PubMed Health⌕ Search

Biomedical subjects

N Yoshimura

Publications and source records attributed to N Yoshimura.

At least 127 records · Page 7Linked to original sources
PubMed1999

Synthesis and pharmacokinetics of a novel macromolecular prodrug of Tacrolimus (FK506), FK506-dextran conjugate.

A novel macromolecular prodrug of Tacrolimus (FK506), FK506-dextran conjugate, was developed and its physico-chemical, biological and pharmacokinetic characteristics were studied. The conjugate was estimated to contain 0.45% of FK506 and the coupling molar ratio was approximately 1:1 (dextran-FK-506). Adsorption experiments using ion exchangers indicated that FK506-dextran conjugate acted as a weakly negatively charged macromolecule. Low molecular weight radioactive compound(s), which was eluted in the same fractions as [(3)H]FK506, was released from [(3)H]FK506-dextran conjugate by chemical hydrolysis with a half-life of 150 h in phosphate buffer. In vitro immunosuppressive activity of the conjugate, as assessed by the rat lymphocyte stimulation test, was almost comparable to that of free FK506, suggesting that biologically active FK506 could be liberated from the conjugate. In vitro biodistribution studies demonstrated that conjugation with the dextran derivative dramatically changed the pharmacokinetic properties of FK506 after intravenous injection in rats. AUC of the FK506-dextran conjugate was almost 2000 times higher than that of free FK506 and organ uptake clearances of the conjugate were significantly smaller than those of the free drug. Thus, the present study has demonstrated that the FK506-dextran conjugate behaves as a prodrug of FK506 with an extended blood circulating time and can be expected to have an improved therapeutic potency.

Animals↗
PubMed1999

Conversion of right atrioventricular to total cavopulmonary anastomosis in the management of post-Fontan arrhythmia: report of a case.

Both the original and modified Fontan procedures are associated with several late complications such as atrial arrhythmias, thromboembolism, and right pulmonary vein compression caused by a markedly enlarged right atrium. We describe herein the case of a patient who underwent conversion of right atrioventricular to total cavopulmonary anastomosis to control atrial arrhythmia that developed 12 years after a modified Fontan operation. The procedure proved successful in alleviating his symptoms immediately. He is now doing well with no recurrence of atrial arrhythmia 1 year after the operation.

Arrhythmias, Cardiac↗
PubMed1999

Valvular heart disease. A comparative study of results after primary operation, reoperation, and after multiple reoperation.

Reoperation for valvular heart disease has been associated with a higher operative mortality than primary operations, especially in patients who had multiple prior operations. We have analyzed the 226 consecutive patients who underwent valve replacement. These involved 163 primary operations, 52 first reoperation, and 11 second/third reoperations. Preoperative left ventricular dysfunction was more severe, and operation time and cardiopulmonary bypass time were significantly greater according to the number of operations, associated with a greater amount of intraoperative blood loss. The operative mortality after a second/third reoperation was 27.3%, which was significantly higher than that after primary operation (6.7%) (p < 0.05), and that after first reoperation (5.8%) (p < 0.05). Seven (64%) patients who underwent a second/third reoperation had poor preoperative left ventricular function (%FS < 25%), and 5 (71%) of these required postoperative mechanical supports, and 3 (60%) of the 5 patients died of low output syndrome. We have found that poor preoperative left ventricular function and the duration on cardiopulmonary bypass, but not the number of reoperation were correlated with operative mortality. Continued efforts should be directed to decrease the mortality for multiple reoperative valve surgery.

Adult↗
PubMed1999

Biochemical markers of bone turnover and bone loss at the lumbar spine and femoral neck: the Taiji study.

The purpose of this study was to ascertain whether biochemical markers of bone turnover predict bone loss. The survey was carried out in Taiji, Wakayama Prefecture, Japan. From a list of inhabitants aged 40-79 years, 400 participants (50 men and 50 women in each of four age groups) were selected randomly. Bone mineral density (BMD) was measured, and blood and urine samples of all participants were examined to obtain values for eight biochemical markers: alkaline phosphatase (ALP), bone Gla protein (BGP), type I procollagen (carboxyterminal peptide of type I procollagen; PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and urinary excretion of calcium (Ca), phosphate (P), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Each marker was evaluated as a predictor of the rate of bone change in lumbar spine and femoral neck BMD over a 3-year period. The value of Pyr was significantly related to the change of lumbar spine BMD in men (P = 0.009), and that of BGP was found to be significant in women (P = 0.045). By contrast, none of the bone markers significantly correlated with bone loss at the femoral neck. The coefficient of determination at the lumbar spine was 5% and 7% at the femoral neck only. We conclude that biochemical markers of bone turnover cannot predict bone loss rates in middle-aged or elderly Japanese men and women over a 3-year period with sufficient accuracy for use in clinical decision making.

Adult↗
PubMed1999

Expression of heat shock protein 70 mRNA in polymorphonuclear cells responding to surgical stress.

PURPOSE: This study was performed to investigate the expression of heat shock protein (HSP) 70 mRNA in polymorphonuclear neutrophils (PMN) as a possible new biomarker for surgical stress. METHODS: The HSP70 mRNA in PMN of 10 patients who underwent lobectomy was evaluated by Northern blot analysis. Their leukocyte counts, including white blood cells (WBC) and PMN, plasma cortisol levels, and plasma interleukin-6 (IL-6) levels, were obtained by cell counting, radioimmunoassay, and enzyme-linked immunosorbent assay, respectively. RESULTS: The level of HSP70 mRNA in PMN slightly increased at the end of surgery and showed a significant increase 6 h after surgery. It promptly decreased at 24 h postoperatively and returned to the basal preanesthetic level 48 h after surgery. On the other hand, WBC/PMN counts, plasma cortisol, and IL-6 significantly increased at the end of surgery. WBC/PMN counts remained at increased levels until 48 h postoperatively. Cortisol peaked at 6 h postoperatively and gradually decreased. IL-6 reached a maximum at 1 h postoperatively, then tapered down to its basal level at 48 h postoperatively. CONCLUSION: Expression of HSP70 mRNA in PMN that is induced after thoracic surgery appears to be a promising candidate as a marker for evaluating surgical stress.

Journal Article↗
PubMed1999

Castleman disease presenting with ophthalmic signs and symptoms.

PURPOSE: To describe a patient with multicentric Castleman disease who was initially examined with ophthalmic signs and symptoms. METHODS: Case report. A 71-year-old man was initially examined with swelling of both upper eyelids and diplopia of 2 months' duration. RESULTS: Medical evaluation and right axillary lymph node biopsy disclosed Castleman disease. Systemic corticosteroid treatment temporarily resolved signs and symptoms, but the patient died of recurrence with cytomegalovirus and Aspergillus infection 10 months after initial examination. CONCLUSIONS: Multicentric Castleman disease is a rare but distinct disorder that may present initially with ocular signs and symptoms. This disease must be included in the differential diagnosis of orbital pseudotumor and lymphoma.

Aged↗
PubMed1999

Intrahepatic venovenous shunting to an accessory hepatic vein after Fontan type operation.

Because there are various types of systemic venous connections in patients with visceral heterotaxy, unanticipated abnormal systemic venous channels may pose additional problems after a Fontan type operation. We report a case of severe cyanosis caused by anomalous intrahepatic venovenous fistula to an accessory hepatic vein early after total cavopulmonary anastomosis.

Child↗
PubMed1999

Hepatic arterial infusion chemotherapy using percutaneous catheter placement with an implantable port: assessment of factors affecting patency of the hepatic artery.

OBJECTIVE: To assess the factors affecting patency of the hepatic artery during hepatic arterial infusion chemotherapy (HAIC) with an implantable port system inserted percutaneously. PATIENTS AND METHODS: Ninety patients with malignant hepatic tumours were given HAIC using percutaneous catheter placement. An end-hole catheter was inserted into the hepatic artery (conventional method) in 41 patients. An end-closed and side-hole catheter was used in 49 patients, in which the catheter tip was fixed in the gastroduodenal artery and the side hole was placed in the common hepatic artery (fixed catheter-tip method). The patency of the hepatic artery was evaluated with computed tomography (CT) arteriography using the implantable port system and angiography. Then, the factors affecting hepatic arterial patency were analysed. RESULTS: Hepatic arterial occlusion was observed in 15 patients (17%). The overall patency of the hepatic artery was 86.9%, 78.4% and 51.5% at 6 months, 1 year and 2 years, respectively. The patency rate of the hepatic artery was significantly higher in patients with catheter placement using fixed catheter-tip method than those using conventional method (P = 0.01), and in patients without transcatheter arterial chemoembolization (TACE) prior to catheter placement than those with prior TACE (P = 0.01). When the variables affecting patency of the hepatic artery were studied together by multivariate analyses, the important factors were the method of catheter placement and the presence or absence of prior TACE. CONCLUSION: We consider that it is important for long-term patency of the hepatic artery during HAIC to use fixed catheter-tip method for percutaneous catheter placement instead of conventional method, and to select patients without prior TACE.

Adult↗
PubMed1999

Surgery for mitral valve disease in the pediatric age group.

OBJECTIVES: We reviewed a 20-year experience with the surgical treatment of mitral valve disease in the pediatric age group at our institution with 2 objectives: to clarify the long-term results over the last 2 decades and to evaluate the recent advances in mitral valve operation in children. METHODS: Since December 1978, 56 patients have undergone a total of 36 mitral valve repairs and 30 mitral valve replacements. Associated cardiac anomalies were present in 46 patients (82%), and concurrent repair of associated lesions was performed in 37 patients (66%). The age of the patients ranged from 3 months to 15 years (mean, 3.6 years) at mitral valve repair, and ranged from 2 months to 16 years (mean, 5.7 years) at mitral valve replacement. Mean follow-up period was 92.0 months (range, 1-235 months). RESULTS: There were 2 hospital deaths and 2 late deaths in patients who underwent mitral valve repair. Reoperation was performed in 4 patients. Three of these patients underwent mitral valve replacement because of residual mitral incompetence. No hospital deaths occurred in patients who underwent mitral valve replacement. Two late deaths occurred after mitral valve replacement. Six patients had a total of 10 episodes of prosthetic valve thrombosis. Thrombolytic therapy with urokinase was successful in all episodes without serious complications. Five patients required reoperations 49 to 141 months (mean, 78.4 months) after the initial valve replacement for relative prosthetic valve obstruction as the result of somatic growth. A valve 2 or 3 sizes larger than the original prostheses was inserted without death. Actuarial survival and freedom from cardiac events at 10 years after the operation were 87.2% and 72.7% in children who underwent mitral valve repair, and 90.3% and 67.3% for those children who underwent mitral valve replacement. CONCLUSIONS: The current risk of mitral valve operation in the pediatric age group is low, and the long-term results are satisfactory, irrespective of severe deformation of the mitral valve apparatus and associated complex cardiac anomalies.

Actuarial Analysis↗
PubMed1999

Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis.

PURPOSE: This study was conducted to examine effects of nitric oxide (NO) donors on bladder hyperactivity induced by cyclophosphamide (CYP)-induced cystitis. MATERIALS AND METHODS: Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (100 mg./kg.), and then their micturition pattern including mean micturition volume and the number of micturitions during 24 hours was recorded in a metabolic cage before and after CYP treatment. Forty-eight hours after CYP injection, bladder function under urethane anesthesia was evaluated by cystometry with continuous saline infusion (0.04 ml. per minute) or under isovolumetric conditions (0.8 ml. bladder volume). NO donors, S-nitroso-N-acetyl-penicillamine (SNAP, 2 mM) or sodium nitroprusside (SNP, 1 mM), and an NO synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 20 mM) were administered intravesically. Direct action of SNAP on bladder afferent neurons was also tested in a patch-clamp recording study. RESULTS: The number of micturitions significantly increased during the first 24 hours after CYP injection (19.0 +/- 0.88 versus 92.1 +/- 16.3 micturitions/24 hours, mean +/- SE, n = 25) (p <0.001). There was no significant difference in total micturition volume before (12.3 +/- 1.0 ml./24 hours) and after CYP treatment (15.6 +/- 1.5 ml./24 hours). During continuous infusion cystometry, intercontraction interval (ICI) was smaller in CYP-injected rats than in control rats. In CYP-injected animals, NO donors increased the ICI, but did not change the amplitude of bladder contractions. Continuous intravesical infusion of the NOS inhibitor did not alter the cystometric parameters. During cystometry under isovolumetric conditions, contraction frequency was decreased after NO donor administration. NO donors did not influence bladder activity in control rats. In patch clamp recordings, when SNAP (500 microM) was directly applied to dissociated afferent neurons innervating the urinary bladder, high-voltage-activated Ca2+ channel currents were suppressed by approximately 30%. CONCLUSIONS: Intravesical NO donors can suppress CYP-induced bladder hyperactivity. We hypothesize that the effect of NO donors is not due to smooth muscle relaxation, but rather due to an inhibitory effect on bladder afferent pathways that was manifested by an increase in intercontraction interval without changes in contraction amplitude. NO donors may be considered as a possible treatment of CYP-induced and other types of bladder inflammation.

Administration, Intravesical↗
PubMed1999

Bladder afferent pathway and spinal cord injury: possible mechanisms inducing hyperreflexia of the urinary bladder.

Lower urinary tract dysfunction is a common problem in patients with spinal cord injury (SCI). Since the coordination of the urinary bladder and urethra is controlled by the complex mechanisms in spinal and supraspinal neural pathways, SCI rostral to the lumbosacral level disrupts voluntary and supraspinal control of voiding and induces a considerable reorganization of the micturition reflex pathway. Following SCI, the urinary bladder is initially areflexic. but then becomes hyperreflexic because of the emergence of a spinal micturition reflex pathway. Recent electrophysiologic and histologic studies in rats have revealed that chronic SCI induces various phenotypic changes in bladder afferent neurons such as: (1) somal hypertrophy along with increased expression of neurofilament protein; and (2) increased excitability due to the plasticity of Na+ and K+ ion channels. These results have now provided detailed information to support the previous notion that capsaicin-sensitive, unmyelinated C-fiber afferents innervating the urinary bladder change their properties after SCI and are responsible for inducing bladder hyperreflexia in both humans and animals. It is also suggested that the changes in bladder reflex pathways following SCI are influenced by neural-target organ interactions probably mediated by neurotrophic signals originating in the hypertrophied bladder. Thus, increased knowledge of the plasticity in bladder afferent pathways may help to explain the pathogenesis of lower urinary tract dysfunctions after SCI and may provide valuable insights into new therapeutic strategies for urinary symptoms in spinal cord-injured patients.

Afferent Pathways↗