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Biomedical subjects

S Hori

Publications and source records attributed to S Hori.

At least 127 records · Page 7Linked to original sources

Pharmacokinetics of etoposide and carboplatin in cerebrospinal fluid and plasma during hyperosmotic disruption of the blood brain barrier and intraarterial combination chemotherapy.

The present paper investigates the pharmacokinetics of etoposide (VP-16) and carboplatin (CBDCA) in plasma and the cerebrospinal fluid (CSF), in the space left by tumor removal, of patients with glioma. Eight Japanese patients with glioma received a course of hyperosmotic disruption of the blood-brain barrier (HODBBB) and intraarterial combination chemotherapy with 60 mg/m2 of VP-16 and 300 mg/m2 of CBDCA. All patients were initially administered mannitol, followed by infusion of the anticancer drugs into the right internal carotid artery. Blood samples and samples of CSF in the space left by tumor removal were obtained. VP-16 and CBDCA concentration were measured by HPLC, and the pharmacokinetic parameters of these drugs estimated in CSF and plasma. The plasma concentrations of VP-16 and CBDCA peaked at the end of infusion, then decreased in a bi-exponential decay pattern during the remainder of the treatment period. Both VP-16 and CBDCA were detectable in CSF beginning 0.5 h after the initiation of each infusion, and were then slowly eliminated from the space left by tumor removal. The mean maximum CSF concentration of VP-16 and CBDCA was 0.17 and 15.25% of that in plasma, respectively. The mean area under the time-CSF concentration curve from 0 to 24 h after VP-16 and CBDCA infusion was 1.91 and 113.6% of plasma, respectively. In two of the eight patients, the clinical response to treatment was a partial response and other patients showed no change. HODBBB and intraarterial combination chemotherapy with VP-16 and CBDCA may be useful in patients with brain tumors for maintenance chemotherapy.

Aged↗

Nonischemic ST-segment elevation induced by negative inotropic agents.

The present study investigated whether regional ventricular dyskinesia (ie, systolic bulging) is a direct cause of ST-segment elevation in canine hearts in vivo. Regional ventricular dyskinesia was induced in 33 anesthetized open-chest dogs by injection of negative inotropic agents into the left anterior descending coronary artery (LAD) without disruption of coronary blood flow. Regional myocardial contraction was assessed in terms of the percent systolic shortening (%SS) and percent systolic bulging (%bulging), which were measured using ultrasonic crystals. The ST-segment elevation of the LAD-perfused area was measured with a unipolar electrode. Lidocaine, a sodium channel blocker, nicorandil, a potassium channel opener, propranolol, a beta-adrenergic blocker, or verapamil, a calcium channel blocker, was administered by intracoronary injection during maximal vasodilation induced by adenosine. All drugs induced dose-dependent ST-segment elevation in association with a parallel reduction in %SS and a parallel increase in %bulging. The absence of myocardial ischemia was confirmed by the absence of NADH fluorescence. It was concluded that regional ventricular dyskinesia had an important role in ST-segment elevation not associated with myocardial ischemia.

Adenosine↗

Dose-related increases in cerebrospinal fluid concentrations of methotrexate in a postoperative patient with glioblastoma.

OBJECTIVE: To investigate the postoperative pharmacokinetics of methotrexate in the plasma and cerebrospinal fluid (CSF) in the space created by tumor removal of a patient with glioblastoma during hyperosmotic disruption of the blood-brain barrier (BBB) and intraarterial chemotherapy with a stepwise increase in the methotrexate dosage. CASE SUMMARY: A 30-year-old Japanese woman with glioblastoma received four courses of hyperosmotic disruption of the BBB and intraarterial chemotherapy with a combination of peplomycin, vindesine, nimustine, pirarubicin, and methotrexate. The patient was initially administered mannitol; anticancer drugs were then infused into the left internal carotid artery. Following the first, second, third, and fourth courses of treatment, methotrexate 350, 700, 1000, and 1500 mg, respectively, were administered for 30 minutes. Samples of blood and CSF from the space created by tumor removal were obtained. Methotrexate concentrations were measured by fluorescence polarization immunoassay and the pharmacokinetic parameters of methotrexate in plasma and CSF were estimated. RESULTS: The plasma concentration of methotrexate peaked at the end of drug infusion, then decreased in a biexponential decay manner during the remainder of the treatment period. The CSF concentration of methotrexate in the space created by tumor removal peaked two hours after drug administration, then monoexponentially decreased. Although the maximal CSF concentration of methotrexate in the space created by tumor removal was lower than that in the plasma, the CSF concentration of methotrexate in the space created by tumor removal exceeded that in the plasma six hours after drug infusion. The half-life of methotrexate in the CSF exceeded that in the plasma. The AUC for the plasma and CSF methotrexate concentration increased parallel with the methotrexate dosage. The mean CSF AUC of methotrexate was 59.4% of that found in plasma. CONCLUSIONS: The CSF AUC of methotrexate in the space created by tumor removal increased parallel with the methotrexate dosage during hyperosmotic disruption of the BBB and intraarterial chemotherapy.

Adult↗

Ehlers-Danlos syndrome associated with multiple spinal meningeal cysts--case report.

A 40-year-old female with Ehlers-Danlos syndrome was admitted because of a large pelvic mass. Radiological examination revealed multiple spinal meningeal cysts. The first operation through a laminectomy revealed that the cysts originated from dilated dural sleeves containing nerve roots. Packing of dilated sleeves was inadequate. Finally the cysts were oversewed through a laparotomy. The cysts were reduced, but the postoperative course was complicated by poor wound healing and diffuse muscle atrophy. Ehlers-Danlos syndrome associated with spinal cysts may be best treated by endoscopic surgery.

Adult↗

Temporal and spatial profile of apoptotic cells after focal cerebral ischemia in rats.

The significance of apoptosis in focal ischemia was investigated in the spatial and temporal profiles of apoptotic cells caused by permanent and transient focal ischemia induced in male Wistar rats by intraluminal vascular occlusion. Animals were sacrificed at various times and coronal sections of the brain at the level of the optic chiasm were examined histologically by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling. Animals in both groups showed apoptotic cells in the infarcted area, particularly in the border zone. Animals with permanent ischemia showed more extensive infarct and more rapid appearance of apoptotic cells. Activation of apoptosis might depend on the severity of the ischemic insult. Apoptotic cells were observed at 7 days after the ischemic insult in animals with transient ischemia, suggesting apoptosis is involved in the developments of delayed infarct.

Animals↗

[A case of craniopharyngioma with intratumoral hemorrhage].

A patient of craniopharyngioma associated with intratumoral bleeding was reported. A 44-year-old female was admitted to our department with sudden onset of headache suggesting pituitary apoplexy. On admission, she complained of mild bifrontalgia and neurological examination revealed no abnormality except bitemporal hemianopsia. Hormonal examination indicated hypopituitarism with masked diabetes insipidus and chronic thyroiditis. MRI showed a cystic 12 x 10 x 10 mm tumor with an enhanced rim at the intra- and suprasellar region. The MRI findings of the cyst suggested intratumoral bleeding with various stages. CT and plain tomography revealed plane calcification adjusting or aligning itself to the floor of the sellar. This calcification was difficult to distinguish from the sellar floor on MRI. Under the diagnosis of craniopharyngioma, almost all of the tumor was removed, using the transsphenoidal approach. The cyst consisted of old hematoma and cholesterin. The histological examination revealed a stratified squamous epithelia with numerous immature blood vessels. Such findings are unusual in cases of craniopharyngioma. Craniopharyngioma is rarely associated with intratumoral hemorrhage. The mechanism of this hemorrhage was discussed with reference to the literature on this subject.

Adult↗

[Cortical deafness due to bilateral temporal subcortical hemorrhages associated with moyamoya disease: report of a case].

A 51-year-old male with moyamoya disease had experienced a left putaminal hemorrhage 14 years previously, in 1983. Left encephalo-duro-arterio-synangiosis (EDAS) was performed in that year. The left putaminal hemorrhage reoccurred in 1990 and in 1994. Left superficial temporal artery-middle cerebral artery anastomosis (STA-MCA anastomosis) was performed. He was symptom free after the surgery. However, he suddenly suffered from deafness in 1997, when computerized tomography (CT) revealed the right temporal subcortical hemorrhage. Deafness continued for three days. It gradually improved and completely disappeared in two months. The damage to the bilateral auditory radiation was suggested as the cause of deafness in this patient. Cortical deafness is a rare symptom that is most often associated with cerebral infarction. This may be the first report of moyamoya disease which developed cortical deafness.

Cerebral Angiography↗

[Detection of serum p53 antibodies in colorectal cancer patients and the clinical significance of postoperative monitoring].

p53 protein overexpression was found to induce the production of antibodies in patient serum and, recently, the easy detection of serum antibodies has been made possible. The aim of this study is to determine the significance of serum p53 antibodies in patients with primary colorectal adenocarcinoma in comparison with their clinicopathological features, and the tumor marker sensitivities of carcinoembryonic antigen (CEA), carcinoma antigen 19-9 (CA19-9) and alpha-fetoprotein (AFP). Thirty-nine of 86 patients (45.3%) were positive for serum p53 antibodies. However, there was no relation with the cancer progression or clinicopathological findings. The sensitivities of CEA, CA19-9 and AFP were 36.0%, 38.4%, and 8.1% respectively, but there was no relation between serum p53 antibodies and these three markers. When the sensitivity of serum p53 antibodies and CEA was evaluated according to clinical stage, the presence of serum p53 antibodies was more significantly associated with stage 0, I and II colorectal cancer than was CEA. Thirty-three patients who showed preoperative positivity for serum p53 antibodies were followed by serial evaluation of circulating antibodies after resection. Negative conversions after resection were significantly higher in the "Cur A" group than in the "Cur B" or "Cur C" groups. Serum p53 antibodies appear to be a useful tumor marker independent of the other markers, especially in the early stage, and are expected to be useful in the development of a method of early diagnosis for mass screening, and as a postoperative monitoring marker for colorectal cancer.

Adult↗

Laparoscopically assisted splenectomy following preoperative splenic artery embolization using contour emboli for myelofibrosis with massive splenomegaly.

Laparoscopically assisted splenectomy with an 8- to 10-cm left upper paramedian laparotomy was performed following preoperative splenic artery embolization using painless contour emboli (super absorbent polymer microsphere) with early successful results in two men (46 and 37 years old) with myelofibrosis accompanied by massive splenomegaly. Dissection around the lower part of the spleen and the hilum initially was performed intracorporeally with the usual laparoscopic view under 12 mm Hg pneumoperitoneum. The alternating changes of viewpoints between the direct view through an 8- to 10-cm incision and the usual laparoscopic view with or without application of a retraction method were effective for safe hilar devascularization. Preoperative splenic artery embolization at the distal site was effective for safe dissection around the enlarged spleen. The patients did not complain of pain before operation. Preoperative painless embolization and laparoscopically assisted splenectomy with small laparotomy promotes the feasibility and safety of minimally invasive splenectomy for myelofibrosis with massive splenomegaly.

Adult↗

Alteration of the properties of gastric smooth muscle in the genetically hyperglycemic OLETF rat.

Membrane responses were recorded from isolated gastric smooth muscle of Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats, using microelectrode techniques. At the age of 68-76 weeks, the blood sugar level was 181 mg/dl in LETO rats and 350 mg/dL in OLETF rats. In both rats, the membrane potential was stable in fundus muscle and spontaneously active with generation of slow waves in antrum muscle. The resting membrane potential was about - 46 mV in fundus and - 55 mV in antrum muscles of LETO rats, and the values were 3-7 mV lower in OLETF rats. The slow waves were generated regularly in LETO rats, while they were irregular and of small amplitude in OLETF rats. Transmural nerve stimulation evoked a cholinergic excitatory junction potential and following inhibitory junction potential in LETO rats, and only an inhibitory junction potential of smaller size was generated in most of OLETF rats. The acetylcholine-induced depolarization was greater in OLETF than in LETO rats. The level of hyperpolarization produced by noradrenaline was similar between OLETF and LETO rats. Thus, the reduction of the resting membrane potential, weakening of spontaneous activity, impairment of cholinergic transmission and cholinergic supersensitivity were associated with hyperglycemia. These alterations were considered due to the development of diabetes mellitus.

Acetylcholine↗

Premorbid personality traits of patients with organic (ICD-10 F0), schizophrenic (F2), mood (F3), and neurotic (F4) disorders according to the five-factor model of personality.

The present article aims to examine premorbid personality traits of psychiatric patients with various diagnoses by asking their close relatives to retrospectively rate the patients' usual self with a questionnaire designed for the five-factor model of personality, a rapidly emerging comprehensive theory of personality structure. Data for 140 patients and 84 controls were analyzed. Although psychiatric patients as a group were characterized by high neuroticism and low conscientiousness when compared with the healthy controls, there were only a few traits that distinguished a particular diagnostic group from either the normal control or from the rest of the patients: neurotic disorder patients had higher neuroticism scores than the normal controls; unipolar depressives had a higher conscientiousness score than the rest of the patient group. No salient premorbid trait was noted for patients with organic mental disorders, schizophrenic disorders or bipolar disorders.

Adult↗

Novel mutations of the endothelin B receptor gene in patients with Hirschsprung's disease and their characterization.

Hirschsprung's disease (HSCR) is a congenital intestinal disease, characterized by the absence of ganglion cells in the distal portion of the intestinal tract. Recently, three susceptibility genes have been identified in HSCR, namely the RET protooncogene, the endothelin B (ETB) receptor gene (EDNRB), and the endothelin-3 (ET-3) gene (EDN3). To investigate whether mutations in EDNRB could be related with HSCR in non-inbred populations in Japan, we examined alterations of the gene in 31 isolated patients. Three novel mutations were detected as follows: two transversions, A to T and C to A at nucleotides 311 (N104I) and 1170 (S390R), respectively, and a transition, T to C at nucleotide 325 (C109R). To analyze functions of these mutant receptors, they were expressed in Chinese hamster ovary cells. S390R mutation did not change the binding affinities but caused the decreases in the ligand-induced increment of intracellular calcium and in the inhibition of adenylyl cyclase activity, showing the impairment of the intracellular signaling. C109R receptors were proved to be localized near the nuclei as an unusual 44-kDa protein with the extremely low affinity to endothelin-1 (ET-1) and not to be translocated into the plasma membrane. On the other hand, N104I receptors showed almost the same binding affinities and functional properties as those of the wild type. Therefore, we conclude that S390R and C109R mutations could cause HSCR but that N104I mutation might be polymorphous.

Adenylyl Cyclase Inhibitors↗

Biphasic activation of the JAK/STAT pathway by angiotensin II in rat cardiomyocytes.

This study was designed to demonstrate the characteristic pattern of angiotensin II-induced JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) activation in cultured rat cardiomyocytes by comparing it with leukemia inhibitory factor (LIF)-induced activation. Angiotensin II (10(-7) mol/L) induced rapid phosphorylation of JAK2 and Tyk2, but not JAK1, and phosphorylated STAT1 and STAT2, but not STAT3, in the early stage up to 30 minutes. The time course of JAK/STAT activation by angiotensin II was apparently slower than that by LIF. Interestingly, angiotensin II phosphorylated STAT3 and rephosphorylated STAT1 in the late stage at 120 minutes. We also found that angiotensin II induced the formation of interferon-stimulating gene factor (ISGF) complexes biphasically, in the early stage at 15 to 30 minutes and in the late stage at 120 minutes, and that angiotensin II induced delayed activation of the sis-inducing factor (SIF) complex at 120 minutes. Formation of ISGF and SIF complexes in response to angiotensin II paralleled the phosphorylation pattern of STAT1 and STAT3 and was quite different from those obtained in response to LIF. The phosphorylation of STAT1 was suppressed by pretreatment with the angiotensin II type-1 (AT1) receptor antagonist CV11974, but the delayed addition of CV11974 failed to suppress phosphorylation of STAT3 at 120 minutes. In conclusion, angiotensin II-induced JAK/STAT activation in rat cardiomyocytes is biphasic and entirely different from LIF-induced activation.

Angiotensin II↗