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Biomedical subjects

K Tsugawa

Publications and source records attributed to K Tsugawa.

At least 37 records · Page 2Linked to original sources

Role of nitric oxide and endothelin-1 in a portal hypertensive rat model.

BACKGROUND: Portal hypertension is often accompanied by a hyperdynamic circulation state. Some reports have suggested that nitric oxide (NO) plays an important role in this hyperdynamic state. On the other hand, although endothelin (ET)-1, a powerful vasoconstrictor, was recently identified, little is known about its role in portal hypertension or about the interaction between NO and ET-1. The aim of this study was therefore to investigate whether or not the inhibitor of NO synthase (NOS) might improve portal hypertension, and also to clarify the relationship between NO and ET-1. METHODS: Portal hypertensive (PHT) rats, in which hypertension was induced by a two-step ligation of the portal vein (PVL), were used. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), and serum levels of NO and ET-1 were determined in PVL rats treated with two NOS inhibitors with different functions: N(G)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG). Control (CTR) rats. treated by a sham operation (SO), were also studied. RESULTS: Two-step PVL treatment induced a significant increase in the serum level of NO3-and ET-1 in the portal vein. L-NAME and AG administration significantly decreased PP at doses of 50 mg/kg in PHT rats after 60 min administration, while no inhibitor effected any modification in the CTBR rats. Both NOS inhibitors increased MAP and decreased PP and BFV in the portal vein, gastric mucosa, and spleen, in addition to decreasing the serum levels of NO3- and ET-1 in the PHT rats, while neither blockade modified any parameters in the CTR rats. In PHT rats, L-arginine, a NO substance, reversed the effect of L-NAME, while it did not induce any recovery from the AG effect. CONCLUSIONS: In PHT rats, NO seems to contribute to portal hypertension. PVL increases not only the serum level of NO3-, but also that of ET-1 in the portal vein. Both L-NAME and AG reduce PP and BFV of the portal vein, spleen, gastric mucosa. and liver. In addition, the inhibition of NOS diminishes the serum level not only of NO, but also of ET-1. Use of an appropriate NOS inhibitor may therefore positively affect the hyperdynamic state in portal hypertension.

Animals↗

Endoscopic ligation of oesophageal varices compared with injection sclerotherapy in primary biliary cirrhosis.

BACKGROUND AND AIMS: Oesophageal varices are an important complication in primary biliary cirrhosis (PBC). However, there have yet to be any studies made on treatment of oesophageal varices in PBC. We therefore studied the efficacy and related complications of endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) as an initial treatment in primary biliary cirrhotic patients. METHODS: From December 1985 to March 1999, 29 biliary cirrhotic Japanese patients with portal hypertension and oesophageal varices were treated in our clinics. Eleven patients were treated with EVL and EIS, and 18 patients underwent EIS only. The liver function, renal function and respiratory function were studied before and after endoscopic treatment and any complications were also examined. RESULTS: In stages III and IV, significant differences were observed in the serum levels for total bilirubin and gamma-glutamic pyruvic transaminase only in the EIS group. Significant differences were observed in the rate of appearance of pyrexia, retrosternal pain and pleural effusion between the EIS and EVL groups. CONCLUSION: EVL significantly reduced the adverse effects associated with EIS at the initial session in primary biliary cirrhotic patients.

Esophageal and Gastric Varices↗

Role of vascular endothelial growth factor in portal hypertensive gastropathy.

BACKGROUND AND AIMS: Portal hypertensive gastropathy (PHG) is now recognized as a distinct entity; however, the angiogenesis in the portal hypertensive gastric mucosa has yet to be elucidated. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in both physiological and pathological angiogenesis. The aim of this study was thus to examine the function of VEGF in the portal hypertensive and non-portal hypertensive gastric mucosa. METHOD: Forty-five cirrhotic patients were divided into 3 groups as follows. Group I included 15 patients without PHG who were treated with 1.5 g teprenone/day for 8 weeks: PHG(-)-t. Group II included 15 patients with PHG who were not treated with teprenone: PHG(+)-n. Group III included 15 patients with PHG who were treated with teprenone for 8 weeks: PGH(+)-t. The gastric mucosal blood flow (GMBF), the concentration of gastric mucosal VEGF and hexosamine and the endoscopic findings were studied both before and after medication. RESULTS: Before teprenone treatment, the GMBF in the antrum, fundus, fornix were significantly higher in PHG(+)-n than PHG(-)-t. After treatment, the GMBF in the fundus and fornix significantly decreased more than before treatment in the PHG(+)-t. After treatment, the GMBF in the antrum increased significantly more than before treatment in PHG(-)-t. The gastric VEGF and hexoxamine concentration in the antrum were significantly higher in PHG(+)-n than in PHG(-)-t. After treatment, the gastric VEGF and hexosamine concentration in the antrum significantly decreased in PHG(+)-t while no change in concentration was recognized in PHG(+)-n. In the endoscopic findings, a decrease in the PHG score was recognized in 2 patients in PHG(+)-t. CONCLUSION: Portal hypertensive gastric mucosal change was thus found to trigger a high concentration of VEGF and hexosamine. Such increased activity of VEGF and hexosamine may thus account for the presence of active congestion in PHG.

Adult↗

Prognosis of node-positive breast cancer patients who underwent parasternal lymph node biopsy during surgery followed by doxorubicin- or mitoxantrone-containing adjuvant chemotherapy.

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.

Adult↗

[Sentinel lymph node biopsy and axillary lymph node dissection].

Sentinel lymph node (SLN) biopsy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. A combination of dye- and gamma probe-guided methods can identify SLN more accurately and easily than either of these techniques alone. On the other hand, SLN biopsy is highly accurate and sensitive in patients with small tumors, and no false-negative SLN biopsy has been reported for a breast cancer < 1.0-1.5 cm. Moreover, extensive intraoperative examination of SLNs using frozen sections can attain a sensitivity comparable to that obtained by histologic examination on the permanent sections. In practice, therefore, axillary dissection can be avoided in patients with small tumors in whom the SLNs are negative.

Axilla↗

Leiomyosarcoma of the thyroid gland with rapid growth and tracheal obstruction: A partial thyroidectomy and tracheostomy using an ultrasonically activated scalpel can be safely performed with less bleeding.

Primary leiomyosarcoma of the thyroid gland is rare, and to the best of our knowledge only nine well-documented cases have been previously reported in the world literature. We herein report a 90-year-old female patient with primary leiomyosarcoma of the thyroid gland who showed a rapid tumor growth and tracheal obstruction. The patient was successfully treated by a partial resection of the thyroid gland using an ultrasonically activated scalpel and emergency tracheostomy. Immunohistochemically, the tumor cells showed positive reactivity to smooth muscle actin and negative reactivity to thyroglobin. Palliative surgery successfully allowed the patient to recover from the symptoms of dyspnea related to this rare disease. The use of an ultrasonically activated scalpel and tracheostomy thus allowed us to safely perform a thyroidectomy with substantially less bleeding than normal.

Aged↗

Nucleotide sequences of genes for ribosomal protein L41 and tRNAThr(AGU) from Coprinus cinereus.

The nucleotide sequences of genes for the homolog in Coprinus cinereus of the eukaryotic ribosomal protein L41 and for tRNAThr(AGU) are reported. The gene for tRNAThr(AGU) was located upstream of the gene for the L41 ribosomal protein, and these genes were adjacent to each other but in opposite orientations. The deduced amino acid sequence of ribosomal protein L41 exhibited strong homology to those of L41 proteins of several yeasts. The 56th amino acid of the deduced protein was proline, as it is in the L41 protein of a cycloheximide-sensitive strain of yeast. The putative secondary structure of the tRNA gene resembled the characteristic cloverleaf structure of tRNAs. Elements resembling an A-box and a B-box were found in the gene for tRNAThr(AGU). These boxes are known as internal promoter elements in genes for eukaryotic tRNAs.

Amino Acid Sequence↗

The Outcome of Patients with Breast Cancer Who Underwent Breast Conserving Treatment with or without Immediate Volume Replacement with Autogenous Tissue.

BACKGROUND: Breast conserving treatment (BCT) is accepted as an appropriate therapy for most patients with stage I and stage II breast cancer. However, BCT is associated with a relatively high incidence of local recurrence, and aesthetically unacceptable results occur in some patients. A novel method of immediate volume replacement using autogenous tissue has been developed to strike a balance between adequate excision and cosmesis. We determined the oncological outcome inpatients with breast cancer treated with wide excision, immediate volume replacement with autogenous tissue, and axillary dissection followed by radiotherapy. METHODS: One hundred fifty-three patients with TIS, stage I, II, or III breast cancer underwent wide excision and axillary dissection. The surgical margin ofexcised breast tissue was examined histologically during surgery. If involved, the breast tissue adjacent to the primary site was excised. When the margin of re-excision was positive, patients underwent modified radical mastectomy with or without breast reconstruction. After wide excision, immediate volume replacementwith autogenous tissue was perform-ed, unless the deformity was corrected by undermining and conization of the residual breast tissue. Postoperatively, all patients received breast irradiation. RESULTS: Eighteen patients underwent modified radical mastectomy. The surgical margin was negative in 132 of the 135 patients who underwent BCT. The crude local recurrence rate was 0.7% (1/135). Estimated overall and disease-free 5-year survival rates were 96% and 94%, respectively. CONCLUSION: Wide excision with tumor-free margins and axillary dissection followed by breast irradiation provides adequate local control in many patients with breast cancer. Immediate breast volume replacement with autogenous tissue mayavoid some unpleasant cosmetic results associated with extensive local resection. Our technique eliminates the need for mastectomy in selected patients.

Journal Article↗

Results of laparoscopic splenectomy for immune thrombocytopenic purpura.

BACKGROUND: Laparoscopic splenectomy has been demonstrated to be technically feasible and safe for the treatment of immune thrombocytopenic purpura (ITP), hereditary spherocytosis, and Hodgkin's disease. PATIENTS AND METHODS: The study comprised 76 consecutive patients with chronic ITP who were admitted to our hospital from 1968 to 1997 and underwent splenectomy; 35 patients underwent a laparoscopic splenectomy, and 41 had open surgery. RESULTS: Laparoscopic splenectomy involved minimal incision, and a significantly lower frequency of analgesia was required for postoperative abdominal pain (1.4 versus 3.3); postoperative hospital stay was shorter (9.6 versus 20.1 days, P <0.05). Operative time was significantly longer for the laparoscopic surgery (204.5 versus 99.8 minutes, P <0.01), but blood loss was less (154.4 versus 511.7 g, P <0.01). During the present study (range 3.8 to 80 months), accumulative nonrecurrence rate was 67.9% in 5 years after surgery, which is similar to that of the previous open splenectomy. CONCLUSIONS: Laparoscopic splenectomy can become an alternative therapeutic modality in the treatment of ITP.

Adult↗

Sentinel lymphadenectomy in breast cancer: identification of sentinel lymph node and detection of metastases.

Sentinel lymphadenectomy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. However, controversies remain concerning the optimal method to identify the sentinel lymph node (SLN) and detect micrometastases in this lymph node. We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of preoperative lymphoscintigraphy with intraoperative dye-guided and gamma probe-guided methods achieves a higher rate of identification of SLN than any of these techniques alone. (b) Immediate and reliable intraoperative assessment of sentinel node status is vital to the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot always be identified. (c) Hematoxylin and eosin (H&E) staining and/or immunohistochemistry on permanent sections are useful for the detection of micrometastases in the sentinel node. Although a reverse transcriptase-polymerase chain reaction (RT-PCR) method is more sensitive than H&E staining and immunohistochemistry, it would not distinguish benign from malignant epithelial cells in the SLN. Therefore, further study is required before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer.

Axilla↗

Staging efficacy of breast cancer with sentinel lymphadenectomy.

Seventy-two patients underwent dye-guided or dye- and gamma probe-guided sentinel lymphadenectomy (SLND) followed by complete axillary lymph node dissection (ALND). The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) were compared to each other and to the histologic findings in the nonsentinel nodes. The SLN was identified in 62 (88%) of 72 patients. Evaluation of the SLN on the permanent sections yielded a diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100%, although the reliability of SLN diagnosis using frozen sections or imprint cytology is limited. Therefore, it may be concluded that SLND with multiple sectioning and histopathologic examination of the SLNs can predict the presence or absence of axillary-node metastases in patients with breast cancer. However, further studies will be needed to investigate the value of SLND in respect to the long-term regional control and any possible detriment or benefit to survival, before it can replace routine ALND as the preferred staging operation for operable breast cancer.

Adult↗

A selective cyclo-oxygenase-2 inhibitor, NS-398, may improve portal hypertension without inducing gastric mucosal injury.

BACKGROUND AND AIMS: Prostacyclin has been shown to play a role in hyperdynamic circulation in portal hypertension. Recently, a new subtype of cyclo-oxygenase (COX), COX-2, which acts as an inducible synthase in response to various stimuli. The aim of this study was to investigate whether COX-2 contributes to portal hypertension and whether a COX-2 blockade induces the same sort of gastric mucosal injury as a COX-1 blockade. METHODS: Portal hypertension (PHT) in rats was induced by a two-step ligation of the portal vein. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), serum levels of 6-keto-prostaglandin F1alpha (PGF1alpha), thromboxane B2 (TXB2) and gastric mucosal injury induced by pure ethanol were all measured in PHT rats receiving different inhibitors (indomethacin, a highly selective COX-1 inhibitor; NS-398, a highly selective COX-2 inhibitor). Control rats treated by a sham operation were also studied. RESULTS: The NS-398 administration significantly decreased PP to the same extent as indomethacin at doses of 5 and 10 mg/kg in PHT rats after a 60 min administration, while neither inhibitor affected the control rats. Both inhibitors significantly increased PP after a 30 min administration in the PHT and control rats at a dose of 5 mg/kg while both inhibitors significantly decreased PP after 60 min administration only in the PHT rats. Portal vein ligation treatment induced a significant increase in PP and BFV of the portal vein, gastric mucosa, oesophageal mucosa and the serum levels of 6-keto-PGF1alpha and TXB2, while portal vein ligation treatment induced a significant decrease in BFV of the liver. Both blockades increased MAP and decreased PP and BFV in the splanchnic area and decreased the serum level of 6-keto-PGF1alpha and TXB2 in the PHT rats, while neither blockade modified any parameters in the control rats, except that indomethacin administration significantly decreased the BFV of the gastric mucosa. Indomethacin administration significantly increased the ulcer index (UI). The NS-398 had no effect on UI in either the PHT or control rats. Only indomethacin significantly increased the number of rats demonstrating gastric mucosal long lesions (> 2 cm) in the PHT rats. CONCLUSION: In the PHT rats, prostaglandin seemed to contribute to portal hypertension. Both COX blockades reduced PP and BFV of the portal vein and gastric mucosa. NS-398, a selective COX-2 inhibitor, may, therefore, improve portal hypertension without inducing gastric mucosal injury.

6-Ketoprostaglandin F1 alpha↗

Adjuvant chemotherapy with a combination of mitoxantrone, methotrexate, 5-fluorouracil for node-positive breast cancer: phase II pilot study.

A phase II pilot study was carried out on 30 patients to ascertain the toxicity and efficacy of combination chemotherapy with mitoxantrone, methotrexate, 5-fluorouracil (NMF) in the adjuvant setting for axillary lymph node-positive breast cancer. The NMF regimen was mitoxantrone 10 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2 administered i.v. on day 1, repeated every 3-4 weeks for 6 cycles. The median nadir WBC count was 2,000/microl; grade 4 leukocytopenia occurred only in 1 patient. Nausea and vomiting appeared as grade 0 and 1 severity in 26/30 patients. Alopecia was extremely mild, appeared as grade 0 and 1 in 29/30 patients. The overall and relapse-free survival rates were 67.8% and 68.4% at the 82-month follow-up, respectively. The overall survival rate in premenopausal patients was significantly better than that in postmenopausal patients (P<0.05). NMF is a well-tolerated combination regimen, suitable as adjuvant chemotherapy for node-positive breast cancer.

Adolescent↗

The effect of carbon dioxide pneumoperitoneum on the portal hemodynamics in a portal-hypertensive rat model.

As use of laparoscopic surgery grows, various complications with pneumoperitoneum have been reported. However, there are no reports on the relation between the carbon dioxide (Co2) pneumoperitoneum and portal hemodynamics. The purpose of this study was to determine how the pneumoperitoneum affects the portal hypertensive state. Portal-hypertensive rats, control rats, and sham operation rats were studied. The mean arterial pressure, portal venous pressure, central venous pressure, red blood flow volume of the viscera, and liver and renal function were investigated. The findings of this study suggest that Co2 pneumoperitoneum at less than 10 mm Hg does not present any undue risk to the portal hemodynamics in portal-hypertensive rats; however, more attention should be paid to the IAP in PHT patients undergoing surgery.

Animals↗

Dye-Guided Sentinel Lymphadenectomy in Clinically Node-Negative and Node-Positive Breast Cancer Patients.

BACKGROUND: Sentinel lymphadenectomy has been used to assess the axillary nodal status in patients with breast cancer in an attempt to avoid unnecessary axillary dissection. Most studies have examined the utility of this procedure in clinically node-negative patients. However, the clinical evaluation of axillary nodes is often inaccurate for both clinically node-negative and clinically node-positive patients. METHODS: We performed dye-guided sentinel lymphadenectomy in both clinically node-negative and clinically node-positive patients with breast cancer. All patients also underwent a formal axillary dissection. The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) werecompared with each other and with histologic findings of the nonsentinel nodes. RESULTS: The SLN was identified in 30 (79%) of 38 patients with clinically negative nodes, and in 11 (92%) of 12 patients with clinically positive nodes. Forclinically node-negative patients, SLN evaluation yielded a diagnostic accuracyof 90%, a sensitivitiy of 72%, and a specificity of 100%. For clinically node-positive patients, these values were 100%, 100% and 100%, respectively. These values were not significantly different for the two groups of patients. CONCLUSION: Sentinel lymphadenectomy may be useful in assessing the axillarynodal status of both clinically node-positive and clinically node-negative breast cancer patients.

Journal Article↗

Expanding the Role of Breast-Cancerving Therapy Using Immediate Volume Replacement.

Preventing local recurrence and preserving cosmetic appearance are often in conflict in breast-conserving therapy. Immediate volume replacement with autogenous tissue has been developed to allow a wider excision without compromising the aesthetic results. A review of the literature regarding immediate volume replacement in breast-conserving therapy has led to the following conclusions. When excision of the skin overlying the tumor is unnecessary, a transverse or lateral incision should be used which allows wide excision and immediate volume replacement with autogenous tissue while minimizing scar morbidity. The options for immediate volume replacement include the latissimus dorsi flap with adipose tissue, the latissimus dorsi myocutaneous flap, and the lateral thoracic adipose tissue flap. The choice of technique depends on the amount and position of the skin, subcutaneous tissue, and breast tissue which must be excised. These procedures can be used to extend the indications for breast-conserving therapy, eliminating the need for mastectomy in selected patients. Future developments in the endoscopic harvesting of flaps may further expand the role of volume replacement.

Journal Article↗

Sentinel Lymphadenectomy in Breast Cancer: An Alternative to Routine Axillary Dissection.

We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of lymphoscintigraphy and dye-guided and/or gamma probe-guided techniques are superior to either technique alone for identifying the sentinel lymph node. (b) lmmediate and reliable intraoperative information on the sentinel node is vital for the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot be identified. (c) A reverse transcriptase-polymerase chain reaction(RT-PCR)method is more sensitive than immunohistochemistry for the detection of micrometastasis in the sentinel node. (d) Until there are new tumor markers or new imaging techniques to identify axillary metastasis without operative intervention, sentinel lymphadenectomy is a highly accurate, minimally invasive way to assess disease extent. Before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer, however, a large clinical trial will be essential to verify the value of this technology.

Journal Article↗

The Role of Internal Mammary Lymph Node Metastases in the Management of Breast Cancer.

We reviewed the literature regarding internal mammary lymph node metastasis in the management of breast cancer. Internal mammary dissection or radiotherapy provides no survival advantage in breast cancer patients. However, internal mammary nodal metastasis is an important independent prognostic factor. Patients with such metastases are candidates for systemic adjuvant hormonal therapy and/or chemotherapy. Moreover, in patients with histologically confirmed internal mammary metastases, irradiation of the nodes is appropriate for local control. Noninvasive techniques, such as internal mammary lymphoscintigraphy, parasternal sonography, computed tomography, and magnetic resonance imaging, are not satisfactory for the practical diagnosis of internal mammary metastasis. At present, biopsy of the internal mammary nodes in the first and second intercostal spaces is indicated for assessing nodal status and planning treatment.

Journal Article↗