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Biomedical subjects

Takashi Shibata

Publications and source records attributed to Takashi Shibata.

33 records · Page 2Linked to original sources

Effect of preemptive treatment of capsaicin or resiniferatoxin on the development of pre-micturition contractions after partial urethral obstruction in the rat.

PURPOSE: Neuroplasticity in afferent pathways, including C-fiber bladder afferents, is believed to be one of the major causes of changes in bladder function after partial urethral obstruction. We determined if capsaicin sensitive C-fiber bladder afferents are involved in the development of pre-micturition contractions after partial urethral obstruction in the rat. MATERIALS AND METHODS: Female Wistar rats were preemptively treated with capsaicin (100 mg/kg subcutaneously) or resiniferatoxin (0.3 mg/kg subcutaneously) prior to the creation of obstruction. Before and 6 weeks after obstruction micturition profiles were compared among the 3 groups, including obstructed rats preemptively treated with capsaicin (BO/CAP) or resiniferatoxin (BO/RTX) and untreated obstructed rats (BO/-). In addition, conscious filling cystometry was performed after obstruction. RESULTS: Instillation of capsaicin solutions into the eye or bladder induced significant irritative reactions in BO/- but not in BO/CAP or BO/RTX, indicating that the effect of pretreatment with capsaicin or resiniferatoxin lasted 6 weeks. Voided volume per micturition on micturition profiles was decreased after partial urethral obstruction in all 3 groups. On conscious filling cystometry a significant increase in bladder capacity, voided volume and micturition threshold pressure was noted in BO/CAP but not in BO/RTX compared with BO/-. In contrast, there was no significant change in residual volume, voiding efficiency or micturition pressure among the 3 groups. The prevalence of pre-micturition contractions was 100% in BO/CAP and BO/RTX, and 83% in BO/-. CONCLUSIONS: Capsaicin sensitive C-fiber afferents are not essential to induce pre-micturition contractions but they are involved in functional alterations in bladder afferent pathways after partial urethral obstruction in rats.

Afferent Pathways↗

Effects of chronic blockade of N-methyl-D-aspartate receptors by MK-801 on neuroplasticity of the micturition reflex pathway after partial urethral obstruction in the rat.

PURPOSE: To determine the role of N-methyl-D-aspartate (NMDA) glutamatergic receptors in the development of functional bladder changes after partial urethral obstruction we investigated the effects of repeat injection of MK-801, a noncompetitive NMDA receptor antagonist, on the micturition reflex in conscious obstructed rats. MATERIALS AND METHODS: In 9 female Wistar rats 1.0 mg/kg MK-801 was injected intramuscularly once weekly just prior to the creation of partial urethral obstruction until 5 weeks after obstruction. Five to 7 days after the last injection of MK-801 conscious filling cystometry was performed and compared with that in 9 obstructed rats treated with vehicle (saline). Conscious filling cystometry was also compared in 9 and 7 sham operated rats treated with repeat injection of MK-801 and vehicle, respectively. RESULTS: Partial urethral obstruction caused a significant increase in bladder weight. However, chronic MK-801 treatment did not affect bladder weight in obstructed or sham operated rats. In the obstructed/MK-801 vs the obstructed/vehicle group chronic treatment with MK-801 significantly increased bladder capacity (2.29 +/- 0.12 vs 1.73 +/- 0.16 ml, p <0.01) and voided volume (2.00 +/- 0.10 vs 1.56 +/- 0.17 ml, p <0.05) without changes in voiding efficiency (87.5% +/- 1.6% vs 87.8% +/- 1.7%) or micturition pressure (55.8 +/- 2.3 vs 56.4 +/- 3.0 cm water). Interestingly neither the frequency nor amplitude of premicturition contractions during filling was different in the groups. In sham operated rats chronic MK-801 treatment did not change bladder capacity, voided volume, voiding efficiency or micturition pressure significantly. CONCLUSIONS: The results in the current study suggest that bladder outlet obstruction causes NMDA receptor mediated alterations in bladder afferent pathways in the rat.

Animals↗

Immortalized neural stem cells transplanted into the injured spinal cord promote recovery of voiding function in the rat.

PURPOSE: Bladder dysfunction is a serious consequence of spinal cord injury. Cellular transplantation into the injured spinal cord can promote axonal growth and functional recovery. We investigated whether EG6 immortalized neural stem cells transplanted into the injured spinal cord of the rat contribute to a recovery of lower urinary tract function. MATERIALS AND METHODS: The spinal cord of 14 female Wistar rats was injured by compression. In 7 rats 9 days after spinal cord injury BrdU (5-bromo-2'-deoxyuridine) labeled EG6 cells were transplanted into the injured spinal cord. Seven operated (OP) control rats received intraspinal injections of culture medium alone. Voided volume per micturition was assessed in a metabolic cage for 24 hours on days 14 and 28 after transplantation. On day 28 saline was infused via a catheter inserted into the bladder and intravesical pressure was measured in OP control and EG6 transplant rats. RESULTS: EG6 cells identified by BrdU immunocytochemistry survived in the injured spinal cord. Voided volume per micturition significantly increased in EG6 transplant rats by day 28 after transplantation. Micturition pressure significantly decreased in EG6 transplant rats compared with OP controls. Although voided volume did not differ, post-void residual urine was significantly less in EG6 transplant than in OP control rats. Thus, voiding efficiency was significantly greater in EG6 transplant rats compared with OP controls. There was no difference in the incidence of detrusor hyperreflexia. CONCLUSIONS: Transplanted EG6 cells survived in the injured spinal cord and had beneficial effects on the recovery of voiding function after spinal cord injury in the rat.

Animals↗

Multiple-dose escalation, safety, and tolerability study of wood creosote, the principal active ingredient of seirogan, an herbal antidiarrheal medication, in healthy subjects.

Seirogan, an herbal medicine containing wood creosote (CAS 8021-39-4), a mixture of simple phenolic compounds, has been marketed for the past century in Asia for the treatment of acute diarrhea and associated symptoms, such as abdominal discomfort and cramping. The present study was designed to assess the safety and tolerability of an anticipated acute antidiarrheal dosing regimen. Sixty healthy males were randomized into five groups of 12 subjects each (9 wood creosote; 3 placebo) to receive 45-, 90-, 135-, 180-, and 225-mg tablets every 2 hours for five doses. Serial sitting and standing vital signs, ECG rhythm strips, and continuous telemetry monitoring were obtained predose and for 24 hours after the first dose. Clinical laboratory tests and 12-lead resting ECGs were obtained predose and 24 hours postdose. Of the subjects, 27% (12/45) receiving wood creosote and 27% (4/15) receiving placebo reported adverse events. The most common adverse events were altered taste and somnolence, reported more often with 180- and 225-mg doses. Wood creosote had no clinically significant effects on vital signs, ECG intervals or interpretations, or clinical laboratory tests. No clinically significant or serious dysrhythmias were reported on continuous telemetry monitoring. It was concluded that oral doses of wood creosote 45 to 225 mg every 2 hours for up to five doses were safe and well tolerated in 45 healthy subjects. Wood creosote doses ranging from 45 to 135 mg per dose, which are commonly administered antidiarrheal doses in Asia, were associated with minimal side effects.

Administration, Oral↗

Wood creosote, the principal active ingredient of seirogan, an herbal antidiarrheal medicine: a single-dose, dose-escalation safety and pharmacokinetic study.

STUDY OBJECTIVE: To assess the safety, tolerability and pharmacokinetics of escalating single doses of wood creosote, an herbal antidiarrheal and antispasmodic agent. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Clinical research center. SUBJECTS: Forty (32 men, 8 women) healthy volunteers aged 19-42 years. INTERVENTION: By random assignment, 22 men and 8 women received escalating single doses of wood creosote (45, 90, 135, 180, and 225 mg) and 10 men received placebo (for each of the five dose levels, 6 subjects received active substance and 2 subjects received placebo). MEASUREMENTS AND MAIN RESULTS: Vital signs, laboratory tests, and electrocardiograms were assessed; no dose-related or clinically significant changes were noted. Serial blood samples were obtained to determine the pharmacokinetics of four major active components of wood creosote: total (conjugated plus free) guaiacol, creosol, o-cresol, and 4-ethylguaiacol. The most common adverse events were mild headache and dizziness, with no dose-related trends being apparent. Area under the concentration-time curve from time zero to infinity increased in a dose-proportional manner for total guaiacol, creosol, and o-cresol and was not assessed for total 4-ethylguaiacol owing to lack of data at the low dose level. No apparent differences by sex were noted for any of the four active components. All four components were rapidly eliminated. CONCLUSION: Single oral doses of wood creosote up to 225 mg were safe and well tolerated in healthy men and women. Also, the doses of wood creosote were rapidly absorbed, conjugated, and eliminated. Such a rapid onset and short duration of action would appear desirable in the treatment of acute nonspecific diarrhea.

Adult↗

Tethering of the spinal cord in mouse fetuses and neonates with spina bifida.

OBJECT: Tethering of the spinal cord is a well-known complication in humans with spina bifida aperta or occulta. Its pathogenesis consists of a pathological fixation of the spinal cord resulting in traction on the neural tissue which, in turn, leads to ischemia and progressive neurological deterioration. Although well established in humans, this phenomenon has not been described in animal models of spina bifida. METHODS: A fetal mouse model with naturally occurring, genetically determined spina bifida was produced by generating double mutants between the curly tail and loop-tail mutant strains. Microdissection, labeling with 1,1'-dioctadecyl-3,3,3,',3'-tetramethylindocarbocyanine perchlorate, immunohistochemistry for neurofilaments, H & E staining of histological sections, and whole-mount skeletal preparations were performed and comparisons made among mutant and normal fetuses. Normal fetuses exhibited the onset of progressive physiological ascent of the spinal cord from embryonic Day 15.5. Spinal cord ascent resulted, by embryonic Day 18.5, in spinal nerve roots that pass caudolaterally from the spinal cord toward the periphery. In contrast, fetuses with spina bifida exhibited spinal cord tethering that resulted, at embryonic Day 18.5, in nerve roots that run in a craniolateral direction from the spinal cord. The region of closed spinal cord immediately cranial to the spina bifida lesion exhibited marked narrowing, late in gestation, suggesting that a potentially damaging stretch force is applied to the spinal cord by the tethered spina bifida lesion. CONCLUSIONS: This mouse model provides an opportunity to study the onset and early sequelae of spinal cord tethering in spina bifida.

Animals↗

[A case of basilar artery occlusion of traumatic vertebral artery dissection successfully managed by endovascular treatment].

The author describes a case of basilar artery occlusion caused by vertebral artery dissection with vertebral fracture. A 61-year-old man was admitted with neck pain after a traffic accident. His symptoms suddenly deteriorated and cerebral angiography revealed an occlusion of the right vertebral artery, and complete occlusion of the basilar artery. Local-arterial fibrinolysis with urokinase for basilar artery occlusion and angioplasty with the use of a self-expandable stent for the site of the vertebral artery dissection was performed, and the basilar artery was partially recanalized. The patient's symptoms gradually improved. It should be emphasized that in cases of acute cervical spine injury after major trauma, vertebral artery dissection should be considered. Local-arterial fibrinolysis and angioplasty using a self-expandable stent was regarded as a useful treatment for basilar artery occlusion caused by vertebral artery dissection, in the acute stage.

Arterial Occlusive Diseases↗

[Outcomes of patients undergoing microwave coagulation therapy for liver metastases from colorectal cancer].

To evaluate the efficacy of microwave coagulation therapy (MCT) for liver metastases from colorectal cancer, we analyzed the survival and the disease-free survival rate. From 1990 to 2001, 18 patients with liver metastases measuring < or = 3 cm in diameter and number of metastases < or = 3 were treated with MCT. The 3- and 5-year survival rates were 62% and 18%, respectively. These results are almost equal to those for liver resection. The disease-free survival rate was 86% and 52%, respectively. Local recurrence has not been observed, which puts the disease-free interval over 24 months. MCT can be considered an effective therapy for liver metastases from colorectal cancer.

Adult↗

Detrusor instability with equivocal obstruction: A predictor of unfavorable symptomatic outcomes after transurethral prostatectomy.

AIMS: To elucidate whether preoperative urodynamic findings can predict outcomes of transurethral resection of the prostate (TUR-P). METHODS: Sixty-two patients with symptomatic benign prostatic hyperplasia were categorized in three different ways based on findings of preoperative pressure-flow study (PFS) and cystometry: urodynamic obstruction (determined by the Abrams-Griffiths nomogram), detrusor instability (DI), and combination of both. Outcomes of TUR-P regarding symptom, function, and quality of life (QOL) were analyzed by changes in the International Prostate Symptom Score (I-PSS), maximum flow rate in uroflowmetry, and QOL index before and after TUR-P, respectively. Overall outcome was defined as success when all of the three categories showed successful improvement. RESULTS: Neither urodynamic obstruction alone nor DI alone predicted outcomes of TUR-P. However, symptomatic and overall outcomes were significantly worse in patients who were not obstructed but had DI. Postoperative persistent DI was more frequently noted in patients without clear obstruction (60%) than in those with obstruction (27%). Patients with equivocal obstruction showed less satisfactory symptomatic outcomes of TUR-P when DI was accompanied. Persistent DI might be the principle cause of unfavorable outcomes. CONCLUSIONS: Preoperative evaluation of DI is of benefit because it enhances predictive value of the PFS.

Aged↗

A comparison of intraoperative celiac plexus block with pharmacological therapy as a treatment for pain of unresectable pancreatic cancer.

BACKGROUND/PURPOSE: The efficacy of intraoperative celiac plexus block was compared with that of pharmacological therapy in the treatment of pain caused by unresectable pancreatic cancer. METHODS: Twenty-one patients were included in the study: 15 patients underwent intraoperative celiac plexus block (group 1) and 6 received pharmacological therapy (group 2). The effectiveness at 1 week after treatment and from treatment to death was evaluated at follow-up by looking at mean analgesic consumption, mortality and morbidity, and any postoperative complications. Statistical analysis was performed using unpaired t-tests. RESULTS: One week after the operation, the analgesic consumption of 14 patients in group 1 was the same as that before treatment, and 1 patient's consumption had decreased. Pain in 4 patients in group 2 did not change, but in 2 patients it increased. Mean opioid consumption was significantly lower in group 1. Complications related to the block were transient diarrhea and hypotension ( P not significant between groups). There was no operative mortality or major complication related to the block. The incidence of adverse drug-related effects, such as constipation, nausea, and vomiting, was significantly lower in group 1 than in group 2. CONCLUSIONS: Intraoperative celiac plexus block made pain control possible with reduced opioid consumption, representing an effective, safe, and simple tool for the treatment of pain caused by unresectable pancreatic cancer.

Aged↗

Percutaneous microwave tumor coagulation for hepatocellular carcinomas with interruption of segmental hepatic blood flow.

PURPOSE: To assess the effect of hepatic artery occlusion with or without hepatic venous outflow interruption on coagulation diameter during percutaneous microwave coagulation therapy (PMCT) for hepatocellular carcinoma (HCC) by a prospective and randomized trial. MATERIALS AND METHODS: Thirty-one patients with 36 HCCs (10-38 mm in diameter) were randomly separated into two treatment groups as follows: group 1 (14 tumors in 14 patients) was treated with PMCT in conjunction with both segmental hepatic artery embolization with gelatin sponge particles and temporary interruption of hepatic venous flow by means of a 6-F balloon catheter to reduce the portal venous flow; group 2 (22 tumors in 17 patients) was treated with PMCT with segmental hepatic artery embolization only. PMCT under ultrasound (US) guidance was performed with 2,450 MHz of microwave frequency at 40-60 W and a needle applicator 1.6 mm in diameter. The coagulated area was measured at the maximum diameter perpendicular to the needle tract on enhanced computed tomography (CT) performed immediately after PMCT. The local effect of the treatment was evaluated by follow-up enhanced CT (6-33 mo). RESULTS: Patients in group 1 had a significantly larger coagulation area (mean +/-SD = 42.9 mm +/- 8.3), with coagulation times of 5.3 min +/- 1.4, than patients in group 2 (32.6 mm +/- 8.0), with coagulation times of 4.2 min +/- 1.3 (P <.05). Follow-up enhanced CT showed no local enhancement of the tumor, indicating complete necrosis and no local recurrence, except for four tumors. There were no major complications after PMCT except liver abscess that developed after PMCT in one patient with pneumobilia. CONCLUSIONS: PMCT with combined hepatic arterial embolization and temporary hepatic venous flow interruption can coagulate significantly larger volumes of tumor than PMCT with only hepatic arterial embolization.

Adult↗

Generators of visual evoked potentials for faces and eyes in the human brain as determined by dipole localization.

Human visual evoked potentials were recorded during presentation of photos of human and animal faces and various face features. Negative waves with approximate peak latencies of 165 msec (N170) were bilaterally recorded from the occipito-temporal regions. Mean peak latencies of the N170 were shorter for faces than eyes only. Analyses of amplitudes of evoked potentials indicated that the N170 elicited by faces reflected activity of a specific neural system which was insensitive to detailed differences among individual faces regardless of species, and consequently suggest that this system might function to detect existence of faces in general. On the other hand, the mean amplitude of the N170 elicited by human eyes was significantly larger than those by animal eyes. These differences in response latencies and amplitudes of the N170 suggest existence of at least 2 different visual evoked potentials with similar latencies (i.e., N170) which are sensitive to faces in general and human eyes, respectively. Dipole source localization analysis indicated that dipoles for the N170 elicited by eyes were located in the posterior inferior temporal gyrus, and those for faces, located initially in the same region, but moved toward the fusiform and lingual gyri at the late phase of the N170. The results indicated that information processing of faces and eyes separated at least as early as the latency of the N170 at the posterior inferior temporal gyrus as well as the fusiform and lingual gyri, and might provide neurophysiological and anatomical bases to an initial structural encoding stage of human faces.

Adult↗

[Comparison of percutaneous microwave coagulation area under interruption of hepatic arterial blood flow with that under hepatic arterial and venous blood flow for hepatocellular carcinoma].

The study subjects were 49 patients with hepatocellular carcinoma. Twenty-nine patients underwent hepatic arterial blood flow block via thrombosis of the cancer-bearing area with a gelatin sponge, while the other 20 patients underwent a combination of hepatic arterial block and partial blood flow block of the portal vein with a hepatic venous balloon. Percutaneous microwave coagulation therapy (PMCT) was performed on these patients according to the type of hepatic blood flow block, and the diameters of the coagulation areas in the two groups were compared using CT images taken under portal venography. The 29 patients who underwent hepatic arterial block (A-PMCT) had a mean tumor diameter of 19.2 +/- 8 mm, while the 20 patients who underwent hepatic arterial and hepatic venous block (AV-PMCT) had a mean tumor diameter of 25.3 +/- 8.3 mm. PMCT was performed at 60 W. The mean coagulation time and the mean coagulation diameter were 4.2 +/- 1.1 min and 36.3 +/- 12.3 mm, respectively, for the A-PMCT group and 5.5 +/- 1.8 min and 43.9 +/- 9.8 mm, respectively, for the AV-PMCT group. A comparison of the coagulation diameters indicated that the AV-PMCT group had a significantly greater coagulation area than the A-PMCT group (p < 0.05).

Carcinoma, Hepatocellular↗

[Clinicopathological analysis of two patients with local recurrence after microwave coagulation therapy for liver metastases from colorectal cancer].

UNLABELLED: We analyzed the clinicopathological factors in two cases of local recurrence after a disease-free interval (DFI) of more than 12 months following microwave coagulation therapy (MCT) for liver metastases from colorectal cancer. Case 1: A local recurrence was diagnosed at 14 months after MCT for a liver metastasis of 20 mm in diameter from rectal cancer. Following liver resection, the patient remains alive without recurrence at 9 months. Case 2: A local recurrence was diagnosed at 19 months after MCT for a liver metastasis of 20 mm in diameter from rectal cancer. After MCT, the patient remains alive without recurrence at 36 months. CONCLUSION: We treated two patients with local recurrence who have more than 12 months' DFI after MCT for liver metastases from colorectal cancer. MCT or liver resection was performed as a curative therapy in these cases. Caution is recommended for local recurrence at more than 12 months after MCT for liver metastases from colorectal cancer.

Adenocarcinoma↗