Biomedical subjects

Shinichi Miyazaki

Publications and source records attributed to Shinichi Miyazaki.

17 recordsLinked to original sources

PubMed2006

Calcium phosphate cement in musculoskeletal tumor surgery.

BACKGROUND AND OBJECTIVES: Calcium phosphate cement (CPC) is an injectable biocompatible bone substitute that has been used for various applications in orthopedic surgery. However, no extensive clinical studies of the use of CPC to fill bone cavities after curettage of musculoskeletal tumors have been reported. The present study reviewed the results for 56 musculoskeletal tumors treated by curettage and CPC implantation. METHODS: Assessment was based on clinical examination and radiographic findings. Variables for clinical assessment included pain, limb function, and complications. Median follow-up was 18.5 months (range 6-47 months). RESULTS: One patient experienced post-operative fractures. Three patients displayed local recurrence. One patient developed post-operative superficial wound infection, and two patients with large bony defect exhibited non-infectious serous discharge. No serious adverse effects such as deep venous thrombosis, pulmonary embolism were encountered. In all cases, CPC was radiographically well adapted to the surrounding host bone as of final follow-up. CONCLUSIONS: CPC appears to offer a useful bone substitute for the treatment of musculoskeletal tumors. As the follow-up period for this study was short, further long-term follow-up studies are needed.

Adolescent↗

PubMed2006

Phase I/II adenoviral p53 gene therapy for chemoradiation resistant advanced esophageal squamous cell carcinoma.

We investigated the feasibility, safety, biological activity and therapeutic efficacy of adenovirus-mediated p53 gene transfer in patients with chemoradiation resistant advanced esophageal carcinoma. Eligible patients were not surgical candidates and had measurable, advanced squamous cell carcinoma of the esophagus that was resistant to chemoradiation therapy. On a 28-day cycle, intratumoral injections of Ad5CMV-p53 (INGN 201; ADVEXIN) were administered on days 1 and 3 at four dose levels (10 x 10(11) particles to 25 x 10(11) particles) and treated for up to five cycles. Ten patients received a total of 26 cycles with no dose-limiting toxicity. Administration of multiple courses was feasible and well-tolerated. Local tumor responses revealed stable disease in nine cases and progressive disease in one case. The overall responses were stable in six and progressive in four cases. Using polymerase chain reaction (PCR) analyses, gene transfer and p53 specific transgene expression were detected in tumor biopsy tissue from all patients. mRNA levels of p53, p21 and MDM2 increased in all but one case. Three patients showed absence of disease upon repeat biopsies. Substantial improvement in swallowing was observed in one patient with stenotic lesions. Intratumoral injection of Ad5CMV-p53 is safe, feasible and biologically active when administered in multiple doses to patients with esophageal cancer. Observations from this study indicate that this treatment results in local antitumor effects in chemoradiation resistant esophageal squamous cell carcinoma.

Adenocarcinoma↗

PubMed2006

[A case of esophageal arterial bleeding in which transcatheter arterial embolization was useful for hemostasis].

We report a case of hemostatic treatment by transcatheter arterial embolization (TAE) of the left gastric artery and a branch of the left bronchial artery for oozing hemorrhage in the lower esophagus, because of incomplete endoscopic hemostasis. A 52-year-old woman with systemic lupus erythematosus was previously admitted three times to our hospital for endoscopic treatment of hemorrhage in the lower esophageal lesions. The procedure of TAE for esophageal hemorrhage seems to be a useful treatment for cases of incomplete endoscopic hemostasis.

Arteries↗

PubMed2004

Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation.

Antiangiogenic factors are potent endothelial cell growth inhibitors that have been shown to inhibit angiogenesis in vitro and tumor growth in mice. We have demonstrated the synergistic antitumor effect of antiangiogenic genes (mouse angiostatin: pBLAST-mAngio; and mouse endostatin: p-BLAST42-mEndo XV) delivered to tumors by low-voltage electroporation in mouse colon 26 models. A synergistic antitumor effect was strongly suggested by in vivo tumor growth kinetics, as well as in survival studies with the mice. RT-PCR confirmed that the fragments of each gene were transferred by low-voltage electroporation in the tumor. Decreased microvessel density measurements in tumors also confirmed the efficacy of the synergistic antitumor effect of both genes. Significant growth inhibition was observed in mice treated with a 1:1 proportion of angiostatin and endostatin genes, and the order of the both genes transferred (first the endostatin gene, followed 1 week later by the angiostatin gene) had a profound inhibitory effect on tumor growth. These data suggest that in vivo delivery of antiangiogenic genes with low-voltage electroporation could be a possible therapeutic strategy for established solid tumors when both genes were applied in combination.

Angiogenesis Inhibitors↗

PubMed2004

Clonidine effects on all-night human sleep: opposite action of low- and medium-dose clonidine on human NREM-REM sleep proportion.

Norepinephrine (NE) is considered to play a permissive role in the occurrence of rapid eye movement (REM) sleep. Clonidine is an NE alpha-2-receptor agonist, which has been considered to act mainly on the autoreceptors of presynaptic noradrenergic neurons to reduce their release of NE. However, previous studies of clonidine effects on REM sleep have produced controversial results and the effects of clonidine remain uncertain. To clarify the pharmacological effects of clonidine on human sleep, the sleep electroencephalograms (EEG) recorded from 15 young normal subjects after a single administration of either a low (25 micro g) or medium (150 micro g) dose of clonidine were examined, and fast Fourier transformation (FFT) spectral analyses of the C3-A2 EEG were performed. Low-dose clonidine significantly increased the amount of REM sleep and decreased the amount of non-REM (NREM) sleep during the second one-third of the drug nights compared to the corresponding hours of baseline night recordings. In contrast, medium-dose clonidine significantly decreased REM and increased NREM on drug nights compared to baseline nights in the entire night. The opposite actions of low and medium doses of clonidine on NREM-REM proportion may indicate that low-dose clonidine mainly affects the alpha-2-receptors on locus coeruleus-NE neurons presynaptically, reducing the release of NE, whereas medium-dose clonidine acts more post-synaptically.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2003

Possible involvement of antitumor immunity in the eradication of colon 26 induced by low-voltage electrochemotherapy with bleomycin.

PURPOSE: The antitumor efficiency of electrochemotherapy using chemotherapeutic agents and high-voltage electric pulse has been reported. This study was done to define the precise nature of the involvement of antitumor immunity in the regression of tumor nodules in electrochemotherapy, and to evaluate the effectiveness of using low-voltage electroporation. METHODS: Balb/c mice and Balb/c nu/nu nude mice were inoculated subcutaneously with Colon 26 cells or Meth A cells. Electrochemotherapy using bleomycin and low-voltage electroporation (CUY21) was performed as a treatment against tumor nodules. RESULTS: Colon 26 tumors were eradicated in the mice given an intratumor (i.t.) injection of 500 microg bleomycin followed by treatment with electric fields ranging from 50 to 150 V/cm, with complete response rates ranging from 80% to 100%. The mice rejected inoculations of rechallenged Colon 26 cells, but not Meth A cells. In the Balb/c nu/nu nude mice, complete regression of the tumor was not seen after electrochemotherapy under the same therapeutic conditions that resulted in almost complete cure in the Balb/c mice. CONCLUSION: Our results suggest that the generation of T-cell-dependent, tumor-specific protective immunity might be involved in the process of tumor nodule regression in low-voltage electrochemotherapy.

Animals↗

PubMed2003

Spectral analysis of all-night human sleep EEG in narcoleptic patients and normal subjects.

To investigate the pathophysiology of narcoleptic patients' sleep in detail, we analysed and compared the whole-night polysomnograms of narcoleptic patients and normal human subjects. Eight drug-naive narcoleptic patients and eight age-matched normal volunteers underwent polysomnography (PSG) on two consecutive nights. In addition to conventional visual scoring of the polysomnograms, rapid eye movement (REM)-density and electroencephalograph (EEG) power spectra analyses were also performed. Sleep onset REM periods and fragmented nocturnal sleep were observed as expected in our narcoleptic patients. In the narcoleptic patients, REM period duration across the night did not show the significant increasing trend that is usually observed in normal subjects. In all narcoleptic patient REM periods, eye movement densities were significantly increased. The power spectra of narcoleptic REM sleep significantly increased between 0.3 and 0.9 Hz and decreased between 1.0 and 5.4 Hz. Further analysis revealed that non-rapid eye movement (NREM) period duration and the declining trend of delta power density in the narcoleptic patients were not significantly different from the normal subjects. Compared with normal subjects, the power spectra of narcoleptic NREM sleep increased in the 1.0-1.4 Hz and 11.0-11.9 Hz frequency bands, and decreased in a 24.0-26.9 Hz frequency band. Thus, increased EEG delta and decreased beta power densities were commonly observed in both the NREM and REM sleep of the narcoleptic patients, although the decrease in beta power during REM sleep was not statistically significant. Our visual analysis revealed fragmented nocturnal sleep and increased phasic REM components in the narcoleptic patients, which suggest the disturbance of sleep maintenance mechanism(s) and excessive effects of the mechanism(s) underlying eye movement activities during REM sleep in narcolepsy. Spectral analysis revealed significant increases in delta components and decreases in beta components, which suggest decreased activity in central arousal mechanisms. These characteristics lead us to hypothesize that two countervailing mechanisms underlie narcoleptic sleep pathology.

Adult↗

PubMed2003

Correlation between electroencephalography and heart rate variability during sleep.

It is known that autonomic nervous activities change in correspondence with sleep stages. However, the characteristics of continuous fluctuations in nocturnal autonomic nerve tone have not been clarified in detail. The study aimed to determine the possible correlation between the electroencephalogram (EEG) and autonomic nervous activities, and to clarify in detail the nocturnal fluctuations in autonomic nerve activities. Overnight EEGs and electrocardiograms of seven healthy males were obtained. These EEGs were analyzed by fast Fourier transformation algorithm to extract delta, sigma and beta power. Heart rate and heart rate variability (HRV) were calculated in consecutive 5-min epochs. The HRV indices of low frequency (LF), high frequency (HF) and LF/HF ratio were calculated from the spectral analysis of R-R intervals. The sleep stages were manually scored according to Rechtschaffen and Kales' criteria. Low frequency and LF/HF were significantly lower during non-rapid eye movement (NREM) than REM, and were lower in stages 3 and 4 than in stages 1 and 2. Furthermore, delta EEG showed inverse correlations with LF (r = - 0.44, P < 0.001) and LF/HF (r = - 0.41, P < 0.001). In contrast, HF differed neither between REM and NREM nor among NREM sleep stages. Detailed analysis revealed that correlation was evident from the first to third NREM, but not in the fourth and fifth NREM. Delta EEG power showed negative correlations with LF and LF/HF, suggesting that sympathetic nervous activities continuously fluctuate in accordance with sleep deepening and lightening.

Adult↗

PubMed2002

[Treatment of colorectal cancer--hepatic metastases].

The aim of this study was to evaluate the effect of the local therapy for colorectal liver metastases on overall survival. Seventy-two patients who had resected liver metastases from colorectal cancer during the period from 1982 to 2001 were evaluated for survival. There was no significant difference in overall survival by either surgical method for colorectal liver metastases or postoperative arterial infusion chemotherapy. However, the 5-year survival rate of resected metachronous liver metastases with postoperative arterial infusion chemotherapy was 44.9%, and that for patients with no extra hepatic metastases was 57.4%. Patients who have metachronous liver metastases from colorectal cancer should therefore be considered for postoperative arterial infusion chemotherapy. It is necessary to improve the outcome for cases that have extra hepatic metastases.

Chemotherapy, Adjuvant↗

PubMed2002

[Competitiveness in sports activities of the psychiatrically disabled].

In 2002, psychiatrically disabled athletes joined an historic first open game of volleyball at the national sports games for the disabled. Compared to the competitive sports and Paralympic Games that physically and intellectually disabled athletes have participated in, activities for the psychiatrically disabled have not been well-organized. In this paper, we examine a number of problems that have arisen when the psychiatrically disabled joined competitive sports games. We identify two major characteristics of the psychiatrically disabled of particular relevance when organizing competitive sports activities. First, all psychiatrically disabled athletes need treatment of their individual diseases. For example, psychiatric symptoms fluctuate markedly over time, unlike physical or intellectual disabilities, whose symptoms are much more stable. Exacerbations of psychiatric illness are also likely to occur due to the stresses of competitiveness. Second, psychiatric disabilities are manifestations of disorders in the central nervous system, which makes the classification of psychiatric disabilities less straightforward than classification of the physically disabled. These two characteristics require special attention when organizing competitive athletic challenges that include the psychiatrically disabled. However, promoting sports activities that include the psychiatrically disabled would be expected to reduce the prejudice toward and subsequent social disadvantages experienced by psychiatric patients. Thus, with careful planning to successfully integrate psychiatrically disabled athletes, we expect increased promotion of such sports activities in the future.

Competitive Behavior↗

PubMedDate not supplied

Clinical outcome of a novel photodynamic therapy technique using acridine orange for synovial sarcomas.

Synovial sarcoma (SS) is one of common malignant soft-tissue tumors and is encountered most commonly in children and young adults. It frequently involves or invades major neurovascular structures and bones, and its local recurrence rate after simple resection has been reported to be as high as up to 80%. Because major nerves and vessels, as well as an adequate amount of bone, must be preserved to restore excellent limb function in cases of SS, a surgical technique entailing a low risk of local recurrence is needed. Based on the findings of recent experimental studies conducted by us using a mouse osteosarcoma model, we developed a novel therapeutic technique for SS, consisting of reduction surgery followed by photodynamic therapy using acridine orange (AO-PDT), with or without X-ray irradiation at 5 Gy. A preliminary study revealed that low-dose X-rays also excite AO like photons. After an initial study on cell cultures, this novel technique was applied to six cases of SS. A follow-up of the subjects to determine the clinical outcome revealed that none of the cases treated by AO-PDT, including the four cases treated by additional 5 Gy irradiation and the two cases not receiving any radiation, showed any evidence of recurrence or local/systemic complications during the follow-up period of 19-51 months after the surgery. Therefore, we believe that AO-PDT with 5 Gy irradiation may be an excellent novel therapeutic modality with reduction surgery to salvage excellent limb function in SS involving major nerves and vessels or bones.

Acridine Orange↗

PubMedDate not supplied

Effect of the anastomosis-site after Billroth I gastrectomy on the motility of the remnant stomach.

BACKGROUND/AIMS: Gastric emptying, in healthy individuals, is a highly regulated process, and plasma cholecystokinin plays a major role in its feedback regulation. However, the hormonal regulation of postprandial gastric emptying of the remnant stomach after distal gastrectomy with Billroth I reconstruction procedure has not been well described. The aim of this study is to characterize the gastroduodenal motility and gastric emptying of the two anastomosis-methods after Billroth I gastrectomy, while assessing the effect of cholecystokinin on the motility of the remnant stomach. METHODOLOGY: Two types of anastomosis (end-to-end, side (posterior wall)-to-end) after Billroth I gastrectomy were measured with strain gauge force transducers, and evaluated as to gastroduodenal motility, gastric emptying, gastrointestinal hormones (cholecystokinin, gastrin), and blood glucose associated with food administration. RESULTS: Remnant stomachs with side-to-end anastomosis showed superior motility as compared to those with end-to-end anastomosis. Plasma cholecystokinin was higher in the end-to-end anastomosis group. No differences as to gastric emptying, levels of plasma gastrin, or blood glucose were observed between the two groups. CONCLUSIONS: Plasma cholecystokinin may explain the difference in motility index between the two groups.

Animals↗

PubMedDate not supplied

Inhibitory remnant stomach motility by duodenal distention after B-I gastrectomy.

BACKGROUND/AIMS: Although control of gastric motility is a highly regulated process, B-I gastrectomy causes accelerated gastric emptying. We found few reports so far concerned with the mechanical effect of balloon distention of the duodenum on the remnant stomach in B-I dogs. METHODOLOGY: Four weeks after conventional distal gastrectomy with B-I reconstruction procedure, a balloon was inserted into the duodenum, and strain gauge force transducers (SGTs) were sutured onto the wall of the gastric remnant and duodenal serosa in beagles. After a two-week postoperative recovery period, gastro-duodenal motility was measured with SGTs prior to distention, during distention, and after evacuation of the balloon. The motility index (MI) was calculated every 30 minutes. RESULTS: Upon duodenal distention with 4 mL of water, motility of gastric remnant was significantly inhibited, however, no reduction in duodenal MI was observed. The response was maintained for as long as duodenal distension continued. Ninety minutes after evacuation of the balloon, MI returned to predistension levels. Increased plasma levels of cholecystokinin (CCK) were observed upon distention of the duodenal balloon. CONCLUSIONS: Motility of the remnant stomach in B-I dogs was inhibited by duodenal distension. Increased levels of plasma CCK during distention might play a role in this feedback mechanism.

Animals↗

PubMedDate not supplied

Clinical trial of photodynamic therapy using acridine orange with/without low dose radiation as new limb salvage modality in musculoskeletal sarcomas.

Most patients with musculoskeletal sarcoma do not recover satisfactory limb function after limb salvage surgery. To achieve satisfactory improvement of limb function, we developed a unique surgical modality of photodynamic therapy using acridine orange (AO-PDT) and clinically applied it to patients with musculoskeletal sarcomas. Ten patients with primary musculoskeletal sarcomas were enrolled in the study. Of these, 6 had primary malignant soft tissue sarcoma and 4 had primary malignant bone tumor. In the AO-PDT procedure, intralesional or partially marginal tumor excision was initially conducted and microscopic curettage of the remnant tumor, which emitted green fluorescence under blue excitation after local administration of 1microg/ml AO solution, was performed using a fluorescence surgical microscope. Subsequently, blue light illuminated there for 10 minutes. The surgical wound was closed, followed by immediate X-ray irradiation of the resected area with 5 Gy in 5 out of 10 patients to enhance the effect of AO-PDT. The follow-up of the patients ranged from 24 to 48 months. All the patients (AO-PDT alone: 5, AO-PDT with 5-Gy radiation: 5) are alive; only one patient showed local recurrence of the tumor. The recurrence rate was 10%. None of the 5 patients treated by AO-PDT with radiation developed local tumor recurrence. The limb function in all the patients, except for one, recovered to the level before surgery. None of the patients clinically showed any local or systemic complications. AO-PDT may be a promising new limb salvage modality for preservation of excellent limb function in patients with musculoskeletal sarcoma.

Acridine Orange↗

PubMedDate not supplied

Generation of antitumor immunity against large colon tumors by repeated runs of electrochemotherapy.

BACKGROUND/AIMS: Electrochemotherapy, which uses two parallel electrodes for delivery of electric pulses, may be useful for treatment of tumor nodules. However, in clinical fields, tumors that are larger than the distance between the two electrodes are frequently observed, and it would be difficult in such cases to deliver electric pulses to the tumor. This study was done to define how host antitumor immunity is generated by repeated electrochemotherapy treatments, and whether it is associated with regression of even large tumor nodules. METHODOLOGY: Balb/c mice and Balb/c nude mice were inoculated subcutaneously with colon 26. Electrochemotherapy using bleomycin and electroporation (CUY21) was administered as a treatment for tumor nodules that were larger than the distance between the electrodes. RESULTS: In Balb/c mice, growth of large tumors at the start of treatment is not inhibited by a single electrochemotherapy treatment. However, complete tumor regression was obtained through repeated electrochemotherapy treatments. No tumor cure was observed among Balb/c nude mice under the same therapeutic conditions. Inflammatory cells were accumulated in the tumor tissue seven days after the third electrochemotherapy treatment. CONCLUSIONS: Repeated electrochemotherapy is a promising treatment, even for large tumors, such as are usually encountered in clinical practice, by generating T-cell dependent, antitumor immunity.

Animals↗

PubMedDate not supplied

Evaluation of Ki-67 and p53 expression in primary and repeated liver metastases of GISTs.

There has been little research evaluating changes related to tumor cell proliferation between primary and metastatic tumors of gastrointestinal tumors in the same case. We herein report the case of a 50-year-old woman with a gastric gastrointestinal stromal tumor (GIST), who developed metastatic liver tumors three times in the 7 years after proximal gastrectomy for GIST. The primary and all the metastatic liver tumors, except the second, showed fascicular/storiform architecture and the short spindle cell type. The diffuse epithelioid cell proliferation was observed in the second metastatic liver tumor. Although the immunostaining pattern with respect to GIST differentiation markers had been preserved in the primary tumor as well as in all of the metastatic tumors, the latter showed weaker positivity of both Ki-67 and p53 than the primary GIST. The primary tumor showed diffuse positive p53, and the highest value of Ki-67 labeling index (LI) among them. The metastatic liver tumors showed focal, negative or sporadic positive appearances of p53, however, Ki-67 LI were scattering among them. Immunohistochemical assessment of Ki-67 LI and p53 might be useful for evaluating changes related to tumor cell proliferation between primary and metastatic tumors of GISTs.

Biomarkers, Tumor↗

PubMedDate not supplied

High en bloc resection rate achieved by endoscopic mucosal resection with IT knife for early gastric cancer.

BACKGROUND/AIMS: Circumferential endoscopic mucosal resection (EMR) around lesions performed by an insulation-tipped diathermic knife (IT knife) increases en bloc resection rates, suggesting the possibility of expanding indications for EMR. METHODOLOGY: Clinical outcome of EMR performed by IT knife under general anesthesia was evaluated for 26 patients with 29 early gastric cancer. RESULTS: Successful en bloc resection rates obtained by the IT knife were 100, 87.5, 90.0 and 100% for lesions < or =10 mm in size, 11-20 mm, 21-30 mm, and > or =31 mm, respectively. They were significantly higher with the IT knife than those obtained by the conventional method (IT knife method: 93.1% vs. conventional method: 28.5%, p<0.0001). Two lesions were lateral margin positive, and in three cases invasion of lesions was observed as deep as the submucosa. Distal, total, and proximal gastrectomy with D2 lymphadenectomy, respectively, was provided in 3 cases; however, no lymph node involvement was found in any of the resected specimens. Bleeding and perforation were observed in 3 cases, respectively, however, no additional surgical treatment was required for these patients. CONCLUSIONS: EMR by means of the IT knife under general anesthesia can be performed safely and adequately. It is a useful treatment modality for early gastric cancer.

Aged↗