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Biomedical subjects

K Chiba

Publications and source records attributed to K Chiba.

At least 19 recordsLinked to original sources
PubMed2006

No proarrhythmic properties of the antibiotics Moxifloxacin or Azithromycin in anaesthetized dogs with chronic-AV block.

BACKGROUND & PURPOSE: The therapeutically available quinolone antibiotic moxifloxacin has been used as a positive control for prolonging the QT interval in both clinical and non-clinical studies designed to assess the potential of new drugs to delay cardiac repolarization. Despite moxifloxacin prolonging QT, it has not been shown to cause torsades de pointes arrhythmias (TdP). Azithromycin is a macrolide antibiotic that has rarely been associated, clinically, with cases of proarrhythmia. As there is a lack of clinical data available, the cardiac safety of these drugs was assessed in a TdP-susceptible animal model by evaluating their repolarization and proarrhythmia effects. EXPERIMENTAL APPROACH & KEY RESULTS: In transfected HEK cells, the IC(50)s for I (hERG) were 45+/-6 and 856+/-259 microg ml(-1) for moxifloxacin and azithromycin, respectively. Intravenous administration of 2 and 8 mg kg(-1) moxifloxacin (total peak-plasma concentrations 4.6+/-1.5 and 22.9+/-6.8 microg ml(-1)) prolonged the QT(c) in 6 anaesthetized dogs with chronic AV block by 7+/-3 and 21+/-19%, respectively. Similar intravenous doses of azithromycin (total peak-plasma concentrations 5.4+/-1.3 and 20.8+/-4.9 microg ml(-1)) had no electrophysiological effects in the same dogs. The reference compound, dofetilide (25 microg kg(-1) i.v.) caused QT(c) prolongation (29+/-15%) and TdP in all dogs. Beat-to-beat variability of repolarization (BVR), quantified as short-term variability of the left ventricular monophasic action potential duration, was only increased after dofetilide (1.8+/-0.7 to 3.8+/-1.5 ms; P<0.05). CONCLUSION & IMPLICATIONS: As neither moxifloxacin nor azithromycin caused TdP or an increase in the BVR, we conclude that both drugs can be used safely in clinical situations.

Anesthesia↗
PubMed2006

Ischemia-induced disturbance of neuronal network function in the rat spinal cord analyzed by voltage-imaging.

Using a voltage-imaging technique, we analyzed the acute effect of ischemia, hypoxia and hypoglycemia on the neuronal network function of the rat spinal cord. Ischemic, hypoxic, or hypoglycemic stress was loaded to spinal cord slices with an oxygen- and glucose-free, oxygen-free, or glucose-free mock cerebrospinal fluid, respectively. Depolarizing signals in the dorsal horn, induced by dorsal root stimulation, consisted of fast (pre-synaptic) and slow (post-synaptic) components. The slow component was attenuated much more than the fast component under an ischemic condition (P<0.0002). Post-synaptic neuronal activities in lamina III-IV were suppressed earlier than those in lamina I-II. The nerve fiber was relatively resistant to ischemia. As long as the fast component was preserved in the dorsal horn, the suppression of the fast and slow components was reversible. There was a significant difference (P<0.05) in the recovered slow component sizes between the group in which the fast component was suppressed by more than 20% by ischemia and the group in which the suppression was less than 20%. Further prolonged stress irreversibly eliminated most of the slow component, and attenuated the fast component (to 59+/-8%) accompanied by cellular damage in histology. Suppression of neural activity by hypoxic or hypoglycemic stress was less prominent than that by ischemia. Prolonged ischemic stress suddenly and irreversibly eliminated depolarizing signals in the ventral horn accompanied by morphological damage of motoneurons. Immunohistochemical staining was negative for apoptosis. We have, for the first time, analyzed the processes of spinal cord disturbance induced by ischemia, hypoxia and hypoglycemia at the neuronal network level by directly observing the regional neuronal network activities within the spinal cord. We conclude that synaptic transmission in the dorsal horn, especially in deep regions, is vulnerable and first affected by these stresses. Severe ischemic stress induces irreversible dysfunction of neurons accompanied by eventual cell death in both dorsal and ventral horns.

Animals↗
PubMed2006

Surgical outcomes of spinal cord astrocytomas.

STUDY DESIGN: Retrospective case series. OBJECTIVES: To analyze prognostic factors for patients with spinal cord astrocytomas. SETTING: Department of Orthopaedic Surgery, Keio University, Japan. METHODS: Seven patients received total excisions (group T), eight underwent partial excisions (group P), and 15 had excisional biopsies (group B). Impacts of the tumor histological grade, the level of the tumor, the types of surgical interventions, and the use of adjuvant radiotherapies on the survival and functional outcomes of 30 patients (18 in low-grade and 12 high-grade malignancy tumors) were analyzed. RESULTS: The survival rate of the low-grade malignancy group was significantly higher than that of the high-grade group. The survival rate of the patients with thoracic astrocytomas was significantly higher than those with cervical astrocytomas. In both the low- and high-grade groups, the survival rates in groups P/T were significantly higher than those in group B. In the low-grade group, five patients, whose preoperative functional statuses were classified as 'fair' or better, remained 'fair' or better after surgery. In the high-grade group, the postoperative functional statuses were classified as 'no change' or 'aggravated' in all except two patients. No significant difference in the survival rates was detected between patients with and without adjuvant radiotherapy. CONCLUSIONS: The tumor grade and the extent of tumor resection were significant prognostic factors for survival rate. In low-grade malignancy group, good motor function was retained when surgeries were performed before substantial neurological deterioration. The efficacy of postoperative radiotherapy has yet to be determined and needs further study.

Adolescent↗
PubMed2005

Endoscopic resection of cystic lesions in the lumbar spinal canal: a report of two cases.

We report excellent outcomes in two patients with cystic lesions in the lumbar spinal canal who underwent resection using the METRx micro-endoscopic discectomy (MED) system. Pathological examinations revealed the diagnoses of a synovial cyst and a discal cyst, respectively. Both of them were allowed to walk the next day after surgery with complete pain relief. Micro-endoscopic surgery provides excellent visualization of the spinal canal and allows minimally invasive removal of the pathological lesions. This technique can be an effective alternative to conventional open surgery for cystic lesions in the lumbar spine.

Adult↗
PubMed2005

Deep lamellar keratoplasty by deep parenchyma detachment from the corneal limbs.

AIM: To improve the deep lamellar keratoplasty technique. METHOD: For the easy and reliable perfomance of deep lamellar keratoplasty (DLKP), detachment of Descemet's membrane through the corneal limber flap was improved. To expose Descemet's membrane, the parenchyma was detached by hydrodelamination through a sclerocorneal flap made in the corneal limbs. The parenchyma was removed after the pseudochamber between it and Descemet's membrane was maintained with viscoelastic material. The corneal graft was placed with a running suture. 22 eyes were treated. RESULTS: Complete exposure of Descemet's membrane was obtained in 20 of the 22 eyes (91%). The membrane was perforated in five of the 22 eyes (23%) during surgery, and two of the 22 eyes (9%) were converted to penetrating keratoplasty. These two eyes developed keratoconus after acute corneal hydrops. CONCLUSION: Compared with the conventional procedure, this new method provides easy, reliable exposure of Descemet's membrane.

Adult↗
PubMed2004

Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release.

Cefoselis is a widely used beta-lactam antibiotic, but occasionally induces seizures and convulsion in elder and renal failure patients. However, beta-lactams are known not to pass through the blood-brain barrier (BBB). In this study, we examined the BBB penetration of cefoselis in normal and renal failure rats by means of brain microdialysis. Cefoselis was dose-dependently appeared in brain extracellular fluid in proportion to its blood level. The elimination constant from brain extracellular fluid (apparent) was slightly lower than that from blood. These results indicated that cefoselis might penetrate the BBB or be discharged by a certain transport system. In contrast to the result of cefoselis, cefazolin, a leading drug of cephalosporins, could not be detected in the brain extracellular fluid after an intravenous injection. In renal dysfunction rats, the elimination half-lives of cefoselis from both blood and brain were extensively prolonged. This would be one of responsible factors inducing seizures seen in patients. However, the additional factor, such as decrease in brain function related to aging, would be involved in seizures in patient received cefoselis, because an extremely high dose was required to induce seizures even in renal failure rats. A local administration of cefoselis into the hippocampus through the microdialysis probe caused a striking elevation of extracellular glutamate, with a minimum increase in gamma-aminobutyric acid (GABA). However, a systematic cefoselis administration via the tail vein did not elevate extracellular glutamate and GABA concentrations in the hippocampus of renal failure rats that exhibited marked seizures. These results suggested that not the stimulation of glutamate release, but the blockade of GABA receptors might be responsible for the seizure induced by cefoselis.

Animals↗
PubMed2004

Neonatal alloimmune thrombocytopenia due to an antibody against a labile component of human platelet antigen-3b (Bak b).

We report the second case of neonatal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-3b (Bak(b)) antibody. The infant was severely affected with intracranial haemorrhage. Most importantly, we were able to detect this antibody only by using fresh, unfixed platelets as antigen. This antibody was detectable neither by conventional mixed passive haemagglutination, platelet immunofluorescence test using fixed platelets, nor by monoclonal antigen immobilization of platelet antigen assay using solubilized platelets. We assume that this antibody reacts only with fresh platelets and that the antigen is a labile component of HPA-3b (Bak(b)).

Antigens, Human Platelet↗
PubMed2003

The risk of persistent carriage of methicillin-resistant Staphylococcus aureus in hematopoietic stem cell transplantation.

The clinical course of hematopoietic stem cell transplantation (HSCT) recipients was retrospectively analyzed to determine whether carriage of methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for MRSA infection during the neutropenic period. We studied four patients in whom MRSA colonies developed before HSCT. Two patients were previously diagnosed as having MRSA infection and two were carriers of MRSA. We tried to eliminate MRSA before HSCT and succeeded in eradication in two patients. MRSA infection did not develop in one patient who received prophylactic administration of vancomycin (VCM), but MRSA-induced phlegmon developed during neutropenia in one patient who did not receive prophylaxis. Of the other two patients who had been persistently positive for MRSA, MRSA did not develop in one patient who received prophylaxis, but the another patient who did not receive prophylaxis died from MRSA-induced sepsis in the early post-transplant period. We therefore recommend that MRSA be eliminated by prophylactic administration of anti-MRSA drugs such as VCM before HSCT when patients have persistent MRSA.

Adolescent↗
PubMed2003

Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori.

The relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been investigated in several studies. We investigated the prevalence of H. pylori infection and the clinical effects of eradication in 22 Japanese patients with chronic ITP. H. pylori infection was found in 14 (63.6%) of the patients by histologic and culture examinations of biopsy samples obtained by gastrointestinal endoscopy. H. pylori was eradicated by proton pump inhibitors and 2 kinds of antibiotics in 13 (92.9%) of the 14 patients in whom the results of treatment could be evaluated. Five (38.4%) of those 13 patients had platelet recovery (platelet count of more than 100 x 10(9)/L and an increase of more than 30 x 10(9)/L with respect to the baseline value) after eradication. The median follow-up period was 15 months. One patient who had a complete response had a partial relapse after cessation of prednisolone treatment without any evidence of H. pylori reinfection. Another patient, in whom H. pylori was not eradicated even after 2 treatment sessions, had a partial response after treatment. A screening examination for H. pylori infection may be necessary for Japanese patients with newly diagnosed ITP. Although the exact mechanism underlying platelet recovery after H. pylori eradication is not clear, the results of this study indicated that H. pylori eradication treatment is a good option for some patients with chronic ITP.

Adult↗
PubMed2003

Recombinant osteogenic protein-1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads.

This study was performed to determine if recombinant human osteogenic protein-1 (rhOP-1) is effective in promoting matrix synthesis and matrix formation by rabbit nucleus pulposus (NP) and annulus fibrosus (AF) cells cultured in alginate beads. The effects of culturing the cells in the presence of various concentrations of rhOP-1 were assessed by measuring changes in cell proliferation, proteoglycan (PG) and collagen synthesis and mRNA expression, and in the matrix contents of PG and collagen, as indicators of matrix accumulation. At high concentrations, rhOP-1 had a moderate mitogenic effect on both NP and AF cells. It also stimulated the synthesis of PG and collagen in a dose-dependent manner: this was associated with a corresponding increase in the expression of mRNA for aggrecan core protein and collagen type II. The stimulatory effect of rhOP-1 on PG synthesis was more pronounced than that on collagen synthesis. Continuous treatment with rhOP-1 led to an increase in the total DNA, PG and collagen contents in both NP and AF cultures. The results presented here provide evidence of the ability of rhOP-1 to stimulate the metabolism of both rabbit AF and NP cells cultured in alginate beads.

Aggrecans↗
PubMed2003

Changes of cervical spinal cord and cervical spinal canal with age in asymptomatic subjects.

STUDY DESIGN: Prospective study on magnetic resonance imaging (MRI) and radiographic findings of the cervical spine. OBJECTIVE: To elucidate the age-related changes of the cervical spinal cord and the cervical spinal canal and the relationship between the spinal cord and the spinal canal in asymptomatic subjects using MRI and radiography. SETTING: Tokyo, Japan. METHODS: The transverse area of the cervical spinal cord and the ratio of the anteroposterior diameter to the transverse diameter (RAPT) were investigated, using MRI in 229 asymptomatic subjects. The sagittal spinal canal diameter and anteroposterior diameter of the cervical vertebral body were also measured on plain lateral radiographs. The canal body ratio (CBR), which was defined as the diameter of the spinal canal divided by that of the vertebral body, was calculated. RESULTS: The transverse spinal cord area correlated negatively with age. RAPT did not correlate with age. The CBR correlated negatively with age. The correlation between spinal cord area and CBR was significant but weak and the correlation between RAPT and CBR was not significant. CONCLUSION: The transverse area of the cervical spinal cord measured by MRI decreased with age, while RAPT remained unchanged. The bony spinal canal became narrower with age. The spinal cord area and the shapes of the spinal cord were independent from the spinal canal diameter in asymptomatic subjects. These facts should be considered when evaluating radiological findings in patients with cervical spinal disorders.

Adolescent↗
PubMed2003

Mexiletine carbonyloxy beta-D-glucuronide: a novel metabolite in human urine.

1. The study was performed to isolate and characterize a glucuronic acid conjugate of mexiletine that releases mexiletine on acid hydrolysis from urine samples obtained from healthy volunteers following a single oral dose of mexiletine. 2. The [M-H]- ion of the isolated metabolite was observed at m/z 398 in the negative electrospray ionization mass spectrum. This mass number was 44 higher than that of the product generated when mexiletine is subjected to direct glucuronidation. In positive-ion mode, collision-induced dissociation of the quasimolecular ion [M+NH4]+, m/z 417, gave product ions at m/z 224, 180 and 58. These mass spectral data indicated that the metabolite contained a carbonyloxy moiety in its structure in addition to mexiletine and a glucuronic acid moiety. 3. The presence of this carbonyloxy moiety was further supported by the following chemical reactions. When the metabolite was hydrolysed with an aqueous solution of 1 M sodium hydroxide at room temperature, mexiletine was released, whereas the N-methoxycarbonyl derivative of mexiletine was obtained after treatment of the metabolite with methanolic sodium hydroxide solution. 4. The results indicated that the structure of the isolated metabolite was the N-carbonyloxy beta-D-glucuronic acid conjugate of mexiletine.

Adult↗
PubMed2002

del11(p11-13) with overexpression of Wilms' tumor gene during leukemic transformation of myelodysplastic syndrome.

We report a case of leukemic transformation from myelodysplastic syndrome (MDS) with a sole chromosome abnormality of del11(p11-13). The patient had been diagnosed as having MDS (refractory anemia with excess of blast cells, RAEB) in May 1998. At that time, cytogenetic analysis of bone marrow cells showed a normal karyotype. The patient received sequential chemotherapy with low-dose cytosine arabinoside (AraC) and macrophage colony-stimulating factor (M-CSF). Complete remission was obtained with this treatment, but the disease gradually progressed after June 1999. Cytogenetical analysis showed del11(p11-13) in 6 of 40 cells analyzed at that time, and the disease had evoluted to overt leukemia in December 1999 with a gradual increase in the abnormal clone. Furthermore, mRNA of the WT1 gene located at chromosome 11p13 was overexpressed during leukemic transformation, whereas it was not detected at the time of the initial diagnosis of MDS (RAEB) in May 1998. It was thought that this chromosome deletion and overexpression of WT1 resulted in the leukemic transformation in this patient. This is the first case report of del11(p11-13) being considered to be the primary cause of leukemic transformation from MDS.

Blast Crisis↗
PubMed2002

Pneumococcal purulent genual arthritis after allogeneic bone marrow transplantation.

A 21-year-old male patient with non-Hodgkin's lymphoma (diffuse large T-cell type, clinical stage IV) received allogeneic bone marrow transplantation (BMT) from a partially HLA-mismatched unrelated donor in July 1998 and achieved complete remission. Thereafter, he suffered from chronic graft-versus-host disease (GVHD) and was continuously administered immunosuppressive drugs for a long time. Two years after the BMT, he complained of severe pain in the right knee, which was swollen, and was diagnosed as having pneumococcal purulent genual arthritis. He underwent arthroscopic synovectomy and was administered systemic and intra-articular antibiotics, leading to a gradual improvement. Streptococcal infections are often seen in patients in the late phase after allogeneic BMT because of immunodeficiency associated with chronic GVHD and hyposplenism. Most streptococcal infections are respiratory tract infections and septicemia, and there have been very few reports on cases of purulent genual arthritis. Administration of prophylactic antibiotics and control of chronic GVHD, which is a risk factor of pneumococcal infection, seem to be important to prevent purulent genual arthritis.

Adolescent↗
PubMed2002

Successful allogeneic bone marrow transplantation from an HBV-positive donor into an HBV-positive recipient using lamivudine.

A 21-year-old woman with severe aplastic anemia underwent allogeneic bone marrow transplantation from an HLA-identical sibling donor. The patient also had chronic hepatitis B and the donor was an HBV carrier. To decrease HBV and improve hepatic dysfunction before BMT, the patient had received lamivudine for 6 months. After marrow transfusion, administration of lamivudine was continued to inhibit replication of donor-derived HBV. The patient showed hematological engraftment on day 13 without any serious liver dysfunction. Eight months after BMT, she is now alive and well without chronic liver GVHD or reactivation of hepatitis B. HBV-DNA was not detected in the patient's serum. Administration of lamivudine to a BMT recipient with chronic hepatitis B may be a safe and promising way to prevent fatal liver dysfunction in the setting of allogeneic BMT, even in the event of BMT from an HBV-positive donor.

Adult↗
PubMed2002

Lamivudine treatment for reverse seroconversion of hepatitis B 4 years after allogeneic bone marrow transplantation.

Reverse seroconversion of hepatitis B virus (HBV) after allogeneic BMT is rare. We present a case of HBV reactivation late after allogeneic BMT which responded well to lamivudine therapy. A 35-year-old woman with CML received an allogeneic BMT. Before BMT, the patient had immunity to HBV, with serum antibodies against hepatitis B surface antigen (HBsAb), and the donor was completely negative for HBV. Four years after BMT, acute hepatitis occurred with a detectable level of HBV-DNA. Lamivudine rapidly reduced transaminase and bilirubin levels, and serum HBV-DNA decreased to negative. Retrospective analysis revealed that there had been a gradual decrease in serum HBsAb titers after BMT. Administration of lamivudine immediately after HBV replication may be more effective than vaccination of hepatitis B surface antigen-negative donors before BMT.

Adult↗
PubMed2002

Pharmacokinetics, toxicokinetics, distribution, metabolism and excretion of linezolid in mouse, rat and dog.

1. Linezolid (ZYVOX), the first of a new class of antibiotics, the oxazolidinones, is approved for treatment of Gram-positive bacterial infections. 2. The aim was to determine the absorption, distribution, metabolism and excretion (ADME) of linezolid in mouse, rat and dog in support of preclinical safety studies and clinical development. 3. Conventional replicate study designs were employed in animal experiments, and biofluids were assayed by HPLC or HPLC-MS. 4. Linezolid was rapidly absorbed after p.o. dosing with an p.o. bioavailability of > 95% in rat and dog, and > 70% in mouse. Twenty-eight-day i.v./p.o. toxicokinetic studies in rat (20-200mg kg(-1) day(-1)) and dog (10-80 mg kg(-1) day(-1)) revealed neither a meaningful increase in clearance nor accumulation upon multiple dosing. 5. Linezolid had limited protein binding (<35%) and was very well distributed to most extravascular sites, with a volume of distribution at steady-state (V(ss)) approximately equal to total body water. 6. Linezolid circulated mainly as parent drug and was excreted mainly as parent drug and two inactive carboxylic acids, PNU-142586 and PNU-142300. Minor secondary metabolites were also characterized. In all species, the clearance rate was determined by metabolism. 7. Radioactivity recovery was essentially complete within 24-48 h. Renal excretion of parent drug and metabolites was a major elimination route. Parent drug underwent renal tubular reabsorption, significantly slowing parent drug excretion and allowing a slow metabolic process to become rate-limiting in overall clearance. 8. It is concluded that ADME data were relatively consistent across species and supported the rat and dog as the principal non-clinical safety species.

Acetamides↗