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Biomedical subjects

K Akazawa

Publications and source records attributed to K Akazawa.

At least 127 records · Page 7Linked to original sources

Patient registration and treatment allocation in multicenter clinical trials using a FAX-OCR system.

This article describes the design and results of implementation of an automated patient registration and treatment allocation system (RETAS) used in multicenter clinical trials. RETAS was developed using a FAX-OCR system by which handwritten Japanese and English characters, as well as numericals and forms with check boxes, are sent from participating institutions by Fax, processed using an optical character reader, and then transmitted to a host computer at a statistical center. Based on the facsimile data, RETAS can automatically review eligibility, collect patient identification data and provide a randomized treatment allocation. RETAS permits uninterrupted, unattended operation at a statistical center, 24 hours a day, 7 days a week. Therefore, it drastically decreases the workload of personnel at the statistical center needed to support central telephone registration coverage. Consequently, staff members are free to focus on patient registration, treatment allocation, and follow-up of patients. The treatment allocation procedure in this system is based on Pocock and Simon's minimization method combined with Zelen's method for institution balancing. By this system it was possible to balance treatment numbers for each level of various prognostic factors over an entire trial and, at the same time, balance the allocation of treatments within an institution. The system currently supports the protocol of a clinical trial for Adjuvant Chemo-Endocrine Therapy for Breast Cancer in West Japan.

Computer Systems↗

Lymph node metastasis and macroscopic features in early gastric cancer.

The relationship between macroscopic features and the frequency and extent of lymph node metastasis was examined retrospectively in 421 patients with early gastric cancer. Nodal involvement was evident in 48 patients (11.4%): 7 out of 204 (3.4%) with mucosal cancer and 41 out of 217 (19.3%) with submucosal lesions. The incidence of metastasis to perigastric nodes and extraperigastric nodes was 2.9% and 0.5% for mucosal cancer, and 13.8% and 5.1% for submucosal cancer, respectively. There was no metastasis in lesions less than 1 cm in diameter, but the incidence of positive nodes increased with the size of the primary lesion. There was a low incidence of lymph node metastasis associated with lesions confined to the mucosa and less than 3 cm in size, elevated types of I and IIa less than 2 cm, and the flat type of IIb, while types consisting of a depressed portion such as IIc, III, IIc + III, and IIa + IIc often had not only perigastric but also extraperigastric nodal involvement, even when the lesion was small. As early gastric cancer can be cured by surgery, this modality is the treatment of choice. Endoscopic therapy in cases with a low involvement of lymph node metastasis can be considered when the patient is in a poor clinical state of health.

Adult↗

Do patients with intermittent claudication need surgical treatment?

To determine whether surgical intervention is of therapeutic significance for patients with intermittent claudication (IC), 315 patients with IC followed in our outpatient clinics for the past 8 years 3 months (mean of 3 years 10 months), including 142 non-operated and 173 operated patients, were investigated as to changes in symptoms and the prognosis. Changes in symptoms in both groups were analyzed according to the variable distances of claudication and location of the diseased artery. To examine the degree of association between surgery and improvement of symptoms, Goodman and Kruskal's gamma was used. For all subgroups with a variable claudication distance (group A; distance < 100 m, B: 100-500 m, C: > 500 m), surgery inversely correlated with improvement in symptoms (group A; gamma = -0.378, group B; gamma = -0.651, group C; gamma = -0.828). According to location of the diseased artery, surgery correlated with improvement in symptoms in aorto-iliac (gamma = -0.811), aorto-ilio-superficial femoral (gamma = -0.641), and superficial femoral-distal (gamma = -0.533) groups but not in superficial femoral (gamma = -0.427) or infrapopliteal (gamma = -0.194) alone groups. Concerning the prognosis, no significant difference was noted between operated and non-operated groups (p = 0.35). These computed data show that surgical intervention has therapeutic significance for patients with IC, except for cases of claudication with segmental occlusion of the superficial femoral or infrapopliteal artery alone.

Aged↗

DNA polymerase alpha as an independent prognostic parameter in non-small cell lung cancer--an immunohistochemical study.

We examined 70 fresh frozen sections of primary non-small cell lung cancer using a monoclonal antibody for DNA polymerase alpha (POL alpha). The tumors were divided into two groups; those with more than 5% of POL alpha positive cells were designated as POL alpha (+), while those with less than 5% were POL alpha (-). POL alpha (+) tumors were obtained in 33 (47%) cases. The incidence of POL alpha (+) in male patients was statistically higher than in females (P < 0.01). The incidence also correlated with the T(tumor) status; T1 < T2, T1 < T4, with a significance (P < 0.05). Based on data on 70 patients, the 5-year survival rates of POL alpha (+) and POL alpha (-) were 36% and 63%, respectively (p < 0.05). In 48 patients with adenocarcinoma, the 5-year survival rates of POL alpha (+) and POL alpha (-) were 25% and 60%, respectively (P < 0.05). In addition, in 26 patients with a tumor size of less than 3 cm, the 5-year survival rates of POL alpha (+) and POL alpha (-) were 13% and 74%, respectively (P < 0.01). To compare the prognostic significance of the variables, a multivariate analysis was used to show significance for survival in POL alpha (p < 0.05). Our data show that in non-small cell lung cancer, POL alpha expression is associated with the extent of malignancy and survival. Therefore, POL alpha is considered to be a useful prognostic parameter.

Adult↗

Immunohistochemical expression of carbohydrate antigen 19-9 in colorectal carcinoma.

OBJECTIVES: Carbohydrate antigen 19-9 (CA19-9) is one of the most representative tumor markers in colorectal carcinomas. We studied the immunohistochemical expression of CA19-9 in primary colorectal carcinoma to identify its significance as a prognostic factor. METHODS: The avidin-biotin-peroxidase complex method was used for CA19-9 staining in sections from 149 patients with primary colorectal carcinoma. The data were studied by univariate and multivariate analyses. RESULTS: 86 tumors (56%) stained positively. The staining pattern was classified into three groups: group I (a stromal type, 22 tumors), group II (an apical and/or cytoplasmic type, 64 tumors), and group III (no staining, 63 tumors). Eight clinicopathologic variables showed a significant relationship with the staining pattern of CA19-9. The 5-yr survival rate of the group I subjects was significantly lower than that of the other two groups. With the multivariate analysis, the staining pattern of CA19-9 proved to be one of the independent prognostic variables. CONCLUSIONS: In addition to conventional prognostic factors, the staining pattern of CA19-9 is considered to be of value in predicting the prognosis of patients with colorectal carcinomas.

Antigens, Tumor-Associated, Carbohydrate↗

Proliferating cell nuclear antigen expression and argyrophilic nucleolar organizer regions as factors influencing prognosis of surgically treated lung cancer patients.

Cell proliferation in 211 primary non-small cell lung carcinomas was assessed by using an immunostaining of proliferating cell nuclear antigen (PCNA) and a silver staining of argyrophilic nucleolar organizer region (Ag-NOR). More than 5% PCNA positive cells was designated PCNA(+), and less than 5% was PCNA(-). A mean number or more of the Ag-NOR was a high Ag-NOR count, and less than the mean number was a low Ag-NOR count. The proportion of the tumors with PCNA(+) and high Ag-NOR counts showed an increase in patients in an advanced stage of the disease (P < 0.05). In 125 patients with stage I disease, the 5-year survival rate was 20% in patients with PCNA(+) and high Ag-NOR counts, compared with 47% in those with either PCNA(+) or high Ag-NOR counts and 76% in those with PCNA(-) and low Ag-NOR counts (P < 0.05). Our data suggest that the tumors with PCNA(+) and high Ag-NOR counts have a high proliferative activity. The combination analysis of PCNA and Ag-NOR may be useful in assessing prognosis in lung cancer, even in stage I disease.

Adenocarcinoma↗

Relationship between paraaortic lymph node involvement and intraperitoneal spread in patients with ovarian cancer--a multivariate analysis.

In 125 patients with epithelial ovarian cancer (FIGO stages I-IV), 32 (26%) had paraaortic lymph node (PAN) metastases. The estimated 5-year survival rate of PAN-negative patients was 71%, while that of PAN-positive patients was 17% (P < 0.0001). Positive rates of PAN metastasis at each stage level, based only on intraperitoneal spread of the disease, were 2% for stage I, 9% for stage II, 43% for stage III, and 87% for stage IV. According to univariate analysis, histological grade, and all disease site parameters examined, such as subdiaphragmatic surface, liver and spleen capsule, intestines and mesentery, omentum, pelvic peritoneum, sigmoid colon and rectum, uterus and tubes, and peritoneal cytology, showed a statistically significant correlation to the presence of PAN metastasis. Multivariate analysis using the logistic regression model revealed that the omental involvement, uterine and tubal involvement, and histological grade were independently correlated with PAN metastasis. The relative risk of PAN metastasis in the patients with these three factors is 18.5 times higher than that in patients without these factors. The present data suggested that, for the disease with omental and/or uterine and tubal involvement, surgical evaluation of PAN is mandatory in order to perform correct FIGO staging.

Abdominal Neoplasms↗

Serum interleukin-6 and fever at diagnosis in children with acute leukemia.

PATIENTS AND METHODS: We examined serum interleukin (IL)-6 and tumor necrosis factor (TNF) alpha levels at initial diagnosis in acute leukemic children in order to clarify the roles of these cytokines on the febrile and hematological responses in the disease. RESULTS: IL-6 levels were significantly higher in 34 leukemic children than in 18 healthy controls and 15 patients with various malignant diseases in long remission (p < 0.0001). Three patients with apparent bacterial infections showed especially high IL-6 levels of > 100 pg/ml. In all the leukemic children, the high IL-6 levels at initial diagnosis had decreased to a low range at the time of complete remission, regardless of the use of antibiotics. In 10 of 14 leukemic children, TNF levels were high at diagnosis and then decreased to undetectable levels at remission. The relationship between IL-6/TNF levels and clinical/laboratory findings in leukemic children at diagnosis was also examined. Serum IL-6 significantly correlated with elevated body temperature (BT) (p < 0.001) and C-reactive protein (CRP) levels (p < 0.001), but not with other parameters such as leukocyte and platelet counts, hemoglobin levels, lactate dehydrogenase, and serum immunoglobulin. On the other hand, serum TNF did not show any statistical linkage with these parameters. CONCLUSION: These data provide evidence for the role of IL-6 in the pathogenesis of tumor-related fever and other acute phase responses in acute leukemia.

Adolescent↗

Early carcinoma of the stomach.

We analyzed data on 423 Japanese patients with early carcinoma of the stomach with respect to clinicopathologic features and prognosis. All patients were treated in the clinics at which we work. The upper one-third of the stomach was less frequently involved. Therefore, partial gastrectomy was performed more often in patients with early carcinoma of the stomach than in those with advanced carcinoma of the stomach. The differentiated type of carcinoma of the stomach was more frequent and grew expansively. Lymph node metastasis was noted in 11.6 percent of the patients, lymphatic vessel involvement was evident in 13.5 percent and extensive lymph node dissection (R2 or R3) was performed in 86.0 percent. The 15 year survival rate for patients with early carcinoma of the stomach was 89.0 percent. Lymph node metastasis, differentiated tumor type and patient age proved to be independent prognostic factors, as determined by multivariate analysis. Increased detection of early carcinoma of the stomach in its curable stages may be achieved through gastrointestinal series and endoscopy for symptomatic patients. A close follow-up evaluation is essential to detect recurrences, even when a curative resection is performed.

Female↗

Prognostic significance of electrocardiographic findings in patients with dilated cardiomyopathy.

The prognostic significance of electrocardiographic variables was retrospectively investigated in 88 patients with dilated cardiomyopathy and with normal coronary arteriograms. During an average follow-up of 3.7 +/- 2.9 years, 43 patients died, 26 of progressive heart failure, 15 patients with sudden death, and one due to cerebral embolism. Excluding one patient, who died of esophageal cancer, the cumulative survival rate was 73% at 2 years and 60% at 5 years. By univariate life table analysis, abnormal Q-waves, a QRS duration > or = 0.12s, a cardiothoracic ratio > or = 60%, systolic blood pressure < 110mmHg, and left ventricular end-diastolic pressure > or = 15mmHg were significantly associated with increased mortality within 5 years. Multivariate analysis using Cox's proportional hazards model determined the major independent risk factors in the following order: (1) for all patients; the presence of abnormal Q-waves, left bundle branch block or intraventricular conduction disturbances, left ventricular end-diastolic pressure, systolic blood pressure and the cardiothoracic ratio; (2) for patients without left bundle branch block or intraventricular conduction disturbances; abnormal Q-waves, left ventricular end-diastolic pressure and systolic blood pressure. The present study thus demonstrated that the electrocardiogram could provide independent prognostic predictors in patients with dilated cardiomyopathy, possibly reflecting the severity of myocardial damage.

Cardiomyopathy, Dilated↗

Rolling mouse Nagoya as a mutant animal model of basal ganglia dysfunction: determination of absolute rates of local cerebral glucose utilization.

In order to elucidate the neuronal mechanism of the motor disturbances of the Rolling mouse Nagoya (rolling), a neurological mutant mouse (genotype rol/rol) showing frequent lurching and falling over on walking, we determined absolute rates of local cerebral glucose utilization (LCGU) with the [14C]deoxyglucose method. The rates were compared with those of heterozygote (+/rol) with normal behavior, and of normal mice (+/+) of the same strain (C3Hf/Nga). Rolling showed marked and significant increases in LCGU in the structures of the basal ganglia such as the globus pallidus, entopeduncular nucleus, substantia nigra pars compacta and pars reticulata, and subthalamic nucleus, confirming our previous finding with semiquantitative LCGU determination. Additional significant but much less marked increases in LCGU of rolling were found in some structures of the brainstem and limbic system, such as the pedunculopontine nucleus, red nucleus, ventral tegmental area, lateral habenula, and CA1 and CA3 of the hippocampus. Although rolling has been regarded as an animal model of cerebellar ataxia, rolling showed no alterations of LCGU in the cerebellum. The heterozygote showed intermediate increases in LCGU between rolling and normal mice in the basal ganglia structures such as the globus pallidus, substantia nigra pars reticulata and subthalamic nucleus. Our findings indicate that rolling has a definite, genetically determined dysfunction of the basal ganglia. The primary site of the basal ganglia dysfunction might probably be in the striatum, involving both the neostriatum and limbic striatum, and resulting in secondary dysfunction in their target structures.

Animals↗

Early myelination in zitter rat: morphological, immunocytochemical and morphometric studies.

Early myelination in zitter rat was investigated by light and electron microscopic observations, by immunostaining for myelin basic protein (MBP), proteolipid protein (PLP) and myelin-associated glycoprotein (MAG), and by morphometric analysis from the 1st to the 28th day of age. Although the commencement of myelination in zitter rats was not delayed in comparison with control rats, the density or the number of myelinated fibers in zitter rats was significantly below that in controls, both in the ventral column of the cervical spinal cord and in the optic nerve. In contrast, the density or the number of aberrant myelin sheaths was increased in zitter rats, and this difference became more marked with increasing age. The persistent presence of abnormal membranous structures associated with the oligodendroglial nuclear membrane and the increased number of aberrant myelin sheaths were characteristic to the zitter mutation, although these alterations were also observed transiently in control rats. Quantitative analysis supported the proposition that hypomyelination in zitter rats is primarily pathological and becomes more prominent with advancing age. However, the fundamental structure of the myelin lamellae appeared to be normal and the immunoreactivities for MBP, PLP and MAG were slightly delayed and weakend in comparison with age-matched controls. Thus, in zitter rat there is the functional abnormality of the oligodendrocytes to integrate the processes of membrane biosynthesis and to expel excessive production of membranous structures associated with the membranous organellae such as nuclear membrane, and it is postulated that this functional abnormality is characteristic to only the zitter mutation.

Aging↗

Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy.

Three hundred forty-five patients with invasive carcinoma of the uterine cervix, Stages Ib (211 patients) and II (134 patients), underwent radical hysterectomy and pelvic lymphadenectomy. The influence of histologic factors including histologic subtype, maximum depth of cervical stromal invasion, degree of stromal invasion, longitudinal tumor diameter, lymph-vascular space invasion, corpus invasion, parametrial invasion, vaginal invasion, and pelvic lymph node (PLN) metastases on survival were examined by multivariate analysis. Univariate analysis revealed that all the variables except corpus invasion and vaginal invasion were significant in survival (P less than 0.05). Among these variables, however, PLN metastases, histologic subtype, and longitudinal tumor diameter were identified as independent and significant prognostic factors by multivariate analysis using Cox regression models. The prognostic index (PI), defined by the model (an indicator of the patient's place in the prognostic spectrum), was able to divide the patients into three prognostic groups. The key factors in the definition of these groups were (1) squamous cell carcinoma, small tumor diameter, and no PLN metastases for the good prognostic group and (2) PLN metastasis in two or more node groups, adenocarcinoma with one positive PLN group, or squamous cell carcinoma with one PLN group and large diameter for the poor prognostic group. These prognostic findings could predict the prognosis more precisely than that of clinical staging.

Adult↗

Prognostic factors for noncurative gastric cancer: univariate and multivariate analyses.

We performed univariate and multivariate analyses of possible prognostic factors related to postoperative clinical course of patients with advanced gastric cancer. Noncurative resection was done for 119 patients with hepatic metastasis, peritoneal seeding, extensive lymph node metastasis, or direct invasion to adjacent organs, either alone or in various combinations. In the univariate analysis, 6 of 17 items such as peritoneal seeding, lymphatic invasion, vascular invasion, mode of invasion, extent of lymphadenectomy, and width of serosal invasion significantly correlated to the prognosis. The multivariate analysis indicated that three inherent pathologic factors, mode of invasion, lymph node metastasis, and hepatic metastasis, and one treatment factor, extent of lymphadenectomy, were significant variables predictive of the prognosis and that the prognosis was expected to be very poor in cases of infiltrative type, nodal involvement to tertiary nodes, presence of hepatic metastasis, and lymphadenectomy less than R3. Prognosis in terms of the extent of lymphadenectomy shows that extensive lymphadenectomy (R3) proved to be significantly effective in prolonging survival time, even after noncurative gastrectomy. We recommend extensive lymphadenectomy to prolong survival time for such patients.

Adenocarcinoma↗

A visual field quantification system for the Goldmann Perimeter.

We have developed a visual field quantification system that can accurately quantify the measurement results by the Goldmann Perimeter (GP). This system calculates the plural indexes introduced in published papers. In recent years, several isopter quantification methods have been proposed. In these methods, the isopters are digitized and the data are input into a computer, after which a computer program evaluates the changes in the isopters quantitatively. However, each program is only able to evaluate private indexes. We have developed a system that quantifies data using multiple methods. This system used five methods that have been introduced in published papers. With this system, a physician can analyze GP data with multiple methods and can diagnose diseases accurately. We have already input about 2500 GP recording papers into the computer by this system. We then calculated the plural indexes, and visualized the temporal changes in the perimetry.

Humans↗

The effect of a multiple literature database search--a numerical evaluation in the domain of Japanese life science.

In literature database searching, we show that it is necessary to use plural databases for a more improved search. We also compare the results of a single database search with that of multiple database search in the domain of Japanese life sciences. We searched the MEDLINE and EMBASE using the same search terms. There were some differences in the results, owing to differences in the journals and recording methods. We herein show some of the differences in the journals contained in both databases. Furthermore, we show the differences in the number of papers derived from the same journal. Next, as an example of a practical search, we selected some universities in Japan, searched both databases regarding papers published from these universities and then merged the results by hand. According to our results, only 63% of all papers were common to both databases.

Biological Science Disciplines↗