Search PubMed⌕ Search

Biomedical subjects

Y Tokuda

Publications and source records attributed to Y Tokuda.

At least 73 records · Page 4Linked to original sources

Nurses' perspectives concerning do-not-resuscitate (DNR) orders.

The purpose of this study was to investigate the views of the nursing staff concerning do-not-resuscitate (DNR) orders at the Tokai University Hospital where a controversial incident occurred several years ago. A 'Questionnaire on DNR Orders' was circulated and the anonymous answers were collected two weeks later. The questionnaire was returned by 706 of 780 (90.5%) nurses from every ward/specialty, which revealed that 87% of the nurses felt that DNRs were occasionally necessary, with more than 40% of the nurses answering that they took part in DNR. Further, 36% of the nurses stated that patient consent was indispensable, and 64% thought that the patient's family and physician could decide DNR in the event the patient was physically unable to give consent. Moreover, 66% of the nurses expected the establishment of a DNR order sheet to be formulated as a matter of hospital policy; only 5% of the nurses thought that such an order sheet would not be necessary. Comparing these results with a previous study polling physicians at the Tokai University Hospital, nurses are more likely than physicians to think that patient consent is indispensable, and want the establishment of a standardized DNR order sheet as hospital policy. There is, in fact, a "tacit understanding" between physicians and patients' families in medical practice in Japan. However, DNR is definitely a medical decision. Therefore it should be clearly stated in a standardized format, although such a procedure presently seems unlikely, in view of the Japanese traditional value system.

Adult↗

Palpability of breast tumors--correlation with ultrasonic findings.

With the recent development of high-resolution real-time ultrasonic devices and their application to clinical examination and breast screening, small non-palpable breast lesions have frequently been detected and controversy has arisen concerning their diagnosis and treatment. In order to evaluate the relationship between ultrasonic B-mode images and palpability of breast tumors, 71 breast tumors including 21 cancers were analyzed. Five basic measurements on tumor size and location were performed followed by calculation of secondary parameters of palpability. Larger size (D and W), less distance from the skin surface (S-T), less embeddedness within or more protrusion from the mammary gland (G-T) and greater relative size of tumor with respect to whole breast thickness (D/(S-P)) were found to be significantly related to greater palpability of breast tumors. Among the qualitative diagnostic criteria for breast tumors, an irregular shape, rough border, thick boundary echoes, heterogeneous internal echoes and indirect signs were statistically more frequent in palpable than non-palpable tumors, and in malignant than in benign tumors. In cases of cancer, palpability was related significantly only to size and to heterogeneous internal echoes. For early detection of breast cancer, identification of breast cancer among small non-palpable breast lesions less than 1 cm in size in ultrasonic B-mode images is considered to be essential.

Breast Neoplasms↗

Autografting with peripheral blood CD34-positive cells following high-dose chemotherapy against breast cancer.

We report autologous CD34+ cell transplantation performed in 3 cases of recurrent breast cancer. The hematological recovery in these cases was assessed by comparing with that in the previous cases of autologous hematopoietic stem cell transplantation performed with the same high-dose chemotherapy regimen. Patient 1 was a 32-year-old woman with pulmonary and skeletal metastases; patient 2, a 55-year-old woman with pulmonary metastases; and patient 3, a 48-year-old woman with hepatic metastases. On day 1, cyclophosphamide 1000 mg/m2 and epirubicin 130 mg/m2 were administered concurrently with granulocyte colony-stimulating factor, and peripheral blood stem cells were harvested on days 14-16. These stem cells were processed using anti-CD34 monoclonal antibody and an immunomagnetic bead device, Isolex 300i. The high-dose chemotherapy regimen consisted of cyclophosphamide 2000 mg/m2/day, div, and thiotepa 200 mg/m2/day, div on day -5, -4, and -3. The harvested CD34+ cells numbered 3.9 +/- 2.8 x 10(6)/kg (range: 0.73-7.8/10(6)/kg), and the CFU-GM, 8.3 +/- 5.6 x 10(5)/kg (range: 1.2-15.1/10(5)/kg). After the separation, the percent of CD34+ cells was 81.9 +/- 11.6% (range: 65.8-96.4%), the CD34+ cell yield, 71.8 +/- 30.2% (range: 46.0-129.6%), and the CFU-GM yield, 48.9 +/- 9.1% (range: 35.3-62.0%). At the time of transplantation, the number of nucleated cells was 0.55 +/- 0.31 x 10(5)/kg, and that of CFU-GM, 31.2 +/- 17.8 x 10(5)/kg. Comparison of the hematological recovery in these three cases with that in patients receiving an identical high-dose chemotherapy regimen revealed recovery rates significantly faster than in patients having bone marrow transplants, and approximately identical with that in peripheral blood stem cell transplantation cases.

Adult↗

Dose-Intensified Chemotherapy for Breast Cancer: Present and Future Prospects.

With the trend to maximize chemotherapy in breast cancer, the use of peripheral blood stem cells in addition to hematopoietic growth factors to alleviate myelosuppression caused by dose-intensified chemotherapy has been shown to be beneficial. In treatment of metastatic breast cancer, response rates and complete response rates as high as 100%and nearly 80%, respectively, have been reported. Such treatments have shown even greater promise in an adjuvant setting for high-risk breast cancer. High-dose chemotherapy studies, however, involve highly-selected patient populations who are generally compared with unselected patients, and controversy still surrounds the question of whether it is substantially superior to conventional-dose chemotherapy. There are now more than sufficient data to justify ongoing randomized trials, and the most important overall recommedation is to encourage patients to participate in these clinical trials.

Journal Article↗

Un-cross-linked fibrin substrates inhibit keratinocyte spreading and replication: correction with fibronectin and factor XIII cross-linking.

Wound repair is characterized by the presence of a fibrin-rich matrix, but the effect of fibrin on re-epithelialization remains unclear. In this study, we determined the effects of different fibrin matrices on cultured human neonatal keratinocytes. Using purified fibrinogen and fibrin gels generated by the enzymatic action of thrombin, batroxobin (it leads to retention of fibrinopeptide B), or Agkistrodon contortrix thrombin-like enzyme (ACTE; it leads to retention of fibrinopeptide A), we determined the effect of each of these matrices on keratinocyte morphology, attachment, spreading, and replication as compared to tissue culture plastic. Morphologically, keratinocytes seeded on fibrin surfaces were more rounded and formed three-dimensional structures. Specific cell attachment, as measured at either 37 degrees C or 4 degrees C, was not altered on the different fibrin substrates (P > .05) but was increased on fibrinogen and factor XIII cross-linked fibrin (P < .01). However, keratinocytes seeded on fibrin, regardless of the presence or absence of fibrinopeptides A or B, showed a marked decrease (up to 71%) in cell numbers by days 5 (P = .0357) and 10 (P = .0114). Keratinocyte spreading was decreased by 78.8% (P = .0006), 80.3% (P = .0001), and 89.2% (P = .0001) on thrombin-, batroxobin-, and ACTE-generated fibrin, respectively, but not on fibrinogen-coated dishes. However, either the addition of fibronectin or cross-linking of fibrin with factor XIII allowed full keratinocyte spreading to occur (P = .0002 and P = .0013, respectively). We conclude that fibrin inhibits keratinocyte spreading in the absence of other matrix or plasma proteins or cross-linking by factor XIII.

Cell Adhesion↗

Immunohistochemical detection of tumor cells in the bone marrow of breast cancer patients.

BACKGROUND: Contamination of bone marrow and peripheral blood stem cells with tumor cells is a problem that may be encountered when autologous hematopoietic stem cell transplantation is conducted concurrently with high-dose chemotherapy. METHODS: Using monoclonal antibodies to a variety of tumors, the detection of tumor cells in the bone marrow of breast cancer patients was studied by immunohistochemistry. RESULTS: KL-1 and CAM5.2 were strongly reactive with breast cancer cells, but not with normal bone marrow cells. The reactivity of the tumor cells with EMA was not strong, and DF-3 and 115D8 yielded only slightly positive reactions. These latter antibodies also exhibited some reactivity to normal bone marrow cells. When tumor cells were admixed with normal cells, the sensitivity of CAM5.2 and EMA permitted the detection of one cell in 10(4), but with KL-1, the detection of one in 10(5) cells was possible. When immunohistochemical staining was used in testing 40 patients with advanced or recurrent breast cancer, positive reactions were obtained in four of 27 patients (14.8%) with KL-1, four of 26 (15.4%) with CAM5.2, and nine of 37 (23.7%) with KL-1 + CAM5.2, figures similar to those reported by others who studied stage IV patients. CONCLUSIONS: Immunohistochemical staining with KL-1 and CAM5.2 is therefore considered to be a useful technique for detecting contamination by tumor cells.

Antibodies, Monoclonal↗

Ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate: case report.

OBJECTIVE AND IMPORTANCE: We report a rare case of a ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate. CLINICAL PRESENTATION: A 44-year-old woman had undergone microvascular decompression for a right-sided facial spasm. The preoperative vertebral angiogram did not show any aneurysmal dilation. The right anteroinferior cerebellar artery, which was compressing the exit zone of the facial nerve, was detached and fixed to the dura mater with ethyl 2-cyanoacrylate. Nine years later, the patient suffered a subarachnoid hemorrhage caused by the rupture of a newly developed aneurysm of the right anteroinferior cerebellar artery. INTERVENTION: The aneurysm was clipped 2 days after onset of the subarachnoid hemorrhage. It consisted of two bulges in the arterial wall on the proximal side of the meatal loop. One bulge was stuck to the dura mater of the pyramis by ethyl 2-cyanoacrylate, which had been used in the microvascular decompression 9 years previously. CONCLUSION: This is the first reported clinical case of a de novo aneurysm induced by a cyanoacrylate adhesive. Ethyl 2-cyanoacrylate can damage the arterial wall and induce a de novo aneurysm.

Aneurysm, Ruptured↗

Usefulness of MR angiography in detection of persistent trigeminal arteries.

OBJECTIVES: To examine the usefulness of magnetic resonance angiography (MRA) in detection of persistent trigeminal arteries (PTA). MATERIAL AND METHODS: 3D-time-of-flight (TOF)-MRA images obtained from 1100 patients (798 males and 302 females aged 6-75 years with a mean of 55 years) at our and related institutions were examined retrospectively for PTA. The course of the PTA was classified into the posteromedial type and posterolateral type. Charts of the patients were also examined retrospectively for clinical symptoms related to PTA. RESULTS: PTA was observed in 5 (0.45%) of the 1100 patients, and no aneurysm or arteriovenous malformation was noted in any of these 5 patients. PTA was the posteromedial type in 2 and posterolateral type in 3. PTA was possibly related with clinical symptoms in only 1 patient with oculomotor paresis. CONCLUSION: MRA is useful for non-invasive screening for PTA.

Adolescent↗

A case of an inflammatory variant of epidermolysis bullosa acquisita: chronic bullous dermatosis associated with nonscarring mucosal blisters and circulating IgG anti-type-VII-collagen antibody.

A 42-year-old man showed prominent blistering lesions of the mouth and esophagus in addition to a few bullous lesions of the skin. Direct immunofluorescence microscopy revealed distinct linear deposition of IgG and C3 at the epidermal basement membrane zone where slight deposition of IgA and IgM was also observed. In direct immunoelectron-microscopic examination, antibody was detected in the sublamina densa of the basement membrane zone. Immunoblot analysis with dermal extracts demonstrated that the patient's serum contained circulating IgG antibodies against the 290-kD protein, which comigrated with type VII collagen. The lesions healed without any scars. The results of these studies corresponded to the laboratory findings in epidermolysis bullosa acquisita (EBA), although the clinical features were distinct from classic EBA.

Adult↗

[Treatment of advanced breast cancer: current issues].

Because the great majority of patients with advanced breast cancer have been traditionally placed under the care of surgeons, therapeutic planning is usually done by making operative management the key even at the present time when operable breast cancer is appropriately recognized to represent a systemic disease. For advanced breast cancer to be treated more effectively, systematically planned multimodality treatment must be undertaken. The development of G-CSF and stem cell transplantation to counter hematopoietic toxicity have allowed the safe use of high-dose intensity chemotherapy, which has also been applied in the neoadjuvant setting. Recent experience with neoadjuvant chemotherapy (NACT) has shown promise and indeed some good responders have been offered breast conserving surgery. NACT also serves as an in vivo chemosensitivity test, the results of which are to be exploited in chemo-hormonal therapy after locoregional treatment. Although further studies are required to evaluate this treatment more precisely, multicycle dose-intensified chemotherapy can now be safely and liberally incorporated into systematically planned multimodality treatment for advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

A Humanized Anti-c-erbB-2 Monoclonal Antibody for the Treatment of Breast Cancer.

The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers that overxpress the c-erbB-2 gene. Its overexpression is also speculated to be correlated with chemoresistance to doxorubicin. The in vitro and in vivo anti-tumor effects of a humanized antibody directed against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 had direct antiproliferative activity against the SK-BR-3 cell line which overexpresses c-erbB-2. The in vivo treatment, using rhu4D5, of SCID mice carrying xenografts of 4-1ST human gastric carcinoma, which overexpresses c-erbB-2, revealed that the recombinant protein had potent anti-tumor activity. Furthermore, the cytotoxic action of human peripheral blood mononuclear cells against the SK-BR-3 cell line was significantly augmented with the administration of rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might be a more efficacious treatment than previously predicted by preclinical studies.

Journal Article↗

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in breast cancer.

Since 1981 we have conducted four studies of the treatment of metastatic and postoperative high-risk breast cancer with high-dose chemotherapy supported by autologous hematopoietic stem-cell transplantation (AHSCT). Study I, involving 56 metastatic cancer patients, proved that induction chemotherapy produces a lasting complete response (CR) in only a few cases despite the achievement of a CR rate higher than that expected from standard chemotherapy. Study II was designed to examine consolidation chemotherapy in metastatic cancer patients responding to induction chemotherapy. At a median follow-up of 26 months (range 2-66), consolidation therapy produced a 5-year progression-free survival rate of 27.1% in 30 patients showing a CR or a partial response to induction therapy and 58.6% in 13 patients showing a CR to consolidation therapy. No treatment-related death occurred during study II. The same regimen used in study I was employed for 58 postoperative high-risk patients in study III. The 10-year disease-free survival rate recorded for patients with > or = 10 positive axillary lymph nodes was significantly higher (P < 0.05) in the AHSCT-supported chemotherapy group than in the conventional chemotherapy group. A double high-dose regimen was adopted for 21 postoperative high-risk patients in study IV. The 3-year disease-free survival rate recorded for 9 patients with > or = 10 positive axillary lymph nodes was 71.4% at a median follow-up of 25 (range 8-45) months. No treatment-related death occurred during study IV. Peripheral blood stem-cell transplantation shortened the duration of bone marrow suppression more effectively than did bone marrow transplantation, thereby optimizing high-dose chemotherapy.

Adult↗

New immunodeficient (nude-scid, beige-scid) mice as excellent recipients of human skin grafts containing intraepidermal neoplasms.

Engraftment of normal or lesional human skin onto nude or SCID (severe combined immunodeficiency) mice has been used as an in vivo experimental model. However, this model has some limitations, such as shrinkage and loss of the grafted skin over time. To improve the experimental model, we have produced two new SCID-lineage mouse strains, BALB/cA-nude-scid (nu/nu, scid/scid) and BALB/cA-beige-scid (bg/bg, scid/scid) mice, by the method of cross intercross. Intraepidermal neoplastic lesions such as Bowen's disease were grafted onto the back of the mice of these strains. The rate of reduction in the size of the grafts was lower on nude-scid and beige-scid mice than on SCID mice. Rates of survival of neoplastic cells in the grafts were higher in nude-scid mice than in SCID and beige-scid mice (SCID mice 38%, nude-scid mice 55%, beige-scid mice 38%). Neoplastic cells of Bowen's disease grafted onto a beige-scid mouse proliferated and invaded the dermis during 233 days of observation, confirming the progression to invasive squamous cell carcinoma from carcinoma in situ. The present study revealed that nude-scid and beige-scide mice newly produced by us provide a very useful in vivo experimental model for the investigation of carcinogenesis and tumor progression in human skin.

Animals↗

A case of angiosarcoma of the breast.

This is a case report of a 20-year-old woman who had primary angiosarcoma of the left breast, with metastases to the spleen and ovary. Eight months after detecting a mass in her breast, she underwent mastectomy with biopsy of the ipsilateral axillary lymph nodes, splenectomy and bilateral oophorectomy. Five months after the operation, the patient succumbed to lung metastases. Angiosarcoma of the breast is a rare condition with a poor prognosis, and there are no established chemotherapeutic regimens as yet. Immunohistochemical staining for endoglin, known to be expressed mainly on the surface of endothelial cells, was positive. This suggests the possibility of treating angiosarcoma with anti-endoglin monoclonal antibodies.

Adult↗

A case of multiple endocrine neoplasia type 2B.

A sporadic case of multiple endocrine neoplasia type 2B in a twenty-six year old man who manifested medullary thyroid carcinoma, multiple mucosal neuromas of the tongue and a marfanoid habitus is reported. At the time of diagnosis, he also had multiple liver and lung metastases. Genetic analysis of his lymphocytes revealed a point mutation in exon 16 of the RET proto-oncogene. Since multiple endocrine neoplasia type 2B has a relatively poor prognosis because of the occasional aggressive behavior of medullary thyroid carcinoma, the necessity of the genetic diagnosis of multiple endocrine neoplasia in the early stage is suggested.

Adult↗