with and without tube feeding, compared with free-eating elders of both genders (p<0.05). Energy intakes of the patients with tube feeding were 1,171+/-286 kcal/d (about 26 kcal/kg/d), which is comparable to the predicted total energy expenditure (1.2 x basal energy expenditure). Protein intake was 44.9+/-13.1 g/d (about 1.0 g/kg/d) and the percentage of protein per total energy was 15%. These intakes are generally considered to be optimal for bed-ridden patients receiving tube feeding. However, the incidence of protein-malnutrition, as evidenced by decreased arm muscle circumference (<80% of normal) and hypoalbuminemia (<35 g/L), in the patients with tube feeding was significantly higher than that in the healthy elders. In addition, the orally fed bed-ridden patients were also malnourished, suggesting that the bed-ridden patients easily became malnourished even if they were fed energy and protein which approximated calculated predicted values. These findings raise a problem concerning nutritional management of bed-ridden patients.

Aged↗

[Immunohistochemical analysis with anti-cytokeratin antibody in the prostatic epithelium].

PURPOSE: We performed immunohistochemical studies of the prostatic epithelium using three different anti-cytokeratin monoclonal antibodies (35 beta-H11, RCK108, and 34 beta-E12), and also investigated the immunoreactivity of various prostatic lesions with basal cell specific anti-cytokeratin antibody (34 beta-E12). MATERIALS AND METHODS: One hundred and thirty one prostatic specimens were obtained at surgery or biopsy. H-E stained sections were available for review in all cases. They were classified according to histopathology; benign prostatic hyperplasia (BPH), prostatic cancer (PCA), atrophic acini, atypical adenomatous hyperplasia (AAH), and prostatic intraepithelial neoplasia (PIN). ABC or LSAB method was utilized for immunohistochemical staining with 3 anti-cytokeratin monoclonal antibodies. RESULTS: 35 beta-H11 was mainly stained in the luminal cells and RCK108 was stained both in the luminal and the basal cells in BPH. 35 beta-H11 showed highly positive staining in the prostatic cancer regardless of degree of differentiation. RCK108 tended to be less stained in the prostatic cancer cells with lower grades of tumor differentiation compared to those with higher grades. 34 beta-E12 was stained only in the basal cells, but neither in the normal luminal cells nor the cancer cells. Using 34 beta-E 12, basal cells were positively stained in most of the cases with BPH, while not in PCA. Atrophic acini and AAH was stained with 34 beta-E12 as positively as BPH. Basal cells were discontinuously or negatively stained in many cases with high-grade PIN. CONCLUSIONS: The luminal cells in BPH were highly positively stained using 35 beta-H11 or RCK108. RCK108 tended to be less stained in the prostatic cancer cells with lower grades of tumor differentiation. Positive staining of 34 beta-E12 strongly suggested a benign lesion, therefore immunohistochemistry using this antibody would be useful as an aid for pathological diagnosis.

Antibodies, Monoclonal↗

Hydroxyamphetamine increases intraocular pressure in rabbits.

OBJECTIVE: To determine the effect of norepinephrine (NE) released from endogenous ocular stores on intraocular pressure (IOP) and aqueous flow in rabbits. METHODS: The IOP was measured with a pneumatonometer, the aqueous flow with a scanning fluorophotometer, and the aqueous NE by methylation with catechol-O-methyltransferase in the presence of S-adenosyl-L-[methyl-(3)H]methionine. RESULTS: Hydroxyamphetamine increased IOP in a dose-dependent fashion. Surgical removal of the superior cervical sympathetic ganglion eliminated the increase in IOP and pupil diameter; preganglionic section of the cervical sympathetic trunk did not. Hydroxyamphetamine increased the concentration of NE in the aqueous. Increased IOP was not accompanied by increased aqueous flow and was eliminated by blockade of alpha(1)-adrenergic receptors but not beta- or alpha(2)-adrenergic receptors. CONCLUSIONS: Increased IOP after hydroxyamphetamine application is consistent with earlier suggestions that the nocturnal circadian increase in IOP in rabbits is mediated in part by NE released from ocular sympathetic nerves. However, failure of hydroxyamphetamine to increase aqueous flow and of beta-adrenergic blockade to blunt the increase in IOP does not support our suggestion that the nocturnal increase in IOP results in part from NE stimulation of ciliary process beta-adrenergic receptors and increased aqueous flow. CLINICAL RELEVANCE: In addition to increasing pupil diameter, hydroxyamphetamine increases IOP.

Adrenergic alpha-1 Receptor Antagonists↗

[Lobectomy of two or more lobes in patients with lung cancer].

We clinically examined patients who had undergone resection of two or more lobes for lung cancer. The subjects were 50 patients (25 who underwent pneumonectomy and 25 bilobectomy) who underwent lobectomy of two or more lobes from among those with primary non-small cell lung cancers in our hospital between 1975 and 1999; these individuals were assigned to Group A, and compared with 166 patients with lobectomy in Group B. The five-year survival rate was 27.7% in Group A, which differed significantly from the rate of 55.6% in Group B (p < 0.01, Kaplan-Meier method with log-rank test). The percentage of Stage I patients was 34% (17 patients) in Group A and 60.2% (100 patients) in Group B: this difference was significant (chi 2 test, p < 0.01). There were more patients with advanced cancer in Group A than in Group B. However, the five-year survival rates of Stage I patients were 52.4% in Group A and 77.6% in Group B, and significantly different (p < 0.05). In a comparison with respect to histological type, the five-year survival rates also differed significantly between Group A and B (p < 0.01 for adenocarcinoma, p < 0.05 for squamous cell carcinoma, with higher values in Group B for both). Resection of two or more lobes was indicated based on infiltration of the main tumor into adjacent lobes in 19 patients (38%), infiltration of lymph node metastasis into a bronchus or pulmonary artery in 14 (28%), direct infiltration of the main tumor into a bronchus in 10 (20%), and for other reasons in 7 (14%). The five-year survival rates for these groups were 15.8, 22.1, 54 and 42.9%, respectively. There was a significant difference between the patients with infiltration of cancer into adjacent lobes and those with direct infiltration into a bronchus (p < 0.05). The prognosis of patients with resection of two or more lobes was poorer than that of patients with lobectomy even in Stage I. In particular, infiltration of cancer into adjacent lobes accompanied lymph node metastasis in more than 50% in cases, and appeared to suggest a poor prognosis.

Humans↗

[Evaluation of time dependency of the acetazolamide effect on cerebral hemodynamics as measured by 99mTc-ECD single-photon emission computed tomography].

PURPOSE: Kuwabara et al. have examined the cerebral artery dilation with acetazolamide (ACZ) challenge test using PET. And, they reported that ACZ reaction came out time dependently. We have developed a unique SPECT's method using Technetium-99m ethyl cysteinate dimer (99mTc-ECD) to verify the results obtained by Kuwabara et al. METHOD: 1000 MBq of 99mTc-ECD was exactly divided into three syringes. Each of which was intravenous infused (i.v.) at rest, 7.5, and 20 minutes after ACZ administration. Data collection was started using dynamic SPECT immediately after 99mTc-ECD i.v. at rest. Using necessary data only, SPECT images representing each of the three 99mTc-ECD i.v. was reconstructed. SPECT counts were obtained by the ROI method from each images to calculate relative CBF from rest to 7.5 and 20 minutes after ACZ administration. RESULT: The 18 hemispheres of nine patients in the negative control group in whom ACZ was not loaded. CBF was stable during the three evaluation. The measurement error our method was estimated as small. The 18 hemispheres of nine patients in the positive control group who has normal vasodilatory reserve, CBF was increased by 26.2 +/- 8.1% at 7.5 minutes and 29.3 +/- 13.1% at 20 minutes after ACZ administration. Seven patients with and chronic stage unilateral internal carotid artery severe stenosis and/or occlusion were evaluated as the test group. Case of unaffected side, CBF was increased by 17.6 +/- 6.9% at 7.5 minutes and 24.8 +/- 11.3% 20 minutes after ACZ administration. And, increase rate of CBF in the affected side was 2.8 +/- 1.6% at 7.5 minutes and 17.3 +/- 5.0% at 20 minutes after ACZ administration. In the affected side, timing of the maximum CBF increase caused by ACZ was remarkably delayed. CONCLUSION: Our method based on 99mTc-ECD SPECT also revealed delayed cerebral artery dilation in the affected side. It was suggested that ACZ reaction came out time dependently, as reported by Kuwabara et al.

Acetazolamide↗

[A lung cancer patient whose renal scintigram showed transient renal dysfunction after administration of contrast material for CT].

We encountered a patient whose renal scintigram showed renal tubular damage four days after administration of contrast material for CT. As no secretion of radioisotope to the urinary tract was observed on the scintigram and the renogram did not show a secretionary phase, renal tubular damage was suspected. As the renal damage disappeared six days after administration of the contrast material, the damage seemed to be transient, disappearing within five days. Caution is needed with the use of renotoxic drugs such as anti-tumor drugs, especially within five days after administration of contrast materials.

Aged↗

A novel enhancer of insulinotrophic action by high glucose (JTT-608) stimulates insulin secretion from pancreatic beta-cells via a new cellular mechanism.

Insulin secretion from MIN6 cells (a pancreatic beta-cell line) induced by high glucose (greater than 16.8 mM) was potentiated by a novel hypoglycemic agent [trans-4-(4-methylcyclohexyl)-4-oxobutyric acid (JTT-608)] (but not glibenclamide, a sulfonylurea). The extracellular Ca(2+)-free condition, a L-type Ca(2+) channel blocker (nifedipine) and an ATP-sensitive K(+) channel opener, diazoxide, completely inhibited increases in cytosolic free Ca(2+) ([Ca(2+)]i) and insulin secretion evoked by JTT-608 in the presence of extracellular Ca(2+). An electrophysiological study using single-barreled microelectrode techniques demonstrated that membrane potential (V(m)) and input resistance of the cell membrane (R(i)) are depolarized and increased by JTT-608, respectively. The apparent transference number for K(+) was also significantly decreased after the addition of JTT-608. These effects immediately occurred after addition of JTT-608 and very rapidly disappeared after removal of JTT-608, which has not been observed in sulfonylureas. Also, these effects of JTT-608 were diminished, but not completely by diazoxide. JTT-608 did not affect the specific binding of [(3)H]glibenclamide to the sulfonylurea receptor. These findings suggest that JTT-608 mainly inhibits ATP-sensitive K(+) channel activity via a binding site distinct from the sulfonylurea receptor and then depolarizes V(m) to open voltage-dependent L-type Ca(2+) channels. Subsequently, these events stimulate Ca(2+) entry to increase [Ca(2+)]i and induce insulin secretion from MIN6 cells. Therefore, JTT-608 is a unique hypoglycemic agent that enhances high glucose-induced insulin secretion. The present findings indicate that JTT-608 is a more useful new class of therapeutic drug for patients with non-insulin-dependent diabetes mellitus, compared with sulfonylurea derivatives.

ATP-Binding Cassette Transporters↗

[A case with lung metastasis of osteosarcoma occurred 21 years after the operation of osteosarcoma on left tibia].

The patient was a 38-years-old woman. A chest X-ray film demonstrated the presence of an abnormal lesion. Her past history included osteosarcoma on the left tibia for which she received amputation of the left inferior limb at 17 years of age without any relapse thereafter. Considering that the patient might have lung metastasis of osteosarcoma on the basis of lung biopsy performed under CT guide, and then a tumor was removed under the thoracoscope. The tumor, 2.8 x 2.2 x 2.1 cm in size, was located right under the pleura at left S10 with its inside being filled up with fragile necrotic tissues. When compared pathohistologically with the primary lesion of osteosarcoma which had occurred 21 years before, the lung tumor was almost identical in terms of the tumor cell morphology but had a higher cell density without evidence of osteoid formation. The diagnosis of lung metastasis of osteosarcoma was established on the basis of the clinical course and the immunohistochemical staining. It is extremely rare case that osteosarcoma recurs in the form of lung metastasis 21 years after the operation of primary lesion. We report this case as a valuable one to identify the prognosis of osteosarcoma and the development mechanism of lung metastasis.

Adult↗

Pulmonary vein orifice isolation for eliminating paroxysmal atrial fibrillation after ICD implantation.

We treated a patient with dilated cardiomyopathy (DCM) and sustained ventricular tachycardia by an implantable cardioverter defibrillator (ICD). He then suffered from inappropriate ICD shocks triggered by paroxysmal atrial fibrillation (AF). We successfully performed pulmonary vein orifice isolation to eliminate paroxysmal AF. The pulmonary vein orifice isolation was a simple and useful procedure for eliminating paroxysmal AF in patient with decreased left ventricular (LV) function after ICD implantation.

Adult↗

Comparative effect of theophylline and aminophylline on theophylline blood concentrations and peripheral blood eosinophils in patients with asthma.

The comparative effects of a new theophylline preparation (Theodrip) and aminophylline on blood concentrations of theophylline were examined in 74 patients with asthma. Subjects were intravenously administered 200 mg of Theodrip or 250 mg of aminophylline for 1 h. The mean increases in blood theophylline concentration after Theodrip or aminophylline administration were 8.80 +/- 1.80 mg/l and 8.81 +/- 2.15 mg/l, respectively. In addition, these patients were divided into four groups based on baseline theophylline concentrations before infusion of Theodrip or aminophylline: i) naïve patients (not administered theophylline); ii) those with a baseline theophylline concentration of 0-5 mg/l; iii) those with a baseline theophylline concentration of 5-10 mg/l; iv) those with a baseline theophylline concentration of 10-15 mg/l. Mean increases in blood theophylline concentration after administration of Theodrip in each group were similar to those after aminophylline administration. We found no significant differences between Theodrip and aminophylline. However, when the comparative effects of Theodrip and aminophylline on peripheral blood eosinophil counts were examined, Theodrip, but not aminophylline, reduced blood eosinophil counts. With acute exacerbations of bronchial asthma, it is expected that Theodrip, but not aminophylline, may have an antiinflammatory effect. In conclusion, it is suggested that Theodrip is a more useful drug than aminophylline in patients with acute exacerbations of bronchial asthma.

Adult↗