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Biomedical subjects

K Akazawa

Publications and source records attributed to K Akazawa.

At least 145 records · Page 8Linked to original sources

The inflammatory cytokines in measles: correlation between serum interferon-gamma levels and lymphocyte subpopulations.

Interleukin-1 (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were measured in serum from children with measles using an immunoradiometric assay. The IFN-gamma level was increased in 52 out of 54 patients in the acute phase of measles (less than 7 days of illness), and then declined to an undetectable level in the convalescent phase. Neither IL-1 nor TNF could be detected during the course of the illness. The mean serum IFN-gamma level was at its peak on day 4 and could be detected over a 7-day period after the onset of fever, coinciding with the febrile period (6.9 +/- 1.5 days). In the acute phase, the phytohaemagglutinin responses, absolute number of platelets, total lymphocyte counts, CD3+, CD4+, CD8+ cell counts and the CD4/8 ratio were depressed, while stab cell number and lactate dehydrogenase levels were higher than those in the convalescent phase. Using Spearman rank sum test, the IFN-gamma level was correlated negatively with the peripheral lymphocyte (P less than 0.01), CD3+ (P less than 0.05), CD4+ (P less than 0.05) cell counts and the CD4/8 ratio (P less than 0.05) and correlated positively with the stab cell count (P less than 0.01) but not with any other parameter. When the acute phase findings were compared between 28 complicated and 40 uncomplicated patients, the former were younger (P less than 0.01) and had higher maximum body temperature during the illness (P less than 0.05) than the latter, there was no difference in their IFN-gamma levels. These results show that endogenous IFN-gamma appears in the circulation during the acute febrile phase of measles, but does not contribute directly to any complication of the disease.

Acute Disease↗

Hepatitis C virus detection is facilitated by the combined use of c100 protein and GOR epitope.

Assay for the antibody to the c100 protein (anti-c100) lacks sensitivity in terms of detection of hepatitis C virus (HCV) in all samples. The author used anti-c100 and antibody to the GOR epitope (anti-GOR) by the enzyme-linked immunosorbent assay to examine 524 patients with chronic liver disease and 682 volunteer blood donors in Fukuoka, Japan. The prevalence of HCV infection, as revealed by the presence of anti-c100 and/or anti-GOR, was 3.9% in 540 volunteer blood donors, 12.7% in 142 volunteers with abnormal liver function, 7.4% in 135 patients with HBsAg-positive liver disease and 89.5% in 389 patients with non-A, non-B (NANB) liver disease. These results show a higher prevalence than demonstrated only by the anti-c100 in NANB liver disease patients (82.5%, P < 0.01). The concurrence of anti-c100 and anti-GOR in subjects with HCV infection was 23.8% in 21 volunteer blood donors, 44.4% in 18 volunteers with abnormal liver function and 61.2% in 348 NANB liver disease patients. The concurrence seems to increase with deterioration of liver function. We concluded that combination assay for anti-c100 and anti-GOR demonstrated a more accurate prevalence of HCV infection than single assay for anti-c100 among NANB liver disease patients, and that the presence of anti-GOR plays a role in liver disease in anti-HCV-positive subjects.

Adolescent↗

Retrospective study of post-anesthetic mild liver disorder associated with inhalation anesthetics, halothane and enflurane.

The incidence of post-anesthetic mild liver disorder (PAMLD) was compared between 928 patients administered halothane and 1766 patients administered enflurane. They were selected from 19 504 surgical patients administered general anesthesia at Kyushu University Hospital over the past 6 years and 4 months. They had had normal liver function before operation and had no history of blood transfusion. Alanine aminotransferase (ALT) levels exceeding 70 IU. l(-1) within 180 days after operation were found in 226 patients in the halothane group (24.4%), and in 250 patients in the enflurane group (14.2%) ( P < 0.01). Both maximum ALT levels and duration of ALT elevation were higher and longer in the halothane group ( P < 0.01). These results suggest that, not only in the development of fulminant hepatitis but also in PAMLD, enflurane is less hepatotoxic than halothane.

Journal Article↗

Changes in pupillary diameter in relation to eye-movement and no-eye-movement periods in the human fetus at term.

OBJECTIVE: The aim of our study was to reveal whether pupils dilate and constrict in a time sequence in the human fetus and to assess the relationship between changes in pupillary diameter and eye-movement-no-eye-movement periods. STUDY DESIGN: We simultaneously observed pupil and eye movement with real-time ultrasonography in 30 human fetuses at 36 to 41 weeks' gestation. Eighteen were excluded because of data loss. Statistical analysis of pupillary diameter changes were made on the remaining 12 fetuses with the least median of squares regression. RESULTS: Pupillary diameters were found to be differentiated with statistical significance into two groups: 9.7% for the dilated pupil (median 3.0 mm) and 90.3% for the constricted pupil (1.7 mm). The percentage of dilated pupils during the eye-movement period (14.3%) was significantly greater than that during the no-eye-movement period (2.3%; Wilcoxon rank sum test, p < 0.0001). CONCLUSION: These findings indicate a close relation between pupillary dilatation and eye-movement periods in the human term fetus.

Eye Movements↗

The characteristics of erythrocyte Na+ transport systems in normal pregnancy and pregnancy-induced hypertension.

OBJECTIVE: To assess the role Na plays in the pathogenesis of pregnancy-induced hypertension (PIH). METHODS: We assessed Na and K content, the maximum number of ouabain binding sites, Na(+)-Li+ countertransport and Na(+)-K+ cotransport in erythrocytes from women with untreated PIH, normal pregnant women and healthy non-pregnant women. RESULTS: In normal pregnancy, the Na content of erythrocytes decreased, accompanied by the activation of Na excretion systems. In women with PIH, the Na content of erythrocytes and the Na(+)-K+ cotransport activity significantly increased, whilst erythrocyte K content and the maximum number of ouabain binding sites significantly decreased, compared with observations in normal pregnancy. In both normal pregnancy and PIH, there were no differences in Na(+)-Li+ countertransport. CONCLUSIONS: These results suggest that the increase of erythrocyte Na content in women with PIH may be contributed to by a reduction in the number of ouabain binding sites, whilst Na(+)-K+ cotransport and Na(+)-Li+ countertransport may compensate for this effect in women with PIH.

Adult↗

Growth retardation in childhood leukemia and lymphoma. Special reference to patients with CNS relapse.

We studied the growth of 89 patients who were long-term survivors of childhood leukemia and lymphoma. Eight patients with CNS relapse had a greater decrease in height standard deviation score (SDS) after the relapse than 81 patients without CNS relapse (p less than 0.0001). Two patients who received cranial irradiation when they were younger than 2 years of age demonstrated a marked decrease in height SDS more than 3.0 SD. Five patients appeared to have a decline in height SDS before their CNS relapse. There were no apparent changes in the weight of patients with or without CNS relapse. In endocrine studies, all eight patients with CNS relapse failed to show the normal growth hormone (GH) response to arginine, GH-releasing factor, and glucagon-propranolol tests, while spontaneous GH secretion during sleep was normal. Magnetic resonance imaging (MRI) revealed small pituitary glands in seven patients with CNS relapse. These findings suggest that in leukemia and lymphoma patients with CNS relapse, GH secretion is impaired at the hypothalamic level, resulting in a secondary atrophy of the pituitary gland. The MRI together with selected endocrinologic tests may help to clarify the mechanism of growth impairment in such patients. A decline in height SDS in each patient may be a useful marker for predicting a CNS relapse in a child with leukemia or lymphoma.

Adolescent↗

The measles outbreak in Chikuhou District, Fukuoka, Japan, 1990: correlation between herd immunity level and outbreak size.

A measles outbreak occurred in the Chikuhou district of Fukuoka, Japan from May to October 1990, during which 71 patients were cared for at the Itoda Public Hospital. Hospital records revealed a large outbreak in the adjacent town of Kanada. In order to characterize the outbreak, questionnaires were sent to all preschool-age children in Itoda (73% effective response) and in Kanada (76% effective response) requesting information about their vaccination and/or history of measles. The number of patients was 22 (4%) in Itoda and 63 (14%) in Kanada, most of these being preschoolers, while the vaccination rate was 61% and 44%, respectively. The herd immunity levels in age-specific groups were compared between the two towns. Before the epidemic, the immunity level of 1 year old children in Kanada, who showed the higher attack rate, was lower (18%) than that in Itoda (39%), while after the epidemic it rose above 60% in both towns. When we studied the correlation between the attack rate and the vaccination rate, or the number of children susceptible to measles (susceptibility rate) in each preschool, the attack rate correlated negatively with the vaccination rate (correlation coefficient [CC] = -0.818; P less than 0.01), and positively with the susceptibility rate (CC 0.860; P less than 0.01). The regressed equation on the correlation indicated that the immunity level should be more than 70% to keep the attack rate under 5% in preschools. After the epidemic, the immunity levels of all preschoolers reached above 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Countermeasures for urinary incontinence in patients with senile dementia: correlation between urinary incontinence severity, senile dementia severity, and activity of daily living].

The actual conditions of urinary incontinence in 101 patients with senile dementia (23 men and 78 women, average age 80 years) and their urinary control was studied. The three categories of 1) dementia severity, 2) activity of daily living and 3) degree of urinary incontinence, were each divided into five grades and the patients were evaluated accordingly. The correlation among the grades was studied. Of the 101 patients, 87 had urinary incontinence. These 87 were further subdivided into two groups: an ambulatory patient group (25) in which the patients could manage their own daily activity, and the bedridden group (62). The countermeasures for the first group of patients were, usage of a portable chamber pot for 6 patients and induced urination in 5. An anticholinergic agent was administered to 47 of the bedridden patients. The condition of urinary incontinence was reevaluated in both groups 4 weeks later. A high degree of correlation was observed among the grades of dementia severity, activity of daily living and urinary incontinence severity. After the countermeasures taken, improvement in urinary incontinence was observed in the 6 patients who used a portable chamber pot, and in the 5 patients who were subjected to induced urination. No improvement was seen in urinary incontinence in the bedridden patients who were treated with an anticholinergic agent. In conclusion, countermeasures for urinary incontinence in senile dementia should be indicated primarily for patients who can manage their own daily activity.

Activities of Daily Living↗

Distribution of basement membrane antigens in human esophageal lesions: an immunohistochemical study.

The distribution of basement membrane components, type-IV collagen and laminin, was studied immunohistochemically in human samples of normal, hyperplastic, dysplastic and carcinomatous esophageal tissue. The expression of basement membrane components in normal, hyperplastic, and mildly and moderately dysplastic mucosa was characterized by a thick, continuous and linear staining pattern. In severe dysplasia and carcinoma in situ, the basement membrane was thinner and occasionally discontinuous. The distribution of basement membrane in invasive carcinomas varied greatly; well-differentiated, cohesive tumors had a basement membrane, however, poorly-differentiated tumors showing irregular cords, or individual cell infiltration, lacked this membrane at the tumor-stromal interface. Many moderately-differentiated tumors showed probable immature assembly of basement membrane components. The expression of basement membrane was also influenced by the extent of stromal inflammation. The absence or presence (staining pattern) of basement membrane components in esophageal squamous-cell carcinoma did not correlate with the survival rate, but did correlate with the histologic differentiation of epithelial organization.

Adult↗

Factors linked to early recurrence of small hepatocellular carcinoma after hepatectomy: univariate and multivariate analyses.

The purpose of this study was to clarify the factors linked to recurrence of small hepatocellular carcinomas, up to 3 cm in diameter, after hepatectomy. Fifty patients with small hepatocellular carcinomas who underwent hepatectomy between 1976 and 1988 were observed for possible recurrence for at least 2 yr. These patients were divided into two groups: 20 patients who had recurrence within 2 yr and 30 patients who had no recurrence within 2 yr. The recurrence pattern was analyzed by hepatic angiography. Statistical analysis by the chi 2 test and stepwise logistic regression showed that the risk factors linked to recurrence were (a) tumor diameter greater than 2.2 cm, (b) intracapsular infiltration of tumor cells, (c) tumor location deep in the liver, (d) macroscopical and microscopical tumor invasion into the portal vein and (e) tumor invasion into the portal vein or intrahepatic metastasis. When patients diagnosed with small hepatocellular carcinomas have any of these risk factors, postoperative adjuvant therapy and follow-up should be particularly carefully considered, since these patients are at high risk for early recurrence.

Carcinoma, Hepatocellular↗

Micro-mainframe-like personal clinical research system.

We constructed a micro-mainframe-link clinical research system for personal use (Personal Clinical Research System). This system was developed with both a mainframe computer and a personal computer (PC). The prepared programs included a database manager (on the mainframe computer), a user interface program (on the PC), and a communication control program that connected the mainframe computer with the PC. The database on the mainframe computer was constructed by two methods. The first method was to transmit data from the PC to the mainframe computer. The second method was to extract data from the patient information database. Using this system, a physician is able to construct a personal research database that contains interesting data for the physician. In addition, the physician is able to accumulate data on a special field using this system. A discharge summary system is now in operation as an example of this system.

Computers, Mainframe↗

A random allocation system with the minimization method for multi-institutional clinical trials.

This paper describes the random allocation system used to perform precise and rapid treatment assignments in multi-institutional clinical trials. This system is based on sophisticated randomization procedures, according to Pocock and Simon's minimization method and Zelen's method for institution balancing. The major advantage of randomized treatment assignments with this system is to balance treatment numbers for each level of various prognostic factors over the entire trial and at the same time balance the allocation of treatments within an institution. Therefore, the randomized treatment assignments by this system can prevent degrading of the statistical power of a particular treatment factor. This system is designed to run on a small-sized notebook computer and therefore can be set up beside a telephone for registration, without occupying a large space. At present, this system is conveniently being used in two clinical trials.

Algorithms↗

Aseptic meningitis in children: correlation between fever and interferon-gamma level.

We studied the correlation between interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in cerebrospinal fluid (CSF) and clinical/laboratory findings in children with aseptic meningitis. In 19/27 patients (70%), the CSF IFN level was high at initial diagnosis, and reduced to a low or undetectable level during the convalescent phase (5-14 days later) of the disease. There were no differences in IL-1 beta and TNF-alpha levels between the acute and convalescent phase of the patients. The serum IFN-gamma levels in the patients, which were simultaneously examined were undetectable in the acute phase. When we compared the clinical/laboratory findings between the 29 patients with detectable CSF IFN-gamma level and the 21 patients with an undetectable CSF IFN-gamma level in the acute phase, the former demonstrated higher body temperature (P less than 0.01), and higher cell number and protein level in the CSF (P less than 0.05) than the latter. On the other hand, there were no significant differences in the duration of meningeal signs, the titre of C-reactive protein, and the peripheral leucocyte count between the two groups. By the Spearman's rank sum test, the CSF IFN-gamma levels correlated more definitively with the severity of febrile episode (maximal body temperature, duration of fever and body temperature at the first lumbar tap), and the cell number and protein level in the CSF. These results suggest that IFN-gamma produced in the inflamed intrathecal space may be associated with the pathogenesis of aseptic meningitis, especially the production of fever.

Child↗

Tumor necrosis factor in the cerebrospinal fluid of children with central nervous system leukemia.

To clarify the role of cytokines in cerebrospinal fluid (CSF) in the pathogenesis of central nervous system (CNS) leukemia, three cytokine activities, interleukin 1 (IL-1)-beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma, and their correlations with other laboratory studies of the CSF were analysed in 23 children with acute leukemia. These patients were classified into three groups: group A (n = 8)--patients with overt CNS leukemia, group B (n = 5)--patients with CNS leukemia in remission, group C (n = 10)--patients without CNS disease. IFN-gamma in the CSF was undetectable in these 23 patients. There was no difference in IL-1-beta levels among the three groups. However, TNF-alpha levels were significantly higher in group A than in group B, and higher in group B than in group C. By Kendall's rank sum test, high TNF levels in CSF correlated with high CSF leukemic cell counts and low sugar levels. In two patients with overt CNS leukemia, the TNF level in the CSF decreased gradually with intrathecal chemotherapy. These results indicate that TNF released from stimulated cells in the cerebrospinal space may induce CNS leukemia-related symptoms or alter laboratory parameters measured in the CSF. TNF levels in CSF may also prove useful in diagnosing early CNS involvement in children with acute leukemia.

Acute Disease↗

Simulation program for estimating statistical power of Cox's proportional hazards model assuming no specific distribution for the survival time.

Small sample properties of the maximum partial likelihood estimates for Cox's proportional hazards model depend on the sample size, the true values of regression coefficients, covariate structure, censoring pattern and possibly baseline hazard functions. Therefore, it would be difficult to construct a formula or table to calculate the exact power of a statistical test for the treatment effect in any specific clinical trial. The simulation program, written in SAS/IML, described in this paper uses Monte-Carlo methods to provide estimates of the exact power for Cox's proportional hazards model. For illustrative purposes, the program was applied to real data obtained from a clinical trial performed in Japan. Since the program does not assume any specific function for the baseline hazard, it is, in principle, applicable to any censored survival data as long as they follow Cox's proportional hazards model.

Clinical Trials as Topic↗

[3H]MK-801 binding to forebrain of E1 (epileptic) and non-epileptic strains of mice.

The El mouse is an animal model with genetically determined epilepsy. To elucidate the mechanism of convulsive seizures in El mice, the effects of L-glutamate and glycine on the binding of (+)[3H]MK-801 were studied in well-washed membranes from forebrains of ddY, BALB/c and El (stimulated and non-stimulated) mice. There were no significant differences in affinity (Kd) or density (Bmax) among the 4 groups of mice under basal conditions. Incubation in the presence of L-glutamate and/or glycine led to an increase in apparent density, but not in affinity. No significant change was observed in either Kd, Bmax, or the percentage increase in (+)[3H]MK-801 binding amount the 4 groups in the presence of L-glutamate and/or glycine. These results suggest that the seizure susceptibility of El mice cannot be explained by changes in affinity or density of the NMDA receptor/channel complex.

Animals↗

CNS pathology in the neurological mutant rats zitter, tremor and zitter-tremor double mutant (spontaneously epileptic rat, SER). Exaggeration of clinical and neuropathological phenotypes in SER.

The pathological alterations in the central nervous system (CNS) were examined in three kinds of mutant rat; the zitter (zi/zi; Zi), the tremor rat (tm/tm; Tm) and the spontaneously epileptic rat (SER) which is a double mutant carrying both zitter and tremor genes. Two major alterations demonstrated in these mutants were hypomyelination and vacuolation or spongy degeneration. Hypomyelination was observed predominantly in SER and to a lesser extent in Zi, and was accompanied by a redundant or aberrant myelin sheath formation in addition to a decreased number of myelinated fibres. This appeared to be related to the occurrence of tremor. There was no abnormality in the structure of the myelin lamellae and oligodendrocytes or any destruction of myelin sheaths by phagocytic cells. The number of radial components in CNS myelin was increased almost equally in Zi, Tm and SER. Vacuolation was prominent in SER and Tm, especially in the brainstem and thalamus. Zi also developed mild vacuolation with advancing age. Vacuolation seemed to be related to the epileptic phenomena in SER and Tm. Vacuoles consisted mainly of swollen astrocytic processes and enlargement of the extracellular space, as well as occasional enlargement of periaxonal spaces. Thus both pathological findings--the hypomyelination derived from the zitter mutation with tremor, and the vacuolation from the tremor mutation with epileptic symptoms--were mutually exaggerated in SER. It is postulated that the two different genetic loci with zi and tm mutations interact and synergistically reinforce each other both clinically and pathologically in SER.

Aging↗

Human hepatocellular carcinoma sensitivity to antitumor drugs assayed using the succinate dehydrogenase inhibition test.

Chemosensitivity of hepatocellular carcinoma tissues from 72 patients to 6 antitumor agents was assayed using the succinate dehydrogenase inhibition test. Sensitivity was positive in 47.2% of tissues exposed to adriamycin, 53.5% to mitomycin C, 10.3% to 5-fluorouracil, 51.5% to cisplatin and aclacinomycin A. respectively, and 52.9% to carboquone. Eight percent of the tissues were sensitive to all 6 drugs, while the resistance rate to all drugs was 36.5%. The remaining 55.5% were sensitive to only some of the drugs. When a comparison of the sensitivity to the 6 drugs was made between two different areas of tumors in 16 patients, positive or negative sensitivity was in a range of 76.9-92.9%. The hypovascular masses seen on the angiography and the histologically well differentiated tumors were resistant to adriamycin, a drug most commonly prescribed to treat patients with liver cancer. For some of these tumors, mitomycin C or carboquone may be effective. Our observation shows that the succinate dehydrogenase inhibition test is useful for determining which drugs will be effective for a particular tumor.

Aged↗