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Biomedical subjects

Kenji Okada

Publications and source records attributed to Kenji Okada.

At least 37 records · Page 2Linked to original sources

Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma cells.

BACKGROUND: DNA damage sensor proteins have received much attention as upstream components of the DNA damage checkpoint signaling pathway that are required for cell cycle control and the induction of apoptosis. Deficiencies in these proteins are directly linked to the accumulation of gene mutations, which can induce cellular transformation and result in malignant disease. METHODS: Using 48 sets of tumor tissue specimens and peripheral normal lung tissue specimens from 48 patients with nonsmall cell lung carcinoma (NSCLC) who underwent surgery, the authors investigated the expression of hRad9 protein, a member of the human DNA damage sensor family, using immunohistochemical and Western blot analyses. RESULTS: Immunohistochemical analysis detected the accumulation of hRad9 in the nuclei of tumor cells in 16 tumor tissue specimens, (33% of tumor tissue specimens examined). Western blot analysis also revealed elevated levels of phosphorylated hRad9 protein in NSCLC cells that was accompanied by the detection of phosphorylated Chk1, a protein kinase that regulates the downstream signaling of the DNA damage checkpoint pathway. Furthermore, strong expression of hRad9 was correlated with an increase in Ki-67 expression index in the tumor cells that were examined. CONCLUSIONS: The findings made in the current study suggest that Rad9 expression may play an important role in cell cycle control in NSCLC cells and may influence NSCLC cell phenotype.

Adult↗

Surgery for gastric cancer combined with cardiac and aortic surgery.

HYPOTHESIS: Therapeutic strategies for patients who require procedures for both cardiac or aortic diseases and gastric cancer are controversial. Prognostic factors for them should be clearly identified. DESIGN: Retrospective review of 14 patients who underwent surgical intervention for both gastric cancer and cardiac or aortic diseases between January 1, 2000, and June 30, 2004. SETTING: Tertiary referral university hospital. PATIENTS: Cardiac and aortic diseases included coronary artery disease in 5 patients, thoracic aortic aneurysms in 3 patients, and abdominal aortic aneurysms in 6 patients. Coronary artery bypass graftings were performed with an off-pump procedure, and aneurysms were replaced with prosthetic grafts in all of the cases. The surgical stages of gastric cancers were stage I in 8 patients, stage II in 2 patients, stage III in 3 patients, and stage IV in 1 patient. According to our original therapeutic strategies, 4 patients underwent simultaneous procedures and 10 received staged procedures. MAIN OUTCOME MEASURE: Overall survival rates. RESULTS: There was 1 hospital death caused by multiple organ failure. No prosthetic graft infection was noted. Thirteen patients were discharged, and 3 died of cancer recurrence during an average follow-up period of 26.3 months. The cumulative survival rate was 76.6% at 1 year and 68.1% at 3 years. One-year survival rates were 90.0% in stages I and II gastric cancer and 50.0% in stages III and IV gastric cancer. CONCLUSION: Prognosis of patients who underwent surgical intervention for both gastric cancer and cardiac or aortic diseases was mainly limited by the clinical stage of gastric cancer.

Aged↗

Stereoselective taurine conjugation of (R)-benoxaprofen enantiomer in rats: in vivo and in vitro studies using rat hepatic mitochondria and microsomes.

PURPOSE: Identify (R)-BOP-T in rat bile after administration of (R)-BOT over a 12 h period. METHODS: Each benoxaprofen (BOP) enantiomer was administered i.v. to bile duct-cannulated rats at a dose of 5 mg/kg. The optical isomers of BOP and its metabolites in plasma, urine, and bile were quantified using a chiral HPLC column. The amounts of BOP glucuronide (BOP-G), BOP taurine conjugate (BOP-T), and BOP enantiomers excreted into the bile over 12 h after administration of (R)-BOP were as follows: (R)-BOP-G and (S)-BOP-G, 2.1 +/- 0.5 and 6.2 +/- 1.4% of the dose; (R)-BOP-T and (S)-BOP-T, 5.6 +/- 1.8 and 0.7 +/- 0.3% of the dose; (R)-BOP and (S)-BOP, 0.7 +/- 0.1 and 1.7 +/- 0.2% of the dose, respectively, whereas after (S)-BOP administration, (S)-BOP-G and (S)-BOP were mainly excreted into the bile (14.3 +/- 1.8 and 3.0 +/- 0.4% of the dose, respectively). Only after (R)-BOP administration was the taurine conjugate of BOP found in the bile, and the configuration was R. BOP-T could not be found in the bile after (S)-BOP administration. To investigate the stereoselectivity of the conjugation enzymes responsible for BOP-T formation, in vitro studies were performed using rat hepatic organelles. RESULTS: When (R)-BOP was used as a substrate, rat hepatic mitochondrial and microsomal fractions exhibited stereoselective BOP-T formation activity, with microsomal activity approximately 3.0 times greater than that of the mitochondria. That of (S)-BOP was approximately 2.1. Mean (R)/(S) ratios of BOP enantiomer for BOP-T formation in the mitochondrial and microsomal incubations were approximately 1.7 and 2.4, respectively. CONCLUSION: Although in the in vivo studies, only (R)-BOP-T originated from (R)-BOP was found in the bile, the configuration of BOP-T formed by the incubations of (R)-BOP or (S)-BOP with rat hepatic mitochondria or microsomes was S for both.

Animals↗

Successful valve repair for congenital bicuspid aortic valve and degenerated prolapsed mitral valve.

A 54-year-old man with congenital bicuspid aortic valve underwent simultaneous valve repair for aortic and mitral regurgitation. Surgical technique consisted of plication of redundant aortic valve repair and mitral annuloplasty with chordal replacement. One-year follow-up transthoracic echocardiography showed no valve regurgitation. Valve repair for both bicuspid aortic valve and mitral valve regurgitation should be the first option in this subset of patients.

Aortic Valve↗

Left internal thoracic artery graft assessed by means of intraoperative transesophageal echocardiography.

BACKGROUND: We report a method of intraoperative assessment of left internal thoracic artery (LITA) graft with transesophageal echocardiography regarding patency, stenosis, and presence of remnant branch artery. METHODS: In 52 consecutive coronary artery bypass grafting surgery patients, blood flow velocity was measured at the origin of the LITA after coronary artery bypass grafting by means of transesophageal echocardiography. The flow pattern and velocity change at temporary clamping of the graft was examined and was compared with the postoperative angiographic findings. RESULTS: The LITA was visualized in 47 of 52 cases (90.4%). The LITA flow was diastolic dominant, systolic dominant, or equivalent in 41, 3, and 3 cases, respectively. The anastomosis was stenotic in 2 of 6 cases of the latter two groups, but in none of the 41 cases with diastolic dominant flow (p = 0.0139). The branch artery was present in 4 of 6 cases of the latter two groups, but in only 2 of 41 cases with diastolic dominant flow (p = 0.0012). Remnant branch artery was found in all three cases with systolic dominant flow. The LITA flow was instantaneously reduced at clamping and recovered at declamping in every case with graft occlusion but one. The ratio of velocity change at clamping was less than 0.50 in all 41 cases without remnant branch, whereas it was more than 0.50 in 5 of 6 cases with a branch (p < 0.0001). CONCLUSIONS: The transesophageal echocardiographic assessment with the clamp test is feasible intraoperatively in the majority of patients, enabling us to assess LITA graft patency, stenosis, or presence of a remnant branch.

Adult↗

Midterm results of pulmonary vein isolation for the elimination of chronic atrial fibrillation.

BACKGROUND: This study aims to clarify midterm results of chronic atrial fibrillation elimination after pulmonary vein isolation and provides an evaluation of factors influencing results. METHODS: Forty-nine patients were enrolled in this study. We performed a simple pulmonary vein isolation with the aid of cryoablation or radiofrequency ablation directed towards the left posterior remnant of the posterior left atrium. Results were evaluated using elimination rates of atrial fibrillation during the postoperative follow-up for > 12 months. We also examined factors influencing the recurrence of atrial fibrillation. RESULTS: There were no hospital deaths or serious complications among the 49 patients. The total follow-up duration was 137.2 patient years. Forty-seven patients (96%) were followed with serial consultations, but 2 patients were dropped from this study because of changes in residence. Thirty-five of 49 patients (71.4%) showed regular sinus or nodal rhythms at discharge. In 4 patients atrial fibrillation recurred during the follow-up period, whereas in another 4 patients sinus rhythm was restored, although they showed atrial fibrillation at discharge. The cumulative elimination rate was 70.2% (33 of 47 patients), which was determined at the last follow-up period. Large left atrial diameters, a long history of atrial fibrillation, and low-voltage fibrillatory waves in V1 leads were preoperative indicators of recurrence of atrial fibrillation. CONCLUSIONS: Pulmonary vein isolations were effective in the treatment of chronic atrial fibrillation patients and sinus rhythms were restored within the follow-up period.

Adult↗

Surgical results of acute aortic dissection complicated with cerebral malperfusion.

BACKGROUND: In patients with acute type A aortic dissection complicated by cerebral malperfusion, the surgical treatment remains challenging. This retrospective study reports the results of surgical interventions and the clinical features of these patients. METHODS: From 1999 to 2004, 63 patients underwent surgical treatment for acute type A aortic dissection. Sixteen patients (25.3%) showed preoperative newly developed neurologic deficits (cerebral malperfusion). In patients with cerebral malperfusion, the characteristics, neurologic symptoms, computed tomography findings, interval from onset to operation, and operative details (procedure, arterial cannulation site, method of brain protection) were reviewed. RESULTS: The hospital mortality rate was 43.7% (7 of 16 patients) for the cerebral malperfusion group and 17.0% (8 of 47 patients) for the noncerebral malperfusion group (all patients, 23.8%). Multivariate analysis showed preoperative cerebral malperfusion as the sole risk factor for hospital mortality. Six patients, including all patients in a preoperative coma, died of severe brain damage within 1 month after surgery. Most patients were diagnosed with right hemispheric cerebral infarction by postoperative brain computed tomography. The operative details and the time interval from onset to operation were not significant predictors of death. The cumulative survival rate at 4 years was 75.5% in patients without cerebral malperfusion and 50.1% with cerebral malperfusion (p = 0.091). CONCLUSIONS: The results of surgical treatment for acute type A dissection complicated with cerebral malperfusion demonstrated high hospital mortality, but the long-term survival was similar to patients without cerebral malperfusion, with an acceptable neurologic outcome, excluding preoperative coma patients. Appropriate protection of ischemic brain tissue should be implemented to improve the surgical results in these patients.

Acute Disease↗

Newly developed aortic dissection in the abdominal aorta after femoral arterial perfusion.

BACKGROUND: Aortic dissection after femoral arterial perfusion has been reported as a dreadful complication. Apart from such a drastic event, using intraoperative transesophageal echocardiography we detected aortic dissection confined to the abdominal aorta that was associated with visceral malperfusion. METHODS: We examined 11 consecutive patients with aortic dissection in whom the abdominal aorta was intact, and surgeries were performed with femoral perfusion. The abdominal aorta and visceral branches were examined for new development of dissection or malperfusion by means of transesophageal echocardiography before, during, and after cardiopulmonary bypass. These echocardiographic findings were then related to the postoperative assessment and midterm results. RESULTS: Aortic dissection was found in 3 of 11 cases (27.2%). Unusual progression of metabolic acidosis (base excess < or =10 mEq/L) occurred, possibly as a result of malperfusion of visceral arteries, in 2 of these 3 cases, whereas none of the 8 cases presented with such findings. The presence of dissection was later confirmed by postoperative computed tomography in all but 1 case. In the midterm follow-up period, aneurysm formation was found in the infrarenal aorta and iliac arteries in 2 of the 3 cases with new aortic dissection but not in any of the remaining 8 cases. CONCLUSIONS: New development of aortic dissection after femoral arterial perfusion was found in 27% of the cases in this series. Although these occurred without dramatic symptoms, this event may be related to unusual metabolic acidosis during cardiopulmonary bypass or to subsequent aneurysmal formation of the infrarenal aorta or iliac arteries, or both.

Acidosis↗

Thrombosed arch vessels after cardiac arrest because of pulmonary embolism.

An unusual case of thrombus formation in the arch vessels after cardiac arrest because of pulmonary embolism is reported. A 67-year-old woman developed pulmonary embolism that soon led to cardiac arrest. Although percutaneous cardiopulmonary support was started, the blood pressure of her upper extremity was below 20 mm Hg and blood gas analysis showed marked metabolic and respiratory acidosis. Transesophageal echocardiography revealed thrombus in the right pulmonary artery, thrombus with floppy movement in the aortic arch, and 3 arch branch arteries filled with thrombus with little blood flow around it. After thrombolytic therapy, the thrombi gradually shrunk and perfusion in the upper extremities improved. The patient was successfully weaned from percutaneous cardiopulmonary support and was discharged alive. Thrombus formation can occur in the arch branch arteries after cardiac arrest, causing unusual laboratory data. Transesophageal echocardiography is useful for obtaining real-time information in the cardiovascular system at bedside in such a critically ill patient.

Aged↗

A case with four-channel aortic dissection.

A 65-year-old male with four-channel aortic dissection successfully underwent replacement of the thoracoabdominal aorta, reconstruction of the celiac, superior mesenteric artery, renal arteries, and 5 pairs of intercostals or lumbar arteries using deep hypothermic technique.

Aged↗

Malposition of selective cerebral perfusion catheter is not a rare event.

OBJECTIVE: Although malposition of a catheter for selective cerebral perfusion can lead to postoperative neurologic complications, the clinical relevance or even an incidence of this event is not clear because there have been no measures to diagnose it. The purpose of this study is to report the results of intraoperative diagnosis of catheter malposition by means of near-infrared spectroscopy, orbital ultrasound, and transesophageal echocardiography. METHODS: The 35 consecutive patients of aortic arch aneurysm undergoing total arch replacement (13 patients) or transaortic stent graft implantation (22 patients) were examined. The regional oxygen saturation in the frontal lobe was continuously monitored with near-infrared spectroscopy. When cerebral malperfusion was suspected with saturation drop and reduced blood flow in orbital ultrasound, blood flow in the cervical branches and catheter position were examined with transesophageal echocardiography. RESULTS: Catheter malposition was detected in 4 of 35 cases (11.4%). The echo findings included: (1) reduced or absent flow and/or collapsed lumen in the common carotid artery despite an adequate perfusion rate; and (2) the balloon of catheter blocking the inflow to the common carotid artery. There was no unusual changes in parameters of other conventional monitors. After the catheter was withdrawn (three cases) or replaced (one case) based on the above diagnosis, cerebral perfusion was restored, confirmed by these three modalities. An accidental entry of catheter into the right common carotid artery was detected by transesophageal echocardiography in one case, in which there was no abnormal finding of oxygen saturation or orbital blood flow. CONCLUSIONS: Catheter malposition on the right side is not a rare event during selective cerebral perfusion. The catheter can migrate into the right subclavian artery or common carotid artery. Pressure monitoring cannot reliably detect an occurrence of catheter migration into the right subclavian artery. Combined use of near-infrared spectroscopy, orbital ultrasound, and transesophageal echocardiography can be useful for detecting this event and making an appropriate decision without delay to prevent irreversible brain damage.

Aged↗

Thrombin-free fibrin coating on small caliber vascular prostheses has high antithrombogenicity in rabbit model.

Fibrin coatings on prosthetic vascular graft, which are conventionally produced by fibrinogen and thrombin, are expected to improve antithrombogenicity and healing characteristics. Thrombin is one of the factors of blood coagulation cascade; however, it has a possibility to play a negative role in the graft antithrombogenicity. The purpose of this study was to evaluate the performance of our new grafts, thrombin-free fibrin-coated small caliber vascular prostheses. Knitted polyester fabric vascular prostheses 2 mm in internal diameter were coated with fibrin coating with thrombin (Graft I) or without thrombin (Graft II). Both grafts were implanted in bilateral common carotid arteries of 35 Japanese white rabbits, with Graft I in one side and Graft II in the contralateral side. Graft patency, histology, thrombin activity, and platelet deposition were compared between both grafts on postoperative days (PODs) 1, 3, 7, 10, 14, 30, and 60. Both grafts were patent without thrombus or stenosis at each end point (maximal period, POD 60). Macro- and microscopic findings revealed that no obvious difference was observed between both grafts. Before graft implantation, thrombin activities in Grafts I and II were 0.711 +/- 0.086 and 0.009 +/- 0.007 optical density at 405 nm, respectively. Thrombin activity of Graft II was significantly less than that of Graft I in every period after graft implantation, and platelet deposition of Graft II was significantly less than that of Graft I until POD 30. Thrombin-free fibrin-coated vascular prostheses have superior performance of antithrombogenicity to conventional fibrin-coated vascular prostheses with thrombin.

Animals↗

Extrathoracic subclavian venipuncture under ultrasound guidance.

BACKGROUND: Cardiac pacemaker and defibrillator leads are inserted through extrathoracic subclavian venipuncture using ultrasound (US) guidance, but there can be complications. The purpose of this study was to investigate a safer and improved implanting procedure. METHODS AND RESULTS: Venipuncture guided by US with a 7.5 MHz convex transducer was performed to implant 32 leads in 18 patients. US enabled identification and location of the vein and needle tip during puncture and clarified the reasons for unsuccessful venipuncture. Venipuncture was successful on the second attempt or within 2 min in 90.6% (29/32) and 84.4% (27/32) of lead placements, respectively, although the vein was small (mean, 7.8 mm), deep (mean, 22.7 mm), and required a large angle of entry (mean, 52.4). The subclavian artery or lung was adjacent to the vein in 50.0% and 27.8% of cases, respectively. The flexible wall of the vein interfered with the penetration of the needle in 33.3% of cases. It was often difficult to locate the needle tip because of poor visualization. CONCLUSIONS: Ultrasound guidance of subclavian venipuncture enables a safe and time-saving procedure by visualizing not only the needle but also the vein and surrounding structures, although further modifications of the needle are needed for better visualization.

Defibrillators, Implantable↗

Novel Doppler technique to assess systemic vascular resistance: the snuffbox technique.

BACKGROUND: To explore an alternative to the systemic vascular resistance index (SVRI) for monitoring peripheral circulation in patients in the intensive care unit (ICU), the resistive index (RI) in the upper extremity arteries was measured by using surface Doppler ultrasound. METHODS AND RESULTS: The correlation between RI and vascular resistance was assessed in vitro using a vessel phantom in a Donovan-type mock circulation system. In addition, 15 ICU patients who had undergone open-heart surgery were studied. Mean arterial pressure, central venous pressure and cardiac output were measured 30 times at 10 min intervals after patients returned to the ICU following surgery, and the SVRI was calculated from these parameters. At the same time points, 3 parts of the upper extremity arteries (brachial artery in the cubital fossa (BA), radial artery at the wrist (RA), and radial artery at the anatomical snuffbox (SB)) were scanned by Doppler ultrasound, and the resistance index (RI) for each artery region was calculated. In vitro, RI increased with higher vascular resistance, exhibiting a significant correlation (r = 0.982, p < 0.0001). In vivo, the average incidence angles at the BA and RA were larger than 60 degrees , while that at the SB was only 11.5+/-10.8 degrees. The overall correlation between SVRI and RI for all patients was not significant for the BA or RA, but was significant for the SB (p < 0.0001). In individual patients, the correlation of SVRI with RI at the BA or RA was significant in 3 patients only, whereas significant correlation for the SB was observed in all patients. Doppler waveform analysis at the SB revealed diastolic flow reversal with increased SVRI. CONCLUSIONS: Measurement at the SB provides an ideal ultrasound incidence angle for the measurement of blood flow velocity. Hence, RI measured in this way may serve as an indicator of peripheral vascular resistance, and may be effective for the evaluation of peripheral circulatory disturbance.

Aged↗