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Biomedical subjects

Takeshi Okuda

Publications and source records attributed to Takeshi Okuda.

At least 19 recordsLinked to original sources

Factor XIII therapy of anastomotic leak, and circulating growth factors.

Wound healing is far more rapid in the gastrointestinal tract than in the skin. Once dehiscence of a surgical anastomosis in the gastrointestinal tract occurs, the high collagenase activity in the gastrointestinal tract may delay wound healing and promote the formation of a nonhealing fistula. Because factor XIII promotes cross-linking of fibrin during the early phase of wound healing, we investigated the effect of factor XIII concentrate on 16 anastomotic leaks and a nonhealing fistula. A 240-U dose of factor XIII concentrate (Fibrogammin P) was administrated intravenously for 5 days. Factor XIII activity and plasma levels of epidermal growth factor (EGF), transforming growth factor (TGF)-beta, and interleukin-6 were measured before treatment and 1 day and 7 days after the end of treatment. Clinical outcomes were evaluated on the basis of the findings of contrast radiography, computed tomography, and drainage volume. Improvement relevant to the therapy was observed in 15 cases (88.2%). Factor XIII activity increased to more than 70% of the normal value in 11 cases (64.7%) but remained at 40% to 70% of the normal value in 6 cases (35.3%). Plasma EGF and TGF-betalevels increased in patients with improvement but were unchanged in patients without improvement. Our findings suggest that factor XIII significantly accelerates wound healing of anastomotic leaks and nonhealing fistulas by increasing circulating growth factors after systemic administration.

Aged↗

Laparoscopic surgery for gastric cancer: 5 years' experience.

The purpose of this study was to clarify the safety and value of laparoscopic surgery for gastric cancer. This retrospective study involved 101 patients with gastric cancer treated with laparoscopic surgery at the Nippon Medical School Hospital from February 2001 through July 2005. The following variables were evaluated: age, sex, comorbid conditions, tumor size, location, gross type, histological type, depth of wall invasion, and presence or absence of lymph node metastasis. The surgical variables investigated included operating time, blood loss, postoperative complications, and length of postoperative stay. Mean tumor diameter was 24.1 +/- 18.4 mm, and most tumors were located in the lower third of the stomach. Endoscopic examination revealed that 98 of the tumors were early gastric cancers. The mean operation time was 255 +/- 74 min, and mean blood loss was 128 +/- 162 g. Local gastrectomy without lymphadenectomy was performed in 13 cases, and pylorus-preserving gastrectomy with perigastric lymphadenectomy was performed in 16 cases. Distal gastrectomy with systemic lymphadenectomy was performed in 56 cases. Proximal or total gastrectomy with lymph node dissection for tumors located in the upper half of the stomach was performed in 16 cases. The mean postoperative hospital stay was 13.3 +/- 7.6 days. No patients died during the admission. Postoperative surgical complications occurred in 10 patients (10%) and consisted of anastomotic bleeding in 3 patients, pneumohypoderma in 1 patient, and remote infection in 6 patients. The only medical complication was a stroke in 1 patient. We conclude that laparoscopy-assisted gastrectomy is a safe and useful operation for most early gastric cancers. If patients are selected properly, laparoscopy-assisted gastrectomy can be a curative and minimally invasive treatment for gastric cancer.

Adult↗

[Surgical treatment for cerebrospinal fluid rhinorrhea from plaum sphenoidale].

A transcranial approach is frequently employed for the closure of cerebrospinal fluid (CSF) rhinorrhea, occurring after skullbase surgery or associated with anterior skull base fracture. However, the site of CSF rhinorrhea is usually most distant from the site of craniotomy and, because securing of an adequate operative field is difficult, elimination of this type of CSF rhinorrhea tends to be insufficient. We have attempted to reconstruct the anatomical structures with an extended transsphenoidal approach for a case with CSF rhinorrhea from the planum sphenoidale, and have succeeded in achieving a more physiological and reliable elimination of CSF rhinorrhea. This technique is presented, with a representative example.

Cerebrospinal Fluid Rhinorrhea↗

Post-exposure administration of edaravone attenuates noise-induced hearing loss.

We investigated the effects of the antioxidant edaravone against acoustic trauma in guinea pigs. Edaravone (1.722 x 10(-2) M) was infused into the right ear by an osmotic pump, and the left ear was untreated for control. Animals received edaravone 9 h before (-9 h group, n = 7) and 9 h (+9 h group, n = 8), 21 h (+21 h group, n = 7) and 33 h (+33 h group, n = 4) after 3-h exposure to 130-dB noise. Seven days after noise exposure, we examined the shift in auditory brainstem response thresholds and histopathologic characteristics of the sensory epithelia. The smallest shift in auditory brainstem response threshold and smallest proportion of missing outer hair cells were observed in the +9 h group. This result was supported by immunohistochemical analysis of 4-hydroxy-2-nonenal. Our data suggest that edaravone may be clinically effective in the treatment of acoustic trauma, especially if given within 21 h of noise exposure.

Aldehydes↗

Inhibition of caspases alleviates gentamicin-induced cochlear damage in guinea pigs.

The efficacy of caspase inhibitors for protecting the cochlea was evaluated in an in vivo study using guinea pigs, as the animal model system. Gentamicin (12 mg/ml) was delivered via an osmotic pump into the cochlear perilymphatic space of guinea pigs at 0.5 microl/h for 14 days. Additional animals were given either z-Val-Ala-Asp (Ome)-fluoromethyl ketone (z-VAD-FMK) or z-Leu-Glu-His-Asp-FMK (z-LEHD-FMK), a general caspase inhibitor and a caspase 9 inhibitor, respectively, in addition to gentamicin. The elevation in auditory brain stem response thresholds, at 4, 7, and 14 days following gentamicin administration, were decreased in animals that received both z-VAD-FMK and z-LEHD-FMK. Cochlear sensory hair cells survived in greater numbers in animals that received caspase inhibitors in addition to gentamicin, whereas sensory hair cells in animals that received gentamicin only were severely damaged. These results suggest that auditory cell death induced by gentamicin is closely related to the activation of caspases in vivo.

Administration, Topical↗

Postoperative changes in body composition after gastrectomy.

Nutritional status is one of the most important clinical determinants of outcome after gastrectomy. The aim of this study was to compare changes in the body composition of patients undergoing laparoscopy-assisted gastrectomy (LAG), distal gastrectomy (DG), or total gastrectomy (TG). Total body protein and fat mass were measured by performing a multifrequency bioelectrical impedance analysis using an inBody II machine (Biospace, Tokyo, Japan) in 108 patients (72 men, 36 women) who had undergone LAG (n=24), DG (n=39), or TG (n=45). Changes between the preoperative data and results obtained on postoperative day 14 and 6 months after surgery were then evaluated. The mean preoperative body weight of the subjects was 57.6+/-10.7 kg, the mean body mass index was 22.5+/-3.4 kg/m(2), and the mean fat % was 24%+/-7%. In the immediate postoperative period (14 days), the body weight loss in the LAG group was significantly lower than in the DG and TG groups (2.5+/-0.9 kg vs. 3.5+/-1.8 kg and 4.0+/-1.9 kg, respectively; P < 0.0001). The body composition studies demonstrated a loss of total body protein rather than fat mass. Six months after surgery, body weight was not significantly different from preoperative values in the LAG and DG groups (-1.2+/-3.8 kg and -1.8+/-4.7 kg, respectively), but had decreased by 8.9+/-4.9 kg in the TG group (P=0.0003). A body composition analysis revealed a loss of fat mass in the DG and TG groups. The patients who underwent gastrectomy lost body protein mass during the early postoperative period. The type and extent of surgery has an effect on long-term body mass and composition. Bioelectric impedance analysis can be used to assess body composition and may be useful for nutritional assessment in patients who have undergone gastrectomy.

Aged↗

Spurt bleeding from a calcificated gastrointestinal stromal tumor in the stomach.

Calcifications within primary gastrointestinal tumors are rare. Gastrointestinal stromal tumor (GIST) is an unusual nonepithelial tumor that develops in the gastrointestinal tract. In this paper we describe a case of spurt bleeding from a calcificated GIST in the stomach successfully treated by partial gastric resection. A 77-year-old man was admitted for chest discomfort and loss of consciousness. Endoscopic examination revealed spurt bleeding from the top of the submucosal tumor. No other lesions or points of bleeding were found in the stomach. Emergency partial gastrectomy was performed, and the stomach was closed. The cut surface of the tumor had a firm, solid, whitish-gray parenchyma with patchy calcification. Microscopic observation revealed a profusion of spindle-shaped tumor cells with calcification growing from the gastric muscular propria to the submucosa. The cells exhibited low mitotic activity and no prominent signs of nuclear atypia. Immunohistochemical staining of the tumor demonstrated positive reactivity for CD34, KIT, and vimentin, but negative reactivity for alpha-smooth muscle actin, desmin, and S-100 protein. Tumor cells positive for Mib-1 were rare. The diagnosis of the tumor was established as GIST.

Aged↗

Successful long-term deep brain stimulation for hemichorea-hemiballism in a patient with diabetes. Case report.

The authors report a case of hemichorea-hemiballism (HC-HB) that was successfully treated using deep brain stimulation (DBS). A 65-year-old right-handed man exhibited a sudden onset of right HC-HB without a diabetic coma. At admission T1-weighted magnetic resonance (MR) images revealed a high-intensity signal in the left striatum, contralateral to the patient's involuntary movements. The HC-HB continued for 5 months after onset of the condition despite medical treatment and a decreased intensity of the signal on T1-weighted MR images. The patient underwent placement of a quadripolar DBS electrode in the left thalamus, including the left ventral oralis (VO) anterior and posterior nuclei (the VO complex). Postoperatively, the right-sided HC-HB disappeared rapidly during electrical stimulation and there were no neurological deficits. The authors demonstrate that DBS can be an effective treatment for medically refractory HC-HB. This is the first case of HC-HB that has been successfully treated with DBS.

Aged↗

The effect of hypergravity on the inner ear: CREB and syntaxin are up-regulated.

cDNA microarray analysis of differential mRNA expression in the rat inner ear under hypergravity identified 20 up-regulated and 2 down-regulated genes. The results demonstrated that various response and/or adaptation processes occur at the level of the peripheral organs. From among the genes assessed by microarray, up-regulation of CREB and syntaxin was confirmed by real time PCR and these two molecules were found to be immunocytochemically localized in the primary afferent neurons. Since CREB is believed to be involved in the formation of long term memory, and syntaxin is known as one of the synaptic molecules involved in the exocytosis of synaptic vesicles, the up-regulation of CREB and syntaxin may reflect synaptic plasticity occurring in the peripheral vestibular system.

Animals↗

The clinical free radical scavenger, edaravone, protects cochlear hair cells from acoustic trauma.

It is known that reactive oxygen species have toxicity to the cochlea. We investigated the effect of edaravone, a free radical scavenger for clinical use, on the cochleae of guinea pigs subjected to acoustic trauma. We assessed auditory brainstem response (ABR) thresholds to evaluate cochlear function and observed the sensory epithelium. After noise exposure (130 dB SPL, 3 h), we observed that the auditory brainstem response threshold shift in edaravone-treated ears was significantly less than that in untreated ears. This result suggests that edaravone protected the cochleae from acoustic trauma.

Animals↗

Inflammation of the gastric remnant after gastrectomy: mucosal erythema is associated with bile reflux and inflammatory cellular infiltration is associated with Helicobacter pylori infection.

BACKGROUND: Controversy exists concerning the role of bile reflux and Helicobacter pylori ( H. pylori) infection in the development of inflammation of the gastric remnant after gastrectomy. This study was designed to investigate association of bile reflux and H. pylori infection or both with inflammatory changes in the gastric remnant. METHODS: A questionnaire on GI symptoms was returned by 200 gastrectomy patients, and 24-h bilirubin monitoring in the gastric remnant was performed on 55 patients with Bilitec 2000. Upper GI endoscopy evaluated reflux gastritis in the gastric remnant, and the presence of H. pylori infection and chronic, active inflammatory cellular infiltration in the biopsy specimens were examined microscopically with the updated Sydney system. RESULTS: No difference in the incidence of GI symptoms was observed among individual gastrectomy patients. Bile reflux was lower in patients who had undergone a gastrectomy with jejunal interposition, a pylorus-preserving gastrectomy, and a gastrectomy with Roux-Y anastomosis than those who had undergone a Billroth-II (B-II) anastomosis ( P < 0.05). Endoscopy showed positive correlation between mucosal erythema and bile reflux ( P < 0.001). No correlation was observed between the mucosal erythema and chronic and active inflammatory cellular infiltration. Infection of H. pylori correlated with chronic and active inflammatory cellular infiltration ( P < 0.001). Bile reflux did not correlate with the severity of chronic and active inflammatory cellular infiltration or H. pylori infection. CONCLUSIONS: Bile reflux into the gastric remnant was observed by Bilitec 2000. Mucosal erythema and chronic, active inflammatory cell infiltration in the gastric remnant after gastrectomy may be caused by bile reflux or H. pylori infection, respectively.

Bile Reflux↗

Novel method for homogeneous gene transfer to the inner ear.

Viral vectors are widely used in gene therapy due to their efficiency. In this paper we describe a novel method for transfecting the whole inner ear of a guinea pig using adenoviral vectors. Very small perforations are made in both the cochlea and lateral semicircular canal, into which 50 microl of adenoviral suspension (8.9x10(8) plaque forming unit (PFU)/ml) is gently infused. Any excess suspension flows out through the perforation in the semicircular canal and therefore makes no contact with the central nervous system. Our method can therefore be utilized to perform homogeneous gene transfer and may eliminate any effects on other organs, such as the contralateral ear.

Adenoviridae↗

Inner ear changes with intracochlear gentamicin administration in Guinea pigs.

OBJECTIVES/HYPOTHESIS: Transtympanic administration of gentamicin is reported to be a useful treatment for vertigo in such conditions as Meniere's disease, and determining appropriate clinical dosage of gentamicin is difficult. The authors examined the relation between gentamicin dosages and inner ear function in guinea pigs. STUDY DESIGN: This study is a basic science project designed to examine cochlear and vestibular function in animal models. METHODS: Various concentrations of gentamicin solution were infused into the right inner ear of guinea pigs by osmotic pumps. Caloric nystagmus as a marker of vestibular function and the change in auditory brainstem response (ABR) threshold as a marker of cochlear function were observed. RESULTS: After 14 days of treatment, high gentamicin concentrations of 40 mg/mL caused canal paralysis and a rapid shift in ABR threshold. Animals exposed to low gentamicin concentrations of 4 mg/mL showed no obvious change in either vestibular or cochlear function. Animals exposed to moderate gentamicin concentrations of 12 mg/mL showed a moderate shift in ABR threshold and caloric malfunction. Histopathological examination revealed that after 14 days of treatment with 40 mg/mL gentamicin, severe cytoplasmic damage occurred in both vestibular and cochlear end organs. In animals treated with 12 mg/mL gentamicin, hair cells remained in the cochlear third turn and ampulla of the lateral semicircular canal. CONCLUSION: The authors established an animal model that showed the moderate damage of inner ear with moderate-dose gentamicin. The study results indicated that the appropriate administration of gentamicin could establish a stable effect on the inner ear. It may be important to select the protocol that delivers a stable dosage of gentamicin to treat patients with Meniere's disease safely and effectively.

Administration, Topical↗

Cochlear administration of adenosine triphosphate facilitates recovery from acoustic trauma (temporary threshold shift).

BACKGROUND: Adenosine triphosphate (ATP) has often been used in the treatment of acoustic trauma although evidence supporting its clinical use was lacking. The aim of this study was to evaluate the chronic effects of ATP on acoustic trauma in guinea pigs. METHODS: We infused ATP into the perilymph of the guinea pig cochlea concurrently with intense noise exposure to investigate the effect of ATP on the process of recovery after acoustic trauma. We assessed auditory brainstem response (ABR) thresholds to evaluate cochlear function. RESULTS: After noise exposure (120 dB SPL, 5 h), ABR thresholds showed an increase of approximately 50 dB SPL that returned to normal after 14 days. Cochlear function in ATP-treated ears recovered more quickly than in control ears. The effect of ATP was inhibited by the administration of the ATP receptor antagonist: pyridoxal- phosphate-6-azophenyl-2',4'-disulfonic acid. CONCLUSION: These results suggest that ATP mitigates the effects of noise trauma through the ATP receptor.

Adenosine Triphosphate↗

[Clinical significance of a standardized clinical pathway in gastrectomy patients].

UNLABELLED: In traditional practice patterns, physicians take care of all clinical decisions, such as diagnosis, treatment, and recovery. In the Nippon Medical School Hospital a clinical pathway for distal gastrectomy patients, recorded as a post-operative care map, was introduced in August 2000. In January 2001 the post-operative management was analyzed and standardization of practice was carried out with printed order sets, such as drugs and infusion solutions. The aim of this study was to evaluate the clinical significance of the clinical pathway for gastrectomy patients by employing standardized postoperative management and printed order sets. PATIENTS AND METHODS: From January 2001 to December 2001, 87 patients underwent distal (43), total (28), proximal (7) and partial gastrectomy (9) for gastric cancer (stage IA: 47, IB: 9, II: 7, IIIA: 8, IIIB 2, IV: 10) and gastrointestinal stromal tumor (4). These patients were randomly assigned to either the main building or the east building of our hospital. In the main building 38 patients were looked after using traditional practice (control group). In the east building 47 patients were looked after according to the clinical pathway (path group) and 2 patients were excluded from the path group because of neo-adjuvant chemotherapy and severe heart failure. Aspects of the patients' outcomes, including length of stay, the first day of the diet, morbidity, and medical costs, were compared between the path group and the control group. All data were expressed as means+/-standard deviation. Statistical analyses were made using Student t-test, Mann-Whitney U-test, and chi(2) test, and the 5%level was chosen for statistical significance. RESULTS: The length of the hospital stay was 27.1+/-10.0 and 40.8+/-26.1 days (p<0.005) and the length of post-operative stay was 18.1+/-9.5 and 28.2+/-22.3 days (p<0.01) in the path group and the control group, respectively. The post-operative day when the diet was started for the path and control groups was 6.8+/-8.9 and 8.2+/-7.2, respectively; however, the length of the intravenous infusion for the two groups was 11.8+/-1.1 and 16.5+/-1.2 days (p<0.01), respectively. There was no statistically significant difference in the morbidity rate between the path group (3/47) and the control group (5/38). The total cost was 1,502,587 yen +/-41,650 in the path group and 1,932,197 yen +/-131,030 in the control (p<0.001). CONCLUSION: A clinical pathway for gastrectomy patients proved useful to optimize their postoperative care, including medication management and diet education. It is suggested that the implementation of a standardized clinical pathway for gastrectomy patients reduced the length of the hospital stay and the medical costs.

Critical Pathways↗

[Internet survey of the relationship between vertigo and stress].

We studied the relationship between vertigo and stress, using an internet survey. A questionnaire posted on our homepage quantified and measured 4 categories: cause of anxiety, behavioral characteristics, mean of relaxation, and frequency of vertigo. There were 6065 responses. Scores for the cause of anxiety were significantly greater and scores of means of relaxation were less in older than younger respondents. Scores for the cause of anxiety and behavioral characteristics were singificantly greater in more frequent than less frequent vertigo. Scores for means of relaxation were less in frequent vertigo. These findings indicate an intimate relationship between the onset of vestibular disorder and stress.

Adult↗

[A case report of tuberculous meningitis: limits of detection using polymerase chain reaction (PCR) and treatments].

A 40-year-old man with intractable meningitis was transferred to our hospital 6 weeks after onset. On admission, he showed consciousness disturbance, meningeal signs and right oculomotor nerve palsy. MRI demonstrated prominent cisternal enhancement and hydrocephalus. We suspected tuberculous meningitis as the diagnosis, and treated with antituberculotics, though he died of midbrain infarction day 11 of the treatment. Before and during the admission, bacterial cultures, PCR, smear examination of cerebrospinal fluid(CSF) were repeated. But no evidence of tuberculosis was obtained. Cultures of the brainstem fragments detected mycobacterium, which was finally confirmed by a PCR method after his death. PCR provides a rapid and reliable diagnosis of tuberculous meningitis, although there is a potential for false-negative. Thus the clinical, radiological and CSF findings should be stressed. Corticosteroids treatment should be considered in cases with ischemic lesions.

Adrenal Cortex Hormones↗