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Biomedical subjects

Yuko Takeda

Publications and source records attributed to Yuko Takeda.

9 recordsLinked to original sources

Potent and selective cathepsin K inhibitors.

A novel series of cathepsin K inhibitors derived from Novartis compound I is described. Optimization of the P1, P3, and P1' units led to the identification of 4-aminophenoxyacetic acid 24b with an IC(50) value of 4.8 nM, which possessed an excellent selectivity over other human cathepsins and good pharmacokinetic (PK) properties. Oral administration of compound 24b to ovariectomized (OVX) rats showed a trend toward an improvement of bone mineral density (BMD) in the femur bone.

Administration, Oral↗

Arylamine based cathepsin K inhibitors: investigating P3 heterocyclic substituents.

A modification of novel cathepsin K inhibitors I was carried out. The structural design was aimed at reducing the lipophilic character of compounds I for obtaining better pharmacokinetic profiles. This modification afforded several less lipophilic compounds with good inhibitory activities and pharmacokinetic profiles, although the enzyme selectivity over cathepsin S was left at issue.

Amines↗

Long-term outcome of intracardiac repair under simple deep hypothermia.

Development of cardiopulmonary bypass has contributed to pediatric cardiac surgery, but at the dawn of cardiac surgery, simple deep hypothermia was used to avoid the deleterious effect of cardiopulmonary bypass. Between 1981 and 1990, 45 patients with simple cardiac anomalies underwent definitive surgery under deep hypothermia. Age at operation was 35 days to 20 months, and body weight was 2.3 to 8.0 kg. Under morphine and ether anesthesia, a median sternotomy was performed when the esophageal temperature reached 26.3 degrees C +/- 1.3 degrees C by the application of surface cooling. At a minimum esophageal temperature of 19.6 degrees C +/- 2.3 degrees C, inflow occlusion and cold cardioplegia were applied to induce circulatory arrest for 32.4 +/- 10.2 min. Direct cardiac massage was used to restore cardiac activity during rewarming. All but one patient was in New York Heart Association functional class I postoperatively. The latest cardiothoracic ratio was 49.8% +/- 4.7%. All but 2 patients are free from medication. Five of 30 patients showed developmental delay in the long-term; 2 of these had a long circulatory arrest period, and 3 had prolonged heart failure postoperatively. The other 25 patients had excellent physiologic and mental development. The long-term outcome of perfusionless hypothermic cardiac surgery is satisfactory when applied appropriately.

Cardiac Surgical Procedures↗

Bioprosthetic dysfunction caused by preserved native valve in tricuspid position.

We report a 4-year-old girl who underwent replacement of a bioprosthetic valve in the tricuspid position due to rare bioprosthetic dysfunction. The bioprosthetic valve showed marked tricuspid insufficiency as well as stenosis caused by the adhesion of the preserved native valve leaflets to the undersurface of the implanted bioprosthesis.

Bioprosthesis↗

Arch reconstruction without circulatory arrest in neonates.

Between May 2000 and December 2002, 10 neonates underwent arch reconstruction without circulatory arrest. Age at surgery ranged from 1 to 18 days, and body weight ranged from 1.62 to 3.38 kg. The diagnosis was interrupted aortic arch in 4, hypoplastic left heart syndrome in 3, and coarctation complex in 3. A 3 mm polytetrafluoroethylene graft was anastomosed to the innominate artery, and the brain was perfused via this graft while the aortic arch was reconstructed. Regional cerebral oxygen saturation and the right and left radial artery pressures were monitored. There were 2 deaths: one because of low cardiac output syndrome after a Norwood operation; another from multiple organ failure due to preoperatively undetected congenital biliary atresia. Regional cerebral oxygen saturation was kept constant at over 40% during regional cerebral perfusion. There were no neurologic sequelae observed postoperatively. It was concluded that the regional cerebral perfusion technique can be safely applied during neonatal aortic arch reconstruction, and deep hypothermic circulatory arrest should be avoided.

Anastomosis, Surgical↗

[Brain volumetric MRI study in healthy elderly persons using statistical parametric mapping].

PURPOSE: To investigate the age-related changes in the brains of healthy elderly subjects, a volumetric MRI was performed using Statistical Parametric Mapping (SPM) and Region of Interest (ROI) methods. We determined the volumes of the whole brain, the gray matter, the prefrontal cortex, the hippocampus and the entorhinal cortex. SUBJECTS AND METHODS: We examined 61 subjects (29 males and 32 females) aged 61 to 91 years (mean +/- SD = 72.4 +/- 7.85) who were residents of Okinawa prefecture, living at home and highly active as demonstrated by sustained participation in senior citizens clubs and/or group activities at senior citizen welfare centers. They had no history of psychiatric disorders, neurological or significant physical illness. They had Mini-Mental State Examination scores of 24 or above (mean +/- SD = 28.3 +/- 1.57), Japanese version of the Geriatric Depression Scale scores of 9 or below, and Tokyo Metropolitan Institute of Gerontology scores of 11 or above. All subjects were dextral. This study received prior approval by the participating medical institution. Informed consent was obtained from the individual subjects. Volumetric MRI was performed using a 1.5 Tesla MRI scanner (Magnetom Vision, Siemens). T1-weighted images were acquired in the coronal plane (perpendicular to anterior commissure-posterior commissure line) using a 3D-FLASH (fast low angle shot) sequence. Imaging parameters were: TR = 35 ms, TE = 5 ms, Flip angle = 45 deg., Field of View = 240 mm, Matrix 256 x 256, Pixel 0.9375 x 0.9375, Slice thickness 1.5 mm, Gapless. MR image data were analyzed by SPM using an imaging analysis software MEDx (Sensor Systems Inc.) running on UNIX workstation (Sun SPARC Solaris 7, Sun Microsystems, Inc.). Volumetry was performed by automatic segmentation technique using SPM for the whole brain and the gray matter, and manual tracing using ROI based quantitative methods for the prefrontal cortex, the hippocampus and the entorhinal cortex. Local volumes were normalized by the intracranial volume and the gray matter volume. Correlation to age was determined by Pearson's correlation coefficient. Volumetric MRI was performed under blinded conditions. RESULTS: Volumetric MRI of normal brain in healthy elderly subjects showed age-related changes. The whole brain (r = -0.568, p < 0.01), the gray matter (r = -0.406, p < 0.01), the prefrontal cortex (r = -0.470, p < 0.01), the hippocampus (r = -0.305, p < 0.05), and the entorhinal cortex (r = -0.455, p < 0.01) volume significantly decreased with age. The age-related hippocampal volume reduction was similar to the gray matter reduction, but the age-related prefrontal cortex and entorhinal cortex volume reductions were greater than the gray matter volume reduction. The prefrontal cortex and the hippocampal volumes differed by sex, being greater in females (p < 0.05). The hippocampal volume was lateralized: right side was greater than the left (p < 0.01). The entorhinal cortex volume was lateralized so that the left side was greater than the right (p < 0.01). CONCLUSION: As a result of volumetric MRI using SPM, age-related changes of normal brain in healthy elderly persons did not always show unified atrophy. The ratio of atrophy was different by a local area. Our findings suggested that the most marked age-related brain volume reductions were seen in the prefrontal cortex and the entorhinal cortex. The age-related hippocampal volume reduction was similar to the gray matter reduction.

Aged↗

Total cavopulmonary connection via a thoracotomy.

We report a patient who underwent a total cavopulmonary connection with an extracardiac conduit through a right thoracotomy. The thoracotomy approach was useful in circumventing possible hazardous complications at the sternal reentry for the completion of a staged Fontan due to previous mediastinitis in this patient.

Child, Preschool↗