Biomedical subjects

N Tokunaga

Publications and source records attributed to N Tokunaga.

At least 37 records · Page 2Linked to original sources

PubMed1999

Coagulation/fibrinolysis disorder in patients with severe preeclampsia.

We investigated coagulation/fibrinolysis parameters in 50 patients with severe preeclampsia. The coagulation and clinical indices in patients with severe preeclampsia were 1.595 and 1.414, respectively. These indices show a strong correlation between the clinical status and coagulation/fibrinolysis abnormalities. Among patients with severe preeclampsia, a significant decrease in antithrombin (AT) (p = 0.002) and a significant increase in plasmin inhibitor complex (PIC) (p = 0.002), D-dimer (p < 0.05), and thrombin-antithrombin complex (TAT) (p = 0.001) were observed in cases terminated by cesarean section compared with those cases of vaginal delivery. There was no significant difference in platelet count (Plt), however, deltaPlt (the difference between platelet counts in early gestation and before delivery) was significantly larger (p < 0.05) in cases that ended in cesarean section. Furthermore, among cases terminated by cesarean section, a significant increase in PIC (p < 0.01) was observed when pregnancies were terminated because of maternal factors compared with those terminated because of fetal factors. These results suggest that (1) even in patients with severe preeclampsia, vaginal deliveries can be successful when they display a less hypercoagulable state; (2) a decrease in Plt during pregnancy may be a predictive marker for the termination of pregnancy; and (3) an excessive hypercoagulable state in patients with severe preeclampsia may be associated with the termination of pregnancy, especially when there is an aggravation of maternal factors.

Adult↗

PubMed1999

Dehydroepiandrosterone sulphate promotes hyaluronic acid-induced cervical ripening in rabbits.

Hyaluronic acid (HA) stimulates the synthesis of interleukin (IL) 8, while dehydroepiandrosterone sulphate (DHEA-S) induces the expression of IL-8 and its receptor in the human cervical fibroblast. This has led us to investigate the effect of DHEA-S on HA-induced cervical ripening. Experiments were performed in pregnant rabbits using vaginal suppositories containing 1 mg HA, 30 mg DHEA-S, 30 mg DHEA-S + 0.1 mg HA, 30 mg DHEA-S + 1 mg HA, and 500 microl Witepsol-50 base (control). The effects were evaluated by measuring collagenase, gelatinase and elastase activities, water content, neutrophil infiltration, relative collagen concentration and histological assessment. The activities of collagenase, gelatinase and elastase were significantly increased in rabbits treated with DHEA-S + 1 mg HA compared with rabbits treated with DHEA-S + 0.1 mg HA (P < 0.009, P < 0.001, P < 0.009 respectively). Water content was markedly increased in rabbits treated with DHEA-S + 1 mg HA compared with DHEA-S + 0.1 mg HA treatment (P < 0.05). Neutrophil infiltration was markedly increased, while relative collagen concentration was significantly decreased with DHEA-S + 1 mg HA compared with the DHEA-S + 0.1 mg HA approach (P < 0.001, P < 0.002). The histology of cervices treated with DHEA-S + 1 mg HA showed the density of collagen to be markedly decreased, and collagen fibres irregularly separated. Increased vascularity with massive dilatation of blood vessels was also observed in these rabbits. We conclude that DHEA-S upregulates the HA-induced cervical ripening process.

Animals↗

PubMed1999

Induction of hypercoagulability condition by chronic localized cold stress in rabbits.

To evaluate the effect of cold-induced stress on renal and hepatic blood flow and coagulation parameters, rabbits' soles were exposed to ice pad (0 degrees C). Renal and hepatic blood flow was measured after 1 h and 15 days of cold stress. Coagulation parameters (0, 8th and 15th days of stress) and histological studies were performed. Renal and hepatic blood flow was significantly reduced after cold-stress. Decreased platelet count, antithrombin III (AT III) activity, increased fibrinogen (Fbg) level, shortened activated partial thromboplastin time (aPTT) and prothrombin time (PT) was found after 8 and 15 days of cold-stress. Histology showed enlarged glomeruli with fibrin deposition in kidney, ischemic changes and fibrin deposition in liver and hemorrhagic necrosis in adrenal cortex. We conclude that undesirable localized cold induced sympathetic stimulation in daily life may be a predisposing factor for coagulopathy.

Animals↗

PubMed1998

Urinary trypsin inhibitor suppresses vascular smooth muscle contraction by inhibition of Ca2+ influx.

Urinary trypsin inhibitor (UTI) and its precursor form inter-alpha trypsin inhibitor (ITI) are present in plasma. To determine the action of UTI on blood vessels, we performed isometric vascular muscle contraction tests, microcirculation studies and measurement of cytosolic free Ca2+ in vascular smooth muscle cells. An isometric vascular muscle contraction test showed that the contractions stimulated by endothelin-1 or norepinephrine were suppressed in the presence of UTI, and that the contractions were not inhibited in the presence of ITI. The microcirculation study showed that the contraction of mesenteric arterioles of WKY rats induced by norepinephrine were inhibited by treatment of UTI, and that they did not alter by treatment of ITI. Pre-incubation of UTI, but not ITI, with vascular smooth muscle cells inhibited the increase of cytosolic free Ca2+ induced by endothelin-1 or norepinephrine. Cell-binding study by biotinylated UTI showed that vascular smooth muscle cells have specific binding site for UTI, but not for ITI. We propose that circulating UTI converted from ITI has a regulatory effect on local vascular tone by regulation of Ca2+ influx into smooth muscle cells.

Animals↗

PubMed1998

Anemia in patients with colorectal cancer.

Although anemia is one of the signs of colorectal cancer, the relationships between histological findings and hematological findings other than hemoglobin level have not been adequately investigated. We investigated the relationship between hematological findings, serum iron, and histological findings in 358 patients (207 men and 157 women) with colorectal cancer. Their mean (+/-SD) ages were 64.3 +/- 12.4 and 63.8 +/- 13.3 years. A hemoglobin level of less than 10 g/dl was the criterion for anemia, and 20.8% of the men and 25.8% of the women met this criterion. Univariate analysis showed that carcinoma of the cecum, ascending colon, and transverse colon; large-size carcinoma, invasion beyond the proper muscle layer; positive lymph node metastasis: and clinical stage (Dukes' B, C, and D) were factors associated with high incidence of anemia. Histological type did not affect the hematological findings. Multivariate analysis showed that age, tumor site, and tumor size were significant factors related to anemia. Depth of invasion, the presence or absence of lymph node metastasis, and Dukes' classification were not significant factors. In the presence of these factors, mean corpuscular volume and mean corpuscular hemoglobin concentration values were low, and red blood cells were microcytic and hypochromic. The incidence of a low serum iron level was about twice the frequency of a hemoglobin level of less than 10 g/dl. The results of the multivariate analysis showed that none of the factors were significantly related to iron deficiency.

Adenocarcinoma↗

PubMed1998

A new method of evaluating hemorrhoids with the retroflexed fiberoptic colonoscope.

BACKGROUND: The conventional classification of the degree of hemorrhoids does not consider the severity of hemorrhage. The purpose of this study was to establish a new objective method for evaluating hemorrhoids in close relation to the main symptoms, hemorrhage and prolapse, as observed through a retroflexed colonoscope in the rectum. METHODS: The subjects were 531 consecutive patients who complained of symptoms related to the rectum or the anus. The degree of mucosal elevation of the rectal columns, changes in color (the existence and degree of red color sign, dilated vein, and white area), and the existence and size of hypertrophied anal papillae were evaluated by colonoscopy. RESULTS: Red color sign was the finding closely related to hemorrhage (p < 0.0001). Dilated vein, white area, and a large hypertrophied anal papilla were related to prolapse (p < 0.0001). The degree of mucosal elevation of the rectal columns was related to both hemorrhage and prolapse (p < 0.0005, p < 0.05). CONCLUSION: Retroflexing the colonoscope intrarectally facilitated identification of findings in the anal canal related to hemorrhage and prolapse, which are the clinical manifestations of hemorrhoids.

Adult↗

PubMed1998

Experimental assessment of endoscopic mucosectomy with a cap-fitted panendoscope.

BACKGROUND AND STUDY AIMS: The use of a cap-fitted panendoscope is one method of carrying out endoscopic mucosectomy in the esophagus, stomach, and large intestine. The purpose of this study was to determine the optimal volume of physiological saline for submucosal injection, the rate of mucosal extension after saline injection, the initial size of the resected mucosal specimen, and the most appropriate heights for the fitted caps used in the colon and in the rectum, respectively. METHODS: Endoscopic mucosectomies using cap-fitted panendoscopes were carried out on resected surgical specimens from ten patients with colorectal cancer. RESULTS: It was necessary to inject 12 ml of saline under the mucosa to prevent perforation. Submucosal saline injection extended the mucosa by 1.4 +/- 0.2 times. A cap with a height of 7 mm is suitable for performing mucosectomy in the colon safely, while both 7 mm and 10 mm caps can be used in the rectum. The initial size of the resected mucosal specimens obtained with both caps was 12-20 mm (mean 14 mm) in diameter, with no significant differences. As the sizes of resected mucosal specimens reported in the past have been obtained after submucosal saline injection, it appears that larger specimens can be resected with the cap-fitted panendoscope than with conventional methods. CONCLUSIONS: The conditions under which endoscopic mucosectomy using the cap-fitted panendoscope can be performed safely in the colon and the rectum were suggested by this experimental study using resected specimens. A saline injection of 12 ml under the mucosa is necessary to prevent perforation. A cap with a height of 7 mm is the most suitable size for the colon, while both 7 mm and 10 mm caps can be used in the rectum.

Biopsy, Needle↗

PubMed1998

Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was obtained by stimulation of the celiac ganglion with LPS.

Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was developed by stimulation of the celiac ganglion with lipopolysaccharide (LPS) in pregnant rabbits. The renal and hepatic blood flow were measured after stimulation of the celiac ganglion with 10 microL (group 1), 100 microL (group II) and 300 microL (group III) of LPS (10 mg/mL conc.) and with 100 microL of normal saline (group IV). The bifurcation of the abdominal aorta was also stimulated with 300 microL of LPS (group V). A control experiment was also done in this study (group VI). Histopathological studies of kidney and liver tissue were also performed in this protocol. A significant reduction in renal and hepatic blood flow was observed in pregnant rabbits with the times and dosage dependent on stimulation of the celiac ganglion by LPS. Stimulation of the bifurcation of the abdominal aorta with LPS could not produce any changes in renal and hepatic blood flow. Preeclampsia-like histologic changes of kidney and liver tissue were also observed. These results suggest that exogenous stimulation of the celiac ganglion causes decreased renal and hepatic blood flow, resulting in preeclampsia-like histologic changes of kidney and liver in pregnant rabbits.

Animals↗

PubMed1998

Colorectal cancer recurrence in the liver: detection by PET.

Positron emission tomography (PET) has been successfully used in the imaging of various cancers. In this retrospective study, we examined clinical utility of PET in the imaging of liver metastasis from colorectal cancer. Results of PET were compared with those of ultrasonography (US) and contrast-enhanced computer tomography (CT) in 11 liver metastases seen in eight patients with recurrent colorectal cancer. The detection rates were 73% (8 of 11 metastases) by US, 73% (8 of 11 metastases) by CT, and 82% (9 of 11 metastases) by PET. PET correctly identified US-negative and CT-negative liver metastases. However, PET was negative in one patient with minute metastases. The findings in our preliminary study were in agreement with those of previous reports. A prospective study is warranted to determine the optimum role of PET in the management of patients with colorectal liver metastasis.

Aged↗

PubMed1998

[Immunohistochemical staining of thymidine phosphorylase in primary colorectal carcinoma and metastases].

Thymidine phosphorylase (TdRPase) is an enzyme involved in the pyrimidine metabolism. It was reported that many cancers contained higher levels of TdRPase than normal tissues. And TdRPase has been reported to be identical with the platelet-derived endothelial cell growth factor. To clarify the distribution of TdRPase in primary and metastatic colorectal cancer, we carried out immunohistochemical staining of formalin-fixed specimens. We investigated 35 primary colorectal cancers resected surgically, 27 hepatic metastases and 8 lung metastases from colorectal carcinoma. TdRPase was highly expressed in primary colorectal cancer with lung metastases (100.0%) and surgically resected lung metastases cancer (87.5%). The staining correspondence between primary colorectal cancer and metastases was 19 cases (70.4%) in the liver metastases and 7 cases (87.5%) in the surgically resected lung metastases. The above results suggested that immunohistochemical staining for primary colorectal cancer may provide information about the sensitivity of metastases to the chemotherapy.

Adult↗

PubMed1998

[Method of preventing hepatic artery occlusion during continuous intrahepatic arterial infusion chemotherapy of 5-FU].

A randomized clinical trial of combined use of steroids, which have a vascular endothelium-protecting action, was performed to develop a method to prevent hepatic artery occlusion during continuous intrahepatic arterial infusion chemotherapy with 5-FU. The steroid used was dexamethasone palmitate (Limethason), which has a high rate of uptake by endothelial cells. The 24 patients with advanced colorectal cancer were divided into 2 groups randomly and both were treated with 5-FU 250 mg/day by continuous hepatic arterial infusion for three weeks. The weekly dose was 5-FU 7 V (1,750 mg) adjusted to 50 ml with physiological saline in Group A and 5-FU 7 V (1,750 mg) adjusted to 50 ml with Limethason 1 A (4.0 mg of dexamethasone palmitate) in Group B. The reservoir was replaced every week. No changes in the mixture (appearance, pH, granule diameter, dexamethasone palmitate content) were observed up to one week. Hepatic arterial stenosis was observed in 8 cases in Group A (67%), but was not observed in any of the cases in Group B. The above results indicated that Limethason has a preventive effect against hepatic artery occlusion.

Anti-Inflammatory Agents↗

PubMed1997

Hypolumbarlordosis: a predisposing factor for preeclampsia.

OBJECTIVE: The aim of this research was to study the relationship between lumbar lordosis and preeclampsia. STUDY DESIGN: We studied lumbar lordosis of 52 primipara patients with pregnancy-induced hypertension and 59 normal primipara pregnant women. We determined the lumbar lordotic deviation (LLD) from lumbar lordosis measurement device in the lateral recumbent position and standing position. Roll-over test was performed for both groups. Resistance index (RI) of internal iliac artery was also measured by color Doppler sonography. RESULTS: The LLD was 33 +/- 6.1 degrees week 20-29 and 34 +/- 6.9 degrees week 30-40, respectively. In patients with preeclampsia, the LLD was 19.8 +/- 6.3 degrees week 20-29, 21.3 +/- 7.9 degrees week 30-40. The LLD in patients with preeclampsia was significantly lower than in the normal pregnant women. The LLD correlated to the increase diastolic pressure after roll-over test significantly. Hypolumbarlordosis was frequently associated with high resistance of peripheral vessel. CONCLUSIONS: We conclude that hypolumbarlordosis is frequently associated with preeclampsia. It is also closely related to the mechanism for positive roll-over test and increase of resistance of vessels. As lumbar lordosis does not change greatly in individuals before pregnancy, hypolumbarlordosis may be a predisposing factor for preeclampsia.

Adult↗

PubMed1996

Urinary trypsin inhibitor: a new drug to treat preterm labor: a comparative study with ritodrine.

UNLABELLED: Prevention of preterm delivery is one of the difficult problems facing obstetricians. beta Adrenergic agonists, especially ritodrine, are commonly used in these cases. OBJECTIVES: The aim of this research was to study and compare the effect of urinary trypsin inhibitor (UTI) which has anti-inflammatory anti-cytokine effects with ritodrine in treating preterm labor. STUDY DESIGN: Patients in preterm delivery were randomly selected to be treated either by ritodrine or UTI. In the ritodrine group, uterine contractions were initially suppressed by high doses of ritodrine (up to 300 micrograms/min) and then a maintenance dose was given until 35 weeks of gestation. In the UTI group one vaginal suppository (5000 U) was used daily for 2 weeks. Patients with recurrent preterm uterine contraction during the initial 14 days of treatment, who needed course of other drugs to suppress the contractions, were excluded from the study. Patients responding to the drugs were followed until delivery. Tocolytic index and elastase concentration in the cervical mucus was calculated. Recurrence rate of uterine contraction and time of elongation of pregnancy since the beginning of treatment was calculated. RESULTS: UTI was more effective than ritodrine in inhibition of recurrent uterine contraction and elongation of pregnancy. No side effects could be observed after treatment with UTI for the mother or the fetus. CONCLUSION: UTI may be a new therapeutic method for the inhibition of preterm delivery through suppression of cytokines and inflammatory mediators.

Adrenergic beta-Agonists↗

PubMed1995

Immunohistochemical localization of carcinoembryonic antigen as a predictor of lymph node status in submucosa-invasive colorectal carcinoma.

PURPOSE: Submucosa-invasive colorectal carcinoma is a colorectal carcinoma extending only into the submucosal layer. To clarify the metastatic potential of submucosa-invasive colorectal carcinoma, we studied the relationship between the immunohistochemical staining pattern of carcinoembryonic antigen (CEA) and that of lymphatic invasion/lymph node metastasis. METHODS: We investigated 49 submucosa-invasive colorectal carcinomas resected surgically or endoscopically. CEA distribution patterns of the neoplastic tissues were divided into three patterns: Pattern 1 = luminal type; Pattern 2 = apical cytoplasmic type; and Pattern 3 = diffuse cytoplasmic type. We also observed the submucosal stromal staining of CEA. RESULTS: Lymphatic invasion and lymph node metastasis were found in 48.8 percent (21/43) and 11.6 percent (5/43) of the Pattern 2/Pattern 3 cases, whereas these were seen in none (0/6) of Pattern 1 cases. Lymphatic invasion and lymph node metastasis were found in 63.3 percent (19/30) (chi-squared = 21.94; P < 0.001) and 16.7 percent (5/30) of the positive stromal CEA cases, whereas these were seen in 10.5 percent (2/19) and none (0/14) of the negative stromal CEA cases, respectively. CONCLUSION: Pattern 2/Pattern 3 and stromal CEA can be predictors of the lymph node metastasis with 11.6 percent and 16.7 percent risks.

Adult↗

PubMed1995

Small cell neuroendocrine carcinoma of the rectum.

Poorly differentiated small cell neuroendocrine (NE) carcinoma of the colon and rectum is a rare primary epithelial malignancy at this location. A case of a highly aggressive NE tumor of small cell type, combined with non-invasive well-differentiated papillary adenocarcinoma in villous adenoma is reported. The patient died rapidly with massive and progressive liver metastasis. The tumor cells were argyrophilic and diffusely immunoreactive for neuronspecific enolase and synaptophysin. Ultrastructural analysis disclosed NE-type cored granules in most of the small tumor cells. NE tumors of the colon and rectum are briefly reviewed.

Adenocarcinoma, Papillary↗

PubMed1994

[Mechanism of efficacy of erythromycin on diffuse panbronchiolitis--effect of erythromycin on cytokine mRNA expression in human whole blood model].

Recently, "low-dose and long-term" erythromycin (EM) has been reported to be effective in treatment of diffuse panbronchiolitis (DPB), but its mechanism is still obscure. We studied the effect of EM on cytokine mRNA expression by using LPS-stimulated human whole blood as an experimental vivo model. IL-8 mRNA was expressed in biphasic fashion with peak expression at 6 hours and 20 hours from the start of LPS stimulation. When whole blood was pretreated with EM (2 micrograms/ml) for 1 hours. IL-8 mRNA expression was depressed at 20 hours (p < 0.025) from the start of LPS (1 microgram/ml) stimulation. However, when pretreated for 12 hours, it was not depressed. EM (2 micrograms/ml) also depressed IL-1 beta (p < 0.025) and TNF alpha (p < 0.05) mRNA expressions at 6 hours from the start of LPS stimulation. From the above results, it was suggested that the direct inhibition of IL-1 beta and TNF alpha production by EM resulted in subsequent depression of production of IL-8 that is a potent chemotactic factor for neutrophil, and consequently, EM acts to protect the bronchiole tissues of DPB patients from destruction by proteolytic enzymes released from neutrophils. This assumption seems to be supported by our previous observation that when patients with DPB were treated with EM a marked decrease in number of neutrophil in bronchoalveolar lavage fluid (BALF) was accompanied by clinical and radiographic improvement.

Adult↗

PubMed1994

[Antibiotics susceptibilities and other biological properties of methicillin-resistant Staphylococcus aureus: observation in the last 2 years in our university hospital].

We examined biological properties of strains of methicillin-resistant Staphylococcus aureus (MRSA) which were isolated in our ward in 1991 and 1992. A total of 47 MRSA strains were isolated in 1991 and 64 in 1992. The majority of these strains of MRSA were highly resistant to DMPPC, CEZ and IPM, and were intermediately resistant to MINO. All these strains were, however, sensitive to VCM. The number of coagulase type II strains increased from 22 (46.8%) to 51 (79.7%), and that of enterotoxin type A strains from 27 (57.4%) in 1991 to 47 (73.4%) in 1992. The number of strains which produce Toxic Shock Syndrome Toxin-1 (TSST-1) also increased from 19 (40.4%) to 45 (70.3%), and those strains that produce beta-lactamase decreased from 24 (51.1%) to 21 (32.8%). From the above results, we confirmed the recent change in types of the epidemic strains of MRSA. Namely, there was a marked increase in number of strains which produce type II coagulase type A enterotoxin and TSST-1. For the prevention of a patient to patient-, room to room- and ward to ward-spread, strict isolation was indicated both the infection patients, immunocompromised patients who were at high risk for the infection and the proved carriers. Treatment with VCM was started immediately if MRSA infection was thought plausible. These countermeasures seemed to succeed in reducing the incidence of the infection in our ward.

Anti-Bacterial Agents↗

PubMed1994

[Imipenem/cilastatin sodium alone or combined with amikacin sulfate in respiratory infections].

In the present study, we used the envelope method to divide patients with respiratory infections into two groups: a monotherapy group given imipenem/cilastatin sodium (IPM/CS) and a combination therapy group given imipenem/cilastatin sodium plus amikacin sulfate (AMK). We then compared the clinical efficacy and safety between groups. 1. Safety was evaluated in 83 patients in the IPM/CS group and 88 in the IPM/CS + AMK group while clinical efficacy was evaluated in 77 and 80 patients in the respective groups. 2. The overall efficacy rate was 84.4% in the IPM/CS group. Among the main infections, the efficacy rates were 82.7% in 52 cases of pneumonia (including lung abscess), 100% in cases of infected bronchiectasis, 66.7% in six cases of secondary infection of chronic respiratory disease, and 100% in four cases of chronic bronchitis. The overall efficacy rate was 83.8% in the IPM/CS + AMK group. Among the main infections, the efficacy rates were 88.1% in 59 cases of pneumonia (including lung abscess), 83.3% in 12 cases of infected bronchiectasis, and 60.0% in five cases of secondary infection of chronic respiratory disease. No significant differences in efficacies were seen between groups. 3. In the IPM/CS group, the efficacy rates were 92.3% for patients without prior antibiotic therapy in the IPM/CS group and 68.0% for those with prior therapy; in the IPM/CS + AMK group, the respective rates were 83.7% and 83.9%. In the IPM/CS group, there was a significant difference in the responses of patients with and without prior antibiotic therapy (P < 0.05). 4. Side effects were observed in six patients in the IPM/CS group (7.2%) and two patients in the IPM/CS + AMK group (2.3%). Abnormal laboratory test results were noted in 5 patients in the IPM/CS group (6.0%) and in 10 in the IPM/CS + f1p4group (11.4%). There was no significant difference in the incidence of side effects between groups and no severe adverse reactions in either group. These results indicate that IPM/CS alone produces of good response in moderate to severe respiratory infections while IPM/CS combined with AMK is useful in intractable respiratory infections.

Adolescent↗